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PROFESSOR: How many of you that are here today have been
aware for at least a week that we're supposed to have a
mid-term exam next Monday?
All of you know?
You all want it on Monday or would you
rather have it on Wednesday?
I get the impression from talking to people that most
people want to delay it at least a full session.
There are several reasons for that.
I was discussing this with Andrew.
Students had trouble with the last in-class quiz.
When I looked at it again, I shouldn't be surprised.
But I am surprised when a student doesn't know that
spinothalamic is not a descending pathway.
They should know that.
That it goes from spinal cord to thalamus.
They should know that by now.
But it's easy to get confused with all these words.
It takes time.
You're learning the language of the brain, as well as a
map, which is a visual-spatial task.
So if you have good visual-spatial memory, you can
use that memory and associate the words with that.
That's the way I do it.
And I remember those things easily, even though I might
forget your name.
I don't forget the name of anatomical structures.
If I remember some place where I met you, and that's specific
in my mind, then I can remember your name.
But people differ a lot in how they learn.
It's a little easier this year because you have not only the
pictures, but you have the book chapters that I've been
giving you.
Even if that's all you get to, the slides, review the slides
I talk about in class and read those chapters, you can do
well in class.
Now some students, they like to look at other things people
have written.
They want to know where I'm getting all this from.
So I do put other readings up.
And I will ask a few study questions about them.
But you can do well, if you just focus on the things I'm
giving you.
I don't plan on lecturing a lot on Monday.
If I have to, I'll finish the things if we don't
cover it all today.
But that won't take very long.
But I found several review things that will basically
pare down all these study questions that you have to
review for the exam.
I will post those by tomorrow.
I have one of them, I could post it later today, based on
the lectures.
So if you focus on those things and the pictures
associated with those questions, you
should do all right.
We just talked about a delay of the exam until Wednesday.
Giving you an extra session to review, two more days.
Now, we had just gone through the Lorenzen Piper study of
the function of descending pathways.
Is that hard to see?
Do we need that screen lowered at least part way?
Could you pull it down, at least like 2/3 down?
You really can't see the screen if I leave the ones in
the front of the room open.
OK, that's good.
So what is the lesion here?
Where's that lesion?
It's called a pyramidotomy, because it sections, tome
sections the pyramidal tract.
What is the pyramidal tract?
It's mainly corticospinal fibers.
So you eliminate the direct control the neocortex has on
the spinal cord with that lesion.
You also eliminate connections to the caudal hindbrain from
the cortex.
So why in this study did they always do that lesion first?
Because in the monkey, the pathways that originate in the
brainstem have become so dominated by the cortical
input, that the animal does pretty well, even without
those brainstem pathways.
Originally, the brainstem pathways, they
came first in evolution.
And they're very important in many animals.
And they still play a role, even in humans.
But without the corticospinal pathways, then they're
absolutely critical.
So what was the role of the medial pathways that come from
say the vestibular nuclei, the tectum, tectospinal tract,
medial reticular formation, and from the cerebellum?
What's their role?
Control of which muscles?
What kind of movement?
The whole body movements that always involve control of the
body axis, the muscles near the body axis.
Not the distal muscles of the limbs.
Distal muscles of the limbs are involved in
many of those movements.
But the movements they make with just the limb or just the
hand, those depend on these lateral pathways.
That's what was eliminated in lesion 3.
They come from the rubrospinal tract, from the red nucleus or
nucleus rubra in the midbrain.
They also come from the lateral parts of the reticular
formation of the hindbrain.
So pyramidotomy.
Without it, they do lose speed and strength.
And they lose individual digit control.
But otherwise, they do pretty well.
The medial pathways, they lose righting reflexes, they can't
orient well, they have trouble with
their balance and walking.
Not surprising, considering the pathways they're missing.
But they still have distal control.
How do they even test it?
Well, they strap the animal in a chair.
So he doesn't have to control his body axis.
He doesn't have to even sit upright.
They're holding him.
Then he can control his limbs.
And if he's already had a pyramidotomy and he loses
those lateral pathways, like the ones from red nucleus,
then on the side they made that lesion, he
has a lot of trouble.
He can't even grasp.
He uses his whole arm and can't grasp something.
