Physiological Psychology

PSYCH 261 - Spring 2018 - University of Waterloo

Daniel Smilek

Lecture 1: May 2, 2018

Tests: M/c (40-50), short answer (paragraph). Non-cumulative. Based on both lectures and text. 5-6 just from the text.
Participation: register on learn. Start next Wednesday. 2 Freebie classes.

Physiological Psychology

An interest in the nervous system. Intersection between nervous system and these things:

You;re older, bad eating habits. You have stroke - preventing bloodflow to specific region of brain. Nervous tissue starts to die. Seem to recover just fine, but people around you that you're neglecting the left side of space. Occurs when people have a stroke that occurs to the right hemisphere - localized in the superior temporal areas and parietal areas. Referred to as neglect/spatial/hemispatial/unilateral neglect. You fail to pay attention to objects on the left side of space. Damage on right side, ignore left side. Not that you're blind. Visual system is fine. People start to recover over time - shows plasticity - brain can recover after damage. Ignore left side of body. Unaware that they have a deficity - anasognosia. Rare to neglect right side (left damage). contralateral representation. You also neglect left side when you make mental images. Feel like they've perceived everything. Hard to get them to consider the other side. Negative affect linked to the ignored information. Things you tend to ignore, you tend to devalue - rate them as being more negative. Attention and emotion appear to be somehow linked. It's a problem of consciousness.

Split Brain - surgery that cut the corpus callosum. brain conencted by bridge of tissue - corpus callosum. Some patients had heavy cases of epilleptic seizures - overactive electrical brain - electrical storm. Starts in one location and spreads throughout brain. Tensing of muscles, fall over, verbal moans. Maybe if cut corpus callosum, can prevent from spreading to next hemisphere - reduce seizures. It worked. Little disturbance in ordinary daily behaviour, temperament, and intellect of individuals. It seemed like it wasn't so bad. They did experiments to target parts of brain. The two hemispheres have two sperate consciousnesses. The human brain is actually two brains. When cerebrum divided surgically, it's like they have two separate spheres of consciousness. You can get bizarre things going on - alien hand effect - two arms controlled by 2 different hemispheres not talking to each other. Could have a fight with each other.

Procoess visual information in the back of your head - occipital area. You can divide external space down the middle. Right visual field -> left hemisphere. Left visual field -> right hemisphere. Put on left, they don't know. Speech is only on left hemisphere. Speech system can't access the information if it's on the left visual field. Lateralization of Function - some functions are laterlized to one side of hemisphere. There's hemispheric assymetry and there's hemispheric specialization. It was processed by right hemisphere, and left side of body can pick out the object. It has some awareness of what's going on. There are still subcortical connections between hemisphere -but that's not a natural flow of information (agenesis of corpus callosum - developmental compensation). Theory: communication is due to commonality of external world.

Lecture 2: May X, 2018

Historical Perspectives

Focus on key ideas and how they may have changed throughout history.

Early Understanding - Egyptian document bought by Edwin Smith (american archaeologist) - Edwin Smith Surgical Papyrus. Sounds like a semi-modern mental textbook. Has an ailment, tells you how to examine that ailment, possible treatments for that ailment. Gaping wound in the head. Exposed skull, squigglies, throbbing Fontanel. Oil - antibiotic properties. Should not bandage him - want inflammation to leave the brain They could've known a lot more than they wrote.

Early Greeks - 400 BCE. Hippocrates and Aristotle. A lot of Greek writings - what they thought about the relation between the body and the mind. At the time, they used "soul". Different schools of thought.

Even if you could link mind to physical area or particles, is this illsutrative of a link between something that is a physical material and then mind that's a different substance that's non-material. Or is the mind material itself?

Psychic Pneuma - Galen of Pergamon (130-200 CE) - Believed there's an immaterial psychic pneuma that's invisible like air. It was responsible for main aspects of main aspects of conscious eperience - perception, cognition, action. It emenates from ventricles and fills the nerve tubes and animates the individual. (We know now that ventricles, filled with fluid, are spearate from the nerves.)

Rene Decartes (1596-1650 CE) - You have two different substances - the material substance (body) and an immaterial substance (mind/soul) - dualism. Monism - mind and body are of the same substance. Antirealism - monism and it's immaterial. DEscartes argued for a dualistic perspective. The human body is a material machine robot. You have these change sin ventricle pressure that determines behaviour. Some behaviours are just a natural response of this machine. Touch something that's hot, your arm recoils. It doesn't require consciousness. It's a reflex. Animals are completely machine - they don't have a soul. Humans are different cause they have a soul. They are a ghost in a machine. Experiments could be done to test ideas. The mind/soul is an immaterial substance. This immaterial substance communicated with the body through the Pineal gland. The soul would essentially manipulate the pineal gland like a joystick. The seat of the interaction of th ematerial and immaterial would be the pineal gland. It doesn't follow the same physical laws the body does - you have to study the mind a different way. The only way to study, you have to ask people to report what they're feeling - introspection.

Luigi Galvani (1737-1798) - Italian psychologist. (Galvanic skin - measure skin sweat - measure arousal). Already known at the time: electrical stimulation can make the body move, the nerves wwere somehow involved with the communication between the brain and the body but no one knew how they were involved. (Newton believed that the nerves communicated through vibrations like string instruments. Some people believed it was an invisible force) By accident, Galvani's assistant took a scalpel that was statically charged and touched the nerve of an exposed frog leg, and it jumped. Connectign something electrical to the nerve lead to the muscle contraction. Maybe the nerves conduct an electrical impulse. Perhaps there's a key electrical component to the whole system.

Franz-Joseph Gall (1758-1822 CE) - believed that the brain was also responsible for personality traits. There were individual differences in certain personality traits - each trait could be localized to a specific part of the brain. If you had a strong degree of a particular personality trait, then that area of the brain would be larger. As that part of the brain grew, it would push out on the skull, need more space, and create a bump on the surface of the skull. By just feeling people's skulls (where the bumps are), you may be able to infer their personality. But first you need to know what traits correspond to what areas. Student - Spurzheim - believed they were being true scientists.
It doesn't work. Not a good idea. The idea of a localization of function - that idea has been demonstrated/confirmed in a lot of research. Ethically wrong - if I can infer you have this negative trait, then maybe society needs to do something about it. Ideas can have huge impacts on society/individuals. Need to be cautious.

Johannes Muller (1801-1858) - German physiologist. Did a lot of research on the brain/perceptual systems. Known for introducing the law of specific nerve energies. World -> Body -> Mind. I will get an experience of light and it doesn't matter how I experience it (mechanical or real stimulation of eye). Idea: your conscious experience of the world doesn't entirely/exclusively depend on the nature of the stimulus. Doesn't matter how you stimulate - as long as you stimulate the optic nerve, you're gonna get the experience of light. There's a disconnect between the stimulus and your conscious experience. What you experience is partly determined by stimulus, but more importantly by your neural substances being activated within your body. Multiple different kinds of stimulation can lead to the same experience. Won't get other types of experiences. Muller was a vitalist. He believed in the energy in the nerves has a not purely physical quality which enables it to travel infinitely fast to the mind. There's something other than purely physical things required. Dualistic. Travelling really fast through the nerves. He had famous students

Hermann von Helmholtz (1821-1894) - German psychologist, student of Muller. OPhthalmoscope, theory of colour vision, theory of audition, speed of nerve condition. Wanted to know how fast. Measured the speed of nerve conduction - Measure response time of a prick. Was very accurate. They were rejecting dualism. It's all just physical activity. Basically, just made a commitment to a particular worldview. They said "we believe." Muller's theorists were identity theorists - the mind is just activity of the brain. It's the same identity.

Santiago Ramon y Cajal (1852-1934) - Spanish physiologist. He wanted to be an artist, but his father forced him into medicine. In the end, he fused medical training and artistry. One of the first ones to look at neurons under the microscope. He would draw out neurons. At the time, people believed that the whole nervous system were formed from one continous fibre, tangled in a very complex web. He discovered that there were little gaps separating individual neurons. It's not a continous fibre, it's a series of individual cells separated by very small gaps. That means that there might be some sort of communication within a particular neuron. Now you have to communicate across some gap. Idea that you have a nervous system composed of separate cells - neuron doctrine.

Paul Broca (1824-1880) - French Surgon. Examined a patient who suffered a stroke, had a massive speech problem (couldn't produce speech), could only say the syllable "tan." -> Patient Tan. He couldn't produce, but he could take language. Whatever the stroke damaged, it damaged areas responsible of language production. Which means there's a specific spot responsible for this function. Broca did an autopsy and discovered a damaged area - argued that the area (Broca's ARea) was repsonsible for language production. BRoca's Aphasia - if you have damage to Broca's area. Mouth and lip control, auditory cortex to understand language, Angular Gyrus - writing, Wernicke's ARea - if damage, problems with language comprehension, can produce words, it's a word salad (Wernicke's aphasia), hard time comprehending language as well.

Charles Darwin (1809-1882) - English Naturalist. Natural selection. Individuals vary in terms of some traits, there are environmental pressures out there and people with certain traits survive, they pass on their genes to the next generation and their genes get propagated to future generations. Mutations create new traits that could be selecte dfor in new generations. Organisms through this natural selection evolve.

Sir Francis Galton (1822-1911) - Darwin's cousin. English scholar. Argued that intellectual traits - intelligence, morals, personality, were innate/generated by genetics. So they could be things that could be changed by evolution. There are individual differences in these traits and you could measure them. He produced the correlation coefficient - look at which traits were correlated to other traits. One of the first ones to look at regression. Wanted to identify people with these traits. He said it would be bad if people with all the negative traits were to reproduce and have lots of children. It'd be better if we could take people with positive traits and have them breed to make generations of better people - eugenics - selective breeding of the human population. Nazis. Galton was talking about "positive eugenics" - breed people. "Negative eugenics" - steralize people, stop them from reproducing. This was heavily in play in US/Canada leading up to WW2.

Lecture 3: May 9, 2018

Grew into Evolutionary Psychology - cognition and the brain is determined by genetics, therefore it's subject to selective pressure. The kinds of cognitive abilities/brain morphology that are functional are going to be passed down generations, and non-functional will not. Focuses onf unctional explanation. Figure out what those functions were. Focus on past functions. "Our ancestors had... that's why we have..." Typically makes comparisons across species - some degree of relatedness - we come from some organism. Steve Pinker - Blank Slate.

What is the current common view on this? Common view is now: monistic view (only one substance, and that it's matter) - materialism (matter, energy, particles and no other substance); identity position (the mind, consciousness is jsut the activity of the brain/tissue); Reductionism (then we should be able to fully explain all of cognitive functionining and consciousness in terms of the material of the brain. Then we can understand memory, conscious perception, etc. Then we can just talk about neural functioning. Reduce consciousness to basic laws of physics, chemistry, etc. Then all of consciousness can be reduced to basic physical properties of the brain which follows a deterministic, causal sequence. Then you become a biological robot.). Although this is a poipular view, it's based on a certain number of assumptions.

Well known philosopher - David Chalmers - Talks about consciousness and its relationship with the brain. Divides the topic into The Easy Problem (trying to discover what conscious states relate to what source of brain activity - correlational claim. Broca's finding, Neglect. He says that determinign what those relations are easy. It's a solvable thing, just takes time, patients.) and The Hard Problem (Why is there consciousness in the first place? Why would it ever even be? That this organ has this conscious experience. How does brain activity become conscious - 3d theatre? We have no solution for that and no solution forthcoming.) He still wants to be a materialist. The way we're gonna solve it: to stay materialist, must assume that consciousness is a fundamental property of matter. Therefore, you can't explain it. That means that all matter is fundamentally conscious. Chair is conscious, but not as conscious as you are. Brain gives rise to a complex consciousness. Chair has a simple consciousness. Everything around us is conscious.

Cells of Nervous System

Cells divided into

Cerebral cortex has 12-15billion neurons. Cerebellum has 70billion neurons. Spinal cord has 1 billion neurons. Whole brain has ~86billion neurons. 1:1 ratio from non-neurons to neurons. In some parts of the brain, you have way more glial cells than neurons (cerebral cortex), opposite in cerebellum. Lots of cells that create a very complex neural network.

The Neuron

There are different shapes of neurons. Multipolar Neuron - Pyramidal, Purkinje. Bipolar Neuron - cell body with two protrusions - one is an axon, the other is a dendridic stalk with dendritic branches. Unipolar Neurons - cell body and only one stalk coming out of the soma. It biforcates and parts that go dendridic and other that is axon. You can classify neurons by shape and also by their function.

Multipolar neurons are usually motor neurons. Bipolar neurons are often itnterneuron - the connect neurons. Unipolar neurons are often found in the sensory system. A neuron's function is related to its shape. Function and shape typically go together.

Afferent means to bring information TO a brain area. sensory nerves are afferent with regard to the CNS, as they bring information to the CNS. Efferent axons carry information away from the neurons motor neurons carry away CNS to the muscle.

There are ions, charged particles, that move in and out of an axon - right to the terminal button. Triggers a release of a chemical, the neurotransmitter. Which travels across gap, and attaches to the dendrite of another cell, and that's gonna trigger an eletrial chain within that cell. Ion transfer -> electric charge -> chemical signal -> electrical signal.

The Soma

It looks much like any other cell. Within cell, we see a bunch of organelles. Nucleus surrounded by nuclear membrane, which contains the DNA. The nucleolus produces rhibosomes (black dots) - attached to the rough endoplasmic reticulum. The rhibosomes create proteins. DNA starts to unzip, gets copied into a messenger, RNA, which leaves nucleus, attaches to rhibosomes, which gets fabricated into a protein. Protein is a building block to your biological system. The Golgi Apparatus packages things into tiny vesicles, a membrane-bound container, which hasnaturotransmitters, proteins, etc. Lysosome has enzymes in it. Golgi Apparatuses package for transport. Neurotransmitters are often packaged inside Vesicles. Smooth Endoplasmic Reticulum - makes fats, lipids. The mitochondira - energy production - that area requires a lot of energy. Outside of the cell - a membrane - semipermeable membrane - some things can get in and out, other things cannot. The transport of some molecules is tightly composed. Composed of a phospholipid bilayer - the outsides are water-loving/hydrophilic. The insides are hydrophobic. Extracellular/intracellular fluid. Some things can only move through channels.

Dendrites

Dendrites - hippocapal neuron - dendrite has a dendridic shaft, and on the branch are tiny protrusions, the dendritic spines. Dendritic spine has a neck and head. They have proteins that give it structure/form called Actin Filaments. At tip of spine, is the postsynaptic density. Right next to the spine would be another neuron - postsynaptic density. Mitochondria in spine for energy. Post synaptic density has proteins embedded in membrane which are ion channels - with receptors for neurotransmitters - NT will come and attach. Adhesion molecules that connect up to adjacent cell.

Dendritic spines are always dynamically changing. The connections between cells are always morphing and changing. Dynamic system. Spine motility. Down syndrome - too many chromosomes - cognitive impairments, facial morphology, flattening of nasal bridge, etc. 21st chromosome. One of the neural causes: they fail to produce dendritic spines. Spines are important as they increase surface area of dendrites to more connections. Eliminating spines, you can't make as many connections. DS has less connections, less complex cognitive system.

Axon

sometines you have a plain axon, other times you have it wrapped by myelin sheaths that come in segments - between segments is the nodes of ranvier. Electrical signal moves down the axon.

Protein complexes that allow ions to move in/out of the cell. They create electric signal that's moving down the axon. Inside the axon has a number of filaments. Actin Filament - narrow, creates structural shape of the cell itself. Neurofilaments - few more protein components, involved in structural support of cell. Muicrotubules - biggest ones, create structural support, and create a highway system within the axon which allows the transport of various types of cargo to the axon terminal from cell body.

Fast Axonal Transport - The cargo/vesicle - big lipid bilayer ball. They're being carried by proteins called motor protein - Kinesen, dynein, myosin Va. Typically one doing the work with the particular cargo. Different motor proteins serve dif functions.

Different motor proteins with dif movements: From soma to terminal, Anterograde Movement, kinesin - carries cargo - starts to untwist, feet, carry the cargo. wound up proteins that unwind.; (If you damage the transport system, it's a real problem cause youc an't get cargo to its destination) REtrograde Movement - from terminal to soma, might be empy veiscles to get them filled up - dynein; myosin va - attaches onto actin filament and cargo and carries it - sideroad - mostly transports to its final destination - into small location, terminal or spine.

Axon Terminals

Hive of activity. Vesicles - some filled with neurotransmitters that are going to be released. We have ion channels for carrying electrical signal down axon, and right at the terminal button. Mitochondira cause you need a lot of energy. Neutrotransmitter - release and communicate with other neutorns. Receptrs for different neurotransmitters - bind an dlead to changes. Transport proteins - brings things you dont need for recycling. Adhesion molecules that are like the one sint he dendridic spine - connect to a particular dendritic spine.

Down the axon, you have axoplasmic transport which moves packages on microtubules. That's very different from the electrical signal being carried by ions thats moving in and out of the cell. Two separate things.

The Synapse

The junction between axon terminal and dendritic spine of another clel. There's a space there which is the synapse. Adhesion molecules connec tiwth each other. They hold them together and control things.Space is the synaptic cleft. Axon terminal before that is the presynaptic terminal. The dendritic spine is the postsynaptic dendrite. Presynaptic/postsynaptic cell. Neurotransmitters are released from the axon terminal into the synaptic cleft and bind to receptors on the PS dendrite.

Very tight, close relation.

Lecture 4: May 14, 2018

Glia

Neurons - carry electrical signal. Glia - we thought they just had supportive role.

Types of Glia:

The Blood-brain barrier - Endothelial cells makes up the cappliary wall, they junctions are tight. And astrocytes plug it up as well. Allows for a lot of control to what gets in or out of the brain. What is allowed to move passively (green) are some gases and a few fat-soluble molecules (vintamin A, d). Other molecules like glucose, hormones, amino acids, and non fat souble vitamins require active transport. There are transporters that get those out of the bloodstream and into the CNS. Astrocytes mediate. IF you break blood-brain barrier (radiation, toxins, cigarettes) Addiction happens more efficiently if you can shorten the time period between taking drug and shortening time it takes to effect. Nicotine - get it through the blood brain barrier and into brain as fast as you can. Add other things into cig that make it move faster. Some of the toxic chemiclas are designed to help nicotine through the blood brain barrier faster, what you don't want. Other chemicals with flavours - cyanide, tar - all of them end up damaging blood brain barrier. Pharmaceutical companies are battling with this cause they have to figure out how to deliver efficiently to your brain - how to take a ride on these active transporters.

The Action Potential

Electrical signal going down the neuron. There's an electrical signal that starts at the axon hillock, or first ode of ranvier - travel downt he axon (in one direction) to the terminals. The electrical signal depends on the ions (charged particles0, their concentration inside the axon and outside. Inside: intraceulluar fluid, extra cellular fluid (outside). The difference between inside and outside that creates the energy for electrical signalling.

Sodium (Na+), Chloride (Cl-), Potassium (K+) - electron missing or adding, making them charged particles.

Seawater - high in sodium, chloride, low in potassium - makes salt (NaCl). Extracellular fluid (surrounding neurons in your brain) - very similar to seawater - high sodium, chloride. Intracellular fluid - a lot more potassium than sodium, chloride. This imbalance leads to an electrical difference.

