James Burke - The Neuron Suite - A James Burke Special 1982

[Music] [Music] this is the Hotel del Coronado one of the most famous hotels in the world and people of all sorts of reasons for money madam for coming here the reason I'm here is to spend a while contemplating this the human brain in the next 60 minutes you are not going to hear all about how the human brain works and that probably comes as a bit of a relief but you are going to meet some experts some of whom are already here and see some things all of which may give you an inkling of what brain researchers are up to these days mostly spending your money and of how fundamental brain research aids physicians who have to treat diseases of the brain and interestingly enough vice versa and there's something over there we could start with [Music] you on track well right you hold on to that be careful with it it's my only spare aha well it couldn't be a better way to demonstrate the limitations of my brain this game that is a very good example of what brains are for the outside world offers some stimulus which is taken in by some of the five senses in this case vision and hearing and the brain processes that information and then it directs what it considers to be an appropriate response well it should be appropriate what this machine is doing is testing the upper limit of my brain's ability to accept and process information but this is just a fun and games equivalent of a deadly serious situation the one you get into when you're overworked overloaded and you simply get things wrong now if this machine just continued to produce the first two noises again and again over and over I would soon learn to process the stimulus correctly and in the absence of any other task it would become an automatic task and I would become very uncomfortable because I would become bored out of my skull now the psycho jargon word for that is habituation that's nothing to do with habituation to drugs just a [ __ ] ooh an incoming stimulus and a bitumen with no new stimulation to react to is a bored brain and one that is not functioning at its best on the other hand you can't do without of iteration because it's a very important part of what learning experience and memory are all about still I think I'll give this game back to a brain more habituated to it than I am you are genius you try it goodbye when people were trying to explain how brain works they usually try to come up with an analogy you know a computer telephone switchboard a city a library and ant colony a factory and so on we happen to think that the setting for this program is hotel itself is as good an analogy as any after all the hotel goes through the same essential routine as I've just described and it has a very brain like hierarchy of information processing its sensory systems tell it how many guests and conventions to expect that lines busy Mirko bear that information is processed by subordinate and hopefully appropriate activity all over the hotel all of which needs an energy supply the bottom of the hierarchy is the routine housekeeping the equivalent of what your brain is doing right now constantly checking on your breathing temperature control and so on without troubling your consciousness with such minor matters and the ultimate response this giant brain makes to its initial stimulus is of course to keep its guests happy from check-in to checkout [Music] in any given situation at any given time of the day or year an organism has an optimal state that it would like to be in an organism like me or an organism like a bill boy whose optimal state is the state of being tipped but to be serious that optimal state includes not too much stimulus not too little not too tired not too hungry not too desperate to find a sexual partner and so on now if something happens to move the organism out of its optimal range it'll do something to bring yourself back in again leave more stimulus good pair strenuous game like this or whine your intellect up the feeder fish need less service relax by the pool thirsty bring your thirst factor back within optimum in the bar feed sexual stimulation well I dare say there are possibilities but let's take that one for granted shall we the point is that the idea of keeping the organism in an optimal state is also true the hotel it likes to have its rooms booked but not overbooked it likes to have its bars and kitchen busy but not too busy and so on I'm just like a brain it's divided into different functioning areas you [Music] the hotel goes through the same learning process as you do remember habituation the hotel is habituated to doing routine jobs like checking in guests that get done automatically without referring to executive management those jobs are done by what the computer people call stored programs but the hotel also learns by coming across the occasional unexpected or bizarre event for which it doesn't have a stored-program watch this good evening my name is Sheikh Abdullah bin Aseema and I would like a room please do you have a reservation no I was just passing well I'm afraid that all we have left is our most expensive room money is no object I'll take the best suite you have three mister just a moment sir and eight more for my wives your wives sir yes my wives they're waiting in the limousine yes one of the thing sir I have made a most fortunate purchase of six camels from a local dealer they will be brought to the hotel tomorrow at 8 a.m. precisely and they will require stabling for five days see to it just one moment mister what was it my name is Sheikh Abdul Ben as seen one moment please now that's not a situation the hotel has to deal with every day and just like in a brain the new stimulus needs to be referred upwards to higher levels of Management who will decide what to do by association