Can you guess how an anatomist could tell whether that
lateral legion were complete?
That's a very simple neuroanatomical test.
They can do a section of the midbrain and look at the large
cell red nucleus and see if those big neurons are left.
Because the neurons will undergo retrograde
degeneration or atrophy if their axons are cut.
And that's what happens.
So that's how they evaluated the lesions.
It seems a little strange.
You're looking at the effects of a lesion in the hindbrain
by looking at the midbrain.
But that's actually the best way.
Because it's the pathway from the red nucleus that's most
critical in controlling that movement.
So it was a very nice study.
And made some very basic points about descending
pathways controlling movements.
And then I mentioned that the neurocortex, it still becomes
active, even in a tetraplegic that's paralyzed because he's
lost those descending pathways.
But the cortex is still active.
So if we have a way to use that activity in a prosthetic
device, they could still move.
And people have been working on that kind of problem now
for a number of years.
But they've been making advances in recent years and
giving paralyzed people some degree of motor control.
Just a little bit here about corticospinal
projections in phylogeny.
First, these are the three topics.
Here's a brain of an possum on the left and a laboratory rat
on the right.
Look at the rat first, here on the right.
This is primary sensory cortex.
That's the cortex that gets the input from the ventral
posterior nucleus.
So all that activity coming up the spinothalamic tract and
the medial lemniscus from the dorsal
column nuclei goes here.
There's actually several primary sensory areas.
But this is the largest one.
We can it S1, for somatosensory 1.
It gets its input from the ventral posterior nucleus.
Just anterior to it, there's an area we call the motor
cortex that gets its input from the rostral and the
ventral nucleus, the VL, that gets major input from the
cerebellum.
It also get some input from the red nucleus.
We call it motor cortex.
And both of these areas give rise to corticospinal fibers.
There's a few of those fibers come from outside this area.
But the vast majority of axons in the corticospinal tracts
come from these two areas.
Now, if you try to map those areas and look at their
anatomy in the possum, which is an animal believed to be
related to more primitive animals.
That is, more similar to animals that
came earlier in evolution.
It's very interesting.
Because these same two cells groups in the thalamus now
project to both areas.
It's like they're not fully separated yet.
They're amalgamated.
And it was that discovery that led to the hypothesis that
these originated together and then became parceled out or
segregated in evolution.
Now, of course, it could have been a change
that occurred later.
But most likely, this is telling us something real
about the way evolution has occurred.
Because we see this evidence for the same kind of thing in
other systems.
So we think the motor cortex is simply a specialization
part of the somatosensory cortex.
A part that became dominated by inputs other than the
sensory inputs from the ventral posterior thalamus.
Now, if you look at the axons of the corticospinal tract
from that motor cortex and sensory cortex, and look at
just how far they penetrate the ventral horn of the spinal
cord, and you plot it against the neocortical volume here on
abscissa, you see a relationship.
It looks a little bit rough there.
But in fact, these aren't randomly scattered.
The larger the cortex, the more penetration of the
ventral horn.
That indicates more control, closer control, with fewer
synapses to the motor neurons.
And if you just look how far they go down the spinal cord,
you see a similar relationship.
Humans are always there.
Here they don't have human.
But it would be way up here, like the chimp.
Here's human here and some of the monkeys.
But other primates have a little less penetration.
Raccoon still has a lot, but a little less than human.
And then smaller animals.
And non-primates the least.
More interesting to me is the functional correlation, if you
have a measure of how dexterous they are, how easily
can they pick something up with a hand.
And if you plot that against how deep in the spinal cord,
that is how ventral in the spinal cord those axons
penetrate, and how far down the spinal cord they go.
Of course, they're always reaching the cervical cord,
then upper thoracic, mid-thoracic, lower thoracic,
upper lumbar, lower lumbar, sacral, and [? casegial. ?]
You see in humans, it penetrates all the way.
The most dexterous animal.
We are probably as dexterous as the chimp, maybe even a
little more.
So you get that correlation too.
This just shows the neocortex to spinal cord size plotted
against neocortical volume.
And you see it's even more dramatic how much the human
stands out, even from the chimpanzee.
They plotted the neocortical volume here on
a logarithmic scale.
And then this ratio is a simple linear scale.