Inside of cell is a lot more negative relative to outside of cell. Voltemeter electrode inside axon: measures -70 millivolts when axon is at rest - this is called the REsting potential - no major electrical activity happening inside the cell.

Outside of cell has a lot of sodium+chloride ions. Inside has more potassium ions. Why is inside negative? NEgatively charged protein molecules inside the cell - so big that they can't get out - they tip the scales so overall, the inside is way more negative than the outside. Ions are the movers and shakers - they move in and out of the cell because inside the membrane are protien channels - closed/open. Every ion has its own channel it can move in and out. Important on channels: they open/close depending on the voltage across the membranes - voltage-dependent channels. Another protein: the sodium-potassium pump that allows sodium/potassium under certain circumstances. Channel is gonna work without energy, pump requires energy to work. Need pump because ions are in the wrong compartment and need to use energy to get them back to the write compartment. [Positive and negative - relative to each other. -70, 0 means they're realtively equally charged. -70 means you're -70 more negative.]

We wanna move ions across to create electrical activity - what drives it are: 1) diffusion - movement of molecule sfrom areas of high concentration to low concentration across a gradient. (drop of colour in water - concentrated and diffuses out); 2) electrostatic force - these are charged particles and like particles repel, opposites attract. "This might be true about love, but we don't know about that."

Potassium is a lot more concentrated on inside of cell - diffusion would want to push it outside the cell. Because potassium is + and the outside of cell is more +, electrostatic force would wanna push it into the cell. Diffusion and Electrostatic force opposing each other. Chloride (blue) - heavily on outside, diffiusion would wanna push it into cell. But because chloride is -, and intercellular is -, electrostatic force would wanna push it out of the cell -> opposing forces. Sodium is more concentrated outside, so diffusion wants to push it into the cell. It's also + and extra cellular is + so it wants to push it into the cell. If you opened the soidum channel, they would rush into the cell - it would change the electrical difference. Sodium has a parimary imabalance occurring. Other thing we'll see with pump - it will pump sd=odium ions back out and exchanging them with potassium ions, pushing them inside. Pump requires energy - it creates the imbalance - pushing more sodium ions outside.

Potassium channel - cell membrane (green). Protein structure. Closed format - not enough physical space to pass ions in and out. Once opened, it unwraps, it opens a physical pore that allows ions to pass through. Channels are voltage activated. What triggers opening and closing of these is the electrical difference.

Soidum potassium pump - helps create electrical gradient. Has mechanism that allows 3 sodium to exit and at the same time, bring 2 potassium inside cell. Exchange mechanism. Requires energy.

What happens if we were to stimulate the system: look at what happens on our voltemeter. Resting potential: -70. WE can electrically near axon hillock and add some positive charge - then if we measure axon, we would see that it became a little less neg on the inside (cause we added positive charge) - this is depolarization - decreasing - making inside and outside a little more similar. If we inject a little mor eneg charge to axon area - would make inside more negative - hyperpolarization - increasing electrical potential across membrane. Each cell has a threshold of excitation - if we put enough of a positive charge in there to depolarize a cell beyond that point, you would trigger a massive electrical change claled the action potential - it hits the threshold, all this activity breaks loose, you get a massive depolarization - called the upstroke - it hits 0, becomes equivalent, then you get an overshoot, the inside a little mor epositive than outside, and it reverses and you get a downstroke, becoms more neg on inside again, get more neg than resting potential (afterhyperpolerazation), then return to resting potential. That's if we're looking at one location on the axon. Peak to the trough - spike height.

What happens to membrane as action potential unfolds. Potassium channels are slightly open. Slow exchange of potassium in resting state. If stimulate, add a bit more positive charge to axon, and brought to threshold, the soidm channels open, a lot of soidum enters the cell, making the inside of the cell less and les sneg, and more and more pos. The sodium channels open because you hit the threshold of excitation - automatic. The potassium channels open as well - potassium leaving the cell (cause gettign mroe and more pos in there) and some sodium entering the cell. Until you hit the +40, peak, the sodium channels will close and potassium keeps exiting the cell - massive downstroke because potassium is leaving. Potassium channels will close (overshoots hits bottom), then some potassium diffuses away from that location and go to other places, brings it back to its resting state. It returns because excess potassium on outside diffuses away. S-P pump comes in, pumping sodium out, potassium in to regain the original balance where theres a lot more sodium on outside and potassium inside. But it's not pump that gets it back to its resting state.

It's the soidum that has both diffusion and electrical gradient forcing it into the cell. It rushes in - potassium wants to get out.

The action potential travels downt he axon. While time is unfolding, absolute refractory period - cannot trigger another action potential. When in hyperpoerized state, it's relative refactory period - you can trigger another action potential, but you need a lot more stimulation.

Not all neurons are the same with their action potentials.

They faollow an all or none law - once you trigger, it's gonna happen. Independent of the intensity of the stimulus. As long as you have stimualtion, you get the same-sized action potential. Not a bigger action potential, you'll just make more action potentials in a shorer period of time - fires faster. Firing rate of neurons.

Can't go back on axon because of refactory period. Regenerate downstream.

Lecture 5: May 16, 2018

Propagation of the action potential. Action potential is an electrical signal that travels down the axon. Stimulate the axon, see action potential in A, then B, then C. Continuiusly regenerating the action potential. Remain full size at every location. Propogation occurs in 2 dif ways, depends on whether or not hte axon is mylenated. Some axons do not have any myelin sheaths. Prop occurs through passive conduction in unmyelinated axons and salltitory conduction in myelnated axons. Passive conduction - stimulus, positive charged ions move to the adjacent area, depolarizing it; causes sodium to rush into the cell in the new location; it continues on. It's relatively slow beecause it requires a regeneration of action potential in adjacent regions of the axon. When you have myelin sheaths (salitory conduction - once an axon gets sheathed, it eliminates some of the sodium channels; lots of sodium channels at nodes of ranvier; when you stimulate/depolarize a partic region, sodium rushes into the cell, the positive ions flow all the way to the next node of ranvier; depolarize the region of next node of ranvier, depolerizes and recreates action potential; the action potential jumps from node of ranvier to node of ranvier - a much faster form of conduction; development creates myelin sheaths and speeds up and improves stuff.

Multiple sclerosis - an autoimmune disease whereby the immune system attacks the cells in the CNS. What can happen: you can increase the gap between cells that form the blood vessel walls, it allows immune cells, white blood cells to enter the brain - leak through the wall. The oligodendrocyte is quite different - don't recognize oligodendrocyte - it must be a foreign invader - attack those cells. Immune cells attack oligodendrocytes and break them down. Results in demylenation of segments of the axon. Affects white matter in dif locations of the brain - determines the symptoms (weakening of muscles - attack of motor system, visual system - blurry vision, slow decision making). Might develop symptoms, then go into remission, then new symptoms come back. A cycle of increasing symptoms, remission, and getting new symptoms. This is cause the body is able to remylenate some of these axons. NG2 can change into oligodendrocyte to remylenate. Sodium channels were removed from the myelenation so nto enough to propagate action potential. System tries to fix itself by attaching new sodium channels. The brain is learning to compensate for networks affected. First stage - tryna fix itself. Second stage - axons are dying, not enough networks to compensate anymore, symtpoms get worse and worse. A steady downhill. Myelin not used, axon deteriorates. Then you get a retraction bulb - scars over, stuff accumulates. [There are many things in our environment that create an inflammatory response. That inflammation response in preipheral body damages your blood cell walls. Some immune cells wreak havoc in the brain. ]

Key triggers of inflammation of body occurs from the activity in the microbes in the guy. When you eat gluten, it can cause an inflammatory bowel problem - inflammation in the bowels. Most of the wheat we consume has been genetically modification. Changes nature of gluten which out bodies can't tolerate.
You have a health intestine - bacteria that reduces inflammation, resident inflammation, opportunistic pathogens, but it's ok cause you got a lot of good stuff. lllSome nutrients will come up, into the bloodstream, sent out all over your body. T cells - white blood cells that go out and fight off infections. If you mess up the bacterial composition of gut - Disbiosis - lots of opportunistic pathogens - damages the mucus membrane, alloweing some of the bacteria that are supposed to stay in your gut to leave gut and into bloodstream. System needs to attack the bad stuff in the bloodstream - generates immune cells/imnflammatory mediators - they destroy the invaders - you end up hitting your own cells - too much inflammation destroys your own cells. Starts to destroy blood brain barrier and increase the gaps between those cells. Proinflammatory mediators and immune cells entering the brain, they start to think that oligodendrocytes are foreign subjects. And microglia thinking they need to activate their immune response and keep damaging the cells in CNS. Then you end up with MS. What's happening in your gut determines neuro functioning and can trigger a degenerative disease.

Over 90% of seratonin is in your gut. Multiple channels between what's happening in your gut an dwhat's happeniing in your brain.

The Synapse

The synapse involves a presynaptic axon terminal and a post-synaptic dendritic spine. They're connected by protein strands - adhesion molecules. The gap is the synaptic cleft. The communicatoin that happens across the cleft occurs through chemicals called neurotransmitters.

NEurotransmitters - different classes of neurotransmitters.

Start in the presynpatic axon terminal. A microtubule coming in. You can get vesicles being transported, packaged with neutotransmitters. Axonal Transport. Some other types of neutotransmitters are synthesized and packaged in the axon terminal - empty vesicles. Now you have vesicles filled with NT in the terminal button. Through Translocation, some of those vesicles come up to the cell membrane in a place called the active zone - has a whole bunch of proteins in it (SNARE proteins - will attach to cell membrane and the membrane of the vesicle - both have lipid bilayer membranes -same kind of membrane). This process is Docking, it goes through slight chemical change - Priming - preparing it to be released in the synaptic cleft. Vesicle pools. The vesicles are organized into different pools - active zone has a pool of vesicles that is readily releasable pool - they will release contents into synaptic cleft when the action potential comes and depolarizes. The recycling pool - after releasing, they're empty and get refilled and are ready translocate back to the active zone - active recycling process (5-20%). Vast amount of vesicles that aren't often released - the Reserve pool - call up the reserves (once you blow therough your regular men and women). You're not gonna easily run out of vesicles cause of these reserves.

Voltage dependent sodium, potassium channels. The action potential arrives at the axon terminal, at the end here, when sodium enters the cell, it depolarizes the terminal button region. And you have calcium ion channels - 2+ charge, so when depolarize, calcium flows into the axon terminal. The calcium comes up to the docked vesicles and leads to Calcium-dependent exocytosis - releases NTs. The cell membrane of vesicle fuses with the cell membrane of the axon terminal, sometimes it fuses a bit, opens a pore and pinches off into a vesicle, other times it fuses completely. The axon terminal gets bigger, but there's a fix to that problem.

The SNARE proteins are involved in mediating the exocytosis (out). Proximal monolayers will start to fuse with one another, they create a fusion stalk; a depression starts to occur as snare proteins pull things apart in the sides, creates a hemifusion ( a depression); create a rip through centre, a pore; then neurotransmitters will go through this pore. Then it can completely fuse or reverse the process. Snare protein activit y is triggered by thte calcium coming in.

Reverse happens - Endocytosis (in) - a bit of the axon terminal membrane forms a vesicle. Then you have a nurotransmitter uptake, bring sin NT into vesicle and it's ready -> Vesicle Recycling.

In the postsynaptic - you have some ion channels. Some of the ion channels have receptors on them. The receptors are there for connecting to the NTs. NT will attach to ion channel and open the ion channel allowing ions to flow in or out. Sodium in there, then you bring it closer to threshold. Enough positive, depolarization, can trigger an active potential. You're getting an electrical signal to a chemical signal then attach, allowing ion channels to flow ion in/out. Then electrical changes in postsynaptic cell.

Ligand-Dependent - based on a ligand binding to them - Ligand = NT. It functions on a lock and key type mechanism. Ion channels will have receptors that are a specific lock. Each NT is a dif key. Each NT TYPE will activate a dif receptor. Lock and key specificity. It's a physical shape of the NT that fits in there. Ion channels opening in a dif way, by a ligand connection.

Not always will sodium flow in - depends on the channel. Typically effects can be categorized as excitatory or inhibitory - EPSP or IPSP. It's a graded change. Brigns you a little closer to threshold and dissipate. Based on ions entering and leaving. Excitatory - increase likelihood of action potential - it's graded - can open a few or a lot of channels - graded depolerization - small or huge. IPSP - graded hyperpolerization, brings neuron away from threshold.

If small, how do you trigger action potential? 1) way: Temporal Summation - rapidly repeatedly stimulating through a given axon. Bit of depolarization starts to fade, but before it fades, add another action potential, and now you depolerizes enough and it triggers. Summing over time rapid action potentials in succession, leading to enough of a depolarization for action potential; 2) Spatial summation - multiple axons - that add over space to depolarize the neuron enough to trigger an action potential. Do it enough to trigger action potential.

Neural Integration - exitatory and inhibitory signals - a bit of depolarization, a bit of hyperpolerization - they sum together is with no change at all. Excitation cancels out the inhibition and vice versa.

A NT comes in and it'll attach to the binding site (lock and key). It causes the ion channel to poen, and now ions can move through. Ionotropic receptor - the receptor site is right on the channel, it's integral to the channel. A ribbon diagram - divided into a series of units and it goes right through the membrane - they will unwind a bit and increase the size of the space in the middle. Another type of receptor: Metabotropic Receptor - have a receptor segment/protein in one part of the membrane and the actual ion channel is in a separate location. A protein that's added to the receptor. NT goes to receptor site, triggers the release of some of the units of the G-protein which attach to the IOn channel, causing it to open. NT -> messenger -> ion channel.

Why 2 diff? Ionotropic REceptors are very quick responders and short-lived responses. effects last Less than 10ms. Very, very fast. Metabotropic Receptor - slower and longer lasting - effects last at least 10s. Takes time to go through process, but it's open for longer. IT allows for dif kinds of neurocognitive effects. For hearing, you need rapid responses - need ionotropic. For other things like regulating your body temperature - that can take a little longer. Or certain kinds of pain, modulating sleep. Those you can have longer lasting effects that occur at dif rates.

Some NTs can have both ionotropic and metabotropic receptors - diff concentrations in dif parts of system. Sodium - excitatory.

Once you get an activation of ion channels, then the NT is detached. It can do a number of dif things: 1) NT is reuptaken by presynaptic terminal - by transporter proteins. Pumps it back in and repackaged into vesicles to get reused; 2) feedback effects - NT connects to another type of receptor called the autoreceptor - it binds and sends a signal to the inside to say that it's enough; 3) deactivation of the NT - done by enzymes which breaks the NT into pieces, gets taken in, reformed, reused; 4) diffusion - just gets diffused away. The astrocyte can actually absorb some of the NTs; What could happen also is Retrograde Transmission - transmitters released out of the postsynaptic dendritic spine - exocytosis, autoreceptor in presynaptic, which signals feedback to stop releasing.

Key principles: You have 3 dif types of NTs, they each activate a particular metabotropic receptor, and each of those can converge on affecting a particular G protein, which can open a potassium channel. Different NTs can have the exact same effect on the exact same channel.

Divergence - single thing ends in multiple outcomes. One NT which activates an ionotropic receptor which oepns a chloride channel, and another receptor which activates G proten and potassiumc hannel. Can have 2 dif effects. Gives the brain a lot of flexibility. It all depends on what kind of ion channels. Want a case wehre multiple people can access a single room and a single person access multiple rooms.

Astrocyte has NT transporters and ion channels, receptors for NT - can trigger release NT-like chemicals fromt he glia - gliotransmitters. Interaction with astrocyte is also critical. Multiple things going on. Glutamate is also a fundamental glial transmitter.

Axodendrytic synapse -

Lecture 6: May 22, 2018

[Test] - no diagram given. Short answer - might wanna draw a diagram to help you.

Electrotonic Synapses - another exception to the types of synapse. The membranes have protein complexes - one is called a connexin - multiple is connexon - a channel down the middle of it. A bunch of connexons in a membrane of a cell, the membranes of 2 cells line up together which forms a gap junction - ions from inside of one cell can flow directly into the other cell. So closely that you don't need a chemical intermediate step of the neurotransmitter. You can just flow ions from one to the other. Other nutrients can flow through it too.

Neuropeptides - amino aicd chains forming proteins/peptides. A form of neurotransmitter. They have other kinds of functions as well. Primarily released from dendrites. Creates an omega complex through exocytosis in dendrite - proteins release into extracellular space. Receptors in many areas - at other dendtires, terminals, etc. A relatively long half life (20min - released, stiill half of it there after 20 mins). NT have half life of 5ms. They spread everywhere and have its effects there. A variety of functions: postsynaptic electrical changes, influence gene transcription inside cells, facilitate the release of other peptides, impact the formation of synapses, have effects on glial cells. Broad effects for a longer period of time. Can change the context of the neural network. Brain can achieve things in multiple different ways - this is one example of that.

Drugs and Toxins

Action potential coming down the axon, depolarizing the terminal button. Depolarization triggers release of NTs. Certain drugs block these channels. Prevents action potential from occuring. Prevents electrical signal to be passed down axons. Local Anaesthetics - sodium channel blockers - Novacain - drug is absorbed, it blocks the sodium channels for your pain receptors, prevents pain receptors from sending out pain signal. Tetrodotoxin - puffer fish - loss of senssation an dmotion - block ssodium channels - stops peripheral functions (heart, lungs, etc.) Indiscriminate - blocks everything.

Prevent NT release spider - blocks calcium channels Calcium channels is important to trigger the release the NT. ANOTHER type of toxin: Botulinum Neurotoxins - can grow in improperly canned food. Muscle paralysis, autonomic disturbances (internal organ functioning), droopy eyelids, blurry vision (muscles that control eyes), swallowing problems. Listed as a bioweapon. Could be aerosolized (could be spread through the air). easy to produce. Present in Botox - it immobilizes the functioning at the neuromuscular junctions. Lose ability to control the muscle, inject into muscle, prevent them to be able to frown an dcreate frown lines -> fewer aging lines. "That's why these people have this plastic face appearance"
Now used for medical purposes - uncontrolled muscle spacitity - can reduce that.
The toxin will butt up against the axon terminal membrane; as endocytosis is unfolding, toxin sneaks in and gets into the new vesicle; it releases a component of the toxin which exits and cuts the snare proteins; it prevents exocytosis as snare proteins are important for docking and etc; reduced NT release - you've paralyzed the muscle. The main NT is acetylcholine that doesn't get released. Can affect central circuits - can hitch a ride on retrograde transport and enter the CNS. Take a ride from the periphery into your brain/spinal cord. Botox effects can last 2-9 months

Increase NT release - Goldilock's zone - too little/too much is bad.

Preventing NT deactivation - enzymes that break down NTs. Acetylcholine broken down by Acetylcholinesterase, Monoamines are breoken down by Monoamine Oxidase (MAO) (primarily in axon terminal). You can have drugs that will prevent the breakdown of these NTs by inhibiting the enzymes.

Preventing nT reuptake = block transporters, leaving more NT in the synaptic cleft (can't get rid of it).

Blocking REceptors - prevents effect of NT ont he postsynaptic cell

Stimulate REceptors - mimicking the NT. Or receptor molecule might have another binding sight. Falsely stimulate system by the drug.

