"Brain History: Evolution from Molecules to Mind"

welcome everyone I want to welcome you to the 13th annual alumni association i mean--you lecture series thanks so much for coming up tonight I'm gonna introduce Linda Jellison she's the chair and professor of um department of modern and classical languages and literature and Linda Moss will be our moderator and facility facilitator tonight and so it's all I got so thanks very much a whole series of introductions here right thanks it's great to see everybody how many of you have been to this series before not this one but okay see they're almost all returners Chris they just keep coming back I keep coming back it's wonderful to see you all again I want to just make my usual request that you make sure your your cell phone is turned off if you have forgotten to do that thus far I think I'm always asked to introduce people because I introduced very briefly and so the speaker really gets a chance to go on with his with his talk and that's why we're all here I think we're all particularly excited about this series because it's a little bit different from most of the series that we've had and that is this one partly at the suggestion of our Provost who is himself a scientist has to do with science and more particularly brain science and you can bet that I didn't collect all of these brain scientists because I don't know any except my Dean so I have to say that Chris comer has been wonderful in working with us and working for us in assembling a wonderful wonderful set of lecturers and I think we're all going to learn a lot this time I personally have never heard any of these people lecture I think so I'm really excited about it our first lecturer is Chris comer who's standing over there on the other side of the room in the dark but he'll come over here soon he's happens I know him best as the Dean of the College of Arts and Sciences and since I'm a department chair we work together pretty closely chris is a scientist he also chair all branches of intellectual intellectual endeavor however and that's really what we need in a college of Arts and Sciences so we're very pleased to have him working there with us dr. comer came to us from the University of Illinois at Chicago some of you may know that campus he had served as a faculty member there he was also the director of the integrity of neuroscience Center and I think his last role was at as the Dean of the Liberal Arts and Sciences there so he came from a job much like the one which he's taken on and I think his experience has served us well he's interested in all kinds of scientific inquiry and I noticed that he's been away for I think a week or so often England reading a paper and he promises to tell us about whisker stimulation tonight so I'm really excited about that I don't know how you're feeling about it but you know what how good can it get so I'm just going to just say that Chris is a wonderful scientist he is continuing to be as I think everybody expected when he came here a lively active scholar he encourages all of us to be scholars he encourages our students to be scholars and we're just really pleased to have him here he will be both giving this lecture tonight and introducing the last series the let the last session of the series the last session will be a panel discussion amongst all of our lecturers how many I think all of our lecturers for the series are here are you all here would you mind standing up if you're a lecturer in this series and and you're here for the first one I saw ash piquant okay so here are two three four right so is that it that's it so all four of our lectures here let's give them a big hand okay so I've overstayed my welcome I just want to introduce to you I'm very happy to do this dr. Chris comer first thing I have to check is can you hear me okay throughout the room can you put the sound up how's that okay the first thing low the first thing I want to do is issue some thank-yous and lots of them are needed for a talk like this first of all I want to thank the Alumni Association the folks that starting with Anne Boone and and company that got us together to talk about this series of lectures was was a really good group of discussions and I want to thank the the other scientists that are participating in this with me there's four of them directly involved and in every case when I contact them and said would you be willing to come out and give this lecture there was no hesitation they all said yes right away it just gives you a sense of the way people think on this campus and how excited they are to be out and share information about what they care about intellectually the this thing really changes doesn't it yeah I'll just leave it in my pocket lower it okay I'll try not to turn my head I do however tend to walk around when I speak and so that'll be a little bit of a challenge but I'll see what I can do one of the things I want to do is tell you that at the start here I've brought a few materials that you might find interesting so let me point these out the library on the campus has very kindly worked with us to try to make materials available for everyone to read these lectures I'm just going to hold this because it's more comfortable for me and one of the things they're doing is making this available online so you can go to the University website you can go to the library and you can find information on these lectures there's two things I wanted to call your attention to there's a couple of references on there for a couple of organizations around the country that specialize in providing materials to the public about brain science and some of them are excellent one of them is this book here called brain facts and this is an old copy there's a newer version out now this is meant to inform the intelligent public about what's going on these days and brain science it's downloadable free from the Society for Neuroscience it's a wonderful resource so if you're interested please go ahead and download it would be good background on some of the lectures and just interesting information it covers the brain and health and the brain and disease lots of questions get answered so it's a good source next this is also downloadable from the dana foundation and this is a book that's actually about neuroscience and education and that's really where we're going with this series of talks by the last session we're going to be talking about the implications of understanding the brain for how we educate teachers for how we teach in the classroom and how we run high schools and colleges and we're going to be joined for that session by some teachers from MCPS and from some faculty and the Dean of the College of Education here so I expect that's been really exciting a lively discussion so you might check this out and last but not least there's some sheets up here with references for today's lecture so if you're interested feel free to take one what I want to do tonight is this the lecture section is called the beauty of the brain so I've chosen material in part to tell a series of stories about insights into the way the brain works that I think ultimately will lead to our larger discussions about learning flexibility in the brain and the implications for education but I've also chosen the material in part because it's stuff that I think is cool and looks interesting and is beautiful so there's a little bit of a method to my madness here and what I've chosen and I hope I get through this in timely fashion so you can sort of digest it and ask questions but I do want to alert you I have no problem with being stop and ask questions in the middle if I said something that doesn't make sense please stop me and ask and I'll be glad to explain I last thing I want to do is talk around you and not give you the information that you really want okay so here's the three big questions that I want to address tonight the first of these is how similar the brains of various living organisms that might seem like a strange question but until recently we hadn't looked inside the heads of many organisms to find out what the brains were like and we didn't even know much about how a human brain for example compared to say an orangutan brain or something like a tenrec lots of information out there we'd like to know and across all animals what's this look like so I'll give you some background information on that secondly a question I think is really important and very fundamentally central to thinking about education how fixed our brain circuits there's lots of Mythology out there one things I hope to do tonight is to start breaking down some of the mythology you hear statements about how many brain cells you have what happens to kill them whether or not you can replace them there's a lot of misinformation out there and I'm gonna try to start the record I'm sure my colleagues will finish it explaining some of the newer information on how fixed the brains functions really are and last but not least what are the implications of brain facts for thinking about the educational process and that's something that we hope you will have opinions on and by the time we get to the final session you'll be in a a mood to ask lots of good