 I'm going to take the queen and then two slides later, I'll give you the answer. Don't go to the answer before they finish the quiz. And it's this one right here at the top. Great. You can't read up something. No, I haven't. It's the one you just posted. Actually here, I'll give you your drive back. I have visited parents. No, I've gone up to Vancouver tonight. I just came back from chatting with Jim Simons in York, which after 10 minutes I had to leave because he started smoking. There's a lot of smoke coming into my face. Every time he says I'm sorry. Is he reasonably alert these days? You know, he was there for my talk and I chatted with him, and he missed most of the other meeting. You got quite tired and so on. But he's... No, I have to get in a plane. Yeah, sorry. Okay, let's get started here. So, last lecture on learning and memory. For me, before we move on to sort of the last component of the course, there's going to be a bit on emotion, autism, and other diseases of the brain and the mind to finish the course on. So, remember from the last lecture I gave, and also from Henry Lester's lecture, you know that memory consists of multiple stages, both psychologically and neurobiologically. So, there are events at the molecular level that require calcium influx through NMDA receptors and phosphorylation of various proteins that can happen pretty quickly. And then there are events that require gene expression through crept binding proteins and other mechanisms that can result in ultra-structural changes. So, there are multiple stages in time. And remember that psychologically there were multiple stages, short-term memory, long-term memory, iconic memory. And as well, there are multiple types of memory. And so far, we only looked at declarative memory. So, today we'll look at a couple of the different types of non-declared of memory, of which you'll remember there are several. So, remember this picture here just to remind you and see if people have any questions. That was sort of the broadest scheme for getting a memory in and coding. And then there was a set of long drawn-out processes that could go on for years that consolidated the memory. And then there were two types of retrieval, one of which is shown here, the two types of retrieval being recall and recognition. And one thing that I mentioned but didn't go much into that's quite important these days is this reconciliation. So, remember that when you remember a memory, it becomes a stimulus again in its own right. And you can re-encode and re-consolidate that memory. And so, every time you remember something, it becomes plastic and flexible to some extent, and it's re-consolidated. So, if you keep remembering something and talking about it, you can change the memory over time. You can have false memories over time. And this is one mechanism that people have looked at a lot for traumatic memories, phobias, post-traumatic stress disorder and so forth. That one mechanism for trying to help people with those kinds of traumatic memories is to have them recall the memory such that it becomes sort of plastic again and can be re-consolidated with a different memory trace. You have them re-consolidate, you have them recall very traumatic memories, and while they're doing that you can give them drugs or you can do behavioral interventions such that the new consolidation that is laid down can overwrite the previous one and can to some extent cure their traumatic memory. So that's one clinically relevant mechanism. So, again, to get a memory plastic and have a change, you need to retrieve it and then this re-consolidation mechanism can make it to some extent flexible. This scheme we had remember short-term memory which depends mostly on regions in the frontal lobe. There are neurons there that are highly correlated with holding something in working memory in humans and in monkeys. Limited capacity about seven items decays quickly after about a minute or less. And if you keep stuff in here, you keep rehearsing it, there is a bottleneck for transferring information from stuff you're currently thinking about, working memory, into long-term memory which is what you want to do when you memorize material for a course. You can't keep it all in your head all the time. You have to offload it and stabilize it in long-term memory. If you're successful at doing that, so it takes a while, so doing this requires the hippocampus and it's effortful and it's subject to interference, it takes time, etc. But when you do it, in principle long-term memory has no known upper bound in humans and also no bound in terms of time. So you can remember things, an arbitrary number of things for an arbitrary amount of time in principle. And some people are very good at this, so some people seem to be able to remember every day of their lives and it's a big puzzle why not everybody is like that. Make it much easier for this course if you just remembered everything. There are also some people, just to mention it quickly, that either because they're born that way or because of a lot of practice, probably both, that typically are sort of performance artists in Vegas or something that seem to be able to merge working memory and long-term memory and they've done brain imaging studies on these people so they effectively are able to use their long-term memory