It's not an easy world out there.

Looks nice there on the campus today, but it's a

difficult world to survive in.

And we have evolution from it.

So what is going on in mammals, your brain right

now and other mammals and other species?

What we going to focus on will focus on the

core part of today's lecture.

There's textbook reading.

If you go to the reading material from Carlson and

Briquettes for Book on Behaviour, there's some other cool references

to read through.

Not too many, just a few examples to read through

after this.

But the cool thing I want you to take away,

there are two systems in your body for dealing with

stress.

The stress is when your body is under pressure and

you have to maintain homeostasis.

You have to maintain your body, your integrity.

Get on with things.

Doing that is not easy to make us make that

happen.

We have two systems in our body, in mammals, a

sympathetic adreno system called Sun for sure, and the hypothalamic

pituitary adrenal cortical system, the HP system or the HP

axis is a company.

So first of all, let's look at this sound system,

this sympathetic adrenal medullary system.

So here's an example of a lion attacking this would,

for a human, be a very stressful event if it

happens to you, where you happen to be in a

situation where a live lion is attacking you and those

stressful things.

And this is coined by a psychologist and somebody with

the idea of flight or flight.

And in this case, it's flying away from the lion.

You might fight that lion.

Very bad decision for most humans, or you might fly

away.

But either way, you need to respond.

You're kind of sitting relaxed, right, and making notes here.

And your body's set to do that.

But it's not going to be well set to run

away or fight a lion.

It needs to change.

You need more oxygen, more blood flow, a lot of

things in your body ready to make you do that.

Same for rabbits and for any animal trying to escape

What happens in the first.

The second lecture I gave a neuroanatomy.

I put up this slide that says, Here's these two

systems from a autonomic nervous system.

I said, I'll come back to it around today, this

lecture after reading week.

So what we have here on the left is a

sympathetic adrenal system that is critical for your response to

threat like a lion.

So what happens is that in your spinal cord or

a number of you can see on the left hand

side a sequence of neurones that are ready to be

activated to project out to a whole lot of bits

of your body, different organs, right the way out from

your eye down to your bottom, right at the bottom

of your body.

So these all these things in these parallel red fibres

coming out and rise, obviously they're marked and right here

they're not really right in your body, but they go

and do things like increase your heart rate, the heart

rate goes up.

You've got more oxygen in your blood to run faster

away from that line.

It's one of the critical things your your stomach is

going to switch into No longer digesting food.

Your bladder may get rid of any urine.

If you're carrying a lot of weight, you know, you

might pay out a fright and run.

There's a lot of things you can see that are

going on that are regulating your body to make your

pupils dilate, ready to to to react.

And again, sorry, the lighting system I can't control as

high as read these off, but hopefully you can see

that the core idea is on the left is the

system Upregulates Now now, if you kept having this going

on, your heart rates going higher and higher and your

your body's getting ready for threat, you would die.

You overstimulating your body beyond the amount of food you

can take in.

It's not going to digest anything.

It's just going to go into the stress state of

a reaction to a line.

Now, on the right hand side of that diagram, we

have the parasympathetic system which runs on a molecule called

a seat coordinates.

These two systems have their own specific molecules, adrenalin and

noradrenaline as written on the bottom.

There will come into that and there is a seat.

Alkaline is the other molecule on the right.

Now on the right hand side we have the system

allows you to calm down, come down from the heightened

state of threat, analyse your digestion to pick up, lowers

your heart rate, gets your body to digest things as

part of the rest and digest system.

So we've got this circuitry there and you can see

that on the left side, you've got the sympathetic system

coming out of the spinal cord and on the right,

right on the bottom of the spinal cord.

There are some key parts of the sympathetic system, but

a lot of these pathways come out right at the

top of the brain, right at the top of this

of the spinal cord section to regulate the heart.

And some of these are nerves from the cranial nerves

covered light to the heart to regulate the heart, heart

at the top there.

So this is what I'm talking about.

You can see my mind, maybe not up here.

These pathways to the eye and the heart and the

lungs and so on.

Okay.

And there's a little icon to highlight.

This is where we're going to spend a bit of

today's lecture looking at this particular organ in your body

you'd never really think about, here is a kidney.