And this one, all it shows is where the neurons are that
give rise to the cortical spinal neurons.
They can do that kind of study with a
retrograde tracing study.
They inject a retrograde tracer in the spinal cord,
always in the same place in all these different animals in
the studies that were done, and look at where the cells
are densest.
They're always densest in Area 4, the primary motor cortex.
So every time you see the dark color there, that's where
you're seeing the largest density.
And then the lighter color, other places that also project
directly to the spinal cord, including the first
somatosensory area there and the post-central gyrus in
humans and monkeys, with a similar cortex in all these
other animals
And here they plotted the corticospinal neuron number
against the neocortical surface area.
And you can see, it's a very nice relationship.
The larger the neocortical surface area, the more
corticospinal neurons you have.
So that's a very clear trend that corresponds to what's
happened over evolutionary time.
So that gives the review of the main structures.
I want you to know about now the motor control.
Motor control is a very big topic and it will come up
again a number times in the class when we talk about
sensory systems.
For example, each of those systems concerned with
movement control.
And again, when we talk about the cortex.
But right now, to finish the introduction to the motor
systems, I want to talk about how temporal
patterns are generated.
And then a topic sometimes omitted entirely or only
covered a little bit, with very little about function,
the problem of overall state of the brain.
You'll see in my chapter, I have a little functional
description talking about students and children and how
their brain state can change.
And what does that.
So let's see how far we can get with this today.
We'll talk about rhythmic output and timing of the main
types of movement that's studied for controlling timing
in movements.
How do we explain temporal patterns from an anatomical
point of view.
We're talking mainly about structure.
But to find out how that structure originated, it
originated for functional reasons.
So I want to say a little bit about this.
And we will end up by talking about activity rhythms, which
leads right into the problem of behavioral state control.
Because our behavioral state is changing so drastically
with a 24 hour cycle.
So when we talk about temporal patterns, let's just first
start with simple SR models and reflexes, how we get
temporal patterns with just that kind of connection.
And then what gets added to it, various types of feedback
circuitry and endogenous activity.
So we'll first talk about timing in reflexes.
Now in reflexes, what controls the timing of the output from
a single stimulus is simply conduction time and temporal
summation time.
If we take a simple stimulus like that, something very
loud, what does an animcal do if he's not expecting it?
So we'll look at the startled response.
And then how you make that more general, to use it as an
explanation.
It has been used that way.
I mean for a long time in Russian physiology, they only
talked about reflexes.
And once Pavlov had could come up with the idea of
conditional reflexes, learned reflexes, it seemed to be a
complete explanation of behavior.
But in the West, the early example was Karl Lashley, we
realized that in fact many behaviors can never be
explained when you need that sensory input
triggering every movement.
So the temporal pattern in a startle reflex.
The first thing that happens, and it's easy if you're taking
a video of a startle reflex, you always
see this same order.
The eyes blink first.
Then there's a contraction of other facial muscles.
And then there's flexion of the neck, so the person will
seem to hunch.
And then the arms will flex.
And it's a very large stimulus, you see this in
wartime when there's exploding shells, the
legs will flex too.
And it always happens in this order.
The timing is due to the size of fibers and how
long the axons are.
That's why it tends to go down the body.
Synaptic delays and temporal summation times, all those
things take a little time.
And it changes the timing of the output.
So now if you want to use reflexes, of course you need
many stimuli.
You need a stimulus for every movement.
So the idea of the chaining of reflexes was proposed.
Well, one reflex leads to changes in the body, which
then generates other inputs, which then
generate other responses.
So it's a chain of reflexes.
That was the idea.
And some of the best examples of chaining of input/output
relations can be found in ethology.
And so let's talk about that first and then a study of the
swallowing reflex, which as it turns out is
more than just a reflex.
I'm going to take the courtship behavior of this
little fish, the stickleback fish.
I think I have mentioned this in the 920 class.
So some of you have had that.
The interesting thing about this, and there's other fixed
action patterns that are very similar, if you interrupt that
sequence of movements at any point, the whole chain stops.
It can't proceed.
So each step gives a necessary stimulus for
triggering the next step.
That's the defining point about a chaining of stimulus
response events, whether they be reflexes or something more
complex, that we might want to call something else.