it's a pretty safe bet that the word Arab is being used back there in that behind-the-scenes conversation and that's a perfect illustration of the association of ideas camels wives money no object equals Arab by the way one thing is hotel has learned from experience is not too stable people's camels in fact they don't allow pets at all so I suspect I'm about to get the apologetic and brush-off mr. Ben Essene welcome to the hotel I am terribly sorry okay it was all a joke I'm really Jamesburg are mr. hurt we're delighted to have you we have you in the neuron suite hmm they don't seem to respond to humor too well perhaps this hotel is a somewhat primitive brain humor belongs with language up here in the neocortex the most advanced bit of brain the very first time communicating nerve cells got together to make a brain was about half a billion years ago in a fish [Music] the exclusively human bits of your brain are a minor addition to an already complex structure something that's been evolving through more and more complex animals ever since [Music] the cells that act to make-a-monkey jump don't look any different from the ones walking me down this hotel corridor welcome to the neuron suite mr. Burke thank you [Music] enjoy you say mister thank you soon I'm going to explore the brain at cell level with the help of some experts but first I just want to show you that all that stuff about habituation and stored programs isn't just relevant to hotels this is the idea this light is going to put a series of flashes into my eye and these wires are going to record what is ultimately my brains response to that series of flashes now when it starts the brain will say oh what's this and be interested then gradually it'll get more more board it'll habituate because after all what's interesting about a light flash and finally perhaps the response will almost totally drop off let's have a look there's a reaction something new there's still quite interested to see what happens next yes dropping right off the brain is you see habituating they're almost completely to this light flash which is a good thing because a [ __ ] ooh a tional aoz the brain to go off and do more interesting things and look at a light flash however now for something I can do better than electronic games so how is it my fingers which are controlled on a drain if you're doing something this complex while I'm also talking to you not to mention worrying about the camera microphone getting a script right getting the music right and so on the answer is of course that it's a stored-program my consciousness my executive management said get on with music program for one for six while I concentrate on the script matter of fact the detailed finger movements aren't being fed to my brain at all they're referring up the control hierarchy only as far as my spinal cord what is concentrate away from [Music] well all those amazing hierarchical functions are of course carried out by an unbelievably vast network of brain cells like these each cell or neuron is in direct communication with about 1,000 others through its dendrites taking a sort of a democratic vote among these 1,000 on whether to pass the message on to another 1,000 or so information from the outside world comes in chiefly through special dendrites like this one now if it was really to scale it would be more than a half a mile long because it's supposed to represent one that's three feet long in real life when I say brain you see I don't just mean this bit but the direct extension is down my spinal cord and branching out from that the peripheral nervous system that gets literally everywhere it's all the same stuff neurons you're aware though not necessarily consciously of a great deal about what's going on around you the temperature the humidity light level noise level let alone the stimuli you're actually paying attention to the hotel too has to be aware of things like the weather the state of the national economy which affected less directly than the number of people booking rooms for next Tuesday it's tempting to think of that intricate neural embroidery as a sort of super electrical switchboard but although electricity is involved it's not the whole story take a look at this this is the output nerve from a cell somewhere over there it's called an axon now let's say it terminates here on or near the body of this cell now when the parent cell fires and sends an electrical pulse down the axon look here comes that causes this cell to fire and send a pulse down one of its axons like that why don't we do that again because I think it looks rather good here comes the electrical pulse down the axon causing this cell to react and send its own message now if the democratic vote among all these goes against it it won't pass on the message yet it's very similar to electrical switching but look again at what's happening right here in the gap between the two and by the way it's called the synaptic gap see that little spray across the gap it represents a chemical transmitter that in real life is the crucial link between any two neurons in almost all cases there's no direct electrical connection across here at all the brain it turns out is really a chemical machine let me commit murder and show you it's virtually certain the transmitter molecules are stored in little bubbles called vesicles those when the electrical message arrives some of them fixed to this inside surface and let their contents discharge into the synaptic gap and on the other side they find receptors of the right shape by freezing an axon at the exact moment an electric pulse arrives scientists at the National Institute of Neurology have actually caught vesicles in the act of bursting through the surface and releasing transmitters as they open they've also seen the opposite