raw_transcripts/lecture_3.txt

And someone up the back just told me.

It's very hard to tell what the volume is here

at the back.

And you hear me fairly well.

Okay.

Thank you.

And just make sure since I once started a lecture

and got 10 minutes through it until someone told me

they were in the maths department, weren't quite sure what

neuroscience to do with that degree.

We are here for brain and behaviour.

Is that correct?

Good start.

Okay.

Oh, I get a little bit slowly over the next

couple of minutes.

Just make sure if there's any other people who are

coming in can come in.

My name is Sam Coleman or Professor Sam Kaufman.

I don't think I've met you yet.

You may have seen me in the video.

I'm not sure.

I'm the head of Department of Experimental Psychology.

I base is a better way along with you go.

I'm the person you'll be seeing most in this course.

That may or not may not be a good thing.

I feel nervous today because this is the first letter

I have given for about three years, so I apologise

if I'm a little bit stumbling.

I'll get back into the swing of it over the

next few weeks, I hope.

Please come in.

So the aim of these two lectures today and on

Friday is to give each of you make sure you're

all up to about the same place and understanding a

little bit about the cellular function of nerve cells and

how their activity helps us to see the here, etc..

Can I just as a matter of starting point, can

I ask who has done some form of biology before

on neuroscience?

Fantastic.

Who has actually specifically done some form of neuroscience before?

A few of you.

So for some of you, this might be a little

bit of old rope.

For the next couple of lectures.

I hope you'll be able to think about some things

that you might not have thought about.

For many of you, this might be the first introduction

to neuroscience that you've had over these last couple of

weeks, and I hope that you'll be able to get

up to speed to where we want you to be,

where we hope you'll be pretty quickly.

Well, that is a really annoying door squeak, isn't it?

Or just let people come in.

She.

I have a feeling this door is going to squeak

for a while, so I'm going to have to kind

of get started and try and talk over the squeak.

I studied molecular biology when I was an undergraduate.

Sometimes I go back and think things have changed a

lot since I started.

That was 25, 30 years ago.

I practised as a neurophysiologist for most of my life.

Sometimes it's a little bit hard for me to step

back and understand what I do know and don't know

what I should know and should not know.

For these reasons, I'm very happy for you to interrupt

and tell me you don't understand what I'm talking about,

right?

Sometimes it's difficult to pitch something that you know intimately

to the right level.

Okay, So please do interrupt.

I hope that what I'm trying to do is trying

in this lectures to try and keep some of the

flavour of what we learn to do over the pandemic

years.

And and I'm going to try and be a bit

more interactive towards the end of this lecture.

Hopefully we'll get through in time and get through to

it.

I want to get I want to make sure you're

all up to speed about the basic concepts.

There's a lot of additional reading you could do to

understand more detail.

There are some fundamental things I think we need to

understand about nerve cells, about brains, to understand how it

is that our cognition is structured, to understand how it

is that we think about things, to understand how it

is that I see you when you see me.

And that's the purpose of these two lectures.

You might have seen this before.

When I started out, as I said, training as a

molecular biologist.

My second year, I finally found a neurone and after

about a year and a half of studying crab cycles

and everything else, which I tell you, I'm not that

interesting.

This structure was something that really fascinated me.

And this is a neurologist as a basic function of

your brain, a very basic functional unit of your brain.

And neurone has several defining characteristics.

What I want to draw your attention to in this

slide are the dendrites, these profusion of little tree like

structures that come off the cell body or soma, the

thermal self, which is where the DNA in the nucleus

is, for example.

And then the axon, which extends from the SOMA, a

very specialised process and heads out towards the terminal boot.

And this neurone has a bipolar kind of structure.

It has inputs at the dendrites and outputs of the

axon or nerve endings and the functions, the activity of

these neurones, the computations that they perform which underlie all

of what we do.

So I'd like to start off with the central question

Why do we actually have brains?

When I try to ask myself this question, I come

up with many different answers.

And this is one I've said all along over the

last few years as limit brains around the body, this

collection of organs, muscles, etc., to respond to its environment

and to allow plastic control of the body so something

we can adapt to changes in the environment or changes

in the body itself.

If you think about the simplest possible nerve cell circuit

that we have in our bodies, for example, the reflex

circuit that allows us to withdraw our hand rapidly from

a hand that is a very simple circuit.

There are two sign ups as to connections between neurones

involved.

There is a sensory neurones that goes from the periphery

or from this case, the hand goes up the spinal

cord.

Little things and you're on there and then there's a

motor neurone that goes from the spinal cord back to

the muscles that control that hand in this case.

That is the simplest possible neural circuit that we have

in our body.

It allows us to react very quickly to something that

happened in the environment.

In this case, touching something hot that might cause damage

to our skin or other parts of our body.

It is functioning very simple and really helpful.