So here's what the stickleback behavior looks like.
The female appears with her swollen belly.
And that initiates this little dance that the male does,
which causes the female to approach.
And that causes the male to lead her to his nest.
And that causes the female to follow.
The male assumes a special posture at the entrance.
When the female sees that posture, then
she enters the nest.
When she enters the nest, then he trembles with his snout
right at her tail.
That causes her to spawn.
And then he follows her to the nest and fertilizes the eggs.
So if you stop that by artificially interrupting or
some predator happens on them, it stops the whole thing.
Now, we've already thought of swallowing, it's been thought
of by neurologists as a simple reflex.
Detailed studies show that it's not simple and it's not
even a reflex in the full sense of the word.
It involves about 20 different muscles.
It's controlled by neurons from the midbrain to the
cervical spinal cord.
And experiments have shown that the pattern of
contractions is actually centrally programmed.
Once it's triggered by a stimulus in the back of the
tongue, and you can trigger it very easily.
You slide your finger back or a Q-tip.
And go right back.
Once you reach a certain area in your tongue, you go beyond
that, go a little further back.
And you cannot stop from swallowing.
In fact, as long as you apply stimulus there, you will keep
swallowing in a rhythmic pattern.
Try it sometime.
So it's a fixed action pattern.
It's in-born.
You get the rhythmic generation once you stimulate.
You can also get it just by stimulating the superior
laryngeal nerve.
The pattern isn't changed if you eliminate various inputs
that those movements are generating.
In other words, eliminate the proprioceptive
feedback that's occurring.
You can cut the nerves carrying that other input.
And it still generates the pattern.
You can cut muscles that are involved in some of the
movements, just eliminate them.
And it just skips over those movements and still continues
with the same pattern.
When we voluntary swallow, what we're actually doing is
moving the tongue so as to stimulate that input.
We stimulate the part of the tongue.
We induce the response.
And the equally interesting part of that response, is that
in the brain something is building up.
Ethologists call it the action specific potential.
It builds up over time.
So we swallow with almost no stimulus.
The threshold for triggering builds up over time.
Just as it does for all the motivational states.
So when we're deprived of swallowing, we increase the
probability that we will swallow.
And you can realize the important function of that.
Keep the throat lubricated and so forth.
This was done a long time ago by a very insightful professor
of psychology, and we call it physiological psychology or
brain and behavior study, Doty and his student.
Now earlier, Karl Lashley had argued that that same thing is
true for many movement patterns.
He talked for example about a musician playing the piano.
He noted, by recording it and measuring the timing, that the
finger strokes of a musician can reach 16 per second in
passages that call for a definite and changing order of
successive finger movements.
The succession is too quick even for a
visual reaction time.
So these people had to have built up a central program.
It was generated centrally.
And the same thing has been found for innate behavior
patterns, like the pattern of grooming in mice.
Fentress, up at Dalhousie University, did a number of
beautiful studies of this.
He was able to eliminate some of the feedback.
He even studied mice that it had say, forelimbs amputated
when they were tiny, when they first born.
So they grew up without forelimbs
or without one forelimb.
And he would observe their grooming.
You say well, how did they groom their forelimbs.
They don't have forelimbs.
They did.
They groomed as if the forelimb was still there.
So when the normal is doing this, that animal is moving
his shoulder in.
And in the exact right riming, he's doing
this with his shoulder.
And all the movements are there, except
the limb isn't there.
Because it's centrally generated.
It doesn't depend on feedback.
The egg rolling response in gulls is very similar.
Once you trigger that response, even if the egg is
taken away, the bird, the gull will keep rolling the egg in,
as if it were there.
And ethologists have studied movement patterns that seem to
be generated without any stimulus once the motivational
state is high enough.
We call those responses in a vacuum or in vacuo movements.
There have been studies of locomotor patterns.
Likewise in fish, the fin movements for locomotion are
completely internally generated in the spinal cord
by some neuronal oscillators.
And locomotor patterns in mammals are very similar,
except that in mammals you need some kind of input
maintaining excitability of those neurons
generating the patterns.
So you need descending input, for example from the
catecholamine systems or monoamine systems.
Rather, it's usually serotonin.