as though it were working memory. And of course, if you do that, you have an unlimited storage capacity and you can just read, you know, 100 digits of pi or something and it's in there. So there are people that can do that and they seem to be able to not have the same bottleneck for transferring between these two types that you and I have. So there's all kinds of unusual features, but this is how it normally works and there are exceptional memory cases that still need to be explained. This is what we had last time. So remember that there was a graded retrograde amnesia, a complete anterograde amnesia if you have damage to the hippocampus like this patient HM had. One thing that's important to point out is that episodic memory, so remembering a particular autobiographical episode, like exactly what you had for breakfast this morning, where and with whom you went out to dinner last night so that your ability to consciously re-experience something in space and time and as happening to you, that depends on the hippocampus. But over time seems to be converted to another form of declarative memory called semantic memory, which is just memory for facts. So most of your memory eventually gets converted into facts. So I could ask you, what's the capital of France? You would say Paris, and that would just be semantic memory. But if I asked you, well, where did you learn that? What specific episode? Or who's the president of the US? Or even material for this course. After a while, you would know it as facts, even though initially it was encoded as an episodic memory. But so these traces seem to be recoded as semantic memory over time. We just put various types of declarative memory that people have studied up here. So semantic memory depends on your cortex, especially in the temporal lobe, and there are neurodegenerative diseases, for instance, that affects temporal cortex, which will result in semantic dementia and a loss of semantic memory. But this is memory for facts. Episodic memory is memory for specific autobiographical episodes, and that depends on the hippocampus as well as other regions. Your autobiographical memory is a mix. So a lot of it is episodic, but some of it, like just knowing your name or knowing when you're born, that's semantic. So it's a mix. And then people have studied a lot, so-called flash bulb memories, which are events in your own life that are episodic, and remembered particularly well with particular vividness, which are basically all emotional events in your lives. And we just put that up here so they've studied this. More recent studies have looked at 9-11, any sort of public, highly emotional event. And psychologists have then been fond of doing studies on that whenever something like that happens, or the latest incidents in Paris. I'm sure there's psychologists now studying how that's encoded in people's memories. And what you find when you ask people is that they're typically able to recollect a lot of autobiographical detail, much more so than, you know, if you ask them for non-emotional events. And so they've studied this both for real-life events and also in the lab. The basic idea is that emotion serves as a sort of, like a spotlight, as a sort of filter on your encoding and in particular consolidation of declarative memory. So if you look, it's a little hard to see here, if you look at some picture that's emotional or arousing in the middle here because I guess there's a surgery going on. What you will remember is the deep, if I asked you afterwards for your visual memory for this picture, you would remember a lot about the emotional stuff having to do with the surgery in the middle and probably less about people in the background, etc. People have studied this a lot in terms of eye-witness testimony at crime scenes. They'll remember details about the blood or the knife, but they won't remember who the bystanders were and things like that. And the same thing happens in time. If you have, for instance, a stream of words in an experiment, one of which is more emotional than the others, you will remember this word, but your memory for words in the vicinity of that is actually decreased. So it's like a center-surround mechanism, actually, in both space and time that serves to sharpen your memory for that material that's the most salient, in this case, most emotional. And as I said, people have studied this in quite some detail. This is how traumatic memories also arise. And it mostly operates in real life at the level of consolidation. So if people experience a very traumatic event, or if you have rats in a very traumatic event, you can, after the event, you can give them, for instance, protein synthesis inhibitors or drugs that would interfere with memory consolidation and they would not lay down an emotional memory for that event. Okay, so just to summarize, so we talked about declarative memory last time just to make the point that it's extremely complicated and it has lots of different ways in which it is modulated. So this was one example. It can be sharpened by emotional arousal, which is one mechanism that people have looked at a lot. We're going to move over now to considering some aspects of non-declared of memory. Remember, this is a heterogeneous category unlike declarative memory. So for declarative memory, you can say it's memory