If we wanted then elaborated by, for example, reaching out

and touching something.

And for me, that's what the brain does.

It's a centralised way to try and control these circuits

and others like them that allow us to adaptively react

to our environment and to plan and to do things

that we couldn't simply do with a simple two neurone

circuit.

The neurones in the brain allow centralised and plastic control

of the body, and a simple task in these two

lectures is to try and understand how it is that

those neurones allow that form of control to illustrate the

complexity of the issue.

This is a slide.

This raises some of the brains in relative scales of

the species that might be studied in neuroscience, including the

bottom right there, the human brain, about one and a

half kilos of stuff, about 86 billion nerve cells at

the top left there have highlighted a couple of other

animals that are often studied mouse and rat, both rodents.

A mouse, for example, has a brain about half a

gram in weight, and about 71 million cells do quite

a lot, but a far cry from 86 billion.

And then there are other animals like marmosets and macaques,

both of whom are non-human primates, and have been important

models in understanding human brain function.

Now, our brain is substantially bigger than those of these

studied species, mainly study species, but we shouldn't get too

cocky if we look at the size of the brain

of an African elephant, for example, it's much bigger than

ours.

Now I leave it up to you to decide whether

an elephant is smarter than us or not, but I

simply mean that size itself doesn't really matter.

The complexity and function of these brains is all enough

to allow the species to adapt and survive in their

environments.

Now emphasise that there are 8 billion nerve cells in

the brain.

Neurones.

But that's about equal numbers of other types of cells.

These are loosely cuentas glia.

And I just want to explain to you why we're

not going to be talk about and talking about glia

for almost the entire rest of the course.

They are about half the cells in the brain, and

yet we're not going to be talking about them.

Why is that?

So this photo or this series of photos on the

right here that some guy took several years ago now

obtained by a technique called photon microscopy.

We'll be talking about that a little bit next week

in the methods section.

What I've done here is find some cells in the

brain with a substance that makes them appear black in

the slide.

And those cells are astrocytes, a form of glia, one

of these non nerve cells in the brain.

These images are a series of images taken a very

narrow depth about two micrometres or 2000s of a millimetre

apart.

Down through the brain of actually, in this case, a

living rat.

And you can see these different black things here.

Hopefully you can see my area up there.

These black things here are these astrocytes and they have

these lovely processes that connect neurones.

Many of these white holes, the neurones and the blood

vessels, some of these larger one of the blood vessels

in the brain unstained in this preparation.

And can see these lovely processes connecting all these neurones

and blood vessels together.

So those cells are there.

These are just one form of the known neuronal cells,

but we don't really study them.

Now there are three basic types of cells we'll come

across.

One is the neurones, as I said, will get to

them.

Most of this course, these are what we call excitable

cells.

And hopefully by the end of this lecture you'll understand

what I mean by excitable cells.

Two other very common parts of cells in the brain

of the microglia, which are effectively the immune system of

the brain, very important.

For example, there are many diseases which seem to be

basically a malfunction of the immune system of the brain

of microglia.

And then there's these other cells, astrocytes and other known

example cells, for example, which connect these things together, which

seem to provide the kind of super structure in which

these nerve cells can survive and thrive.

They also do other important things like maintaining what we

call homeostasis.

That is the amount of energy that you need for

neurones to survive or the kinds of chemicals that they

need to survive in the brain.

The neurones are excitable and they can send signals over

long distances.

There is no cells capable of integrating and propagating signals

very, very rapidly.

An action potential which we spent a large amount of

this lecture going takes about one millisecond or one thousandths

of a second to occur.

Those action potentials can travel sometimes up two metres down

the axons neurone sends.

These neurones have distinct zones as illustrated before for input

the dendrites and output the axon terminals.

That directional flow of input output allows them to do

computations to take some summation of the inputs, compute and

send a single output.

Neurones also therefore formed these what were called hierarchal networks.

Computations done at one stage of neural processing are then

sent by the axons in the form of action potentials

to the next stage of neurone processing.

And we build up these successive representations, much like we

do in computer models of the brain where we try

to build.

If you're familiar with kinds of nets that Google uses

to do image recognition, for example, these are successive hierarchical

representations of the image, and they're based actually on brain

function, our understanding of the visual system in particular.

On the other hand, astrocytes are not excitable cells, so

they tend to have slow signals, their signals not formed

in the order of one millisecond, but rather on the

order of 3 to 5 seconds, slowly fluctuate much slower

than we think.

The normal perception of cognitive events or perception, you are

able to type much faster than that.

Astrocytes also connect to each other via various things called

gap junctions.

It's a little holes in the membrane between the way

the membranes with true cells meet.

Allows electrical current to flow through these membranes.

So those astrocytes that you saw in those beautiful pictures

from the rat cortex are actually one large network.

We call this a synthetic network.