surface the place the messages are addressed to in sufficient detail for the mechanics of what goes on there to be guessed at and that up-to-date information is naturally incorporated into the decoration of my hotel room this wall is as it were a close-up of a cell surface this is the outside down here the inside usually kept at a different voltage from the outside and separating in this area here the cell wall called the cell membrane some of these chunky things floating around in the cell membrane are actually little channels look they can open to allow ions in or out now ions are electrically charged atoms that change the voltage in here and cast their vote as to whether or not the cell should fire what opens a channel the chemical transmitter that crosses a gap there comes a molecule of it you can see how we've scaled it up if this great lump is a molecule it fits exactly into one of these clefts called receptors and that opens the channel well this model can't be absolutely accurate because nobody knows quite how it happens but it seems certain that there are receptors that recognize specific neurotransmitters and open specific channels into the cell it really does seem that cells just like whole organisms have an optimal state they'd like to be in and these receptors act almost like sense organs to get chemical information about the environment that whole process of message exchange is called neural transmission and of all the bits of this hotel it's most like this one yes this is the neuron suite could you please set up a cup of coffee and a plate of mashed potatoes that's right mashed potatoes thank you neurotransmission is an electrical message that causes the discharge of a chemical substance later mashed-potato bomb now this place is of course like one neuron in the brain receiving and sending various kinds of messages and me firing up my electrical message is now causing it to discharge some chemicals to one or 650 locations in this hotel in particular to the neuron suite but real neurons are organized in a much more complex way if there are 10 million of them and each one is in contact with about a thousand others then the total number of possible neural pathways is worse than astronomical now why do you need such a big number because often a decision is very much more complex than it looks those chefs over there for instance are discussing the menu for an eight-course banquet + - why now say they have a choice that five dishes for each course and 20 for each wine such is the power of mathematical fermentation that though they don't realize it they are choosing one at impossible 156 million 250 possible ways of putting that meal together now imagine a backup of 1,000 courses with 10 billion choices for each course and you've got the mathematics of a neural network it's an unimaginably vast canvas for nature to paint animal behavior on and only because of that complexity one simple fact becomes credible the courtship of fish the Tigers strategy she stalks her prey even the highest human artistry is all a matter of the right combination of neurons stimulating each other still more amazing it's now certain that the process more commonly works the other way around from what you might expect instead of turning on this cell the incoming electrical and chemical signal they often turns it off inhibition it's called look here's a cell working here comes a signal down the axon and bam the cell turns off neurons are often arranged in sequence and if you inhibit an inhibition you get an action so an action can be set off by a whole chain of inhibitory neurons imagine the hotel pouring the coffee I've just ordered by a whole series of devices all keyed up to work but inhibited until something dis inhibits the first one watch this dis inhibit [Applause] [Applause] Oh I believe you ordered some coffee and mashed potatoes sir yes thank you very much you know what coffee does to you gets you a bit aroused disinhibited well it may just be but the caffeine molecule attaches to a receptor somewhere around here making it harder to open a channel and so harder to inhibit the cell many natural substances seem to latch on to receptors that are designed for the brain's specific neurotransmitters if I was bitten by that the last thing I got before I died would be a practical lesson in Europe chemistry the molecules of its poison plugged directly into receptors somewhere in my nervous system in contrast to those rare big molecules the electrically charged atoms the ions remember it passed through this channel are some of the commonest things around two of them click up this stuff common salt sodium positively charged usually turns cells on chloride negatively charged usually turns them off sodium plus chloride equals salt the absolutely standard way the brain inhibits its neurons is by allowing chloride ions into the cell and this that opens the channel and let it in represents the most ubiquitous neurotransmitter in the brain it's called gaba gaba was identified in potato tubers a year earlier than it was found in the brain so whoever said today's brains are yesterday's mashed potatoes may have been stating more literal truth than he perhaps realized and the first of our expert hotel guests registering on the hotel computer is the man who first identified GABA as the major inhibitory neurotransmitter dr. Eugene Roberts well as many as thirty to forty percent of all the neurons in the brain and spinal use gaba answer transmitter yeah gaba neurons help sculptor the information right from the time it enters the organism to the time that executive action is taken by the cortex in telling what action is to be taken in responding adaptively to the environment in jean-robert's lab at the City of Hope they're still working to unravel the intricacies