for facts and events. It's relational memory, spatial memory. It depends critically on the hippocampus at encoding and consolidation. So we know a lot in a fairly homogeneous system. Non-declared of memory is a whole bunch of stuff that depends on a whole bunch of different brain systems. Before we do that, we're going to have a short quiz that Henry just gave me. And so if you can get a pen and a piece of paper. Alright, so we had types of memory. Now we're going to go on to talking about some types of non-declared of memory. So there are two broad types which are associative and non-associative. And here's the definition of these. So non-associative learning, you've probably heard about both of these before, is learning with respect to a single stimulus. You're not associating two stimuli. There's just one stimulus that's happening, but of course you have plasticity, and so learning in a very simple sense there. Does anybody know what kind of phenomenon you have that would count as learning in this very simple sense for just repetitions of a single stimulus? Any guess? Well, either increments or decrements in response. So some change. And decrements are habituation, and increments would be sensitization. So those two, those have been studied a lot. Associative learning is learning about relationships between two stimuli, that's Pavlovian conditioning. We'll take a look at that in a minute. Or between a behavior and an outcome or a stimulus and an outcome, which is instrumental learning. So those are the two big kinds, which just lists them here. So this just says what I said. Your book goes through non-associative learning in the sea slug, where Eric Candel, who's one of the co-authors of your book, and his colleagues did a lot of work and won the Nobel Prize for a lot of the work that they did. You can find these animals here if you go out to the tide pools in the ocean. So they're just little mollusks. They'll put out jets of ink. And I guess you could, while you pretty can't do this, take them apart a little bit to actually touch them. Well, you can probably touch them and you could see what happens. But you could do the same thing to a slug or a snail. Maybe you've done this when you were a little kid. If you touch part of the animal, it will withdraw parts of its body. If you do that again, it'll withdraw and it'll take even longer to come out. If you then wait a long time, you can start over again. So there are changes over time in the synaptic efficacy with which a sensory stimulus causes a motor response. And this has been worked out in some detail. Here's the little circuitry. And in particular, if you record from the sensory neuron, from the motor neuron, and look at what might happen in between those two, where you find the change is in the synaptic efficacy of the sensory motor onto the motor neuron. So the sensory neuron responds the same all the time. That's what's shown in this trace. If you keep touching the siphon on this aplasia, it will become habituated because there is less transmitter release. So you can ask very mechanistic questions about exactly where, at which synapse these plastic changes that define the change between stimulus and response actually occur in these simple nervous systems. So your book goes over that in detail and it has, of course, been mapped out. And one nice feature of this is that it also has this hold of molecular machinery here. This is for sensitization in aplasia. It has been worked out in a great detail and distinguishes the molecular mechanism for short-term memory, which depends on just phosphorylation of receptors and ion channels, like the serotonin receptor here. So that's not that permanent, but it can take place quite quickly. And long-term changes, which depend on changes in gene expression. So cyclic AMP has to bind to the cyclic AMP response element binding protein and bind to DNA. There's differential gene transcription. New protein synthesis is required for this. And new proteins can be made. New receptors can be inserted. There can be ultra-structural changes and so on. And you can manipulate these as you would expect. So in general, if you block short-term memory, you also block the induction of long-term memory. But you can have short-term memory going on. But if you have, for instance, a protein synthesis inhibitor, you will block the induction of long-term memory. And there are many different versions of this that initially behavioral psychologists have studied. And now we know a lot about the neural underpinnings of many of these. So there are associations between stimuli responses and outcomes, which is what these letters stand for. In terms of just basic things to know, these here, so an unconditioned stimulus, is a stimulus, the response to which you don't need to learn. So it's innate. And so if you see something dangerous, if you see a snake or something like that, or if you get electric shock, you don't need to learn to fear that. You would respond to that in an unconditioned way. So you have unconditioned responses to unconditioned stimuli. For which learning is not essential. And then conditioned stimuli are the opposite. For those, you have to learn the conditioned response. And so in typical, for instance, Pavlovian conditioning setups, you pair stimuli with unconditioned stimuli, with