And those that network, the activity, that network very slowly

over time and space, again, incommensurate with what we think

cognitive events are like, which are precise, rapid and very

particular events.

So for these reasons, we do not think the glia

are important for the particular structure of cognition that you

have.

They are almost certainly very important for maintaining the neural

signals.

Failure in astrocytes and other forms of glia can lead

to neural malfunction and disordered activity of neurones.

But we don't think that the activity of those cells

that are important for the kind of cognitive events that

we experience.

Instead, we think those are the job of the nerve

cells, those 86 billion nerve cells in your brain, not

the 86 billion other cells.

I, as I've said, carry on.

Euroclear clears word for glue.

You can tell what the unanimous thought of them when

they made up that name.

I thought provide physical support that actually struck to the

brain to remove debris and vacuum cleaners, basically provide immune

function, work out when things go wrong.

They also provide things called myelin while sheath, which we'll

get to in the second, which help nerve cells communicate

to each other.

No particular cell types are called Oligodendrocytes.

And they relative in the peripheral system out there and

the arms are called formed cells also make myelin.

Now, I've mentioned that astrocytes help maintain homeostasis, and I've

shown you in those pictures that the blood vessels and

the neurones are connected by these networks of astrocytes.

And actually those astrocytes are doing two basic functions, at

least one or two, but two that we need to

think about.

One is they actually help communicate energy levels or energy

from the blood vessels, from the blood supply to those

neurones, help those neurones work.

And the second thing they do is actually signal to

the local blood supply whether they need more energy or

not.

So if the local area of neurones is being very

active, the energy supply like a fabulous.

I think it's gone up.

It didn't.

See if you somewhat.

Is this one working?

So these astrocytes help communicate to the blood vessels that

they need more energy.

And when that happens, those blood vessels expand, they dilate,

the blood flow to that area increases, and the energy

to that local area increases supply.

As important for understanding, for example, the bold signal with

the blood oxygen level dependent signal that you see in

the AFM range.

That is a change effectively in the blood flow to

particular parts of the brain that is organised by those

astrocytes in response to local neuronal activity.

And you can show this by, for example, using this

technique, like I said, called to photon microscopy to stimulate

the little processes of those astrocytes surrounding blood vessels.

When you do that, you see the blood vessels increase

in diameter, allowing more blood, more nutrients to get to

local area.

So they help these astrocytes help brains maintain local energy

homeostasis.

The oligodendrocytes that I mentioned.

These helped make the myelin sheets, these little fatty liberty

things that surround the axons.

And we'll get to the importance of that in a

second.

You can see them here.

These myelin sheath, they are interrupted.

They're not the entire acts neurone toppled by little slices

of exposed membrane organised around here.

And you can see that these oligodendrocytes make these little

seeds.

One oligodendrocyte may be making seeds for many different axons.

Similarly, in this one person in the periphery.

Important is low seats are very important, as we'll see

in the second disorders of the root of many of

the disruptive brain diseases that we know.

For example, multiple sclerosis is a demyelination disease, removing the

myelin from the axons.

Why would that be important?

We'll try to find that out in a couple of

slides time.

So I'm taking you through them the basic function of

several of those non neuronal cells.

Just to illustrate to you that they are important.

There's a reason that 6 billion in the brain.

I hope the photo to why we're not going to

study them, why we think that the neurones which can

provide these very rapid hierarchically organised signals are the ones

that are important for the structure of thoughts, perception, cognition.

And that is the last, I would say, almost certainly

of glial cells in the next ten weeks.

So I illustrated you before I sent it to you,

by the way.

Now, I'm going to interrupt these things into a little

section that will become clearer if we go on.

This might be a bit of time for us to

understand whether or not it went to some issues with

talked about so far.

Are there any questions you'd like to resolved in the

meantime off the back of your own?

Sorry.

You have to speak up a little bit is.

Really happens here.

Sorry.

Let me just come up closer.

And is.

It's a very good question.

I'm not going to go into it because there's actually

several things wrong with that slide.

And it does make me want to just make clear

there are some small white lies I'm going to tell

you over the next lecture.

Bear with me.

Including that one.

Okay.

Bear with me.

It's to help us all understand the basic issue of

energy supply, for example, not the particular aspects of the

cycles that they go through.

So I understand the question.

I just don't want to try and make it too

complicated at the moment.

There are a couple of white lines here.

I hope that neither of them make it problem.

Why are they metabolising lactate, not glucose that was there?

I think that was the question.

There's an answer to that, but I think it's beyond

what we need one after this typical lecture.

Okay, I'll just move on to the next week, which

is the neurones are excitable cells.

So why is it important to understand new signal transmission?

Maybe this is like, Well, duh, but I just want

to try and convince you that it's actually an important

thing.

I've stated already that the function of the brain and

the nervous system in general is to receive, transmit and

process signals.

This is what it does.