So you need to, you know, organise your fluid or

the fluids in your body.

If you're a medic, you'll be learning a lot about

the kidney and you're doing brain and behaviour.

So we're not very interested in the kidney today.

What we are interested in is the adrenal glands.

Your body has all sorts of glands hidden behind it

and one of them is critical for running away from

that line is your adrenal gland.

And this, this adreno, the sympathetic adrenal medullary system is

the medullary part refers to the medulla, the middle part

of this adrenal gland.

And this is where adrenaline is when you you may,

as some of you ever come across EpiPens or this

worry about people eating peanuts and dying from it is

because they, you know, they take an EpiPen with them

filled with adrenaline because it will react.

It will allow their body to increase their heart rate.

The lungs will expand rapidly, bypass this circuit.

But if your body's acting normally, it's not part this

little structure here above your kidneys, the adrenal glands, and

does this beautiful job of secreting adrenaline around your body.

Written here is the nephron because that's what the US

system United States, they usually get epinephrine.

They like their own words for different things at times.

Okay on the left.

So that's all that.

That's all the bits of the body drawn.

If you look at this, these two major divisions within

the autonomic nervous system on the left, we have that

sympathetic system for regulating a fight or take flight system

which causes all these different things that including some unhelpful

things like nausea.

If you attack by line, you may feel a bit

sick, but it allows your eyes to expand and get

live raises.

Your heart rate raises your blood pressure.

Everything's ready for running or attacking.

On the right hand side, this parasympathetic system allows you

to eat things, steadies your hands.

Just, you know it.

It's all sorts of different parts of this.

You can see here, lowering heart rate and blood pressure

is also known the rest and digest state.

So this is two key systems for this.

Some this is the sympathetic or the sympathetic adrenal system.

Let's take a real world example to contextualise this.

Just something that came on Twitter.

This is this particular person.

I haven't put their their name and details up here,

but they provided this on Twitter some time ago, several

years ago.

This just describing using a Fitbit.

So monitoring the heart rate and reading text messages.

And that day that girlfriend broke up with them at

exactly noon in their timeline.

And you can see here this person's resting heart rate

just tracking along New noon occurs and up goes the

heart rate and it's sustained.

Go right.

And so midnight after they got this message of a

girlfriend of broken up with them, it's just one real

world example of what happens to your heart rate under

stress.

This is clearly this person describing a very stressful, horrible

experience and breaking up and seeing it live and seeing

that the heart rate has gone up and it hasn't

he hasn't gone back to rest and digest.

Yeah, even at midnight.

This is a carrying on the process.

So we've covered that same system.

We're now going to turn to this HD access system.

The other one, the two systems, because you just saw

in this example, the upregulated heart rate set to react.

Now a line is an immediate threat.

Breaking up with your partner, like maybe you've be with

your girlfriend for two years and you break up.

It's really severe.

And as your brain is going to think about all

the implications of Break-Up and what this means for me,

what are my what am I going to do with

my social life?

Lots of things go on.

That heart rate is going to be raised, raised for

some time, this extra stresses.

But it doesn't just have a rapid response, it has

it organised.

Longer term response allows you to adapt to challenging situations.

So what we've shown here is the human brain.

Here's the nose of the challenge we discussed and we're

looking at the corpus callosum, for example, not coloured in

just so you can identify them are number of little

nuclei here in the middle of the brain.

Now in a rat or of old or something, these

are really big because they're really important words for humans

have a huge amount of cortex.

We've added all round that these, these key subcortical structures.

And again in my, my second lecture in your anatomy

talks about cortex cortical structures and sub cortex.

Today we're looking at to keep it of that.

There's a whole load of this here.

There's a familiar body will come in a couple of

weeks time to someone who had a snooker cue smashed

into their face skewering and damaging their military bodies.

And I explain what happened to that patient.

But it bypassed that type of thalamus, went under here,

and it didn't have the problems I'm going to talk

about today.

So they didn't have any stress responses.

So here it's hard to build different nuclei in the

real brain.

They're not coloured.

This is just coloured to highlight them.

And these are the hypothalamic nuclei hypothalamic.

The word hypo just means lower.

So here's the thalamus above you that does all the

processing you need for connecting the cortex together.

But underneath is the hypothalamus and has these different nuclei.