of the Galan Network it takes some very ingenious biochemistry cut a thin slice of a rat's brain and you can see it's crude structure but you can't see gather teasing out the neurons that transmit and receive GABA is a matter of soaking the tissue in a whole series of bio chemicals derived from different animal serum after days of patient work the brain slices can be stained and GABA terminals seen under the microscope as black dots a typical cell turns out to have scores of GABA input points at lower magnification there's so much gather around that the black dots merge into a gray brainscape from the oldest to the newest parts of the brain gaba is omnipresent we might compare the role of gaba neurons to that of grammar in language the words themselves don't mean anything unless they're put into the proper structure is the fact that it's found in the old part of the brain of any special significance I think it means that right from the beginning of the development of nervous systems Gavan neurons probably played a very important role what every brain researcher would like to have on his office wall is a complete wiring diagram of the human brain that may never be achieved but jean-robert's is making a start by sketching out the way inhibitory circuits shown here in red modulate and control the main paths of excitation the drive isn't just to understand how brains work but to understand how and why they sometimes fail and it's not surprising at all that complex circuitry sometimes goes wrong even the best hotels once in a while someone orders toast and jam and gets rose town but imagine something far worse causing the whole hotel to go crazy starting say in the bar where for no particular reason the barman starts pouring hundreds of drinks no one has ordered the mania spreads and soon the whole place is needlessly over-performing chefs racing to create banquets that won't be eaten chambermaids making beds that once slept in dusting where there's no dust emptying ashtrays that are already empty and vacuuming everything in sight including each other [Music] Life Guards at what would normally be a quiet poolside aggressively rescuing everyone whether they're running or not well that spasm of inappropriate activity is sort of what happens during an epileptic fit and if you could only see the hotel from the outside you wouldn't know what had gone wrong much less how to cure the problem epilepsy is one of the many diseases almost certainly caused by a malfunction of the chemical messengers in the brain and the supreme payoff of neurological research would be a clear understanding of those diseases looking into a living brain like looking through the roof of the hotel is the impossible dream of all clinical neurologists that is until now thanks to where I am at this moment in the tender loving care of a computed positron turma Graf CPT for short that can be used to look right through a slice of the brain in this case where that band of laser light is on my foreign they've done some amazing things with this machine for instance they feed into the brain through these different stimuli and those stimuli activate different areas of the brain and you can actually look at that activation outside in the control room yeah for instance is a look inside the brain of somebody listening to speech and the red color showing activity is mostly in the left hemisphere as expected where language is processed now music involves the other half of most people's brains and here's a right hemisphere appreciating nice music but they've also done this fascinating scan of an expert musician processing music partly in the right hemisphere like the rest of us but look over on the left the musicians brain is analyzing the music and decoding it as though it were a language so how is this little miracle achieved you may be asking yourself well so did I until just now when I was told by the man who designed this when a brain cell is active it uses energy in the form of glucose so what they do is inject a patient with some radioactive glucose now that's not dangerous at all but the tricky bit is that it's got a very short half-life about 20 minutes and what that means is it's breaking down and spitting out radioactivity so fast that after 20 minutes there's only half of it left in the patient's body so the isotope is rushed here by a pneumatic tube from the cyclotron about 400 yards away and kept behind heavy metal shields until the patient's ready in here radioactivity detectors are set around that ring and a very clever computer adds up their inputs and deduces what's happening in the particular cross-section of brain you're interested in now this multi-million dollar machine was not built of course just for people like me to fool around with TV cameras the idea is that it will be able to diagnose malfunctions in some parts of the brains chemical circuitry now that has already been achieved on an experimental basis take a look for instance at this see this little projection here it's a piece in the center of the brain that helps to coordinate bodily moon it's a different brain and see that nothing going on in that area this brain belongs to someone who has Huntington's chorea that's a genetic disease that invariably shows itself quite late in the victims life and the main symptoms are uncoordinated movement like this it kills people is no known cure and it's almost certainly caused by a breakdown of transmitters or receptors right in that central area with machines like these there's just a chance that they might find out why that happens and an even smaller chance that that in turn might lead to a cure let me go back to epilepsy which is much more obvious on the CPT scan look at this this really is the view through the hotel roof it's a patient actually having an