So to understand how the brain works, we need to

understand how it transmits processes.

Those signals is no point otherwise.

And if further, if we understood how the brain does

this, this would allow us to do things like understand

how little anaesthetics work.

Who here has had a local anaesthetic before?

Anyone.

They wanna know what a local anaesthetic is.

Little you might rap on something.

Injections you've got.

I have to get these things called basal cell carcinoma

for my face every so often.

I grew up in Australia.

It's terrible.

I get so many injections of local anaesthetic in my

face.

Hate me.

Has anyone else had anaesthetic injections?

What are they?

What do they help?

You do not feel pain or anything or anything.

Is that where he said that or anything?

Not feel anything?

Exactly.

Actually, it's a really strange sensation.

And it's like a an absence of anything.

Not actually a presence or some or lack of in

something.

And hopefully we'll understand why they work in a second.

They hope this knowledge would also help us understand how

anti-depressants work, how drugs affect the brain, how diseases like

multiple sclerosis and Alzheimer's disease damage the brain, and why

they cause the symptoms they do, as well as these

aspects of cognition.

I want to make clear to you that I think

that understanding how nerve cells processing was actually at the

core of all of brain and behaviour, all of psychology,

for example, because without that understanding it's very difficult to

know what it is we are trying to explain.

So this is going to be a bit of another

white lie, but just bear with me about this again,

helps us understand, I hope, the kind of signals we'll

be talking about.

So in the old days, by the old days, I

mean probably starting the beginning of last century.

This is how most of neurophysiology, the physiology of nerve

cells was conducted.

A large squid would be captured.

It's giant Exxon, which is huge, much larger than any

of your icons, is excised and put into a bath

of saltwater seawater.

A couple of fine glass electrodes are pooled on some

machine which can pull them.

These electrodes have small tips filled again with another salty

solution.

And we generally take two of those electrodes or at

least one of those bathymetry and something else like a

piece of wire.

We put the wire in the salt bath and put

the electrode into the axon and you can record the

difference in electrical potential between these two things.

And that's what's recorded on something like a little camera.

So this photometry is recording the difference between the inside

and the outside of the cell.

In this case, the axon of that cell.

That whole time, too, was very much like a light

lotus when you attach it to the both ends of

the battery.

Potential difference of process to enter the battery causes current

flow and the like per well.

So we're going to do something similar to that with

electrical device.

This is the only bit of chemistry you need to

know.

From my perspective.

I don't.

Who here knows what an island is?

We all remember back to those dark organic chemistry days,

but some little bit like ions, atoms and molecules that

have lost or gained one or more electrons.

So an iron is positively charged.

What we call the cation is one that's lost an

electron, for example, a sodium atom.

And a sodium has this one little poor electron wandering

around on this outer shell.

If it loses that electron, it becomes positively charged with

electrons themselves and negatively charged it lose.

The electron becomes positively charged, and we denote this item

now as having an A plus plus relative charge.

Similarly, if a atom gained electron would become negatively charged

if the sample chloride gains electron becomes negatively charged.

We do know that with a little minus sign.

The substances we call salts, combinations of these positively and

negatively charged molecules ions.

So, for example, table salt, the stuff that we eat

is a combination of sodium chloride.

When you put into water, those two ions can dissipate

and move around freely.

Coming in sodium, potassium chloride minus.

And the body is basically 80% water.

So you can imagine the pool of ions floating around

in there, including the brain.

Okay.

The next bit of that is, I think, over chemistry.

We're going to have to know.

The next bit is just to try and get you

through some terminology that we're going to use as well.

Way to think about cells.

I sometimes find that we talk about self and then

don't really think about what they are.

So this is a sale, or at least if I

had a blackboard, I would put it that this is

a cell.

What's distinctive about this thing?

Anyone with a.

Tell me.

Or the.

Wants to think about that.

It's a regular.

Thing.

Regular.

They will ignore that for the moment.

What else is there?

It's not so long.

It's got a cell wall or a membrane.

Exactly.

It's got an inside and outside.

It's basically a bag of stuff.

Right.

That membrane or cell wall, whatever you want to call

it, which is a bunch of fats.

Sometimes phospholipid is a little formula bag in which you

stick stuff.

And those phospholipids are really tightly bound and don't allow

things to move across the membrane fairly impermeable to a

lot of the things you think are important.

So this bag means there's an intra or within cell

and extra or outside cell space, three different spaces for

two different things.

And inside the cell is what we're kind of concerned

about.

Although to understand what's happening inside the cell, we have

kind of also understand what's happening outside the shell.

It's that's itself just a bag of spice.

A bag of stuff includes the nucleus, includes, you know,

the DNA and gene stuff and proteins and things like

that.

But in the end, it's a bag, this bag formed

by cell membrane.

The next thing is the science.

A little bit of chemistry are not all in the

same place.