Mimicking Retrograde TRansmitters - Justin is all about marijuana, he wants us to take marijuana. Cannabinoid Receptors on presynaptic. REtrograde transmitters - Anandamide and 2-AH released by post-synaptic cell. It inhibits the release of certain NTs, often times glutamate and GABA. Reduces acitivyt at synapse without glutamate. People fele much more relaxed, less motivation. Key ingredient: Tetrahydrocannabinol (THC). Effects at pain synapses - can be an effective drug for pain relief - esp for some cancers. Less addictive. Not great for recreation use - cumulative effects - lack of motivation, engagement in the world. Long-term effects.

Complex drug effects: multiple effects

Lecture 7: May X, 2018

The effect of the drug depends on the way you take the drug (method of administration) Smoking cigarettes vs. Chewing Tobacco. Smoking - peaks faster than chewing tobacco. It cna affect the addictiveness of drug. Rapid uptake - system is better able to associate th eeffects with the drug. Intravenous - fastest, stomach takes longer cause it has to pass through things.

Tolerance and Withdrawal - ramps up, system metabolizes, goes down. As soon as it enters sytem, tries to compensate by removing heroin-like substances. To try to bring you back to homeostasis. Add up drug effect with system. When heroin drops down and neural adaptation, you go lower and want the drug to fix that.
Experienced user - certain environmental cues trigger the start of compensation. Based on those cues, it creates a much larger compensatory response. Actually experiencing a smaller effect - building tolerance.
if you take away the drug, the brain prepares to receive the drug, and now you heavily experience the opposite effects of the presence of the drug.
You can quit using a drug by minimizing withdrawal symptoms: remove yourself from the cues of drug use. Change the cues and envuronemntal cues won't be there to trigger compensatory response and won't feel withdrawal symptoms as bad. Once you come back, you have to battle a little bit, but the system has already reduced the withdrawal.
People have overdoses because they change the context of their drug administration. Cues aren't there to create the compensatory response of an appropriate size, but they're still using the same amount of drug, so they overdose.

Addiction and Reward - a lot of the addictive drugs end up increasing activity in the Nucleus Accumbens Sexual excitement, gamling, video games, watching attractive people. Things we find rewarding activates the Nuclues Accumbens - a reward network. (gamer widows). Rat - added electrode at septal area - the rat was in a box and they can press a lever. Every time you press the lever, it would get stimulation or not. If you reduce stimulation, they would stop bar pressing. If you turn on stimulation, they increase bar pressing. Video games are designed to do - pressing buttons and you get rewards. They get treasured and kill somebody, I don't know why that's a reward. "And you don't even need an ethics protocol to do it. You just need to be a gaming protocol." Activate reward networks that are involved in motivation. Overly motivated to do one thing.

Neuroanatomy

Gross aspects of the nervous system and its structures.

Frame of reference is the neuraxis. When we refer to some areas, the whole coordinate system turns a bit. But Superior-Inferior are always used as above and below - it doesnt change with th ebend in the neuraxis.

The Nervous System:

Sympathetic NS and Parasympathetic NS - connected to involuntary muscles. SNS is divided into different segments - nerves emanate from th ethoracic and lumbar regions - they will go out and synapse with another nerve which connects to the organ. Before/after synapse is preganglianic. Synapses are a sympathetic chain gnaglion. Arousal functions.
PNS - neurons are surrounding the SNS. Comes out of cranal nerves and sacral nerves. Involved in vegetative functions. Preganglianaic neurons are very long. For both, the main NT is acetylcholine. When you get to perophery, the PNS stil uses acetylcholine, but the sympathetic nervous system uses norepinepherine.
Opposing forces. SNS accelerates heartrate, PSNS relaxes it.

The Vertebrate NS - Cross section of spinal cord. Areas of grey matter (H, cell bodyz) and white atter surrounding (axon tracks). Follows a Bell-Magendie Law - the dorsal root ganglion is carrying sensory info and the ventral root is carrying motor info (efferent and afferent - motor neuron is efferent relative to CNS). Sensory neurons are located inside of doral root ganglia. Motor neuron cell bodies are in the grey matter.

Circuit - cell body in dosal root gnanglion. Sensory info comes in, synapses to the intrinsic neuron, and another synapse to a motor neuron, sends it out to affect muscle. 3 neuron circuit. Peteller reflex - hammer knee leg. Only 2 neurons. Sensory directly to a motor neuron. Basic circuits.

The Meninges - layers of tissue that surround the nervous system. Dura mater, arachnoid membrane, subarachnoid space, pia mater, artery going into brain. Layers provide protection around the CNS and cushioning. Inside subarachnoid space is fluid - a water sac to cushion. The fluid carries certain nutrients away. If you're watching one of those crime dramas and somebody says the subject had a blunt force trauma to the head and they died from an epidural hematoma - blood vessels in arachnoid membrane - bleeding between the dura mater and the skull - pool blood at the sac - as it pools, it pushes down on the brain, if big enough, it can put pressure on critical brain areas. Want to drain it as much as possible. Subdural Hematoma - blood boopling between dura meter and arachnoid membrane.

Figure of spinal cord - 3 layers of membrane along the central nervous system. Diagram reversed the orientation of the spinal cord. Looking at the back of the person. Meninges go all the way in the CNS to ensheath.

Key components of the ventricular system - Large lateral ventricles. Third ventricle drains through the cerebral aqueduct to the fourth ventricle and goes through the central canal in the center of the spinal chord. Cereral spinal fluid is produced within the ventricles by choroid plexus - extract fromb lood, the blood plasma, and pump it into these ventricles. Flows through entire system and gets reabsorbed by flowing through the subarachnoid space, into the bloodstream and heart. What can happen is you can get a block in the system (in many places) -> Obstructive hydrocephalus - babies in utero - ginormous head - water on the brain - have to create a shunt to drain the ventricles into the abdominal cavity. If too large, no space for neurons to grow properly. Skull plates aren't fused yet, so they can enlargen to accomodate.

Blood supply - being provided to the brain. A branching that occurs (anterior cerebral artery in blue, middle cerebral artery in red, posterior cerebral artery in green) on both sides. All of them are joined at the base, the Circle of Willis. Symptom of stroke depends on which artery and how far down the line. Visual problems - very likely posterior cerebral artery.

Main parts of the brain - major divisions (occurs already in utero), associated with different ventricles, subdivisions of major divisions, principle structures per subdivision.

Cerebral Cortex - the outer cortex/bark of the brain with all the convolutions. Does not involve the cerebellum at the bottom. Just the outer area.

Name areas on how they are demarcated by sulci. Small ones are sulci, deep ones are fissures.

Corticol Layers - One gyri coming up and different layers of cortex. Typically 6 dif layers - always parallel to the surface of the cortex. Fissures and sulci demarcate areas.

Corticol Columns - perpendicular to the surface of the brain. Cellls organized in functional columns. In visual cortex, columns of cells responsible to right eye, and columns of cells responsible to left eye. A columnar organization.

Can divide surface of cortex to serveral lobes - Frontal lobe in front of the Central Sulcus. Lateral Fissure separates temporal lobe from other loves. Behind central sulcus is the parietal lobe. Occipital lobe. Longitudinal fissure that separates the 2 hemisphere.

Wilder Penfield - Corticol Topography - mapping out functions of different brain areas. Open skull, cut through meninges. Wanted to make sure they weren't damaging anything. Stimulate with a light current, dif areas of the brain. Because patient is awake (no pain receptors). Ask the participant what they experience. Stimulating adjacent areas and you get stimulation in adjacent areas on body. Postcentral gyrus - sensations around the body. Sensory homonculus - mapping person on the cortex. Unequal representation of the body. Direct localization of function. Feet are close to the genitals - maybe cause of way baby is in utero. Found the motor homunculus - precentral gyrus.

Lecture 8: May 28, 2018

Test 1: Intro, 4.1, 1.1, 1.2,, 2.1, 2.2, 3.1, 3.2, all lecture material up to the end of Neuroanatomy. 45-50 M/C. Several short answer - something ocvered in lectures on a couple slides, in textbook. 5-6 points each. Choice of 2 - answer 1. Full sentences. Diagrams. Practicing Retrieval + over time. One for 4.1 - did not cover.

Major subdivisions of the brain - continue with the cortex

Main sulci and fissures that are landmarks that separete the brain. These separate the main lobes.

Primary cortices - primary sensory/motory cortices - Motor control, sensing touch, pain, etc. Primary visual cortex wraps around midline.

A different way to talk about the parts of the brain - Brodmann's Map. Still a lot of papers that use this nomannature. Looked at the cytoaarchitecture (cell structure). Identified 52 different areas, numerically. (Know the examples). The areas pennfield discovered, they have different cytoarchitecture.

Main lobes:

COrpus Callosum - primary fibre tracks that joins stuff. Involved in interhemispheric transfer of info. Fibres. joining corresponding sections in one hemisphere to the other hemisphere. Image using diffusion tensor imaging. Neatly organized.

Basal Glanglia - globus pallidus, caudate nucleus, putamen - heavily involved in motor control. If you damage, you get motor-related deficits - PArkinson's disease (tremors, balance, motor, freezing), Huntington's (jerky movements, genetic), Tourette's (involuntary vocal and facial/movement tics - surgeon who would stop tics).

The Limbic System - broad, general term. A bunch of areas underneath the cortex - emotional processing. Hippocampus, amugdala, oldfactory bulb (just know these 3).

Thalamus and Hypothalamus - 2 thalamuses (1 on each side) - sensory and motor relay center. Coming up from the spine, relay through this. It's a collection of a whole bunch of nuclei - you can separate them by their function - each do different things. Lateral geniculate nucleus - relays info from eye to visual cortex, Medial geniculate - from aditory pathway to cortex, ventral lateral c(cerebellum to primary motor cortex)> If you have a sttroke near axon, you can damage one of those.

Hypothalamus - regulating and controlling hormone release. Through pituitary gland will release hormones. Eating, drinking, sexual behaviour/drive, other motivated behaviours. Body temperature. Oxytosin and vasopressin - generated in hypoth, move to posterior pituitary and released into the bloodstream. Stress hormones. Regulatory-type behaviours. Basic homeostatic systems.

Midbrain - Tectum and Tementum

Tectum - bumps - top is superior colluculus (visual stuff), below is inferior colliculus (auditory perception).

Tegmentum - a whole bunch of nuceliu. Substantia Nigra - lots of dopaminergic neurons - movement behaviours. Red Nucleus - connects motor nerves in spinal cord to cerebellum.

Reticular Formation - tracks. Part of red nucleus is in reticular formation. Descending portion control motor areas of spinal cord and connecs to cerebellum. Ascending portion influences arousal and attention - active when you're ready for action. Goes through brain stem.

Hindbrain -

Cerebellum - Use to think fine motor control, but it deals with a lot. Sham rage - feel rage but no stimulus. Active when people are doing tasks - almsot everything we do. Yet we know very little about it.
Agenesis of the cerebellum - or the connecting tissue to the cerebellum, not a major cognitive deficitt and medium motor control deficit, beyond that, they can function like anybody else. Can be missing the entire region that is involved in a lot of things and still be able to do it. Possible that it was cause they were BORN without a cerebellum - compensation.

Pons - joins cortex. Locus coeruleus - arousing the system. Cochlear nucleus (audition), vestibular nucleus ( vestibular function), raphe nuclei (sleep and arousal), superior olive (info from ears, sound localizatio). Basic functionality hapening in brain stem. Medulla Oblongata - control over reflexes, respiration, vomiting, salivation, heart rate - die without it. Inferior olive - cerebellar motor function.

Cranial Nerves - differnet carnial nerves that come out of the brain stem. different places that they go. Know the name of the different nerves that emerge from here and what they're responsible for. Know that the optic nerves, olfactory nerve. Glossopharyngela nerve for taste, throat, larynx, hypoglossal for tongue movement, vagus for internal.

Lecture 9: May 30, 2018

4 slides this class on test.

End of Test 1

Methods

Groups of methods that do different things.

Structure

Determine different structures of the brain.

Lesion

Look at functions of the brain, not just structure. Lesioning often done on animals. A damage made to a nervous system to ascertain the function of the lesion area. Looking for what deficit emerged after the lesion was made.

Device typically used: Stereotaxic DEvice - to figure out where you wanna go, use a BRain atlas. The bregma - landmark to move in the xy plane - cross of coronal and saggital. Guides you where you want to go. Take animal out and it would do its task.

Always want a control condition in these studies. Anesthesia -> Incision -> Lesion -> Sutures. Problem: if animal does task and behaves differently, it could be because it was anesthetized, had skin cut open, and it's sore from surgery. Want to ensure that you have the right explanations. Control group goes through the same procedures, but there's no damaging lesion. If differences - then it's specific to the lesion.

How do we create lesions in humans?

Transcranial Magnetic Stimulation (TMS) - strong magnetic pulse to scramble neural activity. Localize the area using MRI. Use device with a figure 8 current - disrupts the magnetic field of neurons under the skull - disrupts action potentials. Put it over the right spot - do for short period of time and it will knock out the function. Repeated TMS - can be used to treat depression and hallucinations - overexcite certain areas and cause circuits to rewire a bit.

Recording Brain Activity

Lecture 10: June 6, 2018

Patients

Never wanna rely on single cases. Typically, when people have brain damage, multiple areas are damaged so hard to know what's responsible for what.

Study by Karnath and Colleagues - studying pathients with neglect. Collected a lot of patients - 140. Looked at their damaged areas - created overlay plots. Patients who had right brain damage and who also showed signs of neglect. Took other patients with right damage who did not have neglect. A composite map of neglect vs controll - subtracted difference. Then found yellow areas associated with neglect. Isolate specific areas of damage - need a lot of participants.

another trick with patients: Double dissociation - if I'm interested in seeing whether 2 processes are separate or independent of each other, strong evidence comes where I can find a patient 1 who has process A impaired, but process B unimpaired (single dissociation). Stronger evidence coems when you find Patient 2 with process A is unimpaired and process B is impaired (single dissociation between prcess A and B, but opposite). This is a double dissociation. It suggests that process A and B are independent, separate processes. YOu can damage one without damaging the other. Language comprehension and language production. Some patients with damage to Broca's Area that impair production but leave comprehension. Other patients who have damage to Wernicke's area who have comprehension impaired and not production.

Different sptial/temporal resolution for some of the recording techniques. ERP has much better temporal res than fMRI and PET. But fMRI can have better spatial res than ERP. Depending on whawt you want to measure, you would choose the best one. Always changing cause always getting more powerful and better.

Neurodevelopment

What happens with the nervous tissue when you have an embryo early in development.

A series of stages: Conception to adulthood. Faded - ramp up and die down.

Right after conception - 18 day embryo. Lots of cells multiplying. Slice through embryo - 3 layers of tissue: Ectoderm - skin, nails, etc.; MEsoderm - blood vessels, muscle, bpne; Endoerm - digestive, respirtory system; Within the ectoderm, there's a development of a neural plate - called neural induciton - these cells are the cells that give rise to the nervous system later on (Neural plate cells). All of the cells in the ectoderm initially could become neurons - but they're inhibited and they become expressed as outer layer of your body. You suppress all other regions from becoming neurons.
Changes in neural plate - Neurulation - it folds slitely, creates neural groove with folds, folds in on itself until you have the neural tube - center is the Central canal which contains the cerebrospinal fluid in the end (now just amniotic fluids). All nervous dissue comes from neural tube.

From chick embryo - neurulation - live tissue images.

Drawings of changges. Happening in the course of days. Neural plate folds in on itself. Anterior neuropore and posterior neuroopore close up. Over the course of 4 days.

Embryo at 7 weeks - already seein gthe human being here, beautifully being formed. All major divisions are already present at 7 weeks.

Proliferation and Neurogenesis - over weeks after conception. Coronal view - major area - the ventricular zone - contains all the neuralepithelial cells (stem cells that will become the neural tissue within the brain).

Start with NE cells (stem cells), divide and replicat ethemselves - symmetric prolif division - just making more. One will divide into neuro and a radial glial cell - assymetric neurogenic division. The radial glial turns into a neuron. A Glia cell will now split into a neuron and another radial glial cell. and RG cell will split into 2 neurons. RG will extend to create a scaffolding formv entricular zone to other parts of the cortex - a lot of them change into neurons. The cells have the same genetics - it's what you turn on and off - that's what determines what kind of cell it is. You wanna squeeze the most out of NE. You can add an imediary cell (BP - basal progenitors) - which splits into 2 neurons. Then you get a lot more neurons comign from a single NE. Neurogeneic division - when at least one is a neuron. BP coming depends on dif times in devleopment. There is continued Neurogenesis cause NE in adulthood. PLasticity does occur, even though not as much as during devleopment. Want to know how to fix itself more.

Gotz - most of neurons in the brain are derived either directly/indirectly from radial glial cells. How do you know the dif between radial glia and neurons? Look at markers - neurons have certain kinds of proteins, glial have certain proteins - are they present? That assumes you know what proteins are specific to which cell. Inferential, imprecise haze. This is not rocket science, it's neuroscience.

Proliferation - refers to increasing the number of cells. Prliferative - increasing number of NE cells. Neurogenic - make the neurons. Differentiative.

Migration - get them to the right location.

The cortex is getting thicker as cells are migrating - forming the key corticla layers. (dont memorize layers) Know that ventricular zone is right next to ventricle and subventricular zone is next to that - where all the clel division is happening - next to vnetricle. From E30 to 55, get a few changes. Happening ove rthe course of days. If you assaulted the system during this time, chemically, you can do major brain damage caus eyou wouldn't allow this process to unfold - why you have to be careful with what moms consume - there's a placental barrier cause baby's circulatory system is separate - but nutrients have to go through barrier - cettain chemicals can go through and effect the baby. "I was thinking I'd get buckled on the floor now. I have a secret brace. Don't make me laugh, it hurts."

During differentiation is when the neuron starts to take on its very specific characteristics it has. Several things have to happen - need dendritic tree formed and the axon connected up to the right place.

Dendritic arborization - dendrite forms and becomes more complex. Starts out simple and gets more complex. Dendritic branch length increases. The other thing that has to happen: axon has to grow and get to the right location. TIps of the axons have growth cones - they're formed by actin filaments. Protude into fingerlike protrusions called fliopodium. Groves in here (lamellipoddia) - very sensitive to chemical type cues. They wlll follow chemical gradients and guided to particular locations. Repelled by certain chemicals and attraacted by certain chemicals and makes it way through the cells.

Lecture 11: June 11, 2018

Growth cones guides its way. Very sensative to various chemicals. Attached to cells, you have chrmical cues - adhesive substrate-bound cues - they attract the growth cone, they guide them along. You also have repellent substrate-bound cues -repel the growth cones. chemical cues floating in between the cells - repulsive which push growth cones away and attractive that pull growth cones. Growht cones follwo specific chemicals - how it finds its way to its targe tlocaiton.

Roger Sperry and The Newt - Studied a series of newts - optic tectum (visual cortex), the left eye connects directly to the right tectum. Key feature: if you were to cut the optic track, it will regrow. Whereas human tracts don't regrow. He took the eye which is sending axons to the tectum (inversion/reversal), he transsected the optic nerves. The newt would momentarily lose vision in that particular eye. He also rotated the eye 180 degrees. What would happen to the axons as they regrow - would they go to their old locations or folow some rule? They would grow to the same locations as before - something about the locations that they still found their way to that location. It saw everything upside down. It didn't get fixed, continued to be confused. Why does it find its way to the old location? It's all about these chemotropic cues.