unconditioned stimuli, and you can learn about the value, good or bad, of a conditioned stimulus. I'll show you an example in a minute. Well, here's the first one. Ivan Pavlov, who won the Nobel Prize in 1904 for his work on what's now known as Pavlovian conditioning in order, in honor of him. This is a form, in his experiment, it was a form of appetitive conditioning, but you could also do this for aversive stimuli. So in his case, he measured a response in the dog, which was the secretion of saliva and gastric juice, in response to food. So that happens normally without any learning. So if you give the dog food, it will salivate and there will be gastric secretions in the stomach as an unconditioned response. So the food is an unconditioned stimulus. But in addition, you have a bell or some other stimulus that you pair with the presentation of food, as all pet owners know. Your pet will very quickly learn that this stimulus, the sound of the can being opened or any kind of stimulus that is regularly paired with the presentation of food, is predictive of the food and you will get salivation and gastric juice secretion to the tongue after learning. So initially the tongue does nothing. It's meaningless, but it acquires meaning through its regular relationship with the presentation of the food and that's what he measured here. So here's how that would go. These are slides from my colleague, John O'Doherty, who is part of this work or more complicated versions of this in humans with fMRI. But this is the basic idea. You have an unconditioned response to the unconditioned stimulus and if you regularly pair a number of times a conditioned stimulus with this, what will happen is that you get a conditioned response that anticipates the food. So in a sense, you can think of the conditioned response in this simple example being like the unconditioned response only moved forward in time. In fact, it's typically more complicated than that and conditioned responses do not need to mimic unconditioned responses. It's typically more complicated. But anyway, they're predictive responses to a stimulus that predicts a later unconditioned stimulus. Any questions about this? It's clear to people. The basic setup. There are various versions of this that you don't need to know. So we'll skip that one. One structure that's been studied in great detail for Pavlovian conditioning mostly for aversive Pavlovian conditioning so-called Pavlovian fear conditioning. So it's the same thing as what I showed you except that instead of food you have electric shock or some bad unconditioned stimulus but otherwise it's the same setup. Is the amygdala. And the amygdala in the human brain is shown here. This is a postmortem human brain. So it's like the brain that you had in the first discussion section that's been sectioned and stained from myelin. So myelin is black and you see the thalamus here. Here is part of the ventricle and down here where my cursor is circling right now is the medial temporal lobe and this structure here is the amygdala. It's just in front of the hippocampus. So it's a collection of nuclei. Here's how it looks in the structural MRI scan that's involved in a lot of different things but in particular a lot of different learning mechanisms and it interacts with many other brain structures to implement those. So for instance remember I talked briefly just a few minutes ago ago about highly emotional events like the explosion of the space shuttle or 9-11 etc. that you remember extremely well these so-called flash bulb memories the amygdala seems to be responsible for that. So it modulates how the hippocampus functions. It has projections to the hippocampus so that when there is some strongly emotional event hippocampal dependent declarative memory is sort of boosted up and you consolidate that stimulus with more detail. It's also interacts with the prefrontal cortex and the basal ganglia in various forms of instrumental learning and within the amygdala it's involved in Pavlovian fear conditioning and that's been worked out by quite a few people in particular Joe Ladoo and this is how it would work. So again you have a conditioned stimulus like a tone and instead of getting food as in Pavlov's case people typically because it's more efficacious use an aversive unconditioned stimulus so electric shock. So the rat will avoid and startle and have lots of stress responses to just the shock. If you pair the shock with the tone a bunch of times and then only present the tone the rat will behave as though it is afraid of the tone. So it will freeze, its blood pressure will go up etc because it's expecting to get the shock. But so that's the acid test of a Pavlovian fear conditioning paradigm. You give the shock and the tone and the rat freezes and is unhappy. You give the shock and the tone and the rat does it again. You do that a bunch of times and then you only give the tone and the rat will freeze and show fear responses and compare to this learning the tone did nothing. That difference is the difference in learning that's Pavlovian fear conditioning. The difference in response that you see to a condition stimulus before versus after conditioning. The magnitude of that is the magnitude of your learning. And how does that work? Well you have to get the tone so sensory information from the tone