All the top underneath them is another gland, the pituitary

gland.

So this is a bit this is very strange.

Your brain is structured inside your skull, encased in the

skull to protect your brain.

Very important organ in your body sticking just out of

the skull.

And this little stalk is the pituitary gland, and it's

a little gland that goes into your blood system.

And it allows cells to send chemicals straight out of

your brain into your blood circulation outside your skull.

So it's it just sits there inside.

You can see it encased in bone here, but the

blood circulates through it.

So let's dig into this in a bit more schematic,

sort of what are they doing?

So here is the hypothalamic pituitary adrenal axis and stress

system.

So here's the brain we just saw in the last

slide is zoom in.

This little tiny nuclei in here.

We're just going to call these the hypothalamus now.

And the key thing they do here is to release

time into pituitary gland.

There are cells there that produce a chemical called cortical

growth in releasing hormone.

So these cells are releasing a hormone, not a neurotransmitter,

but a hormone into the anterior pituitary gland.

In the anterior anterior pituitary gland, there are a number

of cells that release their the adrenal cortical trophic hormone.

So you've got CRH and 88 C THC.

These two different hormones, the cascade of hormones.

And those hormones go on to land on your adrenal

gland just above your kidney.

So this is like on here is I so seems

a bit like a lot of, a lot of different

steps.

Why not just do one step?

But we'll see.

We'll see why that might be the the adrenal cortex

a bit right on the edge.

So we had that reaction.

That same system is the bit in the middle of

it, but on the edges, the edge of it, the

sort of the outer layer, the adrenal cortex is where

a number of hormones are released.

And if there are, there are glucocorticoids, mineralocorticoid and sex,

steroids, there's a whole lot of that gland is producing

a lot of hormones for your body.

You don't want to damage that gland.

That's very important to you.

The key one, you may have heard all this you

haven't heard anything about stress is corticosteroids is a particular

hormone that goes and then regulates here.

This is called different organs like your heart, your lungs,

your digestive system, all being updated by this hormone.

So these are circulating.

So three steps.

These these kind of ACLs like cortisol as corticosteroid erodes

the cortisol.

So the reason what is always a chemical that you

can use like a salivary test, so you can look

at policemen and say, oh, did they go out and

have to do some particularly difficult experience?

Recently you might take a Swoboda saliva and find you.

Half of them have read high cortisol rates.

It's used very classically in stress studies.

Now this cortical cortisol is it circulates around your body,

has all these effects to regulate your body for better

or.

This distress, but it also goes back into the pituitary

gland that goes back into the hypothalamus.

And you can see these going down or plus positive

driving up signals.

Red pluses have got some blue minus signals here.

These this circulating cortisol goes to actually reduce the responses

in these two.

This is the brain.

This circulates back.

So it's like it's a system that as you produce

more of it acts.

But as you get too much of it, it dampens

it down, but it does more than just short circuit.

So what we've looked at in this previous slide, if

I go back, we've looked at this cascade from the

hypothalamus time.

There are a few more brain areas involved because your

brain is not just your hypothalamus has all these other

amazing that state.

So here's the human brain we're going to you've had

a lecture from Sam Sullivan on the amygdala.

You're going to hear a lot about memory.

And at the campus of the campus will talk about

today in relation to stress is the pituitary gland that

is the hypothalamus.

So here we're going to slice through a kernel section,

through the brain.

Here's a kernel section looking right in the middle of

the brain, and here's the cortex in the side.

Right in the middle is a particular nucleus called the

power.

The let's look at this very carefully, the power of

an ocular nucleus of the hypothalamus, a tiny little bit

of a massive in a rodent, the tiny in your

brain, because you've got a lot of extra bits to

do.

It's the key that is the brain that releases this

molecule that then cascades because the pituitary release, this act,

and then you get this adrenal cortical and cortical means

that they go and feed back into the system that

exist.

But cortisol also acts on the hippocampus and on the

hypothalamus itself.

There's also this higher level process in the hippocampus.

So inhibits these three structures.

Very nice.

Just highlighting this is a negative response is also it's

turning off the activity of these cells in these various

regions in the hippocampus.

So what happens, though?

Okay, so that's your stress response.

