NERVOUS SYSTEM

Day 1

The nervous system is comprised essentially of two different cells: neurons and glia.

You have 100 billion neurons and about 10 times that many glia. Glia are do not confer the

actual physiologically properties of the nervous system, it is the neurons that do that. Neurons

have a number of unique properties that differentiate them from other types of cells, but a neuron

has many of the same things that any other cell has. The neuron has different parts: it has a cell

body and these processes that extend off the neuron. But the cell body is just like any other cell,

it has a nucleus, it has all the cytoplasmic organelles, it expresses genes.

However, neurons are amitotic, they do not divide—they are born and last your lifetime.

If they are injured, they cannot be replaced. If they die, they cannot be replaced. So you are

born with lots of excess neurons. You had twice as many neurons the day you were born as you

do today, and you have twice as many as I have. More is not more, more is less. Right now the

football team is back on campus, there are like 300 of them for summer practice, but the final

football team is 80 guys, and the best football team is not the 80 guys that show up on day 1, it is

the 80 guys that make it to the ballgame. The same thing with us, the neurons you were born

with, although there were lots of them, the actual ones that end up in circuits and functioning and

making contact with other neurons will be found across your lifetime. Another thing about why

they are amitotic: assuming you actually learn something this summer, the things that you might

have learned, how is it stored, where is that learning? All of these things are being done by

neurons, but the neurophysiological basis of all of those cognitive activities result from subtle

changes that occur to neurons across a lifetime, so if the neuron were to have to divide, what

happens to all those changes that you imposed onto those neurons? They are erased. In addition,

say you have an individual whose 6 feet tall; there is a neuron in the motor system that extends

down to the spinal cord, and there is a neuron in the spinal cord that extend to the gastrocnemius

muscles in the calf. There are only two neurons in the calf circuit: the cell body up in the brain,

the cell body in the spinal cord, everything else is this thing called an axon. If the neuron

stopped to divide, what happens to those connections? They are gone. And how would they

form? How would that neuron know how to travel four feet through the nervous system to find

this neuron again? It cannot happen, so neurons cannot divide. They are not like other body

cells that can replace themselves. Neurons are amitotic.

Another property is that neurons have these unique processes, axons and dendrites.

These allow neurons to communicate over long distances—some axons can extend a meter, so

the actual neurons reside significant distances apart, yet they can be functionally connected. The

most important characteristic that neurons have that very few other cells have is having what is

called a nonzero resting potential. That is just a complicated sounding thing, but if I were to take

a neuron and measure the electrical difference between inside and outside of the neuron, the

potential, for any other cell there would be no difference, but for neurons there is a nonzero

resting potential. If I measured the potential across the neuron, it would be about -70 mV. Why

is that important? Because in the nervous system, there has to be something that represents

information, as the function of the nervous system is to generate and process information.

What is information? Go back to earliest stages of electronic communication across

distances: the telegraph. What information was being sent over those telegraph lines? Just a

series of small bursts of electricity that were either very short or a little longer: dots and dashes.

The entire alphabet was constructed out of dots and dashes, so if you wanted to send a message,

you had to write out the word, click in the dots and dashes, and on the other end the receptacle

would listen to the noise, decode the dots and dashes, and reconstruct the words. Those little

electronic bursts were codified information. The nervous system has to have some type of way

to codify information also.

How do neurons create information? It comes from the fact that it has a nonzero resting

potential. Here is a neuron, we measured its potential, and periodically under very specific

conditions, that potential will change and will create what are called action potentials. What is

important here is the following: the neuron has two states, it can be at rest or generating this

action potential. Once you have two different states, you now have the ability to create a code,

like the binary code in computer language, 0’s and 1’s, on or off. Neurons have two functional

states and can therefore codify information. The only trouble with the neuron is that it is not fast.

Does anyone know how fast their computer processor is? The fastest laptop processor you can

get is 7 gig, meaning it can process 7 billion bits of information per second. That’s pretty damn

fast. How fast are your neurons? How much information could a neuron process per second?