REtina has topography dorsoventral which is high in concentration in the dorsoal quadrant and low in ventral quadrant. In tectum you have high in ventral, and low in dorsal. So the neurons in high concentration in dorsal will find the tectum location with high concentration. Same with Antherior/Posterior with topography anteriorposterior. Something about their chemistry distinguishes them which guides it ot the location.

Once axonf inds its way to chemical locations. As the growth cone approaches, it starts to shape into the terminal button. As it's doing that, the post synaptic membrane starts to get receptors with a lot more vesivles piling in. Growing into a mature neuron and synapse. This happens throughout development. Throughout and into late adulthood - always forming synapses, but much lower rate when older.

Next step: myelination. Around birth. 1Development of organizational tracts. Oligodendrocytes are forming the myelin. WAnt to start in spinal cord first because that's where you want stuff happening. Last is frontal lobe - not fully myelinated until 18-21 - explains why teens have lapses of judgement. (young people tend to not care about making errors - could be related to this).

Final stage: synaptic pruning and apoptosis.

Apoptosis - preprogrammed neural death. Some neurons ultimately will be killed off. First, you make way mor eneuron than the brain neeeds - overproduces neurons and synapses. Then it cuts them back as th eorganism is engaging in the world. The brain realizes that there are some neurons that I don't need. Neurotrophins promote the survival and activity of neurons. Muscles release Nerve Growht Factor - tells the neuron to continue to live, get stronger. Cells that are not used don't get exposed to neurotropins trigger the cell death process.

Massive decline is apoptosis - when the baby is bigger, responding to environment around it, then it plateaus off.

Synaptic Pruning - useless connections trimmed back. Depends on the brain area. This is jus ttrimming synapses, not killing neurons. Might chop off branches. Some people refer to it as Neural Darwinism - overproduce, and select the best ones.

Critical Periods

critical periods that emerge during developmental stages. Brain is very sensitive to assault (viral, chemical).

FEtal Alcohol Spectrum Disorder (FASD) (chemical assault) - alcohool go through placental barrier and affect fetus. It's a neural inhibitor. It could reduce the amount of firing of the neurons in a developing fetus - reduces NGF, and early cell death and the brain doesn't develop as much. You get tall-tale physical features - narrowing of eyes, no groove abvoe upper lip, thin upper lip. All depends on how much alcohol. Cognitive deficits - poor executive control (frontal lobe), attentional deficits, impaired learning, memory.

Smaller brains than control participants. Areas that are most affected - inferior parietal area (a major reduction). Brain abnormalities all over the place.

CDC: sex and alcohol don't mix well. No known safe level of alcohol during pregnancy. Regular medications, even ibuprofen, can affect the fetus (fetus can get more feminine traits). Generally: stay away from all chemicals when pregnant. FASD occurs on a continuum

While this mouse is pregnant, the mouse's diet, levle of stress, physical infection are gonna influence the millieu of the mother, as a result it can influence the biochemical makeup of the placenta. The maternal stress can infect the biochemical makeup of the placenta. Can make male fetuses more feminine, female fetuses more masculine. Environmental exposures can also affect the germ cells of the fetus and the genes that are expressed in the fetus. The female fetus already has the eggs - it also affects the eggs/germ line, soi it affects another generation down - transgenerational epigenetics. Changes that can manifest several generations down the line. If the father is stressed out, there's actually epigenetic changes to sperm cells which can have transgenerational effects.
The gene centric view is not correect - you're not just passing on the genes, you're passing on a cell. Those cells have all the machinery to read the genetic code - what matters is genes AND what genes you're turning on. Imagine you have an instruction manual - what matters is what parts you read. Imagine skipping a chapter. The turning off and on of the genome is affected by things all around us.

Prolonged stress.

also during development, environmental richnes sis also a big player. Studies with animals: put animals in enriched condition (toys, running wheels) and a control/standard condition (cage). Way more neural development occurs in enriched scenarios. Greater spine density. Early in development, wanna make sure organism is exposed to enriched conditions. Most of these studies, the standard condition is by themselves, in a cage, with nothing to do. Enriched condition is when around some other animals, has some running wheels, and could run around the lab. Standard condition is more of a deprived condition. Showing the negative condition. They just put rats in cages and said that's normal, but that's not normal! Giving them more stimulation might not actually have a benefit, the worry is deprivation. When people raised in normal situations, adding more things might not help. One worries that you're trianing them to be constantly stimulated - that might be diagnosed as ADHD or somehting.

Plasticity in the Adult Brain

Evidence that there are new neurons that are forming, even in adulthood. Involve hippocampus and dentate gyrus. Ventricular zones - lining of ventricles - where a lot o fcell prliferation/neurogensis occurs ind evelopment and adulthood. Some in the striatum - might be some evidence of neural growth later in adulthood.

In the Dentate Gyrus of the Hippocampus - Type 1 Radial Stem Cells - glial cells but have the capacity as stem cells to reproduce and become something else. Type 2 non-radial stem cells become immature neurons, and placed into dif layers of the dentate gyrus. This is happening in adulthood.

700 new neurons per day. continual turnover in hippocampus.

In subventricular zone - Type A, B, C cells. Type B cells are astrocytes - they can regenerate themselves or change to type C cells, proliferative precursors. C can differentiate into neurons. They come from astrocytes in adulthood. In mammals, migrate from ventricle to olfactory bulb because olfactory cells are always turning over fast.

Corpus stratum - not sure. Maybe coming from SVZ.

How can I facilitate the creation of new neurons in my adult brain? You can increase neurogenesis.

BDNF (Brain Drive Neurotropin Factor) - special molecule/factor that's heavily involve din triggering neural growth. BDNF is transported in the anterograde fashion and released from the synapse and moved in the retrograde fashion, released and affects the presynaptic terminal of other cells. Going both ends. When it makes contact, it upregulates the production of proteins to make cells healthier and produce. Have BDNF being released. Once they bind to post synaptic cell, cna increased receptor activity. It's doing things all over the place. This seems to be what leads to neurogenesis.

Goal is to upregulate BDNF. Key factors is physical exercise. Way more BDNF mRNA in the exercise group than sedentary group. Depends on how much exercise you get - more distance run, the more BDNF produced.

In humans, exercise has been associated in improved executive control, improved various control control processes, spatial abilities, cognitive speed. People exercising are cognitively healthier. Prominent in older adulthood.

Another way: through dietary restriction. We tend to overeat. Shocking. This is a negative stressor on our bodies. If you have dietary restriction, you can increased BDNF. Ad-libitum - whenever you want vs. REstricted scheudle.

whole lot of benefits: increases neurotrophins (stimulate growth); increases antioxidants; increases removal of damaged molecules; increases beneficial ketones; reduces inflammation; reduces oxidative stress (huge generation of free radicals when you eat a lot of food)

why does it work? Both exercise and dietary restriction provide a good level of stress that put the system on alert and make it work more efficiently. Whereas overeating gives you a bad level of stress, too much load on the system that's ultimately not good for you.

Endurant exercise and intermittent fasting can have a number of benefits. Independent of what you're eating.

Different regimes - Time Restricted Feeding - all your eating in 8 hours. Increases the amount of time without food - mild stressor - let's clean up, get ready. Caloric restriction - reduce number of calories, eat less. Intermittent Energy Restiricion - do it on some days and not others. 5:2 diet - 5 days regular, 2 days restrict. Alternate day fasting: day 1, the next day you just don't eat at all. Alternate day restriction - eat day 1, day 2 is restrictive. IER probably has the best effect - switching it up. It works, but loses its effects. Keep system off balance, make it try to adjust, right level of readiness. Trigger neural growth in adult brain.

Nutrition - lots of individual differences - waht you need at what time. Rats: LFCC diet vs. HSFRS diet. Low fat, complex carb rats had way more BDNF production. What you eat also matters. HFS is not good for your brain. Eat natural food that grows in the world, and is not made in a factory/laboratory. If it has more than 3 ingredients, don't buy it. Go to Tim Hortons and ask them for th eingredients for the muffins. You will never eat a muffin again.

Lecture 12: June 13, 2018

Test average: 73%

The effects of learning and experience on brain plasticity throughout life. The expreriences that we have continually modify our brains. String players - people playing violin. Looked at their cortex. Compare somatosensory cortex to control - physical shift in th elocation and strength of response increased. Depended on the age on when they started to learn. Greatest strenght of activity in the cortex were those that started early in life. changing your brain. Squirrel monkeys - manual taks where they have o retrieve a food pellet. Post-training - a lot more brain matter devoted to the fingers (red). 12 days of training only for plastic changes. People who were learning how to juggle. Grey matter changes in certain areas of cortex. Left P I sulcus (hand eye coordination) getting bigger. Mid-temporal area (perceiving motion) - more. Brain size changes for keyboard players (15 months). Grey matter size (size of cortical area). Increased area in right precentral gyrus (motor control), corpus callosum (coordinate between hands), right heschl's gyrus. Whenever we learn, we're actually changing something physiologically in our brain. The strength of the synapses between neurons. Getting more dendritic branching, more connections forming, incporaritng new neurons.

Plasticity After Brain Damage

Many different ways for brain damage:

TRaumatic brian injury - trauma to the head. fall off bike, hit with ball. Areas of maximal damage: where you made contact with the damage, the coup (right under) and on the other side (contre coup). In the motion, you get a lot of tissue shearing/cutting. Cutting axons, fibres, and small blood vessels. Very common in sports. You only need one bad conscussion to have lasting affects. Cognitive change,s memeory/attention deficits, some motor deficits with recurrent concussions. Takes one concussion = problems, more conscussions = many more problems. Strongly associated with depression.

Brain 70 hrs after TBI. ventricles are being compressed and difficult to see. Don't see any gyri and sulci as if they were filled in - cortex is swelling up so no grooves to see. Get small multiple hemmorheges - light colours. 6 hours later, must've damaged a slightly larger blood vessel - hematoma - pool of blood in the tissue - deform the brain tissue around it, pushing it.

Important to get repeated scans.

Stroke - Cerebrovascular Accident - 2 kinds:

Hemorrhagic core - from BTI which ruptured arteries. Bloodpooling. 36 hours later, see dark space around - brain edema starting to take hold. Swelling - IN PNS, trying to get white blood cells and immune markers into the affected area. The artery becomes more porous. A way to get the immune system focused on the area. In joints, immobilization. In the brain, it's not helping you.

Cytotoxic Edema - Why do the neyrons die, and why do you ge tthe swelling? ;

  1. GCutting off the blood - insufficient nutrients. Then you can't produce enough energy, which leads the sodium potasium pumps to start to fail. Can't make ATP. "This is the mitochondria here, it looks like batman." When SP pump fails...
  2. accumulation of sodium in the cells - depolarizing the cell
  3. eleads to an increased of release of glutamate (Exitatory NT) - more glutamate going into synapse
  4. getting more activity at the synapse. You have this beautiful astrocyte involved - it pulls out glutamate with transporters. It's also starving for energy and working hard to get rid of glutamate - they get overwhelmed and failed, and now are spitting out of transporters.
  5. Way more activation of glutamate receptors. A lot more sodium getting into post-synaptic cell.
  6. NMDA receptor is a glutamate receptor - when you get a lot of the postsynaptic depolarizaiton, calcium flows in. Getting a lot of positive charges accumulating
  7. they damage mitohondira leading to less ATP.
  8. that leads more sidiump pumsp to fail; This positive cycle of positive activity, overactivity, breaks down everything.
  9. when mitochondira starts to fail, it starts to release free radicals. They give off electron and damage tissue. Invader coming in, you wanna kill. But there is no invader so starts killing its own cells. Damages all otheorganelles.
  10. increase of positive charges create an osmotic pressure, which drives fluid outside into the clel, causing the cell to swell - Cytotoxic Eddema. swelling itself disturbs the cell membrane and it could make it mroe permeable (spacing between phosphloipid bilayer). Distrupt ion channels, protien channels, everything.

This is what happens when you have a cytotixc effect - becaus eyou get overactivity.

Can use this to create lesions. Happens within minutes.

Once you have one stroke, it's more likely you'll have a 2nd stroke. Cause the things peeling off, you wanna go on a blood thinner. 8 hours later, 2nd stroke which could've been prevented.

Cytotiic edema happens in other strokes too. Hemmorhagic - arteries will start to tighten up, provide less blood. Proper way of delivering blood is cut off.

Hemorrhagic stroke: Additional things happening during stroke: Blood pouring out, flooding region with blood.

  1. blood comiing out, starts to pool, causes pressure on the membrane of the cells, disrupts ion transfer- > buildup of ion cells
  2. constriction of the blood vesesels nearby, reduce the blood supply, causing ischemia (ischmic like stroke)
  3. cytotixic damage and cytotoxic edema, caused by icnreased in cation concentraitons (overactivity)
  4. When you get a bleed like this, want to coagulate the blood and create a patch, Thrombin released by cells that try to block it up to prevent more bleeding (good response)
  5. but thrombin has other efects: makes NMDA receptor more responsive to glutamate (more cations flowing into the cell), increasing excitiotoxicity. Helpful and hurtful at the same tiem (like free radicals).
  6. thrombin actiavates microglia to release proinflammatory markers cause lots of stuff in your blood, immune system wants to kick in to try to take care of those potential invaders flowing into the brain, but these pinflammatory markers further damage the cells within the brain
  7. the blood contains hemoglobin and the heme is made of iron, when blood flows in, enzymes will break fown hemoglobin and creates free radicals, which attack the tissue in the brain
  8. increase of plasma flow into the brain (vasogenic edema) - spacing between cells will allow it in to try to help, but it flows in and fills the space with fluid which causes pressure on the cells. Starts damaging ion channels.

All cells including glial cells are getting hit hard. All cells will die.

What could you do to halt this process? Open negative ion channels, provide ATP, drain the blood, engage inhibitory system. Inhibit glutamate receptors - reduce cycle of toxicity, block sodium/calcium channels. Hard to find things that target the speicfic area that don't have massive negative side effects to the rest of the brain. Main thing: break down the clot.

Macro level - hours and days after stroke. Main area of damage, surrounding area called Penumbra of struggling cells. Goal is to save as much of penumbra as you can. Likely cells at focal damage will die. First, neurons are connecting up to the penubra neuron which may be about to dye off - you have a denervation here - removed this synapse. Dendrites/synapses grow when there's activity, die when no activity. Starts to atrophy - spines to collapse. You get deecreased activity of this neuron. Some axons that are damaged are scarred over, and there's an inhibition of axon growth. 1-4 weeks after the stroke, a bunch of recovery mechanisms coming into play.

Some neurons ynapsing with the dendrite, might start to create collateral sprouts (new sproud from end of axon) that makes an axonal connection with the dendrite. The dendirtic spine remodels. Long distance axons come form a long distance that take vacant regions of the dendrite. System also starts to up regulate growth molecules like BDNF to strengthen the newly formed synapses and happening at the axon terminals. Increased NMDA activity - more potential for xcitatory connections being made. And downregulate inhibiotry GABA receptor activity so the system becomes more active. Right at the time of the damage, the damage caused by overactivity. HOwver, later on, in the ealry times of surviving tissue is underactive, which is a problem. With underactivity, yyou dont get growth factors. Initially, overactivity, then underactivity. Then brain increases activity to save them. There's a TEMPORAL sequence to these things.

Then the networks will start to remodel - network/modeling/reorganization. Took a mouse/rat and created an ischemic stroke. REd region - responsive to hindlimb and green region responsive to forelimb. Caused a lesion. Wiped out a big part of sFL region. Some neurons dying off, spine collapse, reduced neural acitbity. And there emerges some cells that now become repsonsive to both limbs. Then as time goes by, increased activiation and remodeling. Ambidextrous neurons. Some sHL are now resposnive to other things. You get a remodeling. More tissue that's responsive to both limbs - reduced sensory specifificty. 4-8 weeks after, more sensory specificity. Now regained function. This is referred to as spontaneous recovery - brain doing it on its own.

The remodeling can be long distance. Damage to the left subcortical motor pathway (goes up to motor cortex). Damage to left subcortical motor pathway - you increase connectivity after the stroke between ipsilesional motor areas and contralesional motor areas. Simultaneiously decrease cnnectivity in thalamus and contralesional. You're getting changes in connectivity across the hemispheres.

One thing that also happens: Diaschisis - reduced activity in distant areas from the area of primary damage. Different kinds: 1) Connectional diaschisis - red arrows - reduced connectivity, green - increased connectivity; 2) functional diaschisis - some areas more active, some areas will become less active afteerwards.

What if you get some areas taking over other brain areas. Amputations - amputated limb but might still feel that the limb is there. Worse: might feel pain in that limb. Like a muscle tightening. Initially, would assume that it was caused by the terminal end of axon - then cut the limb further. But people would still experience Phantom Limb. Some of it is due to cortical reorganizaiton after the reamutation. You got a sensory area no longer eceiving input. Might get collateral sprouting from adjacent areas into the vacant areas. Adjacent to the arm is the face/lips. So people who have phantom limb might trigger because of stimulation to their face/lips. People with phatom limb - when you touch this face, tou also see activation in the limb reagion. Activation spreads over. Due to collateral sprouting. Legs next to genitals - They would feel an orgasm in the amputated leg. And they liked it.

Face touch could connect to leg pain receptor. Ramachandran Mirror Box.

Reorganization with a bit too much learning. Musicisnas cramp - lose dexterity/control in their fingers. Turns out that it's focal hand dystonia - because person is practicing so much, each finger wants more tissue - the neurons responding to one finger will try to grab neurons from other finger - you get an overlap of the regions responsive to the fingers. You lose discrimination of the sense of touch of the motor system - leads to this clumsy fingering. It's hard to undo - case of overlearning. Musicians typically don't come back from that. Central problem, not peripheral.

After damage: cell genesis - neurogensis that creates both neurons and glia. Some areas after damage are fixed because new cells are being put in their place.

Ca get new neurons or cna travel along blood vessels.

Lecture 13: June 18, 2018

Finish off last few slides on brain damage. Ways that we can minimize the impact of the damage that comes along with strokes, closed head injuries, etc that disrupt the brain tissue.

As the damag eis unfolding, the tissue and penumbra is caused by overexcitation. AS time progresses, it becomes underactive and damage continue s because of underactive. Early on, you wanna reduce overactivity - blocking glutamate synapses or open potassium channels. Idea: make drugs that can do this. But there aren't really any drugs that seem to do the job without having worse side effects.

Indication that Cannabanoids work - controversy. Cannabanoids have antioxidant effects - stopping the overoxidation.

Maybe Omega-3 fatty acids might help - strengthening the cell membranes.

Right now, the main treatment for ischemic stroke: tissue plasminogen activator (tPA) - dissolves clot to improve blood flow. You have to administer within 3 hours, very quickly. May improve chances of recoverin from a stroke.

Within early months, brain spontaneously fixes itelf. Some reorganization. Partly occurs cause edema goes down. Also get recovery of those brain networks. You can engage in training and continue to improve into the range of 1 year after stroke - starting to modify some brain networks.