Or you need some input from the periphery, like at least
one leg present in a frog is enough to get-- it doesn't
matter how the input is coming in.
You need some input to activate the system.
But in fact, the pattern is generated centrally.
So what's happening?
You can of course just connect the neurons in ways that
there's feedback that will give you temporal patterns.
You can get self-reexciting loops for example.
And that could lead to regular bursts of action potentials.
You could have negative feedback systems and form what
we call homeostatic mechanisms.
We know homeostats, if they're done with machines, like in a
thermostat of our house, they will oscillate around a
certain level, the set point of the system.
Here's a simple example of a feedback circuit.
Here's a neuron.
We have to make a few assumptions about it.
We say that this neuron will fire only with temporal
summation of two inputs.
And then this neuron will fire every time it gets input here.
And that that neuron has an axon that branches.
It goes out here, where we're measuring the output.
But also has a input back to the cell that it was getting
input from.
So its got a self-reexciting loop.
So if you've got steady input here, that alone
would not do anything.
But with one little pulse here, you would start a chain
of bursts like that.
What would stop it?
Well, fatigue or some inhibitory input.
And you could theoretically at least, get much more complex
patterns just by combining such circuits.
Studies of things like breathing, which have this
regular pattern generated all the time, can be at least
partially explained, and there's a number of studies of
this, can be explained by such circuits.
Breathing gets both input from the periphery that plays a
role in generating the rhythm, but there's also internal
feedback that generates the rhythm, even without the
feedback from the periphery, from the lungs and chest.
So finally, we have endogenous CNS activity, which we talked
about earlier in the class.
They can also generate bursting patterns.
I'll just quickly show you the sea slug neurons that were
studied first by Strumwasser.
And then we'll talk about circadian rhythms.
This is that neuron that Strumwaser studied.
He could put an electrode in the cell and see this
oscillation of the membrane potential.
And if he hadn't blocked the action potentials, every wave
of depolarization would lead to a burst of action
potentials.
They would vary a little bit in number.
But he was able to show that in complete isolation, the
cell would still do this.
And such studies have later led to the discovery of
specific sites in the membrane, the pacemaker loci
in the membrane, that can generate some patterns.
And some cells have more than one pacemaker.
We know now that we have cells like that in our brains that
generate a 24-hour rhythm.
We call those the biological clocks.
There's more than one of them.
And it's important in maintaining a daily schedule
of activities.
We know that a strong reason, probably the initial reason
for the evolution of optical inputs, inputs from the effect
of light on the organism, was input to the neurons in the
hypothalamus that controlled that circadian rhythm, to
synchronize it with the day and night cycle.
It's normally controlled by the day/night cycle.
Differently of course in day active and
night active animals.
We call that entrainment of the rhythm
by the sensory input.
So theories about how movements are generated began
with these very simple concepts, the straight-through
processing; the SR models, like reflexes; models of input
analysis that say [UNINTELLIGIBLE]
and others are developing to explain how we detect objects
in the world, are all based on that kind of processing of
inputs from one stage to another,
with successive filtering.
Then the role of feedback explains homeostatic
mechanisms.
It explains other kinds of patterns in the brain.
A simple example in the spinal cords, the phenomenon of
reciprocal inhibition of movements.
When one movement is generated, another movement
can consistently be inhibited.
And then endogenous activity, which has been studied mainly
for control of circadian rhythms, but for much shorter
rhythms in for example locomotor control.
There's strong evidence both for circuits that connect in
this re-exciting way and control rhythmic production of
the gaits of locomotion and also
endogenous and firing neurons.
We have unfortunately not very much evidence on the kinds of
plasticity for the endogenous control of such rhythms.
But we're learning in recent years about plasticity of the
connections, synaptic connections that can occur.
There's a little more time.
So I can start talking about brain state changes.
I want to discuss the anatomy again of brain states that
underlie changes in behavioral state.
The most obvious ones are what happens when we go to sleep or
we are aroused from sleep or we're aroused from a more
passive state to a more active state.
These are all due to brain state changes.
Something pretty general is happening to the whole nervous
system, or at least a lot of it.
Well, we know about these widely
projecting axon systems.
We also know about chemical secretions that could play a
role in this.
The pathways are fundamentally different from these pathways
that we've been talking about.