Each one of these action potentials takes about 2 milliseconds, so you can generate about 500 of

these per second—but you would never do that. You would have an absolute grand mal seizure,

on the ground frothing and flopping about. A typical neuron generates about 25-50 action

potentials per second, that is your processing speed. If you had a computer out, and I asked you,

what is the square root of 1,817,312, you could do it in just about the same time it took you to

type it in, but you cannot mentally figure it out right now. We do not do that, we are not fast.

The fastest laptops are about 7 gig per second.

How many processors do the best laptops have? The best are quads, they have about four

processors. All of this capacity is being done by four different electronic components. How

many neurons do you have? About 100 billion. How many synapses do you have? Each neuron

makes about 1,000 synapses, so you have 100 trillion synapses, you have 100 trillion processors;

each one of them can process about 25 action potentials per second, so you can generate 25 times

100 trillion—that is your total processing capacity, which is much greater than your computer.

Although a computer is fast, it cannot do anything you can do, it can only do what you tell it to

do. It is never going to drag itself to the top of the tower over there in the midtown and start

shooting co-ads, humans do that, humans do terrible things and great things. Computers do

exactly what you tell them to do, and we try to make them look like us, but they cannot do

anything, they cannot even turn themselves on.

So neurons exist in these two states, and this becomes the most basic neurophysiological

process in the nervous system. Everything else is based initially on that capacity. Let us talk for

a minute on why neurons can do this. Neurons have a number of physiological properties that

allow them to have a nonzero resting potential. First of all, there is current; current simply

means moving charged particles from one location to another. In the electric system of this

building, those charged particles that are moving are electrons; they go very quickly, close to the

speed of light. You do not have electrons zooming through your neurons and axons, all electrical

current in the nervous system results from ions. We simply dissolve an ionic salt in an aqueous

solution and you get ions. If you have something like sodium chloride, in water you would have

sodium ion and chloride ion, things that are charged. Now if you could move the ions from one

location to another, you have current. But, to get current, not only do I need these charged

particles, I need to accumulate them and separate them from each other. So now I have a number

of ions, and I need to separate my charges—that separation results from the phospholipid bilayer

of the neuron, and in any other cell. What other cell have we seen that generates electrical

current? Myocardial cells; they have pacemaker cells, which also have a nonzero resting

potential. The phospholipid bilayer of a cell does not allow small charged particles to pass

through it. If I could accumulate charges on one side or the other, I would actually have a

difference in potential. If I had a whole bunch of positive charges on the outside of my neuron,

and only a small number of charged particles on the inside, the potential on the inside would

appear to be negative. The neuronal membrane allows us to keep charges separated, and

therefore create potential across the membrane. It does not happen spontaneously, there are

other cellular components that are necessary.

In order to get charges to be separated, we need to pump them across the membrane. The

two ions involved in the neuronal potential are sodium and potassium. We have a sodium-

potassium pump that is in what is called an antiport: it moves two things in two different

directions. It pumps out 3 sodiums for every 2 potassiums it pumps in, so even though it is

moving sodium and potassium, each carrying a positive charge, you have moving positives out

and positives in—how does that cause potential? Because you are moving three positively

charged sodiums out for every two positively charged potassiums you are moving in. It is like

your bank account balance; if you took out three dollars for every 2 dollars you deposited, soon

enough your balance would be negative.

Now we have separated charges, and more positive on the outside than on the inside.

How do we get current? The charges cannot spontaneously move through the neuronal

membrane. We need ion channels, these are a type of transmembrane protein. They span the

entire membrane of the cell and touches both inside and outside. There are two types of ion

channels: one for sodium and one for potassium. If you have a dog, and a backyard, and you

have a fence with a gate around the backyard, if the gate is closed, will the dog stay in the

backyard? Yes, but if you open the gate, it’s gone. I need my openings in my fence to be gated,

because otherwise the dog just leaves, so sodium channels have a gate that can be closed. The

sodium channels are selective, they only let sodium through and they are gated, which means

they are only open under certain conditions. We also have potassium channels which select only

potassium, and they have a particular kind of gate called leaky. Potassium can leave, but only

very slowly.