questions if all the folks that are up here so let's get started first thing I want to do is clear up one misconception all biologists think about evolution its central to our discipline it's a bit like gravitation for a physicist but I'm constantly dismayed that out there in the general public sometimes it's misrepresented and I can't point the fingers at others because I've heard scientists speak about it in a sloppy way that doesn't explain the facts so I just wanted to make sure I showed you this so there'd be no confusion about this over here I'm sorry over on that side the left is what is the wrong theory and that is the idea that human beings descended from monkeys Darwin never said that that's not evolutionary theory that's not what biologists believe the theory of evolution simply states that all living things are related and so it means that human beings share some distant ancestry with other animals and in fact our closest relatives we know from lots of information are chimpanzees and we didn't descend from chimpanzees but chimpanzees descended from an earlier life form that we also descended from so we're sort of cousins if you want to think of it that way but sometimes unfortunately we tend to slip and make it sound as if we descended from monkeys and nothing could be further from the truth so that's the shape of it I'm not going to go in the the details of that family lineage on the right but we'll get back there in a little bit before the lecture is over to talk a little bit about some of the forms that preceded humans and what their mental capacities might have been like okay this is a slide that is meant to show you the continuity of an intellectual field on the left is a figure that's on a histology textbook that I pulled off my shelf at home and the book is is fun because it's old it was published in 1917 and that's a picture of a nerve cell to the right is a picture that was taken out of that book I just showed you called brain facts which was published just a few years ago and that's also a picture of a nerve cell and if you notice they look awfully similar the basic parts are there this sort of figures in most general biology textbooks most general psychology textbooks it's everywhere there's a lot of truth in this picture but there's a lot that's not accurate as well so for example this particular neuron happens to be the kind of neuron that's in our spinal cord it controls the contractions of our muscle that's it's got that shape and form and so that picture gets reproduced again and again and again but in fact nerve cells come in thousands of different geometries and different shapes and sizes and that's very important to their function in neuroscience the geometry of a nerve cell dramatically influences the way it processes information and so those subtle differences in geometry are all important and yet in textbooks we tend to show one picture as if this was the whole story so in my teaching I spent a lot of time showing students pictures of the diverse array of nerve cells and how the information processing capacities of our brains are dramatically increased because this isn't the only kind of cell we have so just so you know there's nothing wrong with that picture except it's just a tiny slice in fact it's a picture of a nerve cell you'd find in a human spinal cord but since most of the animals on the planet are actually insects most of their neurons don't look quite like this anyway I would call your attention to the inset on the right and that's a picture of a synapse and first I want to talk at that level the title of the talk is evolution from molecules to mind so I want to start with some chemistry I'll go through it quickly and I just want to give you the flavor of it not so much to dig into the details but I'll be glad to answer questions if that becomes of interest what you see there is the tip of the axon and the tip of that axon has some special contents in it which are vesicles that contain chemicals and those can be released at the tip of one cell latch onto an another cell in the nervous system and activate it but they can also inhibit it they don't always turn one on they can turn a cell off and last but not least there are perfectly good cells in our nervous systems that don't use chemical neurotransmission so once again this is just a slice of what happens but it is a common way of communication and it's actually when it's important practically because most drugs that act on the nervous system act at synapses they affect the way chemicals pass from one cell to the next and so that's tremendously important to medical practice and you'll hear a bit more about that I'm sure in the next lecture okay so I divided my story into chapters each one is brief so not to worry the first one was called the antiquity of neuro chemistry and the point I want to make here is that if we look across animals one of the things that is generally true and of course there's exceptions to it is that many of the chemicals we find in our brains we can find in much much so-called simpler organisms so let's take a look at a family tree this is a family tree for the animal kingdom from a recent review article what it shows here is the lineage leading up towards vertebrates on the far left and there's a mouth shown there as the exemplar of a vertebrate and then it shows lots of other interesting creatures funghi are incredibly basic so they're shown to the far right preference over there those are sponges those are unicellular they aggregate they lack a true nervous system as you go up there cnidarians also quite primitive in most people's way of thinking sometime between just after the birth of the metazoans which is multicellular animals we see the first synapses so if you wanted to know what was the original communication between cells that would become the nervous system you'd have to go back to that level and see what's going on now of course we can't go back there we don't have any way to do that but we can look at animals in some cases that haven't changed so much since those early times and we can get an idea of what their nervous systems were like so what's been done in this case was to show simply that if you look over there insects mollusks vertebrates all of these creatures have roughly similar synaptic structure and then let's ask the question what's the chemical chemical reason review article when I saw this graph I almost fell out of my chair it's a really interesting graph what this shows is it shows all of the proteins that are in the postsynaptic complex so there's two partners in a synapse there's a cell sending information and a cell receiving information if you look at the receiving neuron so-called postsynaptic cell it's doing a lot of information processing and you can harvest that and you can break it up and you can look at the proteins in it you can even ask what genes have been expressed by looking at the proteins and some other tricks what this shows over here is to the far right you see humans so we have mammalian vertebrates non-mammalian vertebrates and then the invertebrates so bees are up there fruit flies are up there zebrafish frogs chickens cows and you look at that it shows you to the far right 100% is the human index that means that's all the different unique proteins we pulled out of a synapse from humans and then what's shown for all those other animals is what percentage of the proteins they have in the synapse are identical or nearly identical to those you see in a human now knowing how complex and differential differentially behaving different animals are you might have expected there be wild differences in the proteins expressed at synapses and all these different animals and yet if you look at this it's almost a straight line you can draw across all the vertebrates there's some variation but it's rather small which is to say that if you look at a frog while it's not identical to a mammal you're gonna see many of the same proteins in those cells the neurotransmitters themselves the things squirted from one cell to the next are also found pretty ubiquitously throughout all the vertebrates so the basic chemistry is not that different to see a big change you have to drop from the vertebrates to answer the invertebrates and then you start to see some differences in the proteins that are present at the synapses so there's this set of smaller bars over here to the left and that means that the proteomic or the chemical complexity of the samhsa's is a bit different in invertebrates than it is in vertebrates and I might have expected that these would vary all over the place maybe even in some systematic fashion and lo and behold they're really quite similar now all summaries like this do some danger to some subtle differences that are very important and I think rich will probably tell you about some of the things that are found at synapses that are quite important and very in subtle ways that make a huge difference to things like learning and memory and so the answer heed that the point here is that if we ask the question how similar our brains across a wide swath of animals at a very micro level of chemistry they're not that different one from the other and