Study with rodents: created an ischemic stroke over motor cortex controlling one of the paws. Divided the animals into several groups. 1) lesion + enriched environment (running wheels, platforms, social interaction, reach m&ms with arm; 2) standard, caged; 3) sham condition - went through all same procedures + enrihched. The performance improvement was greater in the enriched group than the standard group. REceiving training improved neural growth and performance. Sham and Ischemic groups didn't show much difference. This happened in the undamaged motor cortex - filling in, taking on some more function.

Cortical Stimulation - in humans, apply tDCS over and around the ipsilesional motor cortex (same side as lesion) - you can improve motor function of the affected limb.; You can go to the contralesional cortex - can disrupt activity to improve performance in the affected limb - rTMS or cathodal tDCS. The unaffected contralateral motor cortex will start to take over a little bit. By inhibiting the contralateral, you disinhibit the ipsilesional to regain function. Reduce temporarily in th eunaffected hemisphere.

What people are starting to find: you can use stem cells and translant them into the effected region. They will start to change into neurons, astrocytes, or oligodendrocytes. Repopulate a damaged area with damaged cells. Different places to get stem cells - patient's bone marrow, fetal tissue (implanting genetics of another organism and don't know the implications)

We don't have many good ways to help recovery after brain damage. Prevent head injury and stroke (reduce stress, eat healthy). Low stress, low antiinflammatory diet. Avoid foods that trigger inflammation. And of courtse, don't play football.

Different sensory systems

Vision

Vision is the sense we know most about. Point of our sense - take info in world, detect, analyze, so system understands and can respond correctly to the stimulus.

Vision is electromagnetic energy - Eyes are only sensitive to a small part of it - the visible spectrum. PAckets of energy or waves. Waves: wavelength roughly corresponds to the colour you experience. There's a lot of information - colour, texture, space, distance, info about objects far away.

The stimulus enters the eye and processed within the eye and processed within other parts of the brain. Light comes in, hits cornea, through anterior chamber, hole (pupil), then hits lens - just transparent cells attached by a series of muscles - can squeeze or stretch out - focus light at diff distances, goes through vitreous chamber, to retina which sees the energy and transforms it into a neural signal. Blood vessels and axons of nerves leave out of the optic disk. White part - sclera.

Goal for light to get refracted by cornea, lens and focus it on the fovea that's dense with photo receptors.

Myopia (near sightedness) - eye is elongated. Light focuses in front of the fovea. By the time it gets the image, it's a little blurry. Can only see things clearly up close. Hyperopia (far sightedness - eye is squished. focusing point is behind the eye - might be able to see tings far away, but close up you need glasses;
Part of the world where 90% of young people are myopic - theory: bookwork/nearwork theory. Buried on books/devices - very close - eye as it's developing, doesn't develop properly. Evidence that it's also determined by the amount of light you receive as a child affects the growth. If you're spending a lot of time in dimmer conditions, your eyes are not gonna develop properly.

Dan's Retina - darker in the fovea cause dense. Optic disk. Blood vessels going into optic disk. Info falling in onto optic disk is never gonna be processed - a blindspot. Area of space where your're not getting info. It falls on a dif spot on each eye so you can compensate. Important you have continous blood supply to retina. REtinal detachment - retina peels off the back of eye and loses some of its blood supply (to determine if baby has been shaken - brain has whacked around, retinal detachment). PArt of your visual field will seem off - shifted because physically your retina is shifting. Not getting same correspondence. Contact opthamologist immediately to reattach your retina. Suck out some vitruous, air bubble and then reinflate eye. Can never align perfectly, but brain compensates.

Wiring diagram of the retina - pigment epithelium; next to that is the rods and cones - pinner and outer layer; outer plexiform layer where rods and cones connect to bipolar cells which connect up in the iinner pleiform layer with gnaglion cells which send their axons down, out the optic disc, make the connections they need to send info to the brain; Horizontal direction: connecting cones/rods and bipolar cells are horizontal cells; Processes for connecting dif ganglion cells and bipolar cells - amacrine cells; Also have a muller cell which stretches down.

Photoreceptors - Rods and Cones. 120m Rods - abundant in periphery of eye. Good at responding to faint light and motion signals. Not sensitive to colour. Want to use when dusk sets in. Mostly in the periphery; Cones (blue) - most abundant in the foveal region. Need a lot of light to have them be functional. Sensitive to colour vision. When evening comes, you lose colour vision cause not enough light energy to activate the cones effectively enough. Relying heavily on rod type activity. If dim, better to look a little bit to the side cause that region will fall in periphery which has more rods which is sensitive under low levels of illumination. Plopping fovea on there, it's gonna hit the cones which aren't that effective.

Foveal vision - lots of cones; In fovea, only a few receptors send input to each postsynaptic cell. A lot of fine detail information; Need bright lights; many cones - good colour vision;

Periphery - lots of rods or only rods; Many rods that converge onto a bipolar cell - data reduction. only have one cell representing the are corresponding to all the rods. Much coarser representation. Less detail; Faint light; few cones - poor colour vision

Subjective conscious experience doesn't seem to match physiology.

Physiology of retina - photoreceptors that capture light start to transduce it - light has to pass through all of this info before it gets there. That means our retinas are wired backwards. All these cells are quite translucent. Light hits discs where the chemical reactions occur. the bottom purple part - turning over cause damaged fast. Need to regrow. Need access to massive blood supply. They will also heat up a lot (photons) so blood supply creates a heat sink so it can continue to have blood movement diappate the heat quickly.

Within a rod - Transduction - take light energy and translate to neurochemical signal. Requires chemicals called Photopigments.
What happens in the dark: discs contain molecules that contain rhodopsin which consists of retinal and opsin bound together. It's in a form called 11-cis form. Photoreceptor cells produce cGMP which attaches to sodium channels, oening channels, allowing sodium to move into cell. This depolarizes the cell and you release Glutamate. This glutamate release and depolarization is a graded depolarization. Not like an action potential which is all or none. The amount you release will depend on the amount of light. While rod is in the dark, it's releasing glutamate - dark current.;
What happens in the light: light photon hits the retinal and change it into the all-trans form. TRiggers an enzyme to be released that breaks down cGMP. There is less cGMP to open up the sodium channel which closes and you get hyperpolarization. You get less release of glutamate. Adding light reduces the activity/release of glutamate from the rod.

The Muller Cell - light coms in at top, gotta make its way to get to photoreceptors. Muller cells are radial glial cells in the retina. They are there in adulthood. Most in brain will retract or turn into neurons. Exception: the retina. Connect up with rods and cones. They function like optical fibres. Capture the light and funnel it down to the rod and the cone with very little light scattering. They funnel things so it gets you perfectly to where you wanna go. Bypass other cells. Fovea also has a parting of the cells for a direct access.

How we code for subjective exprienence

Colour - Helmholtz proposed Trichromatic Theory of colour vision - there might be 3 dif kinds of cone receptors, each sensitive to a dif range of wave of the electromagnetic spectrum. This is the case. Sense depnding on the relative activation of the cones. Doesn't account for all aspects of colour vision. Colour afterimages - even though white, you see colour there. Theory can't explain that. Can use tricrhomatic theory to understand some of diftypes of colour blindness. Red green colour blindness. Ishihara plate - multiple reds and greens of dif intensities. Can't tell dif on red and green based on intensity. Have to rely on colour of hue. Dif types of this. See things in shades of yellow and blue. No green opsins in green cones to detect.
Trianopia - rare. Lack cones in blue range. Perceive most in red/green. Theory is partly true but doesnt give complete explanation.

Another theory: opponent process theory - perceive colour in terms of opposing pairs: red/green, yellow/blue. Might be bipolar cells that wire this way - 1 will turn on/off. Look at green area, it might get fatigued out so when you look at white, you're not getting activity from green, but only the opposite colour -red. Bopolar cell will inhibit. Getting both red and green but no longer responding to green.

Another kinds of problems with theory - we know about phenomenons like Color constancy. If I have a red apple, it will look red to me regardless of what red I illuminate with it. Might be reflecting a dif wavelength, it will still look red to me. Don't want objects to keep changing colour. Problematic to other theories - color isnt tied to a specific wavelength.

Propose Retinex Theory - colour composed by various info to determine colour. An interpretation rather than an inherint property of an object. Property that you create with your mind. A little wave length of light, but your brain does a lot of work to interpret it. What you see is an interpretion. Colour is a psychological construct. Same wavelengths but dif experiences. "Wait, what?" Experience depending on the surrounding context. Backgroudn tells you about the illumination - bluish light vs whitish light. System takes that into account when trying to compute the colour. Dif peolple's visual systems make dif assumptions about the visual illumination. More/less warm light or more/less bluish light.

Empircal theory of colour vision - it depends on your prior learning. Colour that you experience depends on your prior experience with objects under different types of illumination. As you're growing, the visual system grows up this repretoire to make inferences. Your conscious experience of the colour you think out there is a fabrication/construction of your mind. What's coming from the object are just a series of wavelength. When you experience your colour, you consciously experience as though it's there in space. But it's not, it's being created by your mind. But you experience it as being out here in space. You are consciously projecting a highly detailed, fully coloured hologram out into 3d space fromy our mind. No rays coming out. Conscious experience is something you're generating. Holographially putting it out there in space.

Lecture 14: June 20, 2018

Receptor field - part of visual field that excites or inhibits field. Does something to or changes the activity of the cell. Each receptor is very small - each part corresponds to a point of the external field. Light activates a receptor. Series of receptors connected to bipolar cells whciich all connect up to a single gnaglion cell - the receptive field of this ganglion field corresponds to the summation of the receptors. Multiple points activate multiple receptors, but converge a single ganglion cell - making it cover a large field.

A whole lot of receptors in the middle and in the surround. All of these receptors converge onto a bipolar cell. Horizontal cell makes it so the receptors in the center will turn the bipolar cells on - on0center/off-surround system. An on-center, off-center surround + a ganglion cell. Horizontal and bipolar cells only have graded potentials. Ganglion cell is gonna have action potential.
Illuminate just the center, get a depolarization in biolar cell and incrnease firing in the ganglion cell. If you have a donut shaped light (surround), lead to a hyperpolarization, stop firing the ganglion cell. If entire thing, a bit of a depolarization and a moderte increase in action potentials. If inhibited firing, rebound effect and wills tart firing a lot
Right side: opposite - off-center, on-surround. A lot of the overlapping receptive fields tiling the entire retina/visual field. (last diagram wrong probrably in the lines drawing).

Ganglion Cells - sending their axons to the visual centers in the brain. We have a whole bunch of dif ganglion cells. 1) Monostratified - dendrites in just one segment in the retina. ; 2) Bistratified - dendrites into two different layers; Vary in size, which colours in retina. Most common: Midget, Parasol, Bistratified (large, small) - 90% of ganglion cells. Each sensitive to slightly different types of information. Different kinds of ganglion cells already processing info in parallel diff aspects of the visual field.

Parasol (M Cells - connect to Magnocellular layer in LGN) - responds to large low-contrast objects and movement. Heavily distributed in the periphery in your retina. Very large cells sicne responding to large objects. Large receptive field because need to respond to larger objects and for motion, you need soem space to detect motion.

Midget (P Cells - Parvocellular) - the most common. Motionless objects, and colour (specifically red-green)

Bistratified (K Cells - Koniocellular layer) - info about colour (blue-yellow), detail

Separating what kind of information you're processsing in the ganglion cell level. That info sent up into the brain.

Once they send downaxon, through optic chiasm. 1 pathway: takes info to superior colliculus (10% of axons go there) - control eye and head movement. In the brainstem; 2) geniculastriate pathway - info from both visual fields, go through optic nerve, crossover in optic chiasm, right visual field ends up on left side etc, first connection made at lateral geniculate neucleus of the thalamus(DLGN). Cells from thalamus send theri projections all the way back to primary visual cortex. Geniculate to striate cortex. Main pathway for vision.

V1 - striate cortex. Connec tup to dif layers in the LGN. Parvo has 4 dif layers. Konio has blue layers. Magno has 2 yellow layers. Each send on axons to distinct areas in the V1.

Literal geniculate nucleus how it gets parvo magno and knion info. On one side of the LGN, it's getting from contralateral eye and ipsilateral eye input. Getting info from both sides. Eyes maintain separation all the way to primary visual cortex.

Ocular dominance columns for each eye. Info from right eye is coming into one column of cells, info from left eye into a dif column of cells. Columns of cells that are responsive to specific visual features. Orientation columns that are responsive to horizontal line features. You have feature-detectors in primary visual cortex. Very clean spearable organization of information. Spatio-topic organism - 2 areas close together in visual field are gonna activate nearby cells in retina and will activate nearby/adjacent cells in cortex. REproduced in retina multiple times depending on ganglion cells. Then reproducing that map in the visual cortex. Foveal region takes more of the cortex.

In these cells, we see a center-surround receptor field. Hubel and Weisel. Accidetntly discovered that visual system is responsive to edges/bars differently. Simple cells, complex cells, end-stopped cells.

First we extract some features, then combine features together to create the perception of entire obejcts. Way: the binding problem - how it binds things together so it's not just a smattering of features. But we don't know how it works.

This all occurs in primary visual cortex. It's critical for conscious processing. What happens when you damage PVC: DB - arterial malformation - blood vessels started to misform. Had to try and cut this thing out of PVC to relieve problem. Hemienopia - see nothing from the left side of space (on right side). Just darkness. Not like hemispatial neglect (you have a functioning PVC, info is coming in, but you're just not attending to it. Here, you're getting it to the right side but no tissue to receive it, so not sending it forward. Most of DB's left half field was blind. Could locate objects in left blind field. He can't see but can locate objects. Could it be he's getting info to the super colliculus. Other pathways don't give you conscious perception. This phenomenon: Blindsight.

After Area V1, info goes to other areas. Multiple visual areas. Primary, secondary, etc. End up going to multiple areas of the brain - 2 pathways:

Area V4 - responsive to colour. Depends on both parvo, konio. Important for color, visual attention. Patient with damage. Oliver Sacs - Theh Case of the Colourblind Painter. Couldn't distinguish greek letters, colours. All black and white. Then focus went super. But colourblind. Turns out, it occurs when you damage area V4. Achromatopsia - lose ability to maintain colour constancy (red apple regardless - keeps changing colour) or to perceive colour - Cortical colour blindness. Colour is a construct of your brain. If you damage area that proceses colour, you're not going to see colour anymore. You can be conscious of everything else, but you've turned the dial on colour. Samir Zeki: You can't think of consciousness of one thing - dif areas of brain giving rise to dif aspects of consciousness - multiple consciousnesses that work together.

How processing unfolds as you go down ventral stream in monkey. TEO: Temporal occiptal. TE: Temporal. Receptive sizes of each area. ( you can disrupt visual processing with that electromagnetic thing). Converging onto fewer neurons - receptive field grows bigger cause responsive to more. Prefrontal cortex to provide you with a response. Also happens in temporal lobe. Always adding multiple cells in prev layer convering making receptive field larger. And prcessing more stuff, more complex as you go down.

Ventral aspect of the temporal cortex. Horn of the temporal lobe from bottom. Cells specifically responsive to dif places (PPA), and a dif area responsive to face area (FFA). Dif area resposnive to dif categories of objects. Specific areas responsive to animate and inanimate objects. Responsive to objects reagardless of specific features - whether person is under bright/dark light, looking to left/right, etc. Constancy. Baylis and Driver. Face: Gestalt figure ground stimulus. because border is with background. Neurons respond to face even though it's reverse contrast or changed orientation. If you figure-ground reversal, the neuron stops responding - because white region is enclosed, it reads white region as object. Stop firing even though it's very similar. What matters for ventral/temporal neurons is what the interpretation is, not what the low-level features.

What if you damaged some of these temporal areas? Visual Agnosia - can see visual stimulus, but lose ability to recognise them. Patient shown fountain pen - that's a light. Once touches, recognizes it's a pen. Failure of recognition by vision alone. Big wall mirror - That is a lamp made of glass. Seems to have a horse in it. Donkey -> Napolean. Horse -> Horse. Not all or none. They have graded impairment - how much damage to cortex. Can have category impairment - places, faces. D.F. - damage near occipital - Apperceptive Agnosia - visual form agnosia. Can't put together basic features of objects. Can't copy drawings. Can draw from memory but not that good. IF you ask what they drew, wont remember what they drrew. ASsociative agnosia - get pieces together but cant attach label/meaning of what they're seeing. CAn do things like copy objects. While copying it, no idea what they're drawing. Can match objectes. Trouble drawing from memory. Can get meaning connected to physical features of object. Can't go from book -> image.

Appercetive Agnosic - D.F. - Slot in a circle. She stands back and using vision, she has to orient her hand so it's in line ith the slot. Simulating slot orientation at a distance. ARrow - orientation of slot - others are DF's attempts. Tell DF to post the letter into the slot - she's able to orient her hand quite well. Her perception for action is in tact, but perception for identificaiton of orientation for slot is impaired. Damage to her ventral stream but not to her dorsal stream (action, movement). A spared secondary stream to do well on motor movement but poor on vision type things.

Prosopagnosia - fail to recognize faces. Identify people by remembering a speciifc feature of that individual - just see features, you gate (way you walk), voice.

Lecture 15: June 25, 2018

Visual agnosia - unable to recognize objects through vision. Prosopagnosia - cant recognize faces.

Early preference for facial stimuli. Researchers use habituation - things that the baby will find interesting, they'll look at longer, not itnerested will habituate to them and not look at them. Faces get a lot of looking time. Face perception occurs very early on. Baby is born for the propensity for faces.

Optic Ataxia - specific problem in being able to use vision for action, especially for reaching for objects. In tact ability to recognize objects. They can recognize objects, but cant act on them. Opposite with visual agnosia, where you can't recognize but you can act on it. Double dissociation - dissociating ability for use vision for recognition from using vision for action. Maps on to 2 different streams for perception - vental (recognition) and dorsol (localizing and action) stream.

Dorsal stream - go up. Involved in motion perception. Middle-temporal cortex (MT/V5) . Medial superior temporal cortex (MST); MT has retinal topic representation - adjacent areas in space are in adjacent areas in MT. Also has small receptive fields. Responsive to direction of movement, specific feed at which somehting is moving, changes in speed, objects moving relative to background (car on background); MST has a coarser retinotopic map. Large receptive fields. Involved in expansion and contraction (cue for someothing moving away/towards you), rotation of objects, object movement relative to background; Superor Tempora sulcus (ST) and Inferior temporal sulcus (ITS). Image thinned out gyri - schematic to see stuff.

Case studies of individuals with damage to MT - symptoms: perceive the world as a series of still images (difficult to interact with the world, learn to use other sorts of cues to navigate like sound) - motion blindless / akinatopsia.

Damage to other areas, but spare area MT - people can't see objects, but they can guess with high degree of accuracy which way an object is moving. Might see a motion blur.

Paralell representation from multiple areas.

Deficits? Conditions?

Strabismus - eyes don't point in the same direction. Aka lazy eye. You're getting different, uncorrelated info from the two eyes. There are some areas responsive to both eyes, so it's hard to get a coherent signal to make sense of what's happening in the world. Brain will try to create connections with the dominant eye and not with the lazy one. They will become functionally blind in the lazy eye as the brain is ignoring it - you have deficits that are monocular and bincocular: don't have depth perception, occlusion.
Common old treatment: patch the good eye - force the individual to use lazy eye to do the work, so the brain would make connections. But what you really want is to coordinate both eyes. Now developing interesting games that involve stereoscopic depth perception. Video games where the individual has to control both eyes so that the 3d image pops up.