Here is our neuronal membrane; we have pumped out sodium, so we have a high

concentration of sodium outside and a low concentration inside; we have pumped in potassium,

so we have a high concentration of potassium inside and low outside. We have pumped 3

positive charges out for every 2 positive charges we have pumped in, so the inside of the

membrane is negative. Now our sodium channels are closed, so sodium cannot move.

Potassium channels are leaking; based on its concentration gradient, what does it want to do? It

wants to go out. Based on the electrical field, what does it want to do? It wants to stay in. The

potassium has two forces acting on it, one causing it to go out and one causing it to go in. When

those two forces are equal and opposite, the potassium stops moving, and what potential do you

think you need in order to offset the concentration gradient? -70 mV. You end up with what is

called an electrochemical equilibrium. The forces on potassium are equal and opposite, so when

the neuron is at rest, the potassium’s tendency to move out to reduce its concentration gradient is

offset by the potassium being attracted to the electrical field that is inside of the neuron. When

the neurons are at rest, the potassium is in an electrochemical equilibrium.

That is rest. How do we get the action potential to happen? Here is resting membrane

potential, and this other electric potential here is called threshold. What is the difference

between resting and threshold potential? Remember when we did cardiac function, we said

when something becomes less negative it is depolarized? In order to get the neuron to reach its

threshold value, the neuron has to be depolarized, but that is not something that the neuron does

by itself. That is something that is imposed on it by other neurons. The actual action potential

starts at threshold. The change to cause a neuron to reach threshold is something that happens at

the synapse, the point where two neurons are communicating with each other. Unlike the

pacemaker cells of the heart, where they can bring themselves to threshold spontaneously,

neurons cannot do that. Neurons need to be acted upon by other neurons to reach threshold, and

the actual action potential starts at threshold.

During the action potential, the membrane potential becomes less and less negative, it

depolarizes. During rising phase of the action potential, the neuron is depolarizing; then the

neuron briefly becomes positively charged, and this is called overshoot; then the neuron will

repolarize during the falling phase, and briefly become more negative than it was initially, this is

called the undershoot. Given this set of conditions, what single thing do I need to have to happen

at threshold to start this action potential? I just have to open the sodium channels. Once the

sodium channels open, sodium comes rushing in, decreasing its concentration gradient, following

the electrical field in and bringing its positive charges with it, therefore depolarizing the neuron.

At threshold the sodium channels open. During the overshoot, the sodium channels

inactivate, and at the same time the potassium channels go from leaking to open. When the

sodium channels inactivate, they are not closed, but the channel is obstructed and blocked so that

sodium cannot go through it anymore. At this point, when the sodium channels inactivate and

the potassium channels open, what is the potassium going to do? It is going to rush out, one

because of the concentration gradient and two because previously, it was the electric field that

was keeping it in, but it is no longer negative inside the cell, and even once it becomes negative

again, how negative does it have to be in order to stop the potassium from leaving? It has to be -

70. As long as it is more positive than -70, the potassium will continue to leave, bringing the

neuron back towards resting potential. That is the action potential.

Neuronal activity is tightly controlled; to have meaningful signaling, you have to be

under very specific conditions. First of all, action potentials only occur in axons, it does not

occur in dendrites or the cell body. The actual action potential starts in what is called the axon

hillock, this is the axon, and this is the axon terminal. Action potentials only occur in the axon,

the axon hillock is a part of the axon, the terminal is not. The action potential starts in the hillock

and travels down the axon, towards the terminal. What would make an action potential travel

down the axon? There are a couple ways to think about it. If we divide up the axon into little

areas, and all of these areas have the sodium-potassium channels, and here is our hillock, and we

cause an action potential in the hillock, positive ions will move in, which are the sodium.