even at a synapse which is a very important information processing component of the brain so how do we get complexity well this is a cartoon and it gives you an idea of how this might work and I share with you just to give you a feel for what this shows you is a synapse right here and that synapse has some blue balls and then a red horizontal structure and then some yellow triangles those are just stand-in so those are cartoon standings for different molecular components of a synapse those are the things that receive signals and most of the complexity at synapses seems to be largely dependent on what's there lots of different proteins expressed sometimes of big complexes and they gather signals that are coming in they process those signals they store information they affect the processes of learning so that's important and I've just told you that what's in a human brain is pretty similar to many other animals so then what gives the unique character of a human brain at this chemical level well what it seems to be is if you look at that schematized human brain over there it shows arrows from different color combinations up to different parts of the brain and what that means is that the basic proteins are the same but the way they've been combined differs from one location in the brain to the next so this means it's at a combinatorial solution to the problem you have some basic components and you can shuffle them in very interesting ways and when people do gene expression studies and ask what genes get turned on in one part of the brain to the next they typically find that it's not the same genes being turned on in every location there are subtle differences and once again here's the bottom line message very subtle differences in this chemical expression can lead to very big changes because after all these differences between a human brain and a chimp brain and a rat's brain are not that great so the real question that gets interesting for biologists is how do you define those small difference that differences that make all the difference in the way the organism behaves and maybe it's learning capacity ok chapter 2 is behavioral change difficult we know animals have very different behaviors what would you have to do to a nervous system to suddenly give an animal completely new behavioral capacity now I'm going to rely on some data from my own laboratory and I should say here anytime you show data from your laboratory you have to point out most of the data I will show and I'm only going to show you three slides I didn't get myself my students and postdocs got it and I want to mention very prominently go through Baba who has been opposed talking my lab for years and really it was utterly important getting the data I'm going to show you this is a picture of brain cells from three different insects and the species are shown up at the top there the custom migratory is the common locust purpley neat Americana is the common cockroach and gorillas by maculatus is a cricket we've kept all these different species in the laboratory and they're closely related they're near cousins so to speak in evolutionary terms so we've been interested in how their brain circuits are organized and what difference is we can find from one species to the next that explain their different behavioral capacities so on the left there look us tamargo Toria what that is is the picture of the brain that we could see this under the microscope we had injected that neuron with a tracer a chemical compound that we could precipitate and then we can see the cell and all its glorious anatomy under the microscope that cell it turns out is a very famous nerve cell it was the first uniquely identifiable nerve cell that was ever published so way back in the 60s somebody was working with a locust Polkton micro electrode in the air and pumped dye into it and said not only can I see this cell but every locust I find has exactly this cell right there this is a kind of an interesting idea because when you have billions of neurons in a complex brain one often wonders do the cells a unique identity we can't answer the question quite exactly in a human but in humbler creatures with smaller brains it's very clear that they have very exact neural circuits and the cells have unique identities and I'll come back to that again at the end of the talk so this is really valuable from a scientific point of view because if I want to do an experiment on a mammalian brain cell I actually don't know from one day to the next which cell I've been working on it's just some cell that I happen to get in a locust I can go back to this cell called DC MD descending contralateral uma detector day after day find the exact same genetically identical cell there's this Anatomy now we didn't study this to just go back and study its Anatomy because it had already been described but we studied it because we wanted to find out does the cockroach have the same cell and does the cricket have the same cell and by an exhaustive list of physiological tests we believe the cell shown in the middle for the cockroach and the cell shown to the right for the cricket are the exact same cell they fire in very specific ways for approaching visual targets they very interesting visual dynamics that are signature so we're absolutely sure these are the same cells but notice the anatomy of the cells is not identical you're looking at the brain and the other two as well the st. cells have also been pumped full of dye and if you look at it you can see that there's a blue area circle for all the cells we know from other studies that that's an area where information from the eye comes into the brain and turns on that cell this is a visual neuron responds to moving targets out in the world it turns out the cockroach in the cricket have one subtle but really important difference they have that little branch off the cell that's circled in red we know what that branch does that branch is not a sensory branch it's a motor branch the information in the cell is sent along that branch and there's a population of motor neurons that are sitting there these are cells that go out into the base of the antenna and cause them antennae muscles to move and therefore to move the animals antennae so this is a neuron that gets a visual signal and then has the ability to turn on the cells which will activate movements of the antennae the locust doesn't have this interesting biological difference between anybody know the real salient difference between locusts and cockroaches locusts have stubby antennae cockroaches have glorious long antennae that are about one-and-a-half times body so what happens is locusts don't have these gorgeous visual reflexes where they can locate things with their antennae crickets and cockroaches do and the reason they do it is because the cell in the brain do one extra process so on the glorious grand anatomy of this nervous system this is a really subtle cellular detail but over evolution it gave rise to tirely new behavioral capacity and crickets that isn't present in locusts even though they're close cousins so let me show you what this looks like this is actual footage from the laboratory this is a this is a visual response in a cricket did you see that it's a little bit subtle of plate again his left antenna is held in front of him and when a visual target pops in the in the field he turns and touches it there it is so oddly enough this particular behavioral capacity wasn't really known about until about 10 years ago and it turns out that we now know it's present and a whole variety of insects and it depends on those cells and it's not present in all insects and when it is present it seems to be the re-engineering of the outputs of that cell so how would that happen well from studies in Drosophila we know that there's a whole family of genes that if they're expressed cause cells to send extra branches as they develop and we don't know in this case because we haven't done the genetics but it's most likely that as much as one gene being changing its expression pattern could have led to that cell sending out an extra branch and now making a functional connection to the motor system for the antennae so subtle change major new behavioral capacity okay so this is just a summary of that it shows physiology from these cells in the cockroach and the cricket they both respond to like you pop something in the visual field and what those recordings show is nerve impulses the little electrical discharges that the cell gives when it's been stimulated in this case connected to the eye stimulated by a visual moving object and here's our evolutionary model the cells all have this branch shown in blue where they get visual input in some cases they've grown an extra branch over evolutionary time and then those cells have the ability to drive that motor output and it turns out these cells are massive and they have lots of other branches in other parts of the nervous system and there's lots of other chapters to this story that I'm not going to take the time to tell you now okay let's move to bigger brains chapter three bigger brains present a whole different set of problems but the same questions can be asked how similar