epileptic seizure and they're as clear as can be is the focus of the seizure now if you look at the same brain when it's not having a seizure you can see that the same focal area here instead of being unusually active is unusually inactive because of damage to those brain cells now in the near future they're hoping to do two main things with this Center one make it show 3d images and they're already quite close to achieving that and two to arrange for it to show not just areas of brain activity but places where specific neurotransmitters are attaching to their receptors now supposing you could get radioactive gaba into somebody's brain although that's not likely to be the first neurotransmitter they do that to here but just supposing you could and watch it slosh around doing it's inhibitory thing that would be a major step forward in the understanding of epilepsy why simply because the gaba networks of the brain are understood so imperfectly and drug treatments that act by reinforcing gaba are tantalisingly close it's certain that externally applied gaba can quench neural activity this polygraph shows a cell firing away and the instant effect when gaba is fed to it but that cell was in a culture dish not in a real operating brain the two-dimensional sheets of brain tissue can now be kept alive under a special microscope long enough for pharmacologists to see what effect drugs have on individual living neurons hey how's the activity there's a cell this glass tube is actually five separate tubes drawn down to a tip fine enough to be moved delicately into contact with a single cell enabling microscopic doses of up to five different substances to be tried out beautiful culture this is dr. Herbert Keller's lab at Rutgers University and their special interest is in drugs that relate together either blocking it causing local seizure or enhancing its effect hopefully quenching a seizure like a blanket smothering a fire they're now interested in a recent European discovery the drugs called benzodiazepines fit into natural receptors on the cell surface together and romantically reinforce the effect of gaba in the brain terrific look at that so go beautiful baseline first tiny doses of gaba at regular intervals will reduce a cell's electrical activity in step with the gaba shots add a series of benzodiazepine shots as well and the cell shuts down completely for a second with each shot if the effect of one common class of drug is that direct how many other mysterious little niches are there on a cell surface into which yet undiscovered drugs could fit with desirable results let's just go through some of those logical steps again on the receptor model it may be a bit of a guess but it certainly helps me to understand the new ideas in neurology what the scientists are saying is that there are receptors all over this chloride channel into which molecules fit some precisely because that's what the receptor was designed for some by accident because although their shape isn't precise some part of the molecule just happens to attach and a molecule fitting by accident could have several effects it could copy the action of the molecule that should be fitting here and say over the channel or it could just sit there occupying the site with no result in which case if the natural molecule comes along it can't fit and do what it should that's what's meant by a blocker I said just now that GABA blockers cause seizure here's one schematically it's called by cooling fitted in here and GABA can't open the channel the neuron can't be inhibited and a whole area of the brain goes out of control give a microscopic drop of by Q cool into an animal and the effect is dramatic drugs that act against seizure on the other hand don't necessarily occupy the receptor itself the newly discovered benzodiazepine receptor appears to be somewhere close by and when it's occupied an incoming GABA molecule can still fit and is made somehow more effective the channel opens wider or perhaps stays open for longer dr. Geller's experiments certainly Illustrated that at the level of a group of neurons and if you step back and look at a whole animal the result is equally convincing half the mice in this experiment were given benzodiazepine as well as by cue cooling and the convulsant by ku choline had no effect the same dose of benzodiazepine on its own in a bird's just about everything a mouse or a human would normally be doing there's a puzzle about benzodiazepine receptors but we'll get to that in a minute first take a look at this now my brain is getting information it doesn't normally get about the state of relaxation of my forehead muscles these electrodes are picking up the muscle activity and sending information to that meter with a needle on it and that little box making those funny noises with the red lights now the name of the game if you're going to relax properly is to get the needle to drop off and to get the lights to go out and to get the sound to drop down and seeing and hearing all that helps you to relax even more watch this it's quite extraordinary here we go this biofeedback technique is being used to treat victims of chronic anxiety and it apparently works because it teaches them to relax all over and relieve the anxiety they need are not anxious anymore now this is extremely interesting because benzodiazepines are of course commonly used to treat anxiety so we have a drug and a non drug treatment apparently having the same effect well first this business here can't be magic your new neurons understand only molecules so the suggestion is that in some way this process is mobilizing the natural chemical defenses against anxiety is this business actually making benzodiazepine in my brain well it can't be quite that simple because the benzodiazepine molecule isn't like