Different from the sensory pathways, reflex pathways.
Different from the corticospinal pathways,
tectospinal pathways.
All these pathways of motor control we've
been talking about.
So we'll start by talking about the recticular
activating system, a system discovered for the first time
back in the 1950s, when people were studying comatose cats.
And they found out that if the put electrodes in the midbrain
reticular formation, below the tectum, below the superior
colliculus of the cat, they could wake up the cat.
They could cause a general arousal.
If he was sleeping, he would wake up.
But even if he was in coma, they could wake him up.
And then, there was another discovery.
That was an
electrophysiological discovery.
And I will show you some anatomical correlates of that.
And then was the discovery of the monoamine systems.
They couldn't be seen with the anatomical methods that were
being used.
When I started doing neuroanatomy, we never could
see these axons.
They were very small axons.
Very difficult to stain with our procedures.
But a method to use the chemicals properties of these
axons and get the axons to fluoresce was developed by
Swedish neuroanatomists, Falk and Hillarp.
And the application of those methods led to the description
of the major monamine systems.
And then since then, there's been other widely projecting
axon systems that have been discovered, mostly coming from
the lateral hypothalamus.
And we also know, and this is the least studied here, the
secretions into the cerebrospinal
fluid that can occur.
For example, that happens during the onset of sleep.
If you have two rabbits you have a cannula in their
lateral ventricles and one of them falls asleep, if you take
a little cerebrospinal fluid from that animal and inject it
in the cerebrospinal fluid of the other animal, and of
course you do the control experiments to show that it's
specific to the sleep state, the other animal
goes to sleep too.
Not if you take it from an awake animal
and do the same thing.
But I think because of the difficulty when that was
discovered of doing the chemical analyses, there's not
going a follow up.
But I like to raise it because it's obviously of major
importance.
It's not only these circuits that control this thing.
Here's a neuron I showed you once before.
This is from the work of the Scheibels.
Here's one neuron in the reticular formation of the
hindbrain that has an axon that branches, with
terminations, all away from the upper part of the spinal
cord here, the midbrain, the thalamus, and the
hypothalamus.
It's very widely distributed.
And there are neurons like that throughout the brainstem
reticular formation.
And many of them are cholinergic.
That is they use acetylcholine as their neurotransmitter.
And that's the major type of neuron being stimulated it
turns out when they get this arousal from a coma or from
sleep by stimulating the midbrain.
So I've taken on our Shmoo brain here.
I've just pictured some of those cells.
Here's one in the hindbrain like the one
I just showed you.
I don't show all its branches.
I'm showing though that it projects
heavily into the thalamus.
So it can basically, by that kind of pathway, wake up the
whole hemisphere, the neocortex.
This huge neocortex that we have and another higher
animals with the very large hemispheres have.
The way that arousal ascending reticular activating system
works is through this kind of connection.
And then there's also a group of neurons here
in the basal forebrain.
Here's the hypothalamus.
And if we go from the hypothalamus towards the
olfactory bulbs, we go through the basal
forebrain right there.
It's not part of the hemispheres.
The hemispheres balloon out above that.
But there are cells there, in the basal nucleus, named first
by Meynert, who didn't know all these properties of it.
It turns out they have very widely distributed axons, just
about to the entire hemisphere.
And those have been very important functionally.
And because many of them degenerate in Alzheimer's
disease, I think it accounts for some of the terrible
symptoms of Alzheimer's disease, the
loss of these neurons.
This is a section of a human brain.
It's a frontal section.
We are in front of the hypothalamus there.
There's the crossing of the optic nerve.
Some of the axons are starting to cross.
These are the optic nerves starting to
come together there.
And here are these neurons in the basal forebrain.
This is where they're located.
A few of them are located up in the striatum as well.
And it just shows diagrammatically the kind of
projections they have.
I took this from a well-known text in neuroanatomy there,
the Nolte book.
Now, let's just briefly summarize
the monoamine system.
And I've written about this in the chapter.
And you can see these pictures.
The monoamines are serotonin and the catecholamines.
Serotonin is a 5-hydroxytryptamine.
And the neurons come from the cell groups we
call the raphe nuclei.
"Raphe" means like in the middle.
In the midbrain.