are they how fixed are the connections and what I want to do here is tell you a tale of two rodents what's shown on the left is a common laboratory mouse that's a c57 black mouse and on the right is a lovely creature called a naked mole rat you may have seen these in zoos it turns out we have a colony here on the campus and they're really fascinating creatures quite different from the mouse let me just point out a few of their features notice the prominent whiskers on a mouse that's a very important sensory apparatus that's deeply represented in the brain also notice the the mole rat to the right it's a little hard to tell but it has some pretty unusual features look at those very large teeth those are incisors and you can't quite see it here but the mouth is actually behind the teeth so these are teeth that are not inside the buccal cavity they are outside in addition the two bottom teeth are independently movable their prehensile teeth and the reason is because these are blind mammals that live underground and they dig with those teeth so if you had your teeth inside your mouth would be hard to dig without getting food in there going so it's very important to have switched this around quite often you can learn things by looking at two closely related animals that have solved some environmental problem in a different way so here's what we know about these guys okay this may not work and I may have to switch out of this moment here oh I don't want to show you was something equivalent to what you just saw on the cockroach but in a mammal and this is what happens when an animal has its whisker stimulated so you saw the prominent whisker display in the in the rodents let's see if this works probably won't so what you would have seen here was it was really lovely that the way you record brain activity these days has changed like the old days you always had a poke and electrode into a cell and that's a bit of a tricky thing because you can't see the cell before you try to run the electorate into it nowadays it's a much kinder gentler world you can actually place a voltage-sensitive dye over the cortex and you just have to look through a tiny window in the skull and if you stimulate the animal the voltage-sensitive dye will emit a fluorescent signal and you can just optically sense where there's activity in the brain I was going to show you an example of that but we'll just skip that for now an active touch was to show you that just like with the cockroach if you show mouse something interesting they will project their whiskers toward it and then move it and you see very interesting patterns of activation in the brain but here's what wanted to get to after showing the behavior which is more just for the fun of it I wanted to show you what the brain looks like in a mouse so that left hand side there is a common laboratory rat the mouse is quite similar although not identical and what it shows you there is an area called s1 so if you were to look through the skull take one side of the skull off you'd see that area it isn't color coded in the animal of course and what you see there are some gray fields with lots of black dots each one of those black dots represents a group of cells that responds if you touch one whisker and on each side of the face there are on the order of 40 or so whiskers so it turns out that there's a matrix or an array where there's clumps of cells processing information from each of the whiskers and the first time people saw this back in there I guess it was the early 70s they were quite amazed at this nobody had seen quite this dramatic organization in the cortex before and interesting piece of information there there are actually several of those fields so there's not just one array covering the whiskers there's about four to five different regions each of which is independently processing different kinds of spatial and temporal properties of those whiskers which is a way of saying the whiskers are really important to rodents now remember rodents are pretty much nocturnal they're active under very low light conditions they have to navigate the world with non visual cues so having a very sensitive viral system is absolutely essential of their survival if you look to the right that's a mapping of the brain of the naked mole rat now naked mole rats have a much simpler area of s 1 and s 1 just stands for primary somatosensory that's where their cells are that respond to touch but they don't have as rich a whisker field they have one instead of five so much less processing of whisker information what's mostly in there is processing of the teeth so there's an enormous representation of those two incisors and many many cells probably 40% of the of the cortical area is responding is just the signals from those teeth those digging apparatus you think of it it's a little bit like a hand for us where we do really crucial things with our hand there's a massive representation of our hands in the brain so there's a common way to look at this which just brings it back home in a way that everybody can relate to which is take the information that's representing the brain and draw a character of the organism scaling all the parts on the body - the amount of brain tissue that monitors that part of the body so if you had a huge set of brain cells taking care of the hand this creature would have a large hand if it turns out that when this was first done it was done by Edgar Adrian back in the 30s I think he studied the cortex of a pig it turns out there's an enormous representation of the snout of a pig it makes sense that's really important to the pig lifestyle so here we go for naked mole-rats if you draw it you see over there on the left there's this that's a mole redonkulous that's about the proportions there's a pretty good representation of the of the hind and rear feet there's an enormous representation of those incisors because they're so vital to the animal's life and in fact what I put over there for references that's the human homunculus once again this is found commonly in biology and psychology textbooks but if you look at the area in our brains that represents different body parts there is an enormous over representation of the hands and there's an enormous over representation of the face and the lips and the tongue of course we're vocal creatures and we do very very fine manipulations so you can tell from looking at the map what's behaviorally significant to the organism and in fact if you look across a variety of mammals and you look at their maps all you have to do is look at the brain map with you can tell exactly what kind of behavioral niche they live in in the world it's absolutely one for one it's perfect so the brain is reflecting what the lifestyle of the animal actually is okay now I just want to look at the dynamic so I want to turn to the question of how fixed information is in the brain and how the circuits may or may not be flexible and I'm going to use the same system I threw this picture in there just for fun this is a newer technique you know the old days I refer to having to find a sell blind and inject a chemical into it nowadays what you do is you genetically engineer the animal so that some of the cells express fluorescent proteins naturally and then you can see them under the microscope and this is one of those cells it's also turned out that they've engineered it genetically so that there's a rabies piece of very bees virus in it and the yellow thing you can see there and because the lighting you probably can't see all of its glorious processes but they're pretty extensive that cell is enmeshed in thousands and thousands of other cells but the cells is connected to are labeled red so there's a special compound that's in that yellow cell it diffuses through one synapse through that chemical connection to a nearby cell and any cell that that cells talking to is now in red so in the old days it could have taken God knows how many person hours to record from the cell and try to poke your electrodes are going to find out who else is talking to that neuron and now you can use molecular genetic tricks to get a visual picture of exactly how the cells are connected the reason I'm showing you this is partly because it's beautiful but partly because it looks like a very fixed structure and for a century we've been looking at nerve cells as if they were fixed structures so what I want to show you is that that's far from the truth and this is the one I really want you to see so I hope this will work what I'm gonna do I don't want to break tempo here I'm gonna come back I'll fix this at the very end and I'll come back and I'll show it you because it's quite dramatic what it is is a series of photographs taken of a nerve cells you can see in a pyramidal neuron in a young mouse and what they did is they photographed about 10 minutes worth of its life and then they made it into a movie and it turns out that the cell is moving all over the place and this isn't a one in a million this is the way most cells and the cortex are behaving at this point in life they're extremely dynamic and this is something that wasn't appreciated certainly when I was in graduate school we didn't know this