So, for example, throw mines which are described mainly outside

the neurones in the extracellular space.

Potassium, which is tonight confusingly with this K is mainly

inside the cell.

And calcium, which has two parts because it's lost to

electrons, is also mainly outside the cell.

Or the negative ions or anions.

There's two different types we're concerned with generally.

One is chloride, which is kind of an extra electron

that's mainly outside the cell, and the other are proteins

themselves.

That's stuff that makes up our cellular machinery also usually

in charge, and that's mainly inside the cell to do

with the cell.

So if we look at the cells or a few

cells here, we would see that there are some anions

and potassium ions within the cell.

And then there's a bunch of calcium chloride and sodium

floating around outside of.

And so these different locations, special locations that these islands

are really important because basically there's a gradient between the

inside on the outside of the cells for the concentration

of those ions.

More potassium inside, more sodium outside.

Those gradients of concentration set up.

What are cold set up are the basis of the

electrical potentials that we see in nerve cells.

Now, if we go back to how we measure the

activity of nerve cells of the electorate inside and outside

of the cell.

We find that actually, generally speaking, in fact, almost always

these nerve cells are what we call negatively charged.

They have a resting membrane potential that is in the

absence of anything else of about -70 millivolts.

Minus 70,000th of a vote.

They don't seem like much, but it's a lot.

It's enough.

That negative potential.

The difference between the insight into so and so the

space is the basis for all of new single use

signalling.

And this the statement here is this show is polarised

and it doesn't have the same inside and outside.

So if the potential difference gets smaller, i.e. goes towards

zero, so it gets to 60, we say the will

be polarised, less polarisation.

If it gets more polarised, it gets further way from

zero, like the -80 with a hyper polarised, more polarisation.

So this resting membrane potential, which I've argued, which I

will argue is the basis of all our brain function,

is actually the largest single sink of energy in the

body.

Most of the energy that your brain uses in your

brain uses most the energy in your body towards keeping

this resting resting memory potential at about -70 millivolts.

So again, if we put the electrode from outside into

the axon that we were seeing before, you see the

potential go from 0 to 60 miles, 70 millivolts.

The difference between the inside and the outside of the

cell.

As I explained, to try to explain, I encourage you

to read about this.

Way too many books on this many articles.

You can have a thank you in much clearer way

than I'm trying to do it now.

This potential the rest of member States was a result

of the difference in the ionic concentrations.

So for example, sodium is more common outside the sodium

inside itself.

Potassium is more common inside the cells phone outside the

cell.

And the fact that that membrane so membrane, the fact

that this is a cell is largely permeable to a

lot of these ions.

By impermeable I mean that those ions cannot easily cross.

If I could easily cross half the sodium, we're going

to be the inside of the outside the cell.

And if there was no difference between the inside the

outside.

So the concentration of those ions, there would be no

membrane potential.

So the fact that this membrane, this bag is largely

impermeable to ions is what allows the cell to set

up this potential difference between the inside and outside the

resting membrane potential.

And then what you need is little things in those

membranes, little holes, little pores that you can open and

close to allow ions to flex across.

Once you've made this bag, you then have to put

new pinpricks in it and have it be controllable or

something.

And once you got those three things, the ability to

control the flux lines across the membrane and this difference

between the similar concentration and extracellular content of those items,

you can make a cell.

And they can help us so communicate.

There is a little pump movie which has a on

on the middle side, which I like to look at,

which has an interesting take on this.

I encourage you to look out when I say this.

I mean what I was about for it.

So I've already said the potential requires energy and is

actually responsible most of the brain's energy consumption.

And the reason for that is that there is this

one particular set of proteins sitting in the cell membrane

called the sodium potassium pump.

So I described that there's a difference in interstellar concentration

of ions that doesn't just arrive by chance.

These loop pumps sitting in the membrane, exchanging, constantly changing.

330 miles took them out, bringing through potassium mines, putting

in.

Thereby setting up these concentration gradients across the cell membrane.

This little thing.

This little thing uses adenosine triphosphate, which is the body's

major source of energy.

And it's consistently reactive.

It's always growing.

And that's why the rest of my body was sitting

at 1780 volts.

If it fails, you die.

Having this resting membrane potential allows you to then form

action potential.

This slide looks a little bit complicated.

Very straightforward.

So let's go through if you haven't seen this before,

but it is really straightforward.

We've discussed there's a resting membrane potential about -70 millivolts.

And I've discussed that.

That's not very.

Imagine that there is a little input within you on

the cause of that resting membrane potential to deviate a

little bit.

Go towards zero depolarise.

This little.

Sometimes I just love it.

Yeah, because sometimes it is a critical point that mine

is 6365 millivolts.

At which.

What are called voltage gating.

Gated sodium channels are opened.

Now that voltage gated means a particular voltage potential difference.

At which these channels are open.