through auditory thalamus, auditory cortex that has to get in to the amygdala and information from the shock has to get in through the somatosensory system so you remember which two from lectures you had in the past and then these have to converge on neurons that conform associations between the two and what kind, you might wonder what kind of molecular mechanism could implement this sort of convergence. Well it's exactly like what you heard about before. It's NMDA receptor dependent long-term potentiation in these neurons here in the lateral amygdala such that when they get coincident inputs about the tone from auditory channels and about the shock from somatosensory channels they encode that coincidence and subsequently either one of those alone if you just get the tone coming in is now sufficient to reactivate this memory trace and then the amygdala projects out to a whole bunch of other places that can affect the behavior like freezing blood pressure changes and so on. So that's the basic circuitry for Pavlovian fear conditioning. You can do, as in the case of declarative memory you can add on to this various embellishment and ways of modulating this simple circuit so that it can interact with other forms of memory. So for instance, if you now put the rat into a particular location in its cage and you only do this you only give it a shock when it's in that location well that's a form that requires a form of spatial relational memory which you'll remember depends on the hippocampus. So you can have contextual fear conditioning that the rat becomes afraid of being in a particular place because it always got shocked in that place that depends on the amygdala like Pavlovian fear conditioning but also on the hippocampus because it requires this relational spatial component so contextual fear conditioning if it requires linking a place to an unconditioned stimulus requires both the amygdala and the hippocampus. Okay so these are just some facts to know so Pavlovian fear conditioning in humans and in other animals is dissociable from declarative memory. The amygdala basically is essential for fear conditioning, the hippocampus for declarative. And there's people have done these studies, here's one done by my former colleague Antoine Basharra who's, when he was at the University of Iowa, now at USC in a human patient so here's the experiment, you do a Pavlovian fear conditioning paradigm and you measure two types of dependent measures in this, in people one is just just like what you would measure in the rat this is a measure of the emotional response to the conditioned stimulus skin conductance response that's shown over the left and the other one is a measure of declarative recall that is you ask the person which conditioned stimulus was matched with the aversive stimulus and when you do that you find in controls that there is learning both about Pavlovian fear conditioning so these bars over here are higher and in terms of declarative memory for which stimuli were paired you can dissociate these you can have a patient who has lesions of the amygdala that's shown in this panel here this patient has intact declarative memory for which conditioned stimuli were paired with shock, or in this case it was an aversive tone loud noise but fails to have Pavlovian fear conditioning so this shows you that the amygdala is necessary for Pavlovian fear conditioning but not for declarative memory conversely you can have another patient who has damaged the hippocampus in the bottom panel and he has intact Pavlovian fear conditioning and remember can't tell you anything about the stimuli so experiments like this so this would be considered a double dissociation with respect to the amygdala and the hippocampus show you what that previous slide just summarized the amygdala is necessary for Pavlovian fear conditioning the hippocampus for declarative memory let me show you an actual experiment for how this looks so this person here was a postdoc, former postdoc in Elizabeth Phelps Phelps's lab at NYU is undergoing the fear conditioning experiment so he has an electric shock bracelet on here and he's going to get shocked every once in a while and he's watching conditioned stimuli squares of different colors so he's been watching a yellow square nothing happened so he's not getting conditioned to that yellow square and they're measuring his skin conductance response and other responses and now he sees blue square and as you will see at the offset of this blue square he gets an unconditioned stimulus which was the shock and so this goes on for quite a while and so every time he sees the yellow square nothing happens when he sees the blue square he gets zapped and so he becomes Pavlovian conditioned he becomes fear conditioned to associating the blue square with the shock and so then you can measure that after he's gone through this a whole bunch of times the blue square was only got zapped but not with the yellow square you then unbeknownst to him have disconnected the shock things he's not going to get shocked at all and you only show the conditioned stimuli and measure his response to those so in the case of the yellow square you know there's nothing that's happening and so you will not measure any skin conductance response when he sees that but for the blue square his brain predicts that he would