And if you go through some stress, period and it

lasts like that break up, we saw in that person

an elevated heart rate, eventually the cortisol to bring that

down.

But if you keep going through ongoing stress on and

on, so say you're put into a war zone and

you're in extended war zone.

The Vietnam War went on and on and on and

people did not know when they were coming home from

that war.

They were drafted into it.

So that is an example of a long term for

stress.

Six exposure experience.

What's been what's been studied is that the people who

experience that prolonged stress will end up with a shrunken

hippocampus.

So this is a coronial, sectional coronial section through the

brain.

Here's the hippocampus showing healthy hippocampus here and a smaller

hippocampal.

It's quite hard to see, but you wouldn't want your

hippocampus to be shrunken like in this diagram.

It's not a good effect.

So ends up with this bad effect on the brain.

But if we dive in and look at in more

detail, so we're looking at beyond just humans and brain

imaging, but we can't get that close.

What we can do is study things like primates where

we can look at a situation where some primates are

housed in a slightly stressful situation and end up with

ulcers in their stomach.

These are the ones that they know they were stressed.

They can look at their physiology to check things like

that.

He's not a very pleasant experiment to read about, but

it has highlighted exactly what happens at a cellular level

in primates brains like ours.

And you can see that a control panel here who's

not stressed as nicely organised cells in the campus, and

it's all nicely disrupted in the hippocampus of a stressed

animal.

So that's a problem.

This is not something you want to have.

Your brain reacts to too much stress.

Prolonged difficulties can cause problems in your brain.

Now, this is quite a detailed slide.

This is going back to scanning humans.

We're looking at animals in the last one, but this

is an example of the hippocampus and Gulf War related

post-traumatic stress disorder.

Patients at the end of this course, near the end,

the second to last lecture going go back to post-traumatic

stress disorder, the fascinating condition where treatments have advanced a

lot in the last decade in terms of treatment.

Back when this study was done in 2005, they weren't

so advanced.

What is this showing is that people who experience PTSD

had smaller hippocampi, this they had of it.

People who not healthy controls or even people who has

who had been sent into the war zone are not

experienced this disorder.

So that these PTSD is kind of like flashbacks.

They're afraid generally they panic very easily.

They can't sleep at night.

They get these Night-Time dreams.

And in those cases, you get this reduction in the

hippocampus, and I'll come back to that.

That's an example in humans.

Another experiment was done was to actually administer cortisol.

And so to see if this.

So what we're looking at here is the hippocampus being

disrupted the size this for experiment done some time ago

in 1996 and some time back but it's published in

the journal Science because quite a breakthrough experiment in terms

of understanding what may be going on is that that

stress is a knock on effect.

It shows that over prolonged stress, this cortisol, this is

here the cortical response in on the right hand side.

So a very low response to stress or a high

response to to the cortisol is leads to less memory.

So almost leading down into amnesia and not quite the

person is really stressed, suffered, prolonged stress, you can you

can look flying placebo or so what they did was

they injected either just saline and just the salt water

or this this same saline mixed with the cortisol was

increasing people's response in physiologically inducing stress by injecting the

hormone directly.

And if you if you've had this prolonged stress, your

response is very poor.

A big response to that is people's memory is disrupted.

And we'll come on to the link between the hippocampus

and memory and a follow on nature.

So one way that's been studied and I'll delve into

memory in more detail is instead of taking warzone veterans

and that's hard to study under control, what they'll do

is take mice or rats and put them in.

This is a rat here in a home cage and

introduce a cat.

I picked a ginger cat in this diagram, but it

could be any time cat and the cat is placed

in the environ for 75 minutes.

And that's a very stressful experience for for a rodent

because they are very evolved to smell like there are

smell receptors in the tax cuts as is a threat.

And so it will stress them out.

They'll just high they won't be harmed.

They're just introduced to this potential threat for a period.

And what they can see is that the the what

we're looking at here is this this is a measure

of how close the come back to this top side

of the bottom.

One is, is the easiest one to understand.

So this is this is.

This is a hoax and nothing's happened to the rat.

This is a rat who has been placed in the

specific cage, but nothing happens.

Very boring.

And this is the plot for a cat that has

been sorry.

That rat has been exposed to the cat.