Critical periods; if you deprive stimulation to one eye, system will make connections with the non-deprived eye, reduce connections with deprived eye. If deprive both eyes - more sluggish response, but attain ability to see things. Since no input, there wasn't one eye that outcompeted one eye. System was in limbo for a while. Need early development to experience external world to create a little more pruning of synapses to work with the environment.
If shown horizontal lines only, the visual cortex will not be responsive to vertical lines. Show one type of stimulus, prevents it from reacting to other stimulus.

Audition

What's the stimulus for hearing - compression for air particles. Vibrating vocal chords, compressing air, which travel through airspace and come in contact with ears. Model these compressions with waves.

Compression travleing through air in a wave. Amplitude - height of the hill - corresponds to loudness. Frequency - as it unfolds over time, length of one sinusoidal movement, converts to pitch. Complexity of the wave - a combination of sinusoidal waves, codes for us the quality of the sound. Violin and piano have dif composition. Decompose complex waves into simple pure tones (simple sign waves). Pure tones vs. Comination of pure tones (complex). Decompose using Spectral decomposition. Timbre/colour of the sound.

It's not 1 to 1. Still reconstructing things. Physical vs Psychological characteristics of sound - Psychophysics.

The organ for hearing: ear. Outside: flapping piec eof skin, Inside flappy part: concha. Inside head: connected to Auditory canal - that's the part where you stick the qtip in. If too far, you hit the ear drum. Vibrates the Tympanic membrane (Eeardrum).; Move to segment of middle air (3 primary bones - malleus, incus, stapes - connected to each other and carry vibrations from t membrane to inner ear).; Stapes vibrates antoher membrane, ovla window, which goes to the cochlea. Only chochlea in yellow part is involved in audition. Auditory nerve connexts to various parts of choclea; What you're doing is translating vibration coming from the air particles and moving it through organic tissue.

Cochlea - snail. Long thing. If you cut cochlea and look inside... 3 different spaces. SCala Vestibuli , Scala Tympani - both contain perilymph. Scala Media - contains endolymph (fluid). Red box - organ of corti - where a lot of the work happens. When you vibrate oval window, it will make the fluid move. Movement of fluid will send a wave that will vibrate the basilar membrane, which activats the organ of corti.
uditry nerve fibre coming in. Inner and outer hair cells - poke up into the endolyph fluid and form hair-like protrusions called cilia. Tectorial membrane comes close to cilia (some cases attached).

1. sound comes in vibrates the tympanic membraen; vibration of ... sends a wave of fluid to vestibular canal; if unroll, vestibular canal continuous with tampanic canal. Wave down whole thing; 2) 3) waves push basilar membrane up and down. 4) 5)

End up moving basilar membrane and organ of corti up and down depending on the fluid in the chochlea. It makes the cilia move back and forth within the cochlear duct. Cilia are connected to auditory nerve. Whenver they move, they trigger action potentials in hair cells that get converted to action potentials within auditory nerve. No action potentials in cilia, but in auditory nerve.

Cilia are staggered in their height. They're connected by a very thin fibre.
a hair cell with cilia protruding up, and a spiral ganglion neuron (auditory nerve). They're being bathed in endolyph - very high in potassium. When ion channels open, potassium flows out, but here cause theres so much K+ in endolyph, potassium will flow in.
The cilia aren't all exactly the same height - microfilaments that connect the taller ones to the shorter neighbours - tip links. Tip link is attached directly to an ion channel - potassium. 15% of potassium channels are open, positive charge entering. Some sort of depolarization, which triggers calcium channels to come in, vesicles release a NT (glutamate) and activate spiral ganglion neuron - moderate action. When soundwave comes in, movement of paralimph. Which moves against corti.
From shorter side to longer side. Increasing the distance between tip link cilia - pulls microfilament and pulls open ion channels. Mechanical-gated. (many mechanisms to open up ion channels). All sorts of potassium flows in, larger depolar, more calcium flowing in (voltage gated)
Goes other way, reduces distance, less tension, closes channels, hyperpolarize, stop. Every time cilia moves, you change firing of neurons.
Air pressure changes manipulating vibration of tissue which creates waves in fluid which vibrates membranes which cilia moves and mechanically opens/closes ion channels. Potassium gets pumped out (potassium exchangers - pumps). Many different transfer points.

Hwo do we code for dif types of information? Pitch perception - idea is that pitch is related to frequency of sound wave.

Place Theory - dif places along the cochlea had cells that were sensitive to different frequencies.

Frequency Theory - whole thing moves in synchronity with frquency. Firing rate would code for pitch information. Stiffness - responsive to high freq. Floppy - responsive to low freq. Don't want a lot of movement for high freq.

Now we know, that both things are likley going. Low frquency sounds explaine dby frequency theory - whole basilar memb will vibe in synchronity with frequency of the sound wave. That's gonna cause neurons to fire at a partic frequency - how brain knows what pitch. Problem: we're sensitive to frequencies that outpace the potential firing rate. The neuron can't keep up. Expand frequency theory up to 4000hz by using Volley principle. With relatively high freq, not every one can fire with every single peak. Each neuron might be able to keep up with every 4th peak. Now can rely on neurons working together. One neuron that fires first peak, second neuron fires on second peak, etc. Even though it can only fire every 4th peak, collectively, you have represented a firing with every peak of the sound wave. Higher than 4000hz, you use place theory - neurons in specific places in chochlea that will fire when you reach these higher rates. Collectively reproduce the frequency even though each can't handle it alone. Neurons in specific places in cochlea that fire at partic rates. Multiple thing sin play together.

How would you localize sound in space? Spatial localization - Vision gives us very good spatial info. Audition is not as good, better for temporal info. Vision is sluggish - this is why we can have movies. Monitors work the same way - refresh rate. Hearing: operates at a much faster temporal resolution. Localizing sound is quite challenging.
Mechanisms to localize sound in a horizontal plane. Interaural time difference - sound coming from one side, hits one year before the other ear - delta(t) difference in time between 2 ears receiving info - brain computes time difference. If it hits both ears, its in front or behind. - This is just one cue; Interaural level difference - when sound coming from one side, hits the first ear and is louder than more distant ear because head absorbs some of the sound. Small, but system can detect. delta I - difference in intensity between 2 ears. Best for higher frequency tones. But still cant tell if in front or behind or vertically.; (image 3: f > 2kHz) For vertical/front/back, antoher cue: uses frequency information (pitch). Outer flappy part, pena, has grooves - it creates a spectral notch in the frequency band. Bounce around the sounds and has signature effec ton the wave lengths coming into your ear- very dif depending on angle. If you got nice, big, flappy ears, it's great for sound localization. You should be very excited about that. If you were to remov ethe pena, you can actually do this yourself. Don't chop your pena off. Molds of people's pena - everyone has individual shape - if yoou put someone else's mold of their pena, you stil wont be able to localize sound cause you need your own pena. About 6 dif categories of pena. 1 will capture yours pretty closely.

Auditory stream: in meddula, hit cochlear nucleus - info splits into dif pathways (parallel info transfer), some go to superior olive and on opposite side. Dorsal to inferior colliculus. Lateral lemniscus in pons - pathway. Converges in the inferior colliculus (audition). Some info goes to superior colliculus (combo of vision and auditon info going there). Go to the thalamus - medial geniculate nucleus. (corresponding nucleus for vision -dorsal lateral genic nucleus). sensory relay center. goes to auditory cortex. Add spectral processing in dorsal cochlear nucleus - verticla positioning. ITD and ILD in superior olive. In superior olive, neurons called concidence detectors.

In the superior olive, you have neurons called coincidence detectors - coming from ipsilateral side and contralateral side. Sound info coming from the chochlea nucleus and trapezoid body are sending axons to the superior olvie neuron which has a cell body with denderites coming out. You have excitatory and inhibitaory inputs coming from both sides. EAch one is tuned to maximally respond depnding if info is coming from left side first or right side first. Connecting up info from both sides. Think of it like a temporal summation. If all active at the same time, depolarized heavily and fire. Tuning curve - spike rate highest when sound is coming more from the contralateral side. When contralateral side is leading it's gonna fire. Partic neuron is on one side of the body but is more responsive to the other side.

In the auditory cortex: on superior part of temporal lobe, heschel gyrus where the p auditory cortex is. That part of the cortex - certain areas (a - highly responsive to freq in 3000s range, b: 1000, c: 800) - creating a tonaltopic map, where adjacent freq are represented in adj areas in the cortex. Mirrored axis - f responsive again up to 3000. Some areas specifically (red yellow) more representative of pitch. and other areas mroe responsive to localization of sound. Dorsal - localizing sound. Temporal - pitch.

Lecture 16: June 27, 2018

40 m/c, 2 short answer (choice of 1). end of audition.

[missed a bunch]

Auditory cortex - [...] Auditory imagery - making a sound in your mind, without external stimulus being there. Play very familiar tune - stop and see if you get auditory activatioin after you stopped playing the sound.

Some defiicits in audition:

Conductive/middle ear deafness - interefered with ossicles so sound vibrations don't get to inner ear. Middle ear problem. Bones get calcified/hard and don't vibrate as much. Interfering growth can be removed. Typically amplify the sound to increase the vibration of ossicles in middle ear. Inner ear is just fine, so you can pick up vibrations from inside your body - so you can hear yourself when you speak.

Nerve / inner-ear deafness - damage to chochlea. Problem: you've lost sensory organ. Developed implants that stimulate the axons directly and the wire is placed just under the skin. Through a magnetic communication system, sensory device and stimualtes the neurons within the chochlea. Some problems develop with age- presbiucusis - selective inability to hear high pitched sounds. The mosquito - anti-loitering device for young people.

Tinnitus - persistent ringing in the ears. hear a high pitched sound that doesn't go away. Damage the cochlea or the axons coming from the chochlea. Leaves primary audutory cortex without its input - get some reorganization - some axons from other areas that will stimulate that tonotopic map. Akin to the phantom limb syndrome. Reorganization of PAuditory cortex. Person with tinnitus dont have clear organization - 6000hz is in the wrong place -a ctivated by some other axons that trigger experience of sound even though there are no vibrations. A central reorganization type problem.

Mel Goodale - people who are born blind an develop an amazing aility to use sound to localize and identify object. echolocation to navigate in the world at a high level of accuracy. Produce a click from their mouth - audio waves go out, rebound, and detect changes to identify surfaces. Can recognize texture. They're using visual areas. Network reorganization on steroids. Can use it now for auditory input. Neurons are tuned to detect localization from temporal. Visual cortex have visual layers - can leverage.

TEST 2 END

Other components to inner ear. Part of the vestibular sense. There to giv eyou position of movement to head. Including movement of eyes and balancing. If eyes didn't compensate for visual scene, your visual scene would be going up an ddown. Vestibular sense gives info to compensate. Damage - lose balance.
Saccule and Utricle - reigster angle of head and linear acceleration. Contain otoliths or calcium carbonate particles and fluid. As you move, fluid moves relative. Hair cells, cilia, if you tild your head, gravity pulls otoliths down, moves fuid (gelatinous layer), tilts cilia, leads to action potential. Gives you info abou tthe position of head
3 semicurcular canals - 3d planes - info about head rotation. Fillled with endolymph, fluid sloshes, moves cilia, triggers same kind of process.
Same receptor logic applies to sound and vestibular sense.

Touch, Temperature, and Pain

Exteroception - stimuli that impinge on your skin. one broad category of somatoception. In that class, proporitoception, interoception (organs)

Stimulus: touch, heat, chemicals.

Start with touch - somehting pushing up against skin.

Skin: epidermis, dermis, subcutis. Glabrous skin - no hair follicles. Under skin - low-threshold mechanoreceptors (LTMRs) - don't need a lot of stimualtion to be activated. Pacinian corpuscles (deeper in sucutis), ruffini ending (in dermis), merkel disks (attached to lower end of epidermis, Messiner corpuscles. Axons - AB fibers (alpha beta). Conduct informaiton fast. Axon, axon terminals that connected to or modified by some other type of cell which gives it its specificity of function.

Meissner corpuscle enlarged - AB axon fiber. in between, lameller cells (schwann). Axons sandwiched between lameller cells. Around it, collagen fibers - connective tissue, protein that connects things. Connects it to the epidermal cells of skin.

Skin type - where they're found. Glabrous/hairless - lips, palms, feet, genitals - also where a lot of touch happens. Dif types of nerve endings have dif responses to touch. Slwoly adapting - stimulus turning on and staying on - continued firing - it's slowly adapting. Very good for info on contonious pressure. Rapidly adapting - turn stimulus on, fire quickly, stop firing, until another change occurs. Sensitive to vibrations of high frequency. Pressure, release, pressure, realease. You get all the varieties. Pacinian - onion layers will just dampen the signal. Properties come from how the nerv eendings have been modified by the cells.

Why have skin cells speicfucally sensitive to vibration? for textures - if you move your hand along the surface, texture will register as a sequence of perturbations of the skin.

We're in this world where mos to fthe info pinging on our system can be described in waves. Oscillation/cvibration which we pick up on.

Distribution/density of receptors on your hand. Slowly Adapting Merkels disk - finerrips. Riffuni - more on palm. Receptive fields - how much skin surface. Ruffini - half your palm is a receptor. Slowly adapting, but dif receptor fields. Rapid adapting - small

How well are we able to discriminate touch all over our bodies - depends on mechanoreceptors. Two point discrimination - pricky filaments - half mm. Person itsn't looking - take a filament and prick them 25%, 75% - prick wiht 2 filaments. Judge if pricked with 1 or 2. For 2 - vary distances between them. How close can they go to determine if it was 2 or 1. That's your 2 point discrimination threshold. Centimetres.
Fingertip - 3mm - pint where you can discriminate between 2. Shoulder - cna be 3cm apart and will not notice it's 2. Don't have many receptors in calf - might be activating same receptor on calf. Cortical area corresponds to roughly these points. Areas where you have densly packed receptors get more dense areas in cortex.

Rodent hair. Zigzag hairs. Another set of receptors that surround the hair follicle. Several dif types of fibres with c fibres which do not have myelin. Tjeu convey info slow since unmyelinated. Wider, alphadelta fibres that are myelinated - faster. End of fibres - longitudinal lancealoate Endings - sensitive to movement of hair.
Micrograph w phosforesence - 2 dif hair follicules surrounded by lanceolate endings. Green - alpha delta fibres - come in, surround hair, longitudinal protrusions. Intermixed in, schwann cells that help modify endings. Detect movement of hair follicles. AD fibers - rapidly adapting . C-fibres - slowly adapting. 2 dif tpyes of lanceolate endings responding to dif aspect sof hair follicle movements.
Lanceolate endings - They seem to also be heavily involved in detecting intimate touch. Emotional component. For instance, if you take your... lovely dog. and you stroke the dog, it's partly the movement of the hair thats giving it that social feedback. Hair is very important for that social, intimate touch. So think about that before you shave next time cause youre essentially eliminating a key mode of communication.
It allows you to experience touch away from your skin. whiskers to do all sorts of things. (Blind people with cane - feels like an extension of their own body)

high-threshold mechanoreceptors (HTMRS) - sensing pain and temperature. Picking up noxious info about ocntact - potential danger. All over the skin. Some are C, AD, AB. Free nerve endings. All seem to be slow adapting - as long as stimulus is on, theyll be firing. Sensitive to pain and temperature.
Similarly populated as low threshold. Calf has got a very high threshold.

How do mechanoreceptors work? How much they be sensitive to pain? A number of ways you can open up ion channels mechanically.

Heat Transduction - You have certain kinds of receptors and free nerve endings - transient receptor potential vanilloid 1 (TRPVI) ion channel. When you have a change in temperature (heat), itll change th eprotein structure of ion channel causing it to open. Temperature-gated. TRPVI ion channels also have a receptor lignad location for certain chemicals such as capsaicin (In hot chili peppers). Chemical makes your mouth feel like burning because it binds to the ion channel and opens it up. It's a temperature related channel so your subjective experience is hot. This ion channel is polymodal - it can be opened by multiple modes.

Cold Transduction - receptors responsive to cold. TRPM8 is an example. Cold comes in, denatures protein, channel opens, ions flow in. Also sensitive to Menthol. Which is why menthol feels cool.

People who eat a lot of spicy food become less sensitive - Gained tolerance. what is the mechnaism by which you adapt to the chemical so it doesnt trigger the crazy response fo ryou? If you eat enough, causes TRPV1 to die out - killing some of the axon free nerve endings. Densititzing mouth by killing off some of the receptors in the mouth. You wanna be careful. Short term effects will just adapt. Long term - killing pain receptors.

Whole ocllection of these - temperature ranges. Whole arsenol. To detect temperature.

Go back to the whole body. Touch/pain receptors systematically go to various parts of the spinal cord. The neurons from a very specific part of the body will go to a specific dorsal root. If you were to damage that par tof your spine, you would lose sensation from the corresponding area of the body. (disc slipping - bulged out, press against nerves) (Stu mcgill. ) (various exercises to push disc back in place. )

Different pathways for touch and pain temp. Up to dorsal medial lemniscus. For temp and pain crosses over midline, goes contralateral and up - spinothalamic tract. [.. missed something] Affect touch on the ipsilateral side. Damage half - may lose touch but not pain cause dif sides.

Long range projection. spinal cord c8 - at medulla - touch pathway travelling up the ipsilateral to contralateral, up to brain stem, connects to thalamus, to primary somatosens cortex. Cleanly organized.

Specific areas in somateosensory cortex corresponding to brodman areas that are responsive to specific aspects of touch. Dif aspects of touch being rep in cortex in sep areas.

Lecture 14: July 9, 2018

Pain and temperature - sensory neurons come fromskin, enter spinal cord, cross over to contralateral. Touch stays on ipsilateral and then crosses over.

Multiple pathways asscoiated with pain. Somatosensory cortex via ventral posterior nuclei of thalamanus - associated with general sense of pain, memories of pain, cues associated with pain that may activate that area; Another pathway: attached to central nuclei, goes to prefrontal cortex, amygdala, hippocampus, cingulate cortex (all associated with emotional processiong).
Somato: evaluating information. Other: giving emotional colour to the pain. The same sensation can be massively aversive or not so, dependin gon how you interpret it. So to deal with chronic pain, psychotherapy - learn to reevaluate the pain you're feeling. You can affect emotional centers and reduce the negative feeling of pain. When you're enduring something painful that will ultimately lead to a good result - bench pressing pain vs being cut.

Pain Relief - opioid mechanisms - morphine, heroin, methodone, fentanyl. Prescribed for pain. People get addicted.
In areas such as spinal chord and periaqueductal gray area of midbrain, you have receptors for opiates - they are on top of axons that secrete NTs associated with pain signal. Typically will release glutamate and a neuropeptide, substance P, it potentiates your sense of pain. Axons have opiate receptors, then you have neurons that release endorphins, which attach to opiate receptors and inhibit the release of substance P.

Another effective way to deal with pain: placebo. Drug that doesn't have a pharmacological effect. Hoever, the drug has certain psychological benefits. Because it's affecting the emotional areas, it reduces emotional processing of pain. Are getting altering in pain processing areas, bu tthe effect is psychological, but not purely psychological. Psych+physio. Convincing your brain that it's being healed and the brain is putting that into action. The medical community should get together and create placebos. Nocebos - told it has negative side effects, you'll have those neg side effects.