get the shock and so he will have a skin conductance response to the blue square because it was always paired with the shock and that passed and you can kind of you can't see unless I showed you a trace of the skin conductance response but you can tell something about his emotional state just from watching his face I guess he was expecting a shock if you measure this in his case he would have electrodes on the palms of his hands that measure skin conductance response as a measure sympathetic emotional arousal you find that the blue square is the conditioned stimulus that was paired with the shock the CS plus elicits a much larger skin conductance response when just shown by itself after training without the shock then does the yellow square the CS minus which is a conditioned stimulus that was not paired with the shock so that difference shows you that standard Pavlovian fear conditioning happened now what's interesting is I could take any of you having just watched this video and put skin conductance electrodes on you and show you those same stimuli the blue square the yellow square and I would find that you would show the same thing that you would also show a larger skin conductance response now to the blue square and to the yellow square even though you yourself never got any electric shock you just observed another person getting electric shock so this is called observational learning and most of what you learn about the world depends on that so it's not actual experience because for something like this like electric shock it would kill you but it depends on observing what happens to other people so a lot of learning is observational learning and there are aspects of this in other animals as well and then I can do something even more removed than that you don't even need to watch the person I can just tell you in the next experiment I can tell you when the blue square comes on you're going to get a shock and when the yellow square comes on you won't and if I do that just mere instruction again I see differences in skin conductance response so at least in humans you can induce Pavlovian fear conditioning through direct experience through observation and through instruction all of these depend well these two depend on the amygdala this last one may be more complicated but anyways this is one big point that most of what you learn is from observing what happens to other people rather than having to have direct experience yourself there also as you might imagine important constraints on what it is what kinds of associations it is that you can learn in the first place so there's certain stimuli that you can learn about and that you can learn associations for and that animals can learn associations for much more easily than others so it's not all the same it's not equally easy to associate electric shock with any kind of stimulus and depending on what the what the unconditioned stimulus is this can be quite quite narrow okay now let me skip this part here and go on okay so that's one form of non declarative memory Pavlovian conditioning which can be both appetitive like what Pavlov originally did if you have tasty dog food or it can be aversive as in Pavlovian fear conditioning either way you can have a unconditioned stimulus that is either strongly positive or negatively valenced and you can learn about that but you're not doing anything so you're not doing anything the animals not doing anything you're passive and you're simply your brain is just linking statistical associations between stimuli and effects that it sees out there in the world by contrast instrumental learning requires that you actually do stuff so your behavior determines the occurrence of an unconditioned stimulus this goes back to classic work by Thorndike who had these puzzle boxes for cats and so he made these boxes that if the cat pushed just the right kind of lever in here it would open this door and it could get out to what's pretty impossible for you to recognize here a vicious fish and so the cat wants to do this it wants to learn how to behave so that it gets this reward so there's an unconditioned stimulus out here the fish that's highly rewarding but there's not just Pavlovian learning the cat has to do something in order for that unconditioned repetitive stimulus to be obtained you can imagine the converse and the repetitive domain if you had a electric shock that was coming up so you have to push something to be able to escape from the electric shock in either case you have to do something and so animals will learn that that's what's shown here the time required to escape the box decreases over time because the cat learns just by random chance initially and it gets better and better at learning what to do in here in order to get the food reward okay let me just go on to this one here so there were a variety of different kinds of instrumental learning that people have studied some are like what you would see in the case of the cat where you just randomly you know keep learning and you get better over time gradually and so you essentially build up a habit to obtain a reward or escape a shock whatever the learning paradigm is and this is known to depend on parts of the basal ganglia nuclei within the brain that are involved for motor learning and this kind of habit learning there's a more