anything you find in nature and yet it fits the receptor so the puzzle is is there some natural GABA enhancing anxiety reducing molecule in there for which that receptor was originally designed to fit now it doesn't have to be another neurotransmitter it could be a hormone or anything it finds its way into the brain well after what about 40 minutes starting with no knowledge of brain chemistry we have arrived as it were at the very frontier of this particular branch of the subject should we push on into the unknown well we've come this far why not here at the hotel to help us our John Talman and Steven Paul of the National Institute of Health for example we know that with opiates for example that acupuncture analgesia probably functions through this receptor so would not be surprising that techniques to reduce anxiety such as biofeedback or muscle relaxation may not somehow be activating the same systems in brain that will reduce anxiety and maybe that the receptor or this complex the gaba system itself may be involved in this system an endogenous densitizer pain could either act like the benzodiazepines and be what we call an agonist or it could act against benzodiazepines and be what we would call an antagonist and both of those possibilities exist right now and we are in the process of trying to sort out whether those compounds that would act like benzodiazepines exist and whether they are agonists or antagonists I think the important thing to come away with with the benzodiazepine receptor is that it was defined primarily by drug binding techniques and these drugs of course came along very late in evolution and so there must be there just has to be some normally occurring either transmitter or substance that that recognizes this site just as the benzodiazepines do benzodiazepine receptors can be stained and seen under the microscope and a team at Johns Hopkins Medical School has now mapped them throughout vertical cross sections of the brain but whether there really is an endogenous or naturally occurring molecule that fits them is still very controversial as is practically everything about the brain the controversy about benzodiazepine will undoubtedly be resolved one day and in the process the knowledge of what's going on in here will be vastly increased that's typical of the way progress is made each new piece of information about the latticework of the brain is argued over for years before any of it emerges is established fact and if you're beginning to think we're on the verge of breaking out of the forests of ignorance about the brain into some effortless clear vista of understanding the next hotel guest will cure your optimism he's Floyd Blue he knows as much as anyone in the world about brain cell activity and animal behavior and what he knows best of all is that what he knows is next to nothing that it compared to what we have to know we're about in the position this hotel was when they first began to run the telephone lines in from the street there's a primitive line of communication that we can trace but we know that the depths and complexities of what we have to learn our far in excess of what we can see right now so far you've only talked about one neurotransmitter and for many years we've worked in the brain as though there were only one and it would tell us everything about how all nerve cells communicated but as the process of discovery has gone on and on we recognize that there right now are perhaps two dozen molecules worthy of being considered here are transmitters and if we look at the parts of the brain that we don't understand at all there may be several hundred there are many forms of excitation and perhaps many forms of inhibition and the nuances of chemical communication are just starting to be recognized at this time there's a definite sense of excitement among brain scientists as the pace of advancing knowledge picks up excitement about the knowledge for his own sake but even more about the prospect that sick people can be better helped by that knowledge already computers are modeling what receptor surfaces must actually look like and trying out new drug molecules for fit [Music] all this is very different indeed from the way drugs used to be developed by trial and error there's only been one example so far of a successful drug developed because of a knowledge of the underlying neural causes of a disease the disease this gentleman has Johnny you've got Parkinson's disease what is it like to have it well it's a very frustrating disease to have number one because it affects your equilibrium number one and number two you have the fear of falling all the time you'll have a salivation and very lot of frustrating in this disease and what was it like when it first struck you it struck me like a bolt of lightning I just told my head apart I felt nauseated I felt very nervous and a very dry mouth after that I was so weak that I couldn't tell until my work so then I was taken to the hospital where it was diagnosed as a small stroke but three months later I felt this tremor in my left knee and it was a slight tremor and I thought it was just a muscle spasm due to the stroke and then after seeing a neurologist he confirmed that I had parts of the disease one would expect somebody suffering from Parkinson's disease to shake and yet you're not uh it's because of the medication intake that uh you take it at certain prescribed hours and there's certain time during the day when you don't have the term urges as much as when you don't take the medication how often do you have to take the medication or the medication I started off with three think pills a day I know is that part of your symptoms not being able to answer the question yes I think the loser perspective of answering a question that this particular time yes