In the midline.
So the raphe nuclei are midline cells groups in the
hindbrain and midbrain.
And they use serotonin as a neurotransmitter.
They're already there in amphioxus.
So these are very old
We know they play a role in sleep and in waking up from
sleep and in arousal, when we wake up.
And we know they play some role in nood stabilization.
You know that serotonin re-uptake inhibitors are used
in psychiatry.
In Prozac, for example.
And Allman has an interesting discussion of these properties
of serotonin.
And I've given you the pages there.
And then the catecholamines, two other widely distributed
axon systems.
These serotonin axons go down the spinal cord
and up to the brain.
They go all over the place.
Similarly, the norepinephrine axons.
In rats, there's like 1,600 cells that give rise to axons
that distribute over the whole nervous system.
They go into the spinal cord.
They go into the cerebellum.
They go into the midbrain.
They go into the diencephalon.
The go to the whole cortex.
They release their neurotransmitters in a
paracrine fashion.
That is instead of specific synapses affecting one cell at
the synapse, they spritz their neurotransmitter out and
affect a bunch of nearby cells.
They're know to play important roles in sleep and waking up
from sleep and arousal.
And then we have dopamine, which also is widely
distributed.
But not as widely as these other systems, the
acetylcholine, the serotonin, the norepinephrine systems.
Dopamine arises in mammal from the ventral tegmental area,
part of the limbic midbrain.
And we know it's associated very specifically with reward.
What we call reinforcement in learning.
It's basically the pleasure chemical in the brain.
So here's serotonin.
There's where the raphe nuclei are located
in the human brain.
And it just shows diagrammatically the
projections into the cerebellum and
down into the cord.
And then the ones from the midbrain here and rostral
hindbrain that are going all over the hemisphere.
And here's the norepinephrine cells.
And many of them are coming from this little place below
the cerebellum we call the blue
place, the locus coeruleus.
It just means the blue location, because of the blue
pigment contained in those cells.
Like I said, only about 1,600 in the rat.
And there's not that many in any animal.
And yet they have this huge distribution.
And they were first seen by this means of
getting them to fluoresce.
You basically expose them to formaldehyde vapor.
And it makes them fluoresce.
And that wasn't knosn until in the '60s, '70s.
I think in the '70s.
I took this from another neuroanatomy text by Lennart
Heimer, who was here with Nauta when I was being trained
in that field.
And here's the more limited distribution of
the dopamine axons.
You can see it originates there, the ventral tegmental
area and the substantia nigra of the midbrain.
They project into the striatum, the amygdala.
And they project also to the frontal lobe, the cortex.
So I'll mention this at the beginning, just before we do
the review.
But you can read this about the other cell groups and the
hypothalamus that have these widely-- these are less known,
less studied.
We don't know about them.
But I do something here in the book, that I just put it into
a slide here, asking this question.
Just how many of these general states of the brain are there?
So I make a very simple assumption.
Just say that there's only four of them.
And that each of them has three possible states, no
activity, low activity, high activity.
Of course, it could easily be more than that.
And then I assume these three systems in the brainstem and
four in the diencephalon.
So it gives seven systems, each with
three possible states.
So that ends up, the combination will give you
2,187 different states.
And if you add dopamine to it, you tripled it.
And if you make four possible states, instead of three, you
get a much larger number, 16,384.
You add dopamine to that, you're up to almost 50,000.
Different states, without dealing with specific sensory
inputs, without specific responses.
Just general states, the whole nervous system, controlled by
these widely-spread systems.
Psychologists haven't even begun to deal with that.
But I put it in that chapter because I think it's a very
important issue and will become more
important in the future.
And we've had some MIT students that after this
class, have gotten interested in that.
And I hope they do good research in the near future.
OK, I will you on Monday.
And we'll do a review, trying to get you ready.
But don't waste the weekend.
Do spend a little time reading these chapters.
I held back putting Chapter 17 up that
covers these brain states.
But I will put it up now.
And then I have a little review chapter too.
And in that, I list the cranial nerves.
But I will put a note there.
I don't ask you to memorize the cranial nerves for this
first exam.
Because I didn't warn you about that.
We didn't do that yet.
So other than that, you can learn what I give you on the
review questions.