And this is a task where rats have to scurry

through a maze to find bits of food at the

end of different alleyways.

And if they remember very well, though, avoid going back

down alleyways.

The food is not very good at memory.

They'll keep going back down the same alleyway and it's

forgotten they've eaten the food there.

And this is that normal rat.

Fantastic.

Rats are very good at this.

But the rat has just been exposed to the cat.

Keeps to getting ready to go.

That stress, putting it just 75 minutes with the cat

has induced this the stress response in that in that

rat and it's having a harder time remembering where the

food is in a maze and different school the radio

maze as these little alleyways radiating out from the centre

of it.

So this middle one will come back to is a

measure of synaptic plasticity.

Like you two, you learned about neurones in the sign

ups in the way they can form and communicate with

each other.

In brief, in synaptic plasticity they sign up to this

can change and you can measure using different methods, increases

or decreases in the way in which sign in sign

ups.

This can cause cells to communicate with one another to

send action potentials.

And what's shown here is that if you take this

approach that the rats that had no interaction with the

so very nice, typical robust responses to this procedure of

stimulating its brain to check the synaptic plasticity, this was

being written about in this in this here this this

change to stimulating his brain.

If it's been put in the chamber, we either have

that same response very good plasticity.

But if it's had the cat, there is always nothing.

There's no almost no synaptic plasticity.

This rat is still in a highly stressed state and

is unable to really acquire that new information.

It's not able to update.

So if you combine these two things together, it suggests

that we need we need to this over prolonged stress

can disrupt memory and it disrupts the natural plasticity in

the hippocampus.

So we we can link this these two things together,

these lost memories due to stress.

So here in this diagram, this comes from a review

by Kim and Diamond.

They are talking about low level stress, up to high

levels of stress.

And you can have activation of new neurochemical systems.

This is our assignment for you, which HPI access systems.

And I have some effect on learning a memory.

But as that stress goes higher, it damages the synaptic

plasticity, it causes changes in the structure of the cells,

and eventually here necrosis and cell death and disruptions and

growing of cells in your brain.

And we'll see the hippocampus grows, new cells, all of

that gets highly disrupted.

So you have this sort of how much stress you

got causes brain cells to die and you have the

campus and so on.

So all of these have an impact on learning and

memory in the short term or the long term.

So stress is good for being able to respond to

threat critical.

You need it.

You know, you need to get a focus on an

exam.

And that stress response needs you to be alert and

not sit and just back and digest, but too much

of it, and you'll end up causing problems.

So how do we how do we know about more

of these problems and the social impact?

We're going to dive now into what happens in the

impacts of early life so that the Fitbit example I

gave from that person earlier, he broke up with his

girlfriend at noon, got a text message, heart rate went

up all day, and so the night is really bad.

But that's a one shot late in life.

What happens to stress?

This example looking at Harlow.

It was the key.

Scientists looking at a social bonding will come on to

that on Friday was exploring what happens if you give

adversity early in life.

There's a sort of sense in which we're all born

equal.

We can get on with it.

It's fine.

Well, he was able to do was to study macaque

monkeys.

And look what happened.

This is a photograph is this is back in the

1950s.

This is Harry Harlow.

And he explored the idea that maybe innately our bodies

built to seek out warmth and protection, not just food.

And he did a critical experiment.

We would raise these these small baby monkeys, these really,

really sad to read experiments.

And of course, they haven't been carried out since those

days.

So people don't do these experiments now.

You've established a scientific discovery around early life stress, and

now we can do lots more with it.

Back in the fifties, he was able to highlight the

value of early life intervention for avoiding detrimental impacts.

So these monkeys were given the option of food.

They could they could hang on to a wife or

a mother and an artificial mother for these monkeys that

would give them food, or one that just gave them

no food, nothing at all.

But it was just soft and furry.

And what they found was that the little monkeys, baby

monkeys would go and get the food when they needed

it, but cling on to the fur of the artificial

mother.

And we show that these cloth mothers would be in-built

into their DNA, driven from a very early stage of

their birth to focus on not to seek out that

wolves.

And so that's really important for the development.

He then went on to, sadly, show that they're not

even given this.

These poor little monkeys, unfortunately, end up being what he

described as depressed.