it's only emerged over the last 10 or 15 years that a typical nerve cell certainly at certain points in an animal's lifespan are dramatically mobile and they're moving around tasting the environment forming breaking and remaking connections in a way that we never dreamed of before so I'll come back to that shows you because it's worth it let me however just show you that at a finer level there's another way to look at the details here this is back to the same part of the brain it was telling you before where the the whiskers are represented and it just shows that to the left and to the right there's one neuron that's been labeled with a special fluorescent tag and then it shows you with those boxes where we're going to zoom in and look at the details so here it is this is mouse cortex the pnd up there it says P and D 16 that's postnatal day 16 and then each picture is of the exact same process every day over that approximately one week period so 16 17 18 19 and the beauty of this technique is once a cell is uniquely expressing a tag you can go back and find that exact same neuron one day to the next to the next and ask has it changed is it structures stable or not now from that white line which is the fluorescing nerve cell process going across the field you can see that its basic structure is the same it's there every day it's in the same place it looks to add the same geometry but if you look at those arrows notice the yellow arrows point to two little blurbs coming off the side of that process those are special structures where synapses are made they're called spines and most cortical neurons have thousands of those and what this shows is that the spines at those spots with the yellow arrows were the same every day the cell was sampled so some of those are incredibly stable from day to day but the ones if you follow there on day 19 day 20 there's some red and blue ones that pop up because there's some new spines that are growing out there you see them there over days 21 22 and then they go away by day 25 so they're transient they're there for a while then they go away now that's a level that's much finer than the movie I was going to show you but the reason that's important is because we know that many important classes of synapses the connections are made not randomly on the cell but on the spine so when you see spines changing it means the connectional information of that cell has changed and one of the things we believe to be true is that sometimes during dramatic change in the brain you'll see kinds of structural changes like this that reflect adaptive changes in the way the brain is wired so the nice thing is we can see this now we can measure it we can see how profound it is oh by the way really important question for all of us any of us who are over about 15 years of age we hear again and again that the brain is very flexible in the young and as we age it becomes less flexible this is postnatal day 18 through 25 that's relatively young however this same paper they showed the exact same information for postnatal day 200 210 so it's very clear that this kind of plasticity is not only happening in neonates is happening much later in life and all of the evidence we have lately suggests that the idea the plasticity is only for the young brains is not true that older brains retain a significant amount of plasticity there was a question there yes they occur mostly on dendrites okay and this is the penultimate chapter this is just the quirks of humanity obviously we have some very special features to our nervous system so let me go through that very quickly one of the things that's that's certainly true about humans that's important is just the overall size of the brain we have very large brains in an absolute sense by no means the largest on the planet but brain size generally scales with body size and none of our body size we still have inordinately large brains so what this shows is I'm sorry it shows as a function of body weight what the endocranial volume is that's the size of the cranial cavity in which the brain sits and it's an indirect measure of brain size you can see here that chimpanzees are down here there's a line of dotted colored spots that go up towards the Neanderthals and modern-day humans so that's the lineage that goes up towards humans and as that lineage is being played out brain size is systematically increasing but this doesn't have a time scale just say it's scale the body size so let me show you the time scale time scale is shown here so time is on the horizontal axis and that's millions of years before the present and then the volume of the brain is shown on the vertical axis what you can see here is that australopithecines which are dated to oh three to five million years ago and clearly our ancestors we have lots of fossils from them have pretty small brains a little bit over 400 CCS which is not terribly large as you go out here you get to Homo erectus that was the first hominid creature that actually exited Africa started colonizing the Europe and parts of Asia they had a larger brain size perhaps about a thousand CCS and then you go out there you see modern-day humans to the far right and you can see there that there's a diversity of brain sizes but in fact overall cranial capacity is about 1,400 CCS now I don't want to make too much out of cranial capacity because as you'll notice there's a difference in average cranial capacity between men and women and we all know that that has no significance whatsoever so small changes here probably once again don't make a difference but what's interesting here is there are actually two jumps in brain size so if you look at this graph did you try imagine drawing a line through there just after 2 million years before the present there's kind of a jump and those points go off the horizontal line and and then things stay pretty constant for about two million years or maybe one and a half million years and then suddenly there's another jump which is actually the last 35 to 50 thousand years so this is interesting because it means there were two different events giving rise to our larger brain and we don't know exactly what those were we have some ideas anthropologists spent a lot of time trying to figure out what was going on in a cultural or proto cultural way during these events and biologists are trying to figure out what was going on biologically in terms of genes that were being expressed but and the story is not simple in the sense that it's not a simple increase in brain size it happened at least twice and some of the genes that are being turned on differentially here to cause this the ones we know best are all recent ones that happened in the last 40 or 50 thousand years we know much less about what might have been happening two million years ago but here's one of the things that happened the cortex of the brain dramatically expanded this is something you've probably heard before and this is I think a convenient way to just know about that what it shows you is the amount of cortical surface cortex is the top of the brain when you open the brain case that's the first thing you see in a rat it's fairly large for a rat brain it's quite smooth and the surface area in this particular diagram is meant to be about the size of a postage stamp and if you scaled the cortical surface in a rat to be a postage stamp then on that scaling for a standard monkey like a new world monkey it would be about the size of a piece of note paper so it's much largest surface area if you go to a chimpanzee it would be about the size of a piece of legal paper quite a bit larger suddenly when you go from chimpanzee grade to human grade it's four times that and as you know the brain takes on lots of cranial ations and sulci and gyri because you're compressing a huge surface area into not a very large cranium so it has to have these rivulets to sort of crunch the whole thing together but because the circuitry is arrayed along that surface that increased surface area means an enormous increase in information processing capacity okay what about language very important to us as human beings something that in terms of our phenotype syntactical language processing is something that's rather unique to humans something that's shown here on the left is a classic picture from neurological studies of humans to show that you know language capacity in some way depends in a special sense on what's going on in the left side of the brain and it shows an area called the plane of temporality which is shaded in and cross-hatching there it's much larger on the left side of the brain and those people and it is on the right we also know from physiological studies that the cells there are processing sound information in a way that's relevant to speech and it's obviously very important to the control of speech in humans so that's a specialization we think of as being rather unique to our niche as human beings the question is when did that arise in evolution well about ten years ago somebody thought to get enough specimens from chimpanzees and ask the question do they show this asymmetry with a larger left Planum temporarily and what's shown there on the right is a study from chimpanzees