Otherwise, they closed the when they closed the bags to

the bag with the bag suddenly permeable to throw mines.

Over 30 mines have been sitting outside for sale.

You open this lock.

Suddenly they can go into the cell.

You have a bunch of positively charged demands and flexing

to sell very rapidly.

There are thousands of these channels in the membrane.

Millions of.

All these 30 mines really rapidly rush into the cell,

overwhelming everything else, all that positive charge that comes with

them depolarise it even further.

So you can see here, which is route threshold, a

threshold is open these channels that allows the sodium to

come in and suddenly the cell's potential difference changes dramatically.

It goes back to there and often overshoots because if

too many of these 30 mines come in.

At some point in time, those towns can close again.

Oh, that's not.

Then stuff allows the to return back to resting potential,

in particular the influx of potassium ions.

Also the active action of that 30% pump.

So you have this low threshold offer which is exceeded.

You have this massive in your arms and then a

relaxation back to the basic steady state.

And that is an actual potential.

That's all it is.

Basically, it's transient in Russia, 30 miles.

It's just been get switched on.

Very simple.

But incredibly important because this is what we mean by

this has been excitable.

So if you can and you can make them.

Produce listings.

Does anyone know what the other major example?

Selling bodies.

My muscle cells.

Yeah, muscle cells.

So muscle cells contract because of a very similar flux

of ions based on calcium in this case.

So that movement of muscles, which I've never had, actually

the filaments all work together, driven by this transient change

in the calcium and potential calcium fox.

The brain cells are very much like that, except faster

and different ions.

And different connections.

Clearly they don't move.

I mean, there's a lot of differences between.

By the way, those voltage sodium channels will be blocked

by something called tetrodotoxin or ctcs, often abbreviated because no

one can actually save it for the toxin.

I have to practice for 5 minutes before coming.

You say Dax's neurotoxins about 1000 times more potent than

cyanide.

It blocks those voltage settings.

Of course, if you block this into account for maximum

potential, if you can't perform actual controls, you can't move

your muscles, including your diaphragm.

You can't breathe.

You know.

So that's why Fuku or Pufferfish has been prepared so

carefully, because actually those fish are large source of so.

If you prepare them incorrectly, you'll consume a little bit

of that.

And that's enough to stop your breathing and make it

on.

Blocking the voltage gate to certain terminals is also how

local anaesthetics were very similar.

They stop.

Therefore the sensations from that part of your body.

We have an injection in your arm, for example.

You feel strange absence of sensation as from there, because

the sensory neurones which rely on these certain channels are

not sending the signals anymore.

Now, this what?

Angular?

Slightly different.

So painkillers generally, a lot of painkillers are based on

morphine analogues.

And morphine analogues.

Opioid receptors for morphine, as we've discussed, actually makes it

terrific targets opioid receptors that opioid receptors are really important

to controlling breathing, but they're not actually important in the

regulation of.

As a generation.

Yeah.

Yeah.

What?

Isn't it?

Yeah, well, technology is much more powerful than any local

anaesthetic.

Use The local anaesthetic has been designed to kind of

only work in that slight place.

Referred to a toxin.

Generally speaking, it's consumed and therefore systemically, rather than just

being consumed.

At some point it's very apparent.

Yes, you shouldn't treat like McCain or other local anaesthetics,

like they're being perfectly designed to actually overcome these issues.

They just work in a kind of similar way.

Local versus.

Yeah.

What?

They get cleared out and diluted effectively by the system.

Any other questions?

The.

Just take time.

Okay.

I was going to do this interactive thing, which I

think I've got to wait till next lecture because this

is reminding me how long lectures actually take action potentials

move along that move to the sciences and that little

action potential.

They've been describing all that process, initialisation that takes place

in a place called the Action Hillock.

This is the bit where the action beach itself, on

a blue and a V-shaped thing will be incredibly special

specialised be the membrane.

Recent work by some colleagues in the Netherlands have shown

that the density of the sodium channels is only 37

channels in the axon hill.

It is ten 100 fold greater than anywhere else in

the neurone.

They really important for generating the action potential.

But once the action generated, why is it?

How does it work?

You've got this accent, which is maybe a metre long.

You've got this little bit of membrane potential happening, this

little bit of membrane just where the accent meets the

sun.

For neurones, a signal that explains how to leave the

Soma and get to the end of the axon.

And it does that by a very simple process, which

is basically regeneration.

So if you get an affinity for forming this little

bit of the membrane here.

In the neighbouring little bit of membrane has a little

bit of a deflection.

Depolarisation.

And then that starts the cycle of the action potential

again.

That neighbouring bit of membrane that happens here and and

happens here, it's turning off.

It happens here.

It happens to propagates down the axon.

If you think about it carefully, can imagine it can

happen both ways.

That is actually the case, actually potentially can go from

not only into the action, but also the dendrite.