complicated one for which you require the prefrontal cortex that's called gold directed instrumental learning and there you have more of a model of the world and it's more flexible and you can figure out how to get the food not only by sort of trial and error learning but in a more goal directed way this one is more flexible typically in many cases you do this this one first so learning instrumental learning can often be very effortful you have to know which you have to figure out what sequence of actions to do in order to get some effect after you do it a whole bunch of times it becomes habitized so it's a little bit like in the case of declarative memory where we saw that initially it's dependent on working memory and it's dependent on loops between working memory and the hippocampus but that over time it would get offloaded consolidated into long-term memory same thing here so you can have some instrumental learning that requires you to do a bunch of actions that might be quite complicated to achieve a goal if you do it a whole bunch of times it can develop into a habit and then you don't need to do that anymore but it becomes less flexible as a consequence so for instance if I had to learn how to drive to for my home to get here right and I've done it a whole bunch of times initially it was quite effortful I had a little map in my head of which streets to turn on and so on so it was goal directed instrumental learning after doing that a year I just drove an autopilot but now if I want to instead go to the gym or I want to go somewhere else I start driving and suddenly I'm at lab because this habit kicked in and I just sort of drive an autopilot so habits are less flexible once they're set up and I think this just says everything that I said here okay so Pavlovian fear conditioning again depends on the amygdala contextual fear condition remember depends on amygdala plus hippocampus this one I didn't mention so you don't need to know about it declarative memory depends on the hippocampus and relational and spatial memory remember depends on the hippocampus the storage and recall of declarative memory depends on many other brain regions and interactions between hippocampus and cortex so the main role of the hippocampus is in consolidation of declarative memory and you remember that from the lesions in this patient's HM's brain he didn't lose all of his declarative memory he still had to declare that this was the patient that had bilateral hippocampal lesions he still had memory for very remote events in his past but he had this graded great amnesia so that as long as there was consolidation still going on he needed the hippocampus and then we had these ones just down here that if you have habit based forms of instrumental learning that requires the basal ganglia whereas if it's goal directed it requires the frontal cortex so each of these can be a course and actually there is a course that talks about some of these CS102 CNS102A that isn't offered this year but will be offered next year but the point is that just like when we had the initial taxonomy of memory you can dissociate different types of memory so what you need to know about is Pavlovian fear conditioning declarative memory and instrumental learning and these depend on specific brain structures the full brain circuits are very complicated but these are the sort of essential brain structures if you have damage to the frontal cortex you have problems with goal directed learning if you have damage to the hippocampus you can't consolidate declarative memory if you have lesions of the amygdala you can't learn Pavlovian fear conditioning and so you could imagine a final exam question that would ask you if you had some lesions in various places in the brain what could a patient no longer do and you should be able to predict that from what you've learned here any questions about type the distinctions between these different types of memory and their links to some of these brain structures here it's worth pointing out that some learning can happen very very fast so some learning takes a long time many many trials but there are specialized mechanisms set up and again this shows you that you can learn about some you learn about some things in a certain way it's not that you can learn to associate anything with anything some good examples are for instance taste aversion conditioning so if you get very nauseated after eating something you can develop an aversion to that particular taste and that just requires one trial there's also one that I'll show you a little video of here because it's kind of interesting it's been mapped out in quite some detail depends on the amygdala in rodents in hamsters other rodents have a tube and it's thought to be an animal model of depression of sorts in humans and this is a one trial form of social learning that these animals have conditioned social defeat so what happens I didn't make these little animations here but from somebody else who studies this what happens is that you take a male hamster and you plop them in to the cage of the home cage of another hamster I'll show you a video of this in a second these two animals will fight in a very stereotyped way it doesn't take very long and one of them will establish itself as dominant and the other as subordinate so one stronger and one weaker