to show that in fact they have a very similar asymmetry now chimpanzees don't use language at least not a vocal language recent work suggests that they have a fairly rich gestural language and they do make some vocal calls but nothing like a syntactical language that humans have so this is really interesting because it suggests the reason for the asymmetry in the brain is not language per se because it was there before language or so it's one of those mysteries that is not yet solved there are some interesting speculations these days about why it came up I suspect it has to do with the fact that that part of the brain also has a lot to do with usage of the four limbs and especially the hand and so it may have been involved in gestural communications or may have been involved in tool use which is a very lateralized piece of behavior in most human beings okay last but not least what did genetics tell us about the brain this is just a quick scan to show you what generally is being done these days to find out about when genes may have changed in such a way that they've given us human characteristics this shows a particular gene that has I think it's a hundred and eighteen base pairs in chicken and compared to the chimpanzee it has the same base pairs except there's two that are colored blue that means that over evolutionary time those base pairs changed now there's mutations happening all the time and it was very predictable rate at which mutations tend to show up when you go from chimpanzees to humans and that's a very short time in an evolutionary sense suddenly there's about 17 other base pair changes that have happened what this means is that there's been a rapid change in acceleration and the rate of change in the structure of this gene now this is seen all the time and and at this frequency we have on the order of 26,000 genes give or take there are a small number perhaps 150 that have been found that have started to change very dramatically over the past few million years in the human lineage so the suspicion is that these genes may well be very important to some of the characteristics that make us human so they're very heavily studied at the moment that's the logic of just looking at them and it gives you a sense of what it means to say something has changed rapidly in a recent time here's what some of those genes do there's a normal skull shown in a MRI photograph there's a gene that's been discovered in this scan of the human genome quote a SPM what it stands for is not important but when that gene is not functional it produces microcephaly so there's a picture of somebody with a living human with a brain that's instead of being fourteen hundred CCS is about five hundred CCS in volume these are rare clinically but they do occur and so that's a gene that is related to the production the brain size and it's not the only one that's been found har one is another one when har one is present in a copy that's not functional what happens to the brain is the brain starts to look smooth it doesn't have all the curvy contours so the volume of the cortical surface is dramatically reduced so that brain looks more like a brain of a lower mammal than a typical human both of these show up in clinics har is one is a very devastating condition but both of these genes somehow because we know what goes wrong when they're not properly coding is something to do with brain size the theory is that these certainly must be genes that have been important in increasing human brain size because they've been changing in humans and these are not the only ones there's about five that had been identified in the last couple of years that were clearly changing rapidly and are getting rise to the larger brain in human beings so here's my summary of that I borrowed from da Vinci for this I didn't want to use a picture of a boring human so Lipson in the back here har one is one I just told you about that produces a smooth cortex instead of a a normal properly folded cortex a spm produces a small brain fox p2 is a language gene and quick aside here if this was discovered about early 2000s maybe 2001 and the newspaper report said the gene for language has been discovered bad reporting it was the gene for language there's no such thing as the gene for language there's lots of genes of impact language this is one of them and it's not the gene there's probably no magical one gene for language but it clearly does effect it was discovered in Britain in a small family of individuals that had problems articulating they have problems using proper syntax and grammar but otherwise they're able to understand language perfectly so it affects one component of the circuitry that produces normal human language we don't know the full complement of other genes that affect language but they're being discovered as we go part two is a gene that has changed dramatically recently and it affects the hands and we don't know quite what it does yet but the suspicion is has dramatically changed and we are tool users that it might turn out to be important to the way we manipulate with our hands and lct I want to tell you about really quickly that's the lactase gene and this is really important because the lactase gene is something that allows us to process milk sugar effectively in our digestive tracts now all humans have it active when they're young but in most human populations that gene becomes silent and a functional after weaning so it's not used it turns out that in Northern Europeans the gene stays active it turns out that in three different geographic regions of Africa that gene stays active and the reason is because those people became herders and they brought goats and they brought cattle in and they milk them and they used milk as an important foodstuff and this probably happened between 10,000 and 5,000 years ago so this is a cultural practice that has led to a selection pressure causing gene changes in the Union so this is a really fascinating area and it means and it's just kind of taken off again that there is an interaction between genetics and culture and a level that people didn't appreciate before and I'm sure this is glad in the heart of many an anthropologist to realize that culture is having such a direct effect on biology we always knew it but this is one of the better examples of it so the things that are happening in the human evolutionary story are not just genes changing and genes reading out information it's also culture happening and culture influencing the way genes get selected so there's a definite interplay there between behavior social conditions and the way the brain develops okay I'm gonna skip this because I don't want to take the time I'm gonna go to one last point I'm gonna end on this this is a picture from a paper that came out about a year ago and it's from a new area called connectomics so as we go along we're creating whole new fields in biology what this basically is is a map of all the connections in human brain that are of any significance and it was gathered by doing MRI like scans of the brain in a special way that instead of looking at you know quite often we'll look at things like blood flow to a region of brain to figure out if it's highly active but this tends to do is tends to look at the structure of the white matter the connections between different brain areas and assesses their integrity their thickness and how likely they are to be a strong connection and this is done in an unbiased way so you don't go in and say let's find out how the visual area is connected to the touch area you just simply say let somebody sit in the scanner scan the brain and find out what the connections look like and it turns out that across a series of individuals that were scanned they came up with roughly similar maps and when you do an informatics crunch of all the information there what you get is on the right that's a somebody's called sort of a subway map of the human nervous system it turns out that all of that complexity can be reduced to a few local hubs there are 1 2 3 4 5 7 there and those hubs are local nodes where there's strong connections in and out and then they're each interconnected to the other so while there may be 10 to the 15th connections in the human brain and that's a very large number that's billions of billions the only way to make sense of that is to reduce it to something like this and the interesting thing about this is this probably was mostly done by graduate students who were training in informatics which is sort of a hybrid between biology these days and computer science and they were probably not touching any live creatures they were probably at the computer and what they were expert in is going to databases all over the world finding information and scaling it up against this because now we're trying to look at gene expression against maps like this so there's a whole cadre of scientific endeavor here that has to look at systems like this and try to analyze in an abstract way what's the nature of the complexity here it turns out these connections are not random they obey certain principles of complex systems and there's a whole new science that's evolved to look at this and when you look at