But really, they show very little interaction with other other

other eyes, all monkeys, and they're disturbed through the whole

life.

So you can take away those early supports very early

on and then get them later and it's too late.

They never quite adapt to the social hierarchy and later

lives.

So something's happening early in the early phases.

Development when the primate is born through to growing up

to becoming an adult.

It has profound impacts on social interactions and stress coping.

They won't couch that well with stress.

So this is just a highlight of his that the

care that a mother brings to the children, the offspring

regulates those glucose, those those that the steam that cortisol

is this glucocorticoid.

So this lecture goes on.

There's a number of clues here.

Glucocorticoids as part of the HPI axis.

The core one is corticosteroid is so is cortisol.

Corticosteroid rots, the cortisol is released and it binds to

receptors, has all these effects, raises your heart, does all

the things we need to do, but you can regulate

as paper key paper from this team so that the

maternal care that's given during development affects this is in

rats of a rat.

In rats, they can monitor mother rats.

If you give a lot of care and attention to

their pups, it would change the physiology of their bodies,

increase the capacity for these receptors and the response to

stress.

So the access response is improved in these mothers.

They can show all these is more detail than you

need to know about in this abstract.

Don't worry about the these various details here.

But the main point is all these things that allow

the body that are gone through the HP axis, the

hypothalamus, pituitary adrenal cortex, how to regulate with the cortisol

is upregulated by maternal care.

And this is an example of how you can look

at you can measure this.

So we're looking at rat pups for more nurturing mothers

compared to ones that have low nurturing mothers.

So we're going to track what we're going to do

to two graphs now.

So this is.

Before the intervention this period.

And this is after.

This is the period after.

So how what happens to the body when you apply

these?

The.

The stress hormones.

So what we're looking at is looking and grooming algae.

More how much licking and grooming is applied versus the

grooming and off back nursing.

So grooming and nursing is not positive particularly.

So it's it's you're looking at this licking and grooming

the mother rats do for their pups.

So humans you cuddle and maybe kiss and take care

of and nurture your child and stroke them and sing.

Nursery rhymes is what humans do.

Pups for rats.

They do.

They groom them for and they lick them to make

sure they're good.

Good mothers do that, love.

So here we have a group of rats, the high

treatment and low treatment.

And what we can see is the response, the way

the plasma this this molecule is released by the pituitary

gland.

It targets the the the cortex of the of the

the.

Of the adrenal gland.

This particular hormone is a better, higher response.

So is a.

Is is much higher high response in those those rats

that didn't get the maternal care.

So they're not bringing it back down as fast.

And you can also look at the the cortisol Rask

is up and it stays high throughout that period for

these not very well treated rats.

So these are the the black dots are the pups,

the ones that grew up with that care going to

Harlow's monkeys.

Harlow's monkeys were maltreated.

They didn't do well.

You've got these rats that are not well treated by

the mothers.

And these graphs serve to show like on a on

a evolving basis, the stress response differs between well treated

ups and not treated pups.

They look identical.

And this experiment is taking these two groups of little

pups.

They look fine.

But one thing well treated, the ones not being well

treated.

And this shows evidence that the early life experiences that

care and the parents bring has an effect.

The way we respond to stress.

Sadly, you can go on to look at this in

humans.

So this is the axis of women after sexual and

physical abuse and childhood.

And these women have a higher response.

Their cortisol levels are altered years and years later after

childhood abuse.

So this is quite sad.

It will go on into the images of how sexually

impacts of this.

So you can see you can see these links between

the previous rats experiment.

We can most of this in the lab and we

can measure this six fold change in these women who

suffered abuse.

So what's going on is that we've looked at these

sort of general responses in humans and rats.

So let's dig a little bit deeper.

So what you can see in this diagram here is

a one double helix of DNA.

So, you know, many of you have a biology background,

those that don't.

DNA is the main molecule in our body.

It leads us to storage and assembly.

Information allows you to replicate, and we can pass on

our DNA.

It's the main way in which your children, your offspring,

will pass on the facets of your eye colour, particular

traits.

You have all those things that's in most textbooks.

Most people in society have heard of DNA.

It's quite a common thing, particularly things like Jurassic Park

have highlighted that example.