and once that is set up the hamster that lost will never fight another male and as soon as you present it with another male it won't defend its home cage anymore and it will always try to escape and it seems like a very long term maybe close to permanent a switch in its behavior basically learned that it can't it's too weak as it were anthropomorphizing somewhat and it instead just chose a very large stress response to any other male hamster instead of trying to defend itself sorry let me just show you what it looks like so here what we're going to do we've just plopped in one hamster into another hamster's home cage both males and as I said they will always will immediately fight very quickly they will establish they will figure out it's hard for us to tell but they can figure out which one is stronger and weaker and you can tell that when that happens because one of them, the weaker one will suddenly stop fighting and instead try to escape so it's like a switch and when that switch happens after that switch that hamster will never fight another hamster so here they are initially and they're fighting around just it'll just take a few four seconds so initially this hamster fights and defends its home turf and there suddenly it figured out it was too weak and now it runs away and it won't ever fight another hamster and you can test this now so a week or months later you can take that same hamster that was that experienced conditioned defeat and you can drop in another hamster to its cage so that's what's done here it doesn't fight at all so this hamster was just dropped in wondering why there's nobody here to fight with and the one here that experienced defeat before instead just had the super high stress response and you can measure all these changes in cortisol, stress hormones in this animal and it seems like a permanent switch in behavior so it's just one particular model system but it's very striking it shows you essentially what seems like permanent changes in a single learning episode in a very specific social context and again it depends it depends on the amygdala if you infuse drugs into the amygdala block and endiator receptors this doesn't happen so you can do a lot of manipulations last few slides to end on to encourage you to get more sleep I think I alluded to this very briefly a few lectures ago sleep is extremely important it's essential whenever anybody has tried to deprive an animal of sleep those animals have died so lack of sleep will kill you it does happen in humans with a rare disease fatal familial insomnia but not volitionally but anyway this is how much the National Sleep Foundation says you need to sleep and you probably get a lot less and you might think well what sleep good for can I get by with less seems to subserve many complex homeostatic functions but one thing that it seems to do is to re-normalize the strength of your synapses so during the day there's lots of LTP going on and lots of synapses are potentiated and learning is going on you need to somehow re-normalize that and bring that down and to some extent stabilize certain memories while forgetting others so there's complex mechanisms that have to do with re-normalizing strength of synapses that have been potentiated through experience during the day and stabilizing memories that require sleep so when people have studied this maybe this is fairly clear in humans it depends on certain tasks but you can have people do various tasks so here's one particular motor sequence learning task in humans if you have the same time elapsed between learning the task and then testing and you're awake this is the improvement that you would see here between these two green bars for instance whereas if you have the same time elapsed but after training on this task you take a nap and then you test the person so the time interval is identical except in one case you slept and the other not that sleep leads to a big improvement in performance and this is a very reliable effect that people have found on certain tasks that there seems to be a requirement for sleep such that if you have consolidation of memory during sleep it greatly improves your performance on this is a non declarative memory task just a motor sequence learning task people have done it with other more complicated things let me just show you the last one this is a task the tower of Hanoi here where you have to figure out how to move all of these discs onto another peg here many of you have maybe done this and you can never have a smaller disc underneath a larger one so you have to figure out how to do that so it takes a while when you actually do this and it turns out the same thing happens so when you do this during the day and you wait for some time to elapse and you ask how good are you you are not really much better after several hours but if you sleep on it you get better so this is a much more complicated task that presumably involves elements both of declarative and non declarative learning that essentially is something like insight so insight or the ability to construct more abstract memory representations that can allow you to solve complex problems in humans does seem to require sleep as well so I wanted to end on that note to encourage you all to get sleep because it will help you consolidate what you learned in this course ok