it it turns out that one of the things that's fun here it turns out that this was recently done for the fruit fly and you're gonna hear about fruit flies later I'm not going to tell you any details here but it turns out that at a formal level the subway map for the fruit fly brain has the same general organizing principles as the subway map for the human brain it has about the same number of key nodes it has the same properties of interconnection and by the way I wasn't too surprised because I work on insects on I know insects do really complicated things so there's a good reason for that okay so let me just go to the summary so real quickly the points I wanted to emphasize were just that the while the brains have many similarities there are some nuance to differences not large differences at the molecular level and some of those are probably gonna be terribly important for things like learning and memory and you'll hear about some of those I think from rich as as we get into the next week it's really small changes at the cellular genetic levels that probably can explain major shifts in behavioral capacity in a complex system a small shift in connections can lead to a major shift in behavioral outcomes and then last but not least brain circuitry really is highly flexible and this is something I'm gonna come back and talk about again at the final week in a brief way to talk about how it relates to changes in the brain in children and I think how we want to be thinking about education in an environment where the brain is dynamic flexibly changing and it seems to me very important that we know over what time course it changes how its inputs can be used and that we design educational curricula so we take full advantage of that so war on that on March 22nd and I'll be glad to answer questions now can you hear me now okay we're gonna have some mics around the room so just hold up your hand if you want to ask a question I forgot to mention to you at the very beginning and Chris is gonna try to get his footage going here that on the back of your program you have a free pass to the hands-on Science Museum over in the Skaggs building and they're having a an exhibit called the brain a world inside your head and it's going until March so you have a free pass to go over there this this tells you on the program what the hours are and that kind of thing so if you're interested in this and you want to do a little bit of outside research or homework or anything like that feel free to pop on over there and use your free pass did you get it Chris or ten minutes in the life of the cortical neuron do that one more time those are first thing they really amazed people because it looks like an amoeba more than a typical brain cells we think of it questions anybody right right here Jay right in the middle there the second part how static are the brain maps in view of neuronal motility other really dynamic I have a feeling that one of the later speakers going to show you some examples of this but there's some famous experiments where you could train a monkey to use this hand differentially I see your record from the brain and kind of map out the hand representation you train that monkey to play with textured surfaces to get a reward and you can literally over the space of perhaps a week see the representation of that the specific fingers used in the discrimination will expand in the brain and those kinds of changes wouldn't be happening unless we had dynamic changes in cells of the sort that you just saw on the screen there so the theory is that both at that cellular level and with some important gating processes that are at the molecular level those kinds of changes become allowed over here Dan and Spencer kriste I was really interested in the example you gave about the asymmetry in the brain that was reflected both in human brains and chimps brains and seems to be related to speech in humans but not not that in chimps which suggests maybe that that asymmetry evolved under different adaptor pressures or something but then created the capacity for a later a tapped agent humans perhaps completely unrelated to the original pressure and and I'm wondering how often do we are we seeing that kind of thing where some evolutionary change evolves in and out to be here but that then creates a capacity for a different behavior altogether that wouldn't have arisen without that capacity but didn't arise because of that adaptive pressure if that makes any sense no it doesn't and that's a good question because it makes the point that evolution is a very conservative process and it can't reinvent the materials that's going to use to make something it has to use what it has already in a living body and whatever the adaptive niche was that allowed for brain asymmetry it happened at a certain time and then it was used and was useful for certain needs later on those couldn't been predicted because evolution is not that kind of a process but that happens all the time so evolution is a deeply conservative process it uses what it has and quite often you can track back and show that an adaptive change here that was useful for one purpose several million years later it's still in the population but now it's useful for something else and evolution can make use of it so that's a very common happening anybody else more questions back there in the back I think Tom I was very intrigued by the cultural changes that can influence the brain structure and could you just address briefly the epigenetic influence of brain structure and function and you mentioned you know that genetics is a very slow conservative process but that in epigenetics this can speed up the process significantly and where this is going in the future I'm glad you mentioned that too because that the term epigenesis means the ability of environmental information to influence gene expression in a way work gets stable he passed on from one generation to the next and there were classically a few examples of that that were known and they were considered to be kind of rare and if you've been among professional biologists in the last five to ten years suddenly the term epigenesis epigenetics has recurred again and there's been enormous numbers of examples out there and it's very clear that some of the complexity of the human genome is related to the fact that it can take in signals from the outside under certain circumstances and incorporate that into gene expression and there's been a couple of studies that were done in Europe showing that you know in a couple of countries where they have really good health records you could track back and find out that a mother's behavior while she was pregnant influenced the offspring in a way that was then passed on to the next generation and as you can imagine this is not something we expect to see happening so when it did happen those publications were scrutinized and people looked for replications it looks like that's really true and I would say that if I had to predict what's going to be a really important intellectual challenge in the next ten years and the life sciences and it's not just biology this will affect anthropology it'll affect sociology it's going to be epigenetics we don't fully understand how it works there's a few good examples now where the details have been probed by geneticists but to know that the human genome is that flexible is really kind of startling and it's really a whole new generation of research that will be done I had a question you mentioned that most of the signals are neurotransmitters but there's other ways that information is being communicated in the brain can you talk about that oh sure I had a slide in here that I took out because I had hundreds of slides it was a hard thing was to get it down to a manageable number there's a lot of things floating around on the brain that have really high impact on brain function so for example that chart I showed you where I was trying to explain that the chemicals in the brain are rather ancient many of them not all it turns out that you could do the similar thing for hormones and that you can look back and say ok we have a set of hormones in our body that control physiological functions how ancient are those well a lot of those hormones can be found in things like yeast so they're very ancient hormones get into the brain they powerfully influence different brain centers another area that's really important that I find fascinating and once again it's a relatively recent is to look at the connection between the immune system in the brain lymphocytes in the immune system sprits little chemicals back and forth called cytokines all the time which signal between them and some cells in the brain are sensitive to those cytokines in addition many of the lymphocytes are sensitive to neurotransmitters and hormones so there's a two-way traffic between your immune system in your brain all the time now it's humbling because the the immune system is so complicated sometimes I think it makes the nervous system seem simple it has a huge number of cells but instead of being relatively fixed like they're on the brain they're floating free in your blood system the immune system is capable of memory it's