What I'm showing you here is we can pass on

our DNA to our children, but also the proteins that

line the DNA inside your cells.

Every single cell has a dense copy of your DNA,

and it has these proteins called histones.

It's just the proteins that induce the DNA folding.

These are like little bulls that keep your DNA nicely

tucked up in the cell.

And histones can actually change.

They can change the proteins so you can change those.

And in fact, the particular thing that causes them changes

methylation, a particular really simple chemical reaction.

You can mitigate these histones or demethylation and just a

very simple chemical change in these histones, these DNA winding

molecules.

And the key impressive thing is those changes, if you

change your histones in the cell, can be passed on

because when you cell separates and passes on, it will

pass on not only the DNA, but these histones with

it.

So that's been found away without modifying an animal's DNA.

What you can do is modify the histones, and that

can potentially be passed on generations.

So here's an example of a mother.

We talked about this licking, grooming.

Here's this mother who does high licking and grooming, and

here's a cute little two pups that she's going to

lick and groom.

She's a very attentive mother.

What happens is that her pups we've just heard earlier

have this increased response.

So they particularly show another molecule pick up on that

is serotonin.

So here's written out 5 to 7 receptors.

That's the particular specific scientific name for the receptor for

this molecule, serotonin.

So we've talked about cortisol so far.

We know what happens to serotonin.

And this little pup, it's got this increased serotonin response

that's activated, but also this methylation suppresses activity.

So if they get d methylated, which is near a

particular genes, there's more details in you need to have

a particular gene and r3c1.

And that changes the way the histones around that little

mouse's DNA is operated.

And the effect of that, which is known as epigenetics

is epigenetic effect is a regulation of the licking, licking,

grooming all in this particular gene, that particular gene, this

modified by the mother's licking and grooming.

And this is just the way that geneticists will describe

this, both pathways, the direct effect and this this this

effect on the histones cause a change in this little

mouse that it's got a change in it and inside

of it, cells and its own receptors, his own receptors,

and got up to be able to respond effectively.

And it's dealing.

Is not been changed.

The DNA is changed, stayed the same.

But the way in which these things are configured has

changed and it's now better able to cope with stress.

This lucky little top goes off the stress coping and

the idea is that that can then turn on and

pass down generations.

So there's no DNA changes, no reordering of the actual

genetic structure, but these epigenetic effects I passed on.

So here's just an abstract written out from a key

study.

By this this epigenetic regulation of this glucocorticoid receptor and

human raises.

So you can see examples of this.

That gene I just talked about earlier that one with

the pups is been able to look at it and

people who had suicide victims who are abused or not

have used it.

Charlotte, it's a really sad study.

They can look at the brain pathology post-mortem and see

changes in the regulation of these structures.

Very difficult scientific work to acquire these brains and it's

worth a put a highlight that this work is controversial.

So there's still ongoing debate.

The key thing is here is the extent to which

that epigenetic thing really does go over.

Many generations seem very strong in some animals, but it's

still motivated in and in in mammals.

So a lot of scientists will agree with what I've

just described, that there's an epigenetic passed on through the

histone regulation and others may take the view that the

evidence still needs to be really confirmed in more detail.

So finally, just looking at the early life stress, we

can also see impacts not just on the response of

the sister for in the previous slides have shown changes

in the brain.

Right.

We looked at how these changes in the design, not

the DNA changes in the histones.

What we're looking at in these last slides is really

the fact of of this.

The again, we're going back to rats who were next

to it, who had their nesting material taken away.

So we talked about if I go back to that

last example of that mother, really attentive mother looking after

her pups, great passes on these great skills that you

wouldn't agree with, like a pass it down.

The world's great, right?

But that's not the real world, is it?

So you could have a nice little nice and they

all go well and suddenly something comes in an invader

and all the nest.

And now there's no nesting material for these animals.

It's a bit like an earthquake occurring for humans.

Your house is destroyed.

You have to go live in a tent for a

while.

These are really negative impacts.

What this study in rats looked at was the impact

of having nesting material removed so it's no longer warm.

And so the rats and growing up, they're unable to

be looked after in the same way.

And that means to fragmented nursing and grooming.

The grooming is not happening as effectively What's shown here

is the cortisol equivalent in rats.

Corticosteroids and army is much higher.