Marijuana - inhibit pain conduction. Cancer-related treatments. Not as addictive as opiates.

You can sensitise your pain system. Can learn to feel pain more. Good strategy is to avoid pain. The more signals they send, they more they grow. Get sensitization effects over time.

Sleep and Arousal

Cyclical mechanisms. Rhythms.

Circadian rhythms - over a 24 hour period. Endogenous (internal) circannual rhythms - annually/yearly birds migratory patterns.

There are individual differences. morning people - larks vs. night owls. Changes with age.

Over a 24 hour period. Awareness, Body temperature (drop just before you go to sleep), Growth hormone (fall asleep, growth hormone levels spike), Cortisol (stress hormone - spikes in morning, goes down during day, spikesuup hwen waking up. Leads to energetic feeling in the morning. Fluctuations throughout they dai in repsonse to stressful events. When streessed for long period of itme, levels stay at a high, it'll damage feedback mechanism and cortisol level will stay monotone the whole day. Constantly wired.).

Cycles are governed by an internal mechanism running on its own - FRee-running rhythm and an external event that can affect it - Zeitgeber. Imagine no external cues, your clock runs a little longer than 24 hours. External cues reset that clock making it shorter. A big one is light. Other zeitgebers: Exercise, noise, eating, sleep-related hormones, temperature changes. Increase temp in evening, hard to sleep because you reset clock. Want it cool to trigger sleep

Misalgning cues in environment - Jet Lag. West to East and East to WEst isn't the same.
West to East: Go to bed at 10pm, i tfeels like you're going to bed at 7AM. You have to phase-advance your circadian rhythm.
East to West: 10pm feels liek 1AM. You have to phase-delay circadian rhythm.

Key place: part of the hypothalamus - Suprachiasmatic nucleus - super duper nucleus. Above the optic chiasm. Main control center of CRs(circadian rhythms). I fyou damage, your body rhythms go out of whack. You could take cells out of there and will continue running. They don't require other areas to keep the clock going. But you do have connections that can reset the clock via Zeitgebers.

Light - another pathway coming from retina to brain (3rd pathway) - retionhypothalamic pathway - ganglion cells that have a photopigment themselves that are responsive to light. Have Melanopsin. Send axon through optic nerve, gonna go to the superchiasmatic nucleus - resets the clock. Don't need input from rods/cones to activate these. Sense overall ambience of illumination.
Blind people - can't use light as zeightgeber if heavy retinal damage. It's possible if they have ganglion cells in tact in retina.

Mechanism - you have genes in the superchiasmatic cells. Two types: the period (per) gene that produces PER and timeless (tim) that produces TIM. Gene produces mRNA which produces PER and TIM. When you create protein, it inhibits the production of mrNA. if you reduce concentration of protein, it turns back on the mRNA transcription, which produces more, ... Self-regulating system. Light breaks down the protein so concentration stays low. Not enough protein to inhibit, so mRNA is continually increasing. Butprotein levels kept low cause sun is breaking down the protien. As it goes to night, mRNA will start producing protein that isnt getting broken down, shuts down mrNA. Protein building up, nomRNA to produce anything, then sun comes out.
Basic clock mechanism. If you have a mutation in some of these genes, you're gonna have circadian rhythms that dont match to 24hour clocks.

Superchiasmatic nucleus has clock. Base don that it's gonna control activities. Primarily hormone secretion from endocrine glands. Key: pineal gland, which secretes melatonin (same metabolic pathway as seratonin). SCN triggers pinneal gland to secrete melatonin, a hormone that increases sleepiness. Happens several hours before bedtime. Melatonin concentrations feed back to reset the biological clock. Can buy melatonin pills to simulate the secretion in pineal gland. But you get sleeping pill hangovers - you will develop compensatory responses. Will drop melatonin levels in the evening in anticipation of getting external dose. Useful for switching timezones, but want to try to avoid depending on drugs.

When going to sleep, eliminate all light sources. when sleeping, light goes through eyelids. Eyes are never prefectly sealed. Small amount of light can cause disturbances. Blue range light is problematic - can impair ability to trigger sleepy mechanism. 1. eliminate all light 2. all sounds.

Sleep: during sleep, you're reducing brain activity. (Sleeping pills are inhibitors). Look at it with EEG, combine with polysomnograph (eye movements). Blue: EEG, red: eye movement record. measurements around your eye. 1 second intervals.

Stages in a single night. 90 min cycles. Start at Stage 1, 2, 3, 4, 3, 2, 1, REM. As the night goes on, a lot more time in REM and less time in stage 3 and 4 sleep. Poeple who have sleep disturbances - awake after REM stage.

Proportion of NREM and REM sleep. First 1-2 years, a lot of sleeping. Lots of time in REM sleep. As you get older, total hours of sleep goes down. You can oversleep.

Pattern in mammals: synchronized activity between the area in th epons, LGN of thalamus, and occipital cortex. Pons-geniculate-occipital waves ( PGO). Shot of activity in pons, then LGN, then occopital cortex. System is consolidating visual processing. Each eye movement seems to be couples wiht PGO wave. Constant amount of PGO waves each day.

Brain areas that are involved in the arousal system. Distributed throughout parts of brainstem and prefrontal cortex. Each use specific and diff neurotransmitters. 2 classes: PPT and LDT - activating the thalamus - primary NT - acetylcholine.; Activating the cortex: LC (norepinepherine/noradrenaline - releasing/activaitng cortex), Dorsal/medial raphe nuclei (serotonin/5-hT), TMN (releases histamine - activating the cortex - anthistamines reduces histamines causing less arousal, more fatigue. Non-drowsy - add stimulant/caffeine to conteract the inhibition), LH (Orexin - keeping you awake, MCH), vPAG (dopamine), BF (ACh, GABA - exittatotyr and inhibitatory). Arousal starts out in brainstem areas.

All areas are also controlled by the VLPO. Contain inhibitory NT galanin and GABA, shut down excitatory areas. Two opposing things. flip flops.

Why is it important to sleep?

Lecture 15: July 11, 2018

Test 2 - Average: 73%

Importance of sleep - if you don't get sleep - end up with various impairments. Importance for learning and memory - sleep improves memory for things you learned before you went to sleep. Activation in hippocamus strongly related to memory being very active during sleep. Consolidating memory - making a more durable form of memory while sleeping. Weakening unued synapses and strengthening used synapses that forme dduring learning. Sleep deprivation hurts memory. You become more creative, have more eureka moments. EEMotor sequence learning task - sequences oyu correctly complete per 30 seconds. Get retested later on. Training in morning, reteest in afternoon, if you have sleep, morning you do way better. Something happened while you slept to allow memory to improve. 3: learning in evening, after first training session have sleep, improve learning substaintially. It matters when you sleep. Correlation to percent of stage 2 NREM sleep. EE Practicing retrieval - go through slides without looking at them. Recall without looking.

Why do we dream? aactivation synthesis hypothesis - start out with some activity that activates the cortex, the cortex tries to make an overarching story from all the information that's activated. Emotions involved because you're activating emotion-related areas. This is total speculation. WE just don't know. Studying requires reporting on dreams, requires remembering dream.

Lucid Dreamng - when you become aware that you're dreaming while you're dreaming. Youa re able to become better at lucid dreaming. via presleep autosuggests - tell themselves to recognize the bizarre events of the dream. When someting happens that's bizarre, I must be dreaming. Primarily occurs during REM sleep - acitivation in frontal lobe. Electrooculargram (electrical activity related to eye movements) - electromiogram (muscle activity/movement). Awake but eyes closed, asked to move left to right to left to center. In REM sleep, your peripheral body is shut down (EMG silent, some eye movements in EOG because of rapid eye movement - nons ystematic). Told that when they become lucid, move their eyes in the pattern. EMG is silent, but they do the systematic eye movement pattern.
Scalp potential - measuring eeg from scalp - shown as a power function - power x frequency. Hybrid state - indicate you're aware, but brain is in remlike state.

Sleep disorders

How you can improve your sleep:

Emotion

cognitive neuroscience of emotion. 1884 - William James - What is an Emotion? PRoposed view: natural view of emotion - mental perception of some fact excites the mental affection alled the emotion. You see something that makes you experience the emotion - the later state of emotion gives rise to bodily experession. See the bear, feel the fear, then you run. Perceive, feel, act. He says that's not how it happens. It's reversed. We feel sorry because we cry. Angry because we strike. Afraid because we tremble. The subjective expereicne comes after the physiological type response - James-Lange Theory. Some sort of stimulus - perceive it using cortex; triggers some autonomic(internal)/somatic(muscles) responses; reigsterd by somatosensory cortex; triggers the subjective experience of emotion.

Cannon's critique:

Cannon's View: perceive something, activate the thalamus, lead to subejctive emotion, connected to everything else. Key: it's the thalamus.

Emobidied emotion - body is heavily involved in emotion. stimuli with emotional words. Showed them a picture - what areas of your body you feel are more activated. which areas were deactivated. Combine images - activation map. Found consistency cross cultures/people. Another prediction: if I change your body, I might be able to influence your emotion.

Facial feedbakc huptothes - sgolf tees on brows - furrow your brows - negative expression -> rate how they feel when seeing a picture. When frowny position - reported more sadness. If you wanna feel better, you oughta just smile. Rate comics with regards how funny they are - hold pen in lips or teeth (smile).

Woman with facial parlysis - continued to experience normal emotions - inconsisten with james-lange theory.
botox users experienced blunted emotional experiences - less negative/positive. Immobilized facial apparatus to experience emotions.
People with pure autonomic failure show only slightly blunted emotional experiences. Partially consistent with james lange.

Body is involved, but not the only conduit.

Brain areas

One prominent theory - MacLean - Reptilian, paleomamalian (limbic system), neomammalian. Evolutionarily, cognition in neo, emotion in paleo, basic responses in reptilian. The big idea: one of the key areas in the limbic system - hoppocampus (seahorse) - big relay center, where all the emotions occur. This big emotional, criticla relay center in the brain. Hoppicampus is important for cognitive functions. Still no agreed upon criteria on what belongs in the limbic system. Came out of the simplistic idea. Can't just think of emotion as just being relegated to limbic structures.

Emotion and the Cortex - when people are experiencing dif types of stimulus - emotion is experienced all over cortex. There's no single emotional area. Many emotional areas.

Lecture 16: July 16, 2018

Emotion Perception - there isn't one central area involve din emtional experience. Some areas invlved in emotion perception. Emotion perception involved areas of the brain that are involved in processing bodily things. Study with lesion overlays - red: poor emotion recognition. Right somatosensory area is poor. Consistent with Lang theory (using body to recognize emotions).
emotion recognition of disgust and areas of brain experiecing disgust. Insula heavily associated with experiencing disgust. Areas associated with seeing and experincing overlap. Area used to experience is same as recognizing someone else experiencing.

Emotions are important when making decisions. The Iowa Gambling Task - Decks of cards, card - how much you've gained/lost, some are bad decks - high return, but very high loss - would not gain overall. Participant doesn't know bad deck. Good decks - low return, lower loss - if you stick, you'll make money. Participants just pick cards. Your emotional system starts to pick up the idea that some decks are bad and others are good before you can consicoulsy know. Galvanic salianation someting (skin response) - electircal conduction of skin - if system starts to pick up something is bad, youll sweat a little more. Normal invidividuals wills tart to experiment, picking cards. Spike in skin conductants when going to the bad decks - hapepns before they can consicously tell you. Then they'll realize some are bad/good and go to good deck.
PAtients with dif lesions: lesion prefrontal cortex (making decisions) - don't show galvanic skinr esponse before picking a card from bad deck, they pick from bad deck longer, only after making their pick do they sweat; amgydalal lesions - don't show galvanic skin response before or after picking from the bad deck. PErform the worst.
The early emotional response seems to be able to guide our decision making. Emotion is helpful in certain scenarios.

Especially in ethical decision making - Trolley problem. a) 5 vs 1. Utilitarianism (save 5). b) push the guy over to derail trolley. More people would not push. Very few willing to utalitarian.
5 people in hospital, each one has a failing body part and needs a transplant. All have same bloodtype. Somebody comes in with a headache, but that person matches all 5 people. Is it ok to kill that person and take their organs to make all the other people ok.
Brain activity. Impersonal (not touching anybody) vs. Personal. People less likely to apply utilitarian in b). MFG , PCG, AG - typically associated with emotion. Very active in the case for moral-personal. Emotion system is kicking in in personal, more than impersonal. Areas asscoiated with working memory/rational decision making - moral-personal - those areas become lessa ctive compared to impersonal and non moral. Emotional and rational areas are not equivalently active in different scenarios. (Brodman area coordinates).

Data olooking at people with lesions. VMPC. Proportion endorsing action int hose cases. BDC - ppl with brain damage in other areas. Generally, eqiuvalent in endorsement of nonmoral. Reasonably similar in impersonal condition (50%). Personal scenario - NC, BDC have massive reduction - less people push. People with VMPC damage - still likely to say you ought to intervene. Act a lot more utilitarian. Psychopathy-type/antisocial behaviours. Emotions don't get involved in stuff.

The Amygdala - combo of a number of nuclei. Heavily involved in fear. Rat. Apply shock to feet. Elicits a fear response - central nucleus activated. Also involved in learning about fear. Fear Conditioning - foot shock that natural elicits fear, pair it with a tone that wouldnt normally elicit fear response, over many pairings, tone itself ellicits fear response. Auditory stimulus activateds LA, activates CE, affects brainstem and fear reaction. Can also pair with context - place might still illicit fear response. Those seem to use hoppocampus (memory), connects to BAsolateral and basomedial to CE.

Studyies of patients with damage to amygdala. SM - damage bilaterally. Calcification to amygdala. Have trouble recognizing emotions. Comes close to you, no personal space. Draw faces corresponding to emotions. When to fear/"afraid", didn't know what to draw. Couldn't draw a face that was afraid, but then rememeberd that in cartoons hair was standing, drew baby with standing hair.
Might be partly not a problem with decode emotion, but not attending to emotion-related cues. Might not be a problem of processing emotions, but attending to cues.

Talking with somebody - face to face or video chat - recorded eye movements of SM or control. Red - lots of time fixating. Control - spend most time at eyes and a little to the mouth - subte movements of eyes communicate a lot of emotion to us without being aware of it. SM is not focusing on the eyes at all - focusing on mouth - less info on emotion. If you tell SM to pay attention ot the eye, she becomes better at recognizing emotions.
Peolpe with autism may have same issue. Information acquisition.

Hormones - testosterone an daggresion. (amygdala also involved in aggresion). Big hormone in aggression is testosterone. Male mice - number of biting attacks on ohter mice. Additionally, lots of biting attacks. Then they castrate - remove testicles - no testosterone. reduction in biting attacks. Inject testosterone - biting attacks go up. When you remove testosterone, reduce aggression.

When male testosterone reduced too much, a lot of health problems. T reduces inflammation in the body. Much more likely to feel depressed, lack of motivaiton, inflammatory disease. Don't label testosterone as being bad from the data.

Another important hormone - seratonin. Index seratonin via metabolate of seratonin (5-HIAA). Took adolescent male resus macaques (monkeys), big island. Selected 26 of 4500 monkeys. Obtained blood and CSF samples form each subject. Found: CSF 5HIAA concentrations were inversely correlated wiht escalated aggression. The lower the 5HIAA, the more aggression. Those with physical wounding had lower levels of 5HIAA than subjects with no wounds. Low 5HIAA correlated with greater risk taking (how they swin gfrom tree to tree - how risky the jumps were)
Pigtailed monkeys have higher serotonin/5hiaa levels and lower scores of aggression than rhesus monkeys. More serotonin -> less aggression. But also a dif in populations. Some monkeys genetically have more serotonin, less aggressive. Explain species' aggression differences by looking at serotonin.

Can also look at genetics related to trypotophan hydroxylase, from diet. If you have a less active form TH from genes, you make less serotonin - more aggression.

Serotonin transporter proteins take serotonin out of the synapse. Mice that lack transporters will have more seratonin, turn out to be less aggressive. Link between serotonin levels and aggression. Multiple ways you can affect serotonin levels. High s -> less aggressive than if you have low S.

3rd hormone: cortisol - stress hormone. If very little cortisol, feel low stress, much more likely to engage in aggression.

Hypothesis: Triple Imbalance Hypothesis - impulsive aggression. Imbalance in serotonin levels (low - reduce ability to regulate emotions), high testosterone/cortisol ration (high test, low cort) - increase reactivity (H, A, P are more reactive). You have to have this combo to be impulsively aggressive.

More hormones involved: oxytocin - secreted by pituitary gland, controlled by hypothalamus. HEavily vinvolved in women - triggered and released base don uterine contractions, stimulation of breastfeeding, helps with bonding. Caring/love hormone. Duration of dif kinds of behaviours based on being injected w oxyoticin vs other compounds. Saline(nothing), OXTR antagonist (opposite of oxy). Inject oxytocin, offense behaviour goes down, social exploration goes up.

Vasopressin - regulating water content of blood and restricting arterials to regulate blood pressure. Higher vasopressin, aggression goes up. Positive link. Opposite of oxytocin. Lots of chemicals in system. Normally if you have balance of things, no impulsive. But disregulated, bmight se eincrease in behaviours.

(endocrine disruptors - endocrine society. Broader level. Our environment contains so many computnds that could disrupt the functioning of these hormones. )

Emotion Regulation - distinction between areas of emotion when we just react. PAG and amugdala heavily involved in emotional reactivity, especially insula. dorscal anterior cingulate cofrtex - reacting in the moment. Areas involvd in regulating emotion - unconsciously/implicityly - vACC, vMFFC. Regulating/controlling impulses. Other areas when you explicityly aim to control your behaviour regardless of other factros - parietal cortex, preSMA, dvlPFC. Overall response depends on how these balance each other out (reactivity and regulation).

Mood Disorders

Major Depressive Disorder (MDD) - in DSM-V: category called MDD. Talk about extreme case first.
Depressed mood, loss of interst or pleasure, 4 of the following unfolding over several weeks: ...

Percentage in US over 12 month period: 8.5% females, 4.7% males. majority in 18-25. For males, testosterone may go down, deppression goe sup. Could be that more males don't seek help.

Main line of treatment: antidepressants. CAme upon drug effects of antidepressents by accicdent. Verner Van Bron making rockets, hired by americans to lead space program. Rocket fuel left over after war. Derivative of rocket fuel could be used as a cure for tuberculosis (respoiratrory disase). Would still experience negative symptoms, but they werent bothered by it anymore. Maybe it could influence mood. Iproniazid - first antidepressant. Treat psychological condition with biological compound. MAO - enzyme that breaks down Monoamines - if you inhibit, you get more Monoamines, reduced symptoms of depression.

Later on, people started to develop other drugs: Tricyclic Antidepressants (dont memorize these names). MAO inhibitors, but also block serotonin transporters. Increase amount of NT in synapse. Then realized maybe key is to increase NT. Started to target reuptake transporters. HAve a whole class of drugs developed to inhibit dif types of transporters of Monoamines. SNRI, NDRI, NRI, sSRIs.

Lead to basic idea: Monoamine Hyopthesis - people w depression just have low levels of monoamines in synapse. Do not have lower levels of Monoamines. We know that there are compensatory effects - reduce any articial increses in serotonin at synapse. If you block, will produce less serotonin. When you take drug, it's affecting brain neuro chemistry within an hour but you dont see the symptoms being alleviated for weeks. Takes several weeks for effect. If it relied on the reuptake whatever, symptoms should go away immediately. Something wrong with this hypothesis.