and that is normal can in Parkinson's disease it's because there's a pause that I have to pause and think a little bit yes well I'll ask you it again okay how often do you have to take medication now at this particular time I take it four times a day is it easy to move in all directions I have problems I have problems for example lifting my hand up a tremors were suddenly started yes I see thank you very much quite a lot is known about the underlying neuro chemical causes of Parkinson's disease it's rather interesting and if we're even going to touch lightly on that and other brain diseases we're going to have to get right off the subject of gaba and talk about a couple of different neurotransmitters the main thing that gives people Parkinson's disease is a deficiency in certain central areas of the brain of this stuff it's a neurotransmitter called dopamine and it's very unlike gaba but what is it like well Floyd blooms the man to answer that but I doubt if the answer is going to be straightforward whereas you you've understood the gaba is consistently inhibitory the kinds of information that dopamine may pass on is somewhat more complicated for example we've been working on it for over a decade and some people are really not sure whether it excites or it inhibits as a general rule we tend to be on the inhibitory side but the kind of work that we do may be asking the question in the wrong way the dose of dopamine that we have to give to a cell in order to elicit a consistent effect may be so overwhelming the cell the little droplet that we put down that it may not tell us really what dopamine is doing in the actual conditions of the animal using dopamine to transmit certain processes of information for example the two kinds of things that have been on a behavioral sense attributed to the dopamine system in the brain are not simple commands like inhibition but more emotional or interactive kinds of systems you remember Johnny had difficulty in using his arms to reach for an object and the idea of moving in a coordinated way is a dopamine related function in the absence of dopamine johnny is unable to do it properly it doesn't mean that Johnny uses dopamine to move but to coordinate the systems involved in making the movement another big issue that's been related to the dopamine system is what we like to call pleasure or reward and you've seen the experimental paradigm where wires are inserted in the animal's head the animal will go absolutely zonkers trying to lever press to deliver electrical stimuli to make dopamine systems work in his brain now one might say well the animal is receiving pleasure and that's why he makes a system go over and over again that's the simplest explanation that's consistent with the data here's the image we've all heard about a white rat with electrodes wired into the base of his brain every time he leans on the metal surface in front of him he gets a little electric tickle and whatever the precise effect of that is he's clearly having a good time the reason everybody thinks of dopamine as the pleasure juice is that when it's cut off say by injection of a dopamine blocker the experiment stops working the dose trapped just doesn't seem to be interested in pleasure anymore but if you think that's conclusive evidence that just goes to show you wouldn't make a good neuroscientist elaborate pressors completely cocked out the nose module doesn't appear in Edinburgh in the blue lab at the Salk Institute what totally convinced by the classic explanation of that experiment how difficult was it to get the guys to sniff in the first place there wasn't really a problem at all in fact we had samam alipin burg realized that the part of the brain with the pleasure centers is also involved in initiating behavior perhaps it's just physically more difficult to press a bar if your dopamine is blocked so Edinburgh devised a different system this rats getting turned on without having to press anything he merely has to poke his nose through a hole interrupting a magic eye to get stimulation and in this situation blocking dopamine has absolutely no effect so dopamine's linked with ecstasy is weakened and it's crucial importance to the symptoms of Parkinson's disease is strengthened so why is Johnny still suffering from Parkinson's disease surely a pill or an injection of dopamine bingo cured well what thoughts that excellent idea is a simple physical fact that there's a barrier isolating a brain from the general bloodstream brain is rather choosy about what molecules it allows in and dopamine is not a member of the exclusive club physicians can't partly get round that problem in an ingenious way they send in this stuff l-dopa it does pass the blood-brain barrier and the natural chemical machinery of the brain obediently takes it over and turned it into dopamine it works with a few reservations there's now a theory that very simplified suggests dopamine is involved in schizophrenia but it's the other way around in this case too much dopamine or too many receptors for it and although it's hard to imagine Johnnie's disease having anything in common with schizophrenia the two may be at opposite ends of the same neuro chemical spectrum there are two bits of evidence for the schizophrenia dopamine link one the classic drug for treating schizophrenia chlorpromazine is a dopamine blocker to excess of dopamine receptors have been found in post mortem brains of schizophrenics though that result is now being questioned it seems that the extra dopamine receptors may have been just a response to drugs as the original owners of the brains had been given but further examination is confirming settler chemical abnormalities in schizophrenic brains and certainly few neuroscientists would now be willing to make the traditional distinction