It's a very deconstructive that's on the table.

That means that that's the way we think the signal

progresses.

Little regenerating action potential.

Somehow manages to depolarise this little bit of membrane and

move along that membrane.

What an amazing thing that we evolved.

Now, if you just left it to his own device

to travel down that piece of membrane, probably through about

a metre a second, some general speed for a potential

move down a bit of an.

And insulated membrane.

That's a bit slow.

One second.

You know something?

Hit me.

Like.

So a lot of the major axons in the body

and some of the direct forms in the brain are

in chief.

Myelin with myelin is basically just like wrapping insulating tape

around the acronym.

Stop the actual potential for really from generating at that

point and instead allows maximum potential from this position to

jump across the next note of review.

And so instead of just slowly moving along, it takes

massive, long strides down the axon.

It can speed up transmission tenfold, at least.

Yeah.

Is it likely that people like the signal won't reach

from one?

Like some of the others.

So that's the danger, right?

The mine was too long.

So the question was, isn't there a danger that the

little depolarisation here doesn't reach the next note?

I think of what you are.

And so clearly that's a danger.

So that bit of myelin can't be too long.

Yeah, there has to be critical distance between the two

nodes above which we just to the actual would not

propagate.

At the moment.

She's really important in speeding up production in Europe.

Okay.

I'm going to have to move along.

So we'll just keep by the way, at the end,

later.

I think we're meant to leave this door and I

will wait out there if you have additional questions for

me so that people can come in once we're doing

now.

This is how I think an action potentially works.

Music, all the dinosaurs.

I think anyone ever tried to do this at home.

Right.

Good old school.

Yes.

Okay.

Now, why am I using this analogy?

I made the point before because it was quite impressive

one.

I like to think of that can pretend to be

an asleep and then it gets to some point and

triggers the ball ball moving towards the pocket.

Right.

By the way, this keeps going.

I think this entire video is actually.

What's that.

Is the ball you're.

Tracking?

Yeah.

We'll get there in a second.

So the ball.

The ball, Yes.

Is a basically neurotransmitter.

The pocket is supposed to be cleft.

Let's see if we can understand those statements.

Pretty impressive.

I mean, I'm glad they caught on video.

You can imagine.

So we'll get to that right now.

So bear that in mind.

That's how I think of neurones.

Okay.

So each of these acts on this axon is a

single axon, but it sprouts.

Multiple contacts with the same and about thousand on average,

I think.

Multiple contacts, multiple output points.

So what's happening in each of those Apple points?

That's the question.

So this is a couple of schematics which try to

illustrate to you what it looks like.

Each of these outputs in this case is what we

would call an access somatic finance assignment between the Exxon

and the Soma.

You can also have accident reading between acts on the

dendrite.

This is actually somatic signups.

So if you look on the left, you have this

line at the end of the tunnel, good on the

axon coming to the cell.

We look in there.

This is what it looks like, the green thing here.

That's the sign at the end of the axon.

And over here, that's the post traffic sign personality.

So after the sign ups.

The sign up is actually this whole thing together, the

presynaptic, postsynaptic.

And in between this thing we call the synaptic cleft.

About 20 nanometres in size.

Really?

Really.

Molecules can actually diffuse across that little cleft.

And quite rapidly less than a millisecond.

So if an accent comes down.

That's right.

I can take what comes down this axon.

It enters this sinus presynaptic space.

When it does that, it actually causes the influx of

calcium ions.

Don't worry too much about that.

The presence of calcium.

Causes these little bags, which we're going to call critical.

Wilbanks Within bags or bags?

Within bags, through bags to move towards a membrane presynaptic

membrane.

So this bag contains a little bunch of neurotransmitters, a

particular chemical.

That bag growth was a membrane binds with the membrane.

Cause a little gap in the membrane to open up

the bags of neurotransmitter.

So the neurotransmitter then crosses into the sign of a

cleft.

What is in the Senate declared didn't go anywhere.

But a lot of it goes to the other side

of the cliff and on the other side of the

Senate to propose an epic membrane of things we call

neurotransmitter receptors.

The proteins within the person.

I pick my brain, which are designed to receive these

neurotransmitter signals.

Yeah, I do.

So not supposed to be able to do drugs.

Good question.

I don't know the answer to that.

Look it up.

I mean, this is not a passive process.

There's an active process here.

I'm not exactly sure how to go about coming from

it.

It's a good question.

If we look at the electron microscope picture, this is

a real Darnold schematic.

On the left is a high as a relatively high

power.

This sort of a sign ups in this case is

connected and really connects to the dendrite and the axon.

You can see all these little bags.

These this is what we call a postsynaptic density.

That's a that's the way you can recognise these sign

with an electron microscope.

And there's these bags that kind of near this.

And we looked at this and even more detail we'd

see here these bags, some of which are binding with

the membrane, allowing the neurotransmitters to enter synaptic cleft.