Lecture 17: July 18, 2018

Test 3: Vestibular to monday. ~40-42 M/c.

MAO inhibitors, tricyclic - first generation. Then people focused on monamine synapse - reuptake inhibitors. Idea: block reuptake transporters leaving more NT in synaptic cleft. That was MA hypothesis. But problems with it. 1) depressed ppl dont have low levels of serotonin. 2) when you take RI, increase levels of NT within a short time (45 mins) but you dont see a reduction in the symptoms for roughly 2 weeks, though it should be fixed right away. If antidepressants work, it's not the way people thought they work.

Do antidepressants actually work? blue dash - what you would experience if you took a placebo. You get improvement even if placebo. Initial severity - depressive symptoms. At lower levesls of depression, placebo will improve - psychological effect. Some of it is just that: people get better. Body always just heals, but it's attributed to the medical intervention. Red triangles - studies. Size of shape - sample size. Under low to moderate levels of severity, no signitificant difference - antidepressants do not have an effect than a placebo (over placebo or spontaenous recovery). Extreme clinical depression - sparse data (hard to find samples of peoplw ho are that depressed) - antidepressants do have effects greater than placebo alone. Major depression: antidepressants do have a benefit over and above placebos, but not for low-high levels of depression.

ADM = antidepressant medication. No difference until you get in the very high range. Samples become very small. Take into account of file drawer problem - studies that found no difference so it wasn't published. Publication bias.

These drugs have effects, but not for moderate levels of depression. Side effects. Drug Monograph - information by law. Increased risk of suicidality. Except some of these durgs are better than others, but they're not. They're all equivalently useless for small to moderate depression. SSRIs are no more effective than NRIs. Big difference is the side effects. Doctors prescribe based on which one has less negative side effects for you. Effects other conditions as well. Prescribed for a lot of other things.

Brain deficits associated with depression:

HPA: axis Seems to be that depression is a dysfunction in a particular circuit. Hypothalamus connected to Pituitary. Jippocampus and amygdala. And PFC. Circuit triggered by moments of stress.
Stressful event triggers acitvation of hypothalamus; triggers CRF (axons tha tmove down in anterior pit); AP will secrete ACTH, travels through bloodstream to Adrenal gland - kidneys; from Adrenal cortex, get secretion of cortisol - stress hormone - goes throughout body through bloodstream; cortisol in mod amounts will lead to an increase in actviity (can measure it in your saliva); cortisol also ends up going to PFC, Hippocampus, Amygdala (all have cortisol receptors - glucocoricoids). At mod levels increases functioning of PFC, hoppi, etc. Makes you more cognitnively ready for stuff;
Feedback loop - from Hippo, AG, negatives - inhibitions. You stop the release of cortisol; That's how the system can jack you up for a momen and relax you. Momentary changes in respnse to the stress in the environment;
If the system is overactive, it starts to damage glucocoroicodoid receptors. As a result, system starts to break down. You end up with a heightened level of cortisol. At low levels/short periods of time, cortoisol leads to enhancement acitivties. IF goes too long, you start to get synaptic suppression. For longer, it leads to excitotocixity (overstimulation). The cells become atrophied in prefrontal cortex. Those are the places that get overstimulated and damaged. Having a heightened stress response activated over time damages areas associated with depression.
Diathisis - a predisposition of failing glucococird and environment diathisis that triggers episode. 2 weeks of prolonged stress, you alreaady see atrophy in the prefrontal cortex. 2 weeks studying for an anticipated exam. You don't wanna stress over exams because it impairsyour ability to do well. And you get attention deficits.

Normal neuron vs. chronically stressed neuron.

Stressors - (early childhood stress - abuse, poverty) combine with genetic predispositions to create major depression. But on the other side, another aspect. Inflammation - argument is: during moments of inflammation, PI cytokines (markers) go through your system. They can get through blood brain barrier and trigger the release of micro something. YOur'e getting info in the brain to destroy things. "There's a foreign invader, let's kill cells." When baby is in utero, a single instance of inflammation can have lifelong effects. Anything that triggers inflammation response. The inflammation, if there's enough of it, will start to damage areas leading to major depression.

Time unfolding vs. intensity of response. When you have an acute (momentary) inflammation response, associated with that is Sickness behaviour - similar to behaviours you get when you're depressed. (Overly active when have infection, actively pumping it around). When you're sick, you feel blah.
When you have chronic inflammation, that's associated with depression cause damaging areas in your brain.

Relation between stress + inflammation - if heightened levels of cortisol in system, it triggers inflammation response. Can start to address the problem of depression with inflammation stuff.

Chronically high cortisol levels - always stressed - associaed w same tihngs as depression. Chronic inflammation associated w all things.

At low levels, cortisol acts as an antiinflammatory. Rash is a case of inflammation. prescribe cortisol But at high levels, you get inflammation, which triggers high level cortisol. System can hold bakc inflammation and then let loose once stress is gone. AFter exams can get really sick.

Different interventions peole have used for MDD. 1st gen - MAoI, 2. 2nd gen - RI. Ketamine - relieve depression when other things aren't working. Psychotherapy - cognitive therapy: attack maladaptive beliefs - data shows no significant differecen between psychtheraphy and parhmacotpheraphy. Long-term, psychotheraphy outperforms drug. With CT, you are less likely to have relapse.
For extreme cases, tDCS, rTMS, deep brain stimulation, ECT (electroconvulsive therapy),

Current knowledg eof antirpresdnants - seem to increse BDNF production, increase hippocampabl vaolume, PFG vol, inc glial cells. Do everytihng opposite. Why does it take 2 weeks to see relief? Cause that's when you see all this stuff.

ECT - electric current through brain at a high level to cause a seizure. It causes memory loss (events prior to treatment). These currents are effective cause it increases neural growth in the hippocampus. Not a great thing to be using, but effective in extreme cases.

For moderate to low depression - natural treatments. Increasing exercise levels, monitoring diet (removing gabage food that increases inflammation levels), herbs. St. John's Wort - reduces glutamate release, has effects of BDNF, reduces proinflammatory chemicals (antiinflammatory), reduce hyperactivity of HPA. Also reduces effectiveness of other medications you're taking.

Seasonal Affective Disorder (SAD) - depressive episodes related to a partic season. Winter months - reduced light exposure affecting circadian rhythms. Expose yourself to full spectrum of bright light. Most depressed people are shifted backwards - get tired at night and wake up early in morning. With SAD, have hard to get up cause circadian rhythm hasn't shifted yet.

Biopolar Disorder - alternations between depression and manic episodes. In manic episodes, get a flight of ideas - racing mind - delusions of grandeur. Talk quickly. Lots of energy. Then drop into depressive phases. Try to balance it so highs arent as high, lows arent as low. Use Lithium - maintain much more stable mood. When in manic state, give anticonvulsatans. REgularize sleep. EAt food w polyunsaturated fatty acids (seafood). There is a genetic component, onset in early 20s. "needless to say, we almost drowned."

Learning and Memory

Historical look: Karl Lashley - looking for physical representation of what had been learned in the brain - Engram. Memory has to be soemwhere in there. Gave a rat a task - learn how to navigate maze to get to finish line. Give various knife cut lesions - if cut learning part, performance should go down. It didn't matter where he cut, it matter how much of the cortex he disrupted. Errors go up the more cortex he lesioned. Argued that all parts of cortex contributed equally to learning - law of Equoptentiality. The cortex works as a whole (not modules) - law of mass action. Seems inconsistent to what we know, because we know there is localization. At the time, he didnt' know that yet.

Localization of learning:

Classical Conditioning - an eye blink response. Puff air into eye - eye will close (UCS). Pair UCS with a tone (CS). PAir over and over again, you get a CR. Present tone and eye blinks. This is a type of learning. Trying to figure out where the learning was occurring. Maybe a pathway from INof Cerebellum to red nucleus to cranial nerve. Where does the learning happen? RN or INoC? Started training the animal. Then they lesioned (reversible) the red nucleus - no increase in conditioned response - is that because you've lesioned in the area of the response, or becuse you've lesioned the learning area. They remove lesion, then loook at performance. Right away, you get full on conditioned response, which means that learning was happening if though RN was lesioned. Learning was happening in the background in some other area. Might be in LIP. When lesion, dont get conditioned response. Reverse lesion, nothing has been learned - gotta go through trials to learn. LIP is where the learning occurred. Trianglulate that RN is only a part of the pathway for response, but real learning happens in LIP. Contrary to Lashley.

Lecture 18: July 23, 2018

Case study: HM. fell off his bike as a kid, hit his head, had seizures from that point on. Got worse and worse. Multiple times a day. Didn't have proper ways of dealing with seizures. Did usrgery to remove a part of frontal lobe. Go into skull, remove part of temporal lobe - removed hippocampus (on medial side of temporal lobe). Suck ou tbrain tissue with suciton device. Theory: maybe seizures had a starting point of focus in temporal lobe, so removing it would stop seizures. They wer successful. What they found: he suffered a massive memory problem: amnesia. etrograde amnesia - inability to recall informaion learned before the surgery. Dense anterograde amnesia - inability to form new lng-term memories. Short-term memory functioned somewhat normally. Was in a continued present moment. Can carry on discussion as long as it only relied on info that you discussed just moments ago. As soon as it required knowledge of info from 5 mins ago, he'd be lost.
Patient HM book - by Scoville's grandson who did the surgery.
Can separate short-term memory from long-term memory.

Models:

Atkinson-Shiffrein model - short term memory, unless you undergo consolidaiton (hippocampus), that info is forgotten. Want to get it in the long-term store. To keep things in short-term memory, you need to rehearse them. Large capacity sensory store but only for a few seconds and uch transfer to short-term and then to long-term. You lose tings from long-term memory cause the process of consolidation takes weeks. Consolidation process hasn't finished, and you stop process, so you forget it.

Also learn: even if you get things into long-term memory, there are dif kinds of long-term mememories. Implicit vs. Explicit memory. Implicit - do not need conscious awareness of. Explicit - you store consciously, deliberately. Studying for exam - explicit memory EEMirror Drawing Task. Trace outline of the object with barrier blocking vision and mirror in front of object so you can see it. Everything is revrse - difficult. Takes time to learn how to trace objects. Deviation = error. You get better and better over time. Ask HM if he's ever been there before - he'd say no. He had poor explicit memory of what happened the day before. But he performs better than the day before. he has some memory of doing the task. By Day 3, no memory, but virtually no errors. He's retianing some info over time, but he has no explicit memory. He has this implicit memory. System is learning. Procedural memory. EE

Lon-term memroy is explicit/declarative and implicit/nondeclarative.
Implicit: Procedural memory - Memory of how to do things. Known to be subserved by the basal ganglia (motor type behaviours); Associative learning - classical conditioning, fear, don't need to have conscious recollection, operant conditioning - requires reward/punishment; Nonassociative learning - habituation - exposed to stimulus that's nonaversive repeatedly, you tend to reduce response to stimulus, sensitiization (reverse) - greater response following exposure to stimulus (pain); Explicit: Semantic memory - memory for facts, name, capital of country, etc.; Episodic memory - recalling the exact event in which something occured. Memory of your last birthday vs. your birthday.

Semantic - temporal lobe - antherior/inferior regions. Damage: semantic dementia. Forget definitions of works. Episodic - prefrontal cortex, cingulate cortex. Damage: source amnesia. Lose memory for specific episodes.
Learn a fact, but forget the source of where you learned that. Happens more as you age. Jeremy's presence uncojnscuously brought that joke to mind. You see Jeremy, then you tell him a funny joke, but he told it to you the other day. All these cool things happen to you when you get older. Autobiographical memories are episodic.
Recall of memory is a process of reconstruction - putting things together from fragments, so it's not 100%. Some parts fabricated.

The hippocampus - fibre tract that connects hippocampus with the fornix. One on each side. Medial part in temporal lobe. Peririnal cortex, entorhinal cortex, parahippocampal cortex. (HM h and adjacent areas removed).
Enertorihinal cortex - axons coming into - perforant pathway. Green: dentate gyrus - lots of cells. sends axon (mossy fibers) into Area CA3, some neurons send axons out through fornix, some go to CA2 to CA1, synapse goes out through enterorhinal cortex. Inputs into cortex, and outputs out fornix and back out cortex.
In dentate gyrus, you get new neurons. Get embedded into dif pats of hipocampus.

Hippocampus is involved in Declarative Memory - forming conscious long-term memories. Delayed non-matching sample tasks. Have a container, underneath has a treat. animal can look to see under there. Then give delay, given choice of 2 objects. Wanna see which oobject where they believe the treat is. Animal is supposed to learn, the treat is in the object than the one they saw didnt have the object. In delaye dmathcing, food is under the same shape as before.
Lesion hippocampus. If you have a few second delay. monkey is gonna perform just fine (short term memory). 30 secs or longer, a lot of trouble. Wont be able to hold info into long term memory.

Reason why you can't form longterm memories cause hippocampus goes through consolidation. Long-term mems are instantiated in synapses in the cortex. Happens by varying strengths in the synapses. In order to get written into corticol areas, require the hippocampus sending info to the cortex to have it written there in a more durable form. If you eliminate hippocampus, cant do continual resending of info so you cant form long-term memory. The more consolidated the memory becomes, the less it depends on the hippocampus. REverberating circuits of neuronal activity - repeatedly sending. Happens over time.
That's why HM shows retrograde amnesia, because still some memories that depend on hippocampus. As you extend back in time, memories are already written.
Every time you recall something, you use this hippocampal system - in a form that's more malleable. It becomes changeable. Other info can combine with memory, then use hippocampus rewrites slightly modified. REconsolidation. During reactivation, if you give individual certain kinds of drugs that block protein formation, you can disrupt the memory. Can't properly reconsolidate it into memory.

Hippocampus and Spatial memory - cells that will respond when an organism is in certain special locations, esp in familiar locations. Radial arm maze with rats. Some arms have treats in them. Rat will figure out where it is and go to arms where food is. Give them lots of trials. They learn over time in the spatial layout where the food is. Give them lesions to hippocampal area. If you lesion dif parts, you can disrupt this spatial learning. # of errors the animal makes. Lesion: go to arms that never had treats in them; REpeated visitation into bated arms (inputs and outputs), unbated arms (inputs and outputs. Plexiglass so rats can use room to use as a guide. Some of the learning is learning the spatial relations among objects in the environment.

relational learning. Morris water maze task - ibg tank in middle of room. Submerged underneat water line - platform. Place rat in liquid, find the platform as fast as possible. See how long it takes the rat to find the platform. Cant' use vision - have to remember where it was. Available to animal are room cues.
Constant starting position - same place every trial, lesioned hippocampus. Unlesioned animals - takes a while. On 2nd trial, get it very quickly. Lesioned rats - still take a bit longer to learn, even if in same position. Ultimately, they learn it.
Rat in dif position every time. It has to know where platform is relative to the cues in the env. Normal rats: learn and improve. Damaged h: cannot learn. H is important in learning spatial relations and usin gthat info to guide their behaviour.
People who have to use spatial mem a lot (london taxi cabs) have a larger hippocampus.

Hippocampus als involved heavily in contextual learning. Picking up ont he surrounding context of an event. You can maximize recall by reinstating the context in which it was learned. Scuba divers learn in land or water, and be tested in land or water.Learning was best when you matched the contxxt of test in learning env. Very powerful cues to trigger recall.
Cna also have internal states function as a context. Study and test recall for people who learn/tested either sober or under infl of alcohol. If learned under infl of alcohol, you do better if you do test under infl of alcohol. But overlal, people w alcohol did worse.
Arousal also important internal cue - relaxed studying vs. anxious test state -> massive mismatch in internal state. Relax when doing test. Just reamingining the learning context will reinstate it.

Biological mechanism that is believe to underpin leanring. Has to do what happens within the synapse.

Long-term potentiation - strengthen the repsonse of a synapse after you stimulate the synapse and dendrite (stim prre and post together) at sufficient strenght, you strengrhtne the synapse. You make more receptors, etc. Opposite: long-term depression - don't stregthen synapse, you get atrophy. It gets smaller. Long-term cause physically changes structure of synapse that last for some time.

For successful LTP, you need activation of both pre and post synaptic neurons. You have to have strong activation. Particularly of the post-synaptic cell. Acheive that with one axon and one dendrite. Slow firing rate from axon, typically does not lead to LTP. Cause each firing leads to a small EPSP (small depolarizaiton - occurs and fades, graded). Firing leads to small EPSP, then it fades by the time the next firing occurs so youdont accumualte EPSPs through temporal summation. If fast firing rate, you get EPSP before last disipates, you temporally summate to get a large post synaptic potential. Then you get LTP.

2 axons. Weak connection and strong connection. Because you're getting firing occuring and both synapses, the EPSPs will sum together spatially, leading to large depolarzaiton. Leads to LTP. It'll lead to LTP at strong AND weak synapse. Associative learning. On its own, weak synapse couldnt generate a strong connection, but [airing with strong one, you get a large EPSP.

Axon and dendrite. Glutamate synapse. Dif receptors - AMPA, NMDA. When glutamate activates AMPA, allows sodium to go in an ddepolarize post synaptic cell. NMDA - magnesium ion that physicall blocks NMDA channels. Even though glutamate goes there, nothing enters. A lot of activity happens through AMPA. If add another synapse - sufficient amount of depolarization (positive), electricalyl statically repel the positively charged magnesium atom. That opens up NMDA receptors, allowing sodium and calcium - massive depolarzation. Calcium that enters triggers a cascade of events that ultimately influences the transcription of DNAs to form more receptors, to enlarge the synapse. Then much easier to create a depolarization if you strengthened the synapse. Then you realese retrograde transmitters which travel back to presnynpatic clel. New active zones being developed. Lots of physical changes.

Properties of LTP. Specificity - only synapses onto a cell that have been highly active become strengthehned. Cooperativity - cooperative among inpus; Associativity - to both weak and strong.

syndromes of memory deficits:

Korsakoff's Syndrome - " When you're dirnking all the time, There are a lot of calories. People who drink a lot can become malnourished. Prolonged malnourishment partic Thiamine, will lead to brain damage. Mamillary bodies, dorsomedial thalamus (key areas). Also have other problems from alcohol. Both retrograde and anterograde amnesia. Become HM patients. Damaging parts of hippocampal system. Sometimes don't know they have a bad memory. If they dont' know, they make things up - confabulation. They fill gaps by fabricating.

Alzheimer's Disease - disorientation, affective changes (more easily yupset), progressive memory impairment. 50% of pepolpe over 85. Early onset is genetic (1%). Late onset is not genetically linked. Wide sulci, narrow gyri. Large grooves. Cells are dying. symptoms depends where it's shrinking. Seems to be related to accumulation of amyloid beta protein - membrane protein, when overly accumualted damages. And an abornal formation of tau proteins. Tau is important - hold microtubules together. Phosphate groups attach and sart to unravel. Microtubules dont hold together and disintegrate. Killed transport system. You're transporting in vesicles parts of amyloid beta protien. So when they break apart, you get amyloid beta. So two things related.

Ultimately, amyloid beta creates plauqes and tau causes tnagles within axons. Aging with Grace.