There's a much higher stress response.

And these these animals that experienced that nest removal, so

they're not able to respond more to later life stress.

So this isn't the effect of the nest material being

taken away.

It's when they're nine days later, they've left the home,

these little pups walking around and you give a stress

response and you get this much higher stress response, just

like we saw earlier with the childhood abuse says women

who've been suffered childhood abuse.

Much higher response, of course, is a sixfold higher, really

high.

Here you can see this very little response.

These control mice or rats that grew up with the

rats grew up in a nice, messy environment.

The ones that didn't like the nest material have an

adverse impact later in life.

What's shown here is a spatial memory test that's better

shown, I think, with the diagram.

You take a little rice and you put it in

a nice warm pool of water, like a bath, a

large bathtub, a circular one.

And the not the rat learns to swim around is

looking for a way out of the water.

It's nice and warm, is filled with milk powder so

it can't see anything.

But hidden under the water is a platform.

If the rat finds it, it can get out, It

can give it a treat.

And it's taken out of out of out of this

water maze.

And it's called a morris water maze after Richard Morris,

who developed this task.

Very simple one, but it's used to thousands of houses

and studies.

So here the rat can't see that little maze.

The platform.

And what we're showing over here is a top down

view into a maze with the video cameras tracked.

One of these are rats all over the place.

You can see it's swimming past what they've done.

They're a bit, a bit cheeky and taken away that

platform.

So the mouse is going, Oh, great, I'll go to

the platform.

And this is it heading off to that platform, but

it's not there and elsewhere.

And that's when and you can see it's like circling.

Where is that hidden platform in a sort of.

Estimate what the rats thinking.

What happens if you get that early life stress?

So those rats were raised in their bedding.

All they have was just an estimate table taken away

long back early on.

Take those rats much later.

Give them the same test.

That's horrible.

Screaming all around, unable to remember where that platform is.

So you can see the difference between the ones that

had the control.

Rats were quite efficient at going in the right space,

but the stressed rats were pretty much likely to search

anyway.

They had almost no memory of where the platform was.

So these kind of experiments really have been driven clinical

teams to think, Wow, we really need to intervene.

So that's why we have a very large and we

should have more work on social workers trying to help

make sure small children are really well cared for and

don't suffer these kind of adversities.

Same goes for animals.

There are lots of charities to help make sure we

don't have this kind of negative impact because it's unfortunately

quite, quite impactful.

So this is the last slide.

So summary you've heard about there are particular maternal care,

so you could pass on information from caring mothers and

interactions with peers, and that regulates this access.

We've heard about effects, this epigenome, the histones.

That's what these white things are.

Regulate that.

This is where advisor press and hair will come back

on Friday to learn more about vs the presence of

adrenaline and serotonin molecule that changes the way our brain

operates.

That's what this icon is here that regulates how aggressive

animals in the car, how emotion reactive and how that

cognition and memory operates.

And you get this operative, the social functioning.

So rats, humans, monkeys, whatever mammal you're looking at, will

have to interact socially.

And that's where the stress has one of its most

powerful negative impacts.

You have pathological effects.

If this pathway is badly dealt with, you also have

memory impacts be heard.

But if it's well cared for, you have adaptive, good,

social functioning and on.

So this is the overall summary.

At the end, I recommend you read some of the

last pages of the pages in particular from Costa Rica,

and you can find enough is the cortex book.

You log into these the library, you'll find that and

then to just nice reviews and look at this axis

and explain it in a helpful way.

I'll give you some example essay questions here of how

we might have informed surveillance.

And if you can do those readings, you'll be able

to nail these questions very well.

You can discuss how stress affects the hypothalamic pituitary axis,

how the genes, the environment interact and regulating stress and

questions you might get asked is what does it stand

for?

What does it stand for?

Where is the hypothalamus?

Hypothalamus in a given brain section.

And you saw our point that it too is right

next.

It's just under the corpus callosum.

So if you study all these slides and you look

through and read the material, read the reading are provided,

she'll do very well in exam.

So I will see.

You say you had some negative stories about stress and

bonding and problems.

Friday's lecture over in ICU will be about love and

social bonding, so that will be a more positive experience.

See you next Friday.

Thank you very much.