capable of learning so it's an incredibly immense dispersed information system and it's talking to the nervous system all the time so imagine a field that could take into account all the complexity of the brain and then at the same time factor in the chemical complexity of the immune system and the endocrine system so all of these signals are available to the brain and many different brain centers or lists some of those chemical signals please Chris I have a question about the surface area of the brain so usually when a structure has a particularly high surface area it means something about the exchange between that structure and its surroundings is that playing a role here is the brain exchanging information with the fluid in which it resides or is it just optimize that outer a few millimeters of the tissue yeah that's a good question um I suspect that certainly nutrients are exchanged with some of the surrounding fluid the the blood vessels must conform in some way to the funny geometry of the cortex and I suspect it's not so much for we tend to think of it as being for packing circuitry effectively into that structure rather than for something like metabolic exchange in any simple so the question was do I see a connection between the way the immune system operates and the way the olfactory system operates to process smell information that's an interesting question I guess I would say at a certain level yes the when you study basic biology one of the things you have to do is spend a little bit of time on the immune system because it does some really amazing things with shuffling genetic information to make all the different antibodies and that's an incredibly important paradigm there's millions of antigens in the world and we can recognize a huge number of those and we have specific antibodies for all of them and we make those through genetic techniques but there aren't enough genes in our body to code specifically for that so we reshuffle the genetic information during the development in the in system the nervous system probably does a bit of that at least in a formal sense and that graph I showed you it had a cartoon of the human brain and it showed the postsynaptic receptor mechanisms and it showed them being shuffled in different colors that could well be something of the same sort that some of the receptor complexity could be through mechanism a little bit like the immune system where some of that information is differentially shuffled between genes are being expressed in case of the olfactory system there is some interesting information about how differential gene expression gives rise to the different kinds of receptors across the nasal epithelium but I'm not an expert in that I don't know if you could draw a close analogy between that and the immune system I think it's probably scaled completely differently I was hoping I wouldn't get asked that could I explain the difference between men's and women's brains basically gosh if I could do that really and clearly you know I remember vividly in college reading an article on sex differences in the brain and I thought wow this is gonna explain everything and I read the article and what it really said was that in the female brain of course there's interesting connections between the hypothalamus in the pituitary to explain menstrual cycle okay well that's not too surprising so I wouldn't call that a profound difference but it's certainly real now people have gone out and looked in many different dimensions to see what kind of specific differences they can find into trouble with this is until it's been replicated a number of times you never know what to think about it so for example there was a report oh gosh I don't know eight years ago maybe about the corpus callosum being a bit different in terms of numbers of fibers between men and women and not the whole corpus callosum but certain regions of the corpus callosum that's the the region that connects bundles of fibers between the two sides of the brain and some of that has been replicated and some of it hasn't and frankly even though it's been partly replicated I couldn't tell you what it means functionally those kinds of questions are beyond I think what we know in a really specific operational way right now so I guess I would have to say that there certainly you know you can if you search the web right now you'll find lots of research published research showing some differences between male brains and female brains I would point out that most of those are differences on average that is to say there are very little absolute differences between the two brains and they're more similar to each other than they are different the immune system connection I wouldn't be qualified to answer that I I think it'd be a fascinating question because the so my intuition is there's some really deep connections between the immune system and the service system that we've we've seen just the tip of one of the great researchers who studied language and brain lateralization was convinced that the degree of lateralization the brain was connected to the competence of the immune system in some way and actually had some evidence that that might be true but that mechanisms for it are very unclear and I guess at this point I just have to say that when you have two systems of that complexity there's so much more we need to know before we could point to specific instances of how one affects the other yeah yes so how does the injured brain respond there's a lot of information on that many experiments have been done to look at what happens when one section of the brain is damaged what kind of compensatory changes take place I had a slide in there which I took out cuz just I couldn't fit it but maybe I'll show it on the 22nd of March the new brain imaging techniques the thing I was showing you that had that subway like map that's being applied now to look at people in cases like stroke where region of the brain has been damaged and it's been really interesting cuz there's been a paper a couple papers in the last year that showed you know it's not hard to look on a brain scan and say oh there's a region that the brain was deprived of oxygen and the cells have maybe died and they're not functioning but what about the rest of the brains a massively interconnected system and these new diffusion tensor imaging techniques allow you to ask the question subsequent to that lesion from the stroke have you seen changes in connections to other parts of the brain the answer is yes fairly quickly so you see functional shifts in the way that brain is interconnected and I think a lot of study will have to be done before we know what the significance of that is but I guess that the hopeful thing is at least at this level we have a non-invasive tool that can you can use to look at a brain surrounding the time something a stroke and see what kind of changes are there and seeing them as one thing and then doing something to sort of alleviate the unwanted changes is something else and you know there's there's not much you can do once you've got into the neuroradiology suite and you've seen the changes unless you know the actual molecular mechanism and that's where studies like the kind that rich bridges does get at how do you treat these cases how do you know how to control or gate the plasticity that might be there and that's really the key to it right if you know the brain is flexible we know that there are some chemical properties that change up and down can regulate the amount of plasticity if you can learn to turn it on and turn it on selectively when it's needed for a damaged brain you might be able to lead to very improved outcomes for people that have had a stroke for example that's a huge area of interest right now that if you went on Google the number of hits you get for brain changes following stroke would be you know many thousands okay all the smartest people are left-handed how many people well that's not quite as contentious as explaining the difference between men and women but know that there's a whole host of really interesting correlations with that one things I would point out and that is you know I'm a zoologist by training so when I think about that as a question for human behavior I immediately jump to the fact that there's lots of handedness in the animal kingdom lots of the neural asymmetries we see in humans turn out to be present in lots of other creatures so for example when birds sing they tend to use one side of the brain to control singing not the other what we tend not to see is splits in the population like we do in humans where some subset does it one way and another subset does another in birds it's pretty much all the left side of the brain control singing but no I wouldn't want to venture to explain left handedness in any mystical sense anybody else thanks everybody very much I think we have to stop now but we'll see you again next week thanks everyone you you

Channel: University of Montana

Views: 18,025

Keywords: University of Montana, Missoula, science, research, biological sciences, higher education, alumni, lecture, faculty, UM

Id: Tg5beAvAfy4

Length: 81min 29sec (4889 seconds)

Published: Mon Aug 01 2011