What happens when a neurotransmitter enters unhappy cleft?

On the other side, you have these neurotransmitter receptors.

Each of these are designed to be sensitive to one

or very small number of molecules.

When that molecule wanders across the crest of bonds, this

protein that spans the postsynaptic membrane.

That protein undergoes what we call inflammation, trying to change

the shape.

When it changes shape, it creates a pour in the

membrane, when it creates that pore in the membrane.

IONS In fact, through the membrane.

So, for example, glutamate, which we call an exaggerated neurotransmitter,

a lot of its receptors which bind glutamate, open up,

allow sodium lines to flex across the membrane for 30

lines, are positively charged.

That polarises the person.

I think so.

Gabba.

Gabba Gabba Gabba is an inhibitory neurotransmitter because its receptors,

generally speaking, open up a loophole that allows corridor lines

to cross the membrane of Florida ions and negatively charged

that are hyper polarised so they inhibit activity.

Deconstruction of these receptors might be sensitive to a particular

type of neurotransmitter and allow particular type of ion to

cross the membrane.

These are called iron or tropic receptors because they directly

flex the lines of the membrane in the neurotransmitter.

There are another class of neurotransmitter receptors which we will

encounter in the next lecture called metabolic Tropic.

They rely on post processes inside the postsynaptic cell that

in turn called the flux lines.

I don't really open pore in the membrane.

I just want to spend 2 minutes playing them.

Why?

These are important.

If you imagine glutamate and GABA, imagine a neurone here

which has three sign ups, two green, one red green

sign ups as we're going to call glutamatergic sinuses.

That is glutamate is released to the presynaptic space causes

the membrane synaptic membrane.

The other sign ups is a inhibitory neurone.

It's a sign.

It uses GABA release from release from prison up in

space.

Causes a cleft or the postsynaptic membrane.

So this neurone has two glutamatergic finances and one refinance.

As I said before, government allows positive ions into the

next year.

So they polarises.

The person I think you're on is that it allows

negative ions.

I almost imagine the sequence of events over several milliseconds

here.

Whereby one of those finances is active, government finances is

active and therefore allows a small excited person, active potential

dps p small depolarisation away from the rest and the

potential towards the threshold for activation of certain channels.

Now that may not be sufficient to reach that threshold,

but if you have the two sign ups as active,

then you might increase that threshold allowing that neurone to

generate an action potential.

On the other hand, for example, inhibitory signups, since everyone

here would continue on to operate away from the resting

potential, or if you activate that inhibitory sign at the

same time as to group protected classes, effectively cancel out

one of those two glutamatergic sign ups, therefore stopping the

neurone from firing.

So these little neurotransmitter receptors in these different sinuses allow

this neurone to compute.

If it crosses the threshold, the signal crossed threshold for

an action potentially only crosses the threshold if the neurones

input in have enough inputs.

And that exactly input outweighs the inhibitory input.

There is a simple algebraic computations.

He says what in your and does?

It sums to hundreds and thousands of inputs that it

gets to ten drives to produce a single number of

the axon hillock which says Am I above or below

the threshold for generating maximum potential?

And then sends that signal number one or zero down

to the axon terminals.

That is the fundamental computation of frame systems is what

allows us to see allows us to think of what

allows us to hear, for example.

And that is the fundamental point I want you to

take away from this lecture.

All little chemical transmitters, etc. allow these neurones to perform

simple functions to some eight inputs.

But those when you cross those functions, make them hierarchical,

as we'll discover in the later lectures.

You can now build into that.

Interesting.

But it all relies on this very simple process.

One last question.

What decides what your interests?

That's a great question and we'll get back to that

in the next lecture, actually.

So the question is, which neurotransmitter has been expressed by

the presynaptic, Kiran, that makes it exciting or inhibitory?

And the answer to that is very complicated and has

to do with evolution and genetics and everything else.

But it will get back to the major point that

one expects.

All right.

Thanks, everyone.

If you can leave by this time.

You.

I now feel less nervous.

It's a great warming up at the believe through here.

I'll wait out there if you have any questions as

well.

Thanks.

Yeah.

I just want to be very aware of the network.

Right outside of the other.

Networks.

Thanks.

So.

Yeah.

I'll be out there and checking out.

What is.

If we had questions, if we just wait outside for

the people to come in and we'll be out there

and giving.

All right.

Those questions.

Do we just wait out?

Oh.

Humphrey with the math right now, I.

We see it in the summer.

But yes, I've.

Yes.

It'd be great to chat with you guys.

I think they're going to try to.

I forgot how long it takes.

I have this whole exercise.

If you can actually help me out.

I didn't like.

Yeah.

You can just follow me outside, then.

That's fine.

No, I'm sorry.

Let me just check to make sure.

Think.

Okay.