between mental and physical illness if you took our hotel to pieces you'd find nothing it wasn't physical so it looks more and more as if it all comes down to biochemistry in the end oddly enough besides the metaphorical link between the hotel and this there's also a direct link between one of the greatest challenges in neuroscience and this captivating California seascape and it's something that will take us away from the fascinating business of what neurotransmitters do to keep you healthy and into an area of profound importance to you and me even if we never get sick again you see in this part of the Pacific you find these things giant sea snails sometimes affectionately known as sea hares now they're quiet old things that they wouldn't win any beauty contests but they do have a particular attraction for certain urologists because they have an extremely simplified nervous system and what there is of it is nice and big so that you can take it to bits and see how it works pretty well all the major discoveries on the biological side of neuroscience were first made on simple marine animals like these then extended to mammals and then finally to man and in some cases that's a very long step but what these little things are now teaching us a bit about is the biggest mystery of all in brain function what memory is [Music] memory is something so complex that the only way of approaching it at all is to study its simplest form sea snails real name Aplysia have a memory of a kind they habituate like I did to the flashing light remember because nobody's ever persuaded a sea snail to sit still and watch a light flash the animal has to be placed in a special water tank with its Gill coverings held aside normally a tiny electric stimulus causes the gill to retract but after about 10 identical stimuli the animal stops withdrawing its Gill and that memory lasts several hours a Columbia University team has studied that simple fact so closely that they've been able to draw this incredible wiring diagram of the connections between the sensory neurons of the Aplysia snail and the motor neurons that actually move its Gill connections that seem to get weaker as the animal acquires memory leader of that team is dr. Eric Kandel our last hotel guest so one of the interesting things that we learned about the modification of behavior by experience is that developmental and genetic processes determine the precision of connections and the properties of the neurons that wine diagram is invariant in every member of the species that we've examined with a genetic of the program the developmental processes do not program for is the exact strength of certain connections in this particular case the connections between the sensory neurons and the motor neurons and it is this aspect of the wine diagram the strength of certain specific connections that learning acts upon here is one of those connections under the electron microscope clearly showing round vesicles transmitting chemicals into a synaptic gap but Craig Bailey who took these photographs assigned a more efficient type of synapse where one surface wraps around the other making more surface area for vesicles to attach to Bayley has sketched this in three dimensions and he thinks the two types of synapse may be the strong and weak connections candles talking about in other words a change from one type of synapse to the other may be the actual mechanism of memory it's a very attractive idea that Craig Bailey is interested in testing one likes to think that the difference between short-term memory and long-term memory is likely to involve some kind of a structural change even if that does turn out to be true can the habituation of a sea snail really have anything to do with the sophistication of human memory it throughout biology one finds that the same kinds of mechanisms are retained by evolutionary processes the mechanism of the action potential is the same the pleasure is in humans the mechanisms of synaptic transmission are almost identical in simple forms and complex forms the structure of the neurons are remarkably similar and therefore I feel that it is very likely that the kinds of processes that were in fines for bitching and sensitization in simple forms are likely to be found in mammals including human types of learning and the reason it is important to try to understand the control of transmitter release and molecular terms is that that is one very important handle for trying to develop a rational way of modifying the learning process pharmacologically it would be nice in the long run if various memory defects could be treated in a really rational pharmacological way [Music] James Burke Johanna I asked mr. Burke the neuron suite did you enjoy your stay yes it is very interesting well I hope that this all-too-brief visit has served to remind you of what an extraordinary structure the human brain is of how incredibly complex and rewarding the research just to find out the simplest things about how it works and the most exciting thing of all that each one of us has one pact with the potential to change your life if only its full powers could be harnessed I believe that within our lifetime some of those powers will be harnessed to aid memory - perhaps cure old age - abolish a need for sleep but that those gifts of science will bring with them enormous responsibilities that we all have to share to ensure that they are used for the purpose for which they were intended the purpose behind all science to use this more wisely mr. Burke I believe you were talking about optimal States oh yeah you're learning [Music] [Music] [Music] [Music] [Music] [Music]

Channel: Benny The Bouncer

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Id: FjxMWQ2dImQ

Length: 58min 2sec (3482 seconds)

Published: Fri Dec 09 2016