Ions do not have consciousness, purpose, or direction; those charges enter into the inside

of the axon and the current is distributed in all different directions. Some of the current will then

go downstream into the axon. What is going to happen, as the depolarizing current that happens

in axon hillock, reaches the axon? It is going to open the sodium channels in the next segment,

and positive charges will rush into that one, and then that current is going to go in all different

directions—and what is going to happen when it gets into the next segment? It is going to open

the sodium channels in the next segment. It will happen over and over again, like lining up

dominos. As long as the distance between the dominos is smaller than the height of the domino,

when you tip the domino over, it tips the next domino over, over and over again. The current

created in the hillock invades the axon and opens its sodium channels, and when it opens the

sodium channels there, it invades the next segment. Why does that have to happen? Why

doesn’t just one current wander all the way down the axon? Sometimes the axon is described as

leaky; if you had a garden hose extending from the side of your house and out to the garden, and

you left it in the yard and ran over it a couple times with your tractor, and cut a number of holes

in it, what would happen if you turned it on? Would any water come out into the garden? No.

So if I started one action potential here, and I measured the potential at different points along the

axon, the current would get smaller and smaller and never reach the end, because the current is

being lost as it is travelling down the axon. That is why we need to keep starting more and more

action potentials, so the current in this segment starts an action potential in the next segment,

which does the same, and so on. The action potential has to propagate, reproduce over and over

again. Without that happening, the current created in the axon hillock would never reach the

end, it would be lost to other types of passive processes.

What causes the action potential to start? Sodium channels opening. Now imagine the

following situation: sodium channels can only either be closed or open or closed. We start out

with all of our sodium channels of our axon closed, and we start an action potential here—its

current invades the axon, so what happens to the sodium channels here? They open. Then that

current creates an axon potential, and that opens the next one, but the current is not going in one

direction, it is going in all directions. What would happen if these went from closed to open

back to closed? What would happen if, when these became open and the current went back

upstream? It would open again, and it would bounce back and forth forever, there would be no

purpose.

But action potentials only go in one direction, and how is that possible? Because the

sodium channels do not just go from closed to open to closed, they go from closed to open to

inactive. Here they are closed, here they are open, here they are inactive, and here they are

closed. There is a period of time where the channels cannot be opened, and this is the period of

time where that current is being passively moved in the axon. The current then dissipates, goes

away, and could not bring this segment back to threshold. This is called the absolute refractory

period. There is a period of time where it is not possible for part of the axon to have an action

potential, that is when the sodium channels are either open or inactive. The reason we need that

is so that the action potential only goes in one direction. When we talk about neurons, we have

neuron A communicating with neuron B, the signal only goes in one direction, from A to B to C

to D. It can never go in the other direction. The signal that neuron A sends to be B is called an

efferent signal. From B’s perspective, the neuron receiving the signal, it is an afferent signal.

Communication in the nervous system is unidirectional, always going away from the cell body

toward the terminal. The reason why it can only go in one direction is because the sodium

channels inactivate to prevent back propagation along the axon.

Here is the absolute refractory period. This period down here is the relative refractory

period. The sodium channels are closed, so you can have another action potential, but remember

to get the action potential to start you had to reach threshold. What would it take to reach

threshold during the undershoot? You need more depolarizing current, so even though action

potential is possible, it takes a little more stimulation. So the two refractory periods are 1)

absolute where no additional action potentials can happen, and 2) relative refractory period

where another action potential can happen but only if there is additional stimulation. Let us say

the neuron was at -70 and threshold was -60, I would have change it by about 10 mV, but then

during the undershoot it was -80; if I wanted to have another action potential, from 80 to 60, I

need 20, so even though it is possible, I need to stimulate it more, that is why it is called a

relative refractory period.

The next thing we want to talk about is how the neurons communicate with each other.

The action potential travels down the axon and reaches the terminal. What is it about the axon

that lets it have action potentials? They have sodium-potassium channels; in the terminal there

are no sodium-potassium channels, so the current enters into the terminal and you cannot have an

action potential in the terminal. In addition, there place where the neuron connects with another

neuron is called a synapse, and in all synapses there is a gap between the neighboring neurons,

called a cleft, and there is no way for the current that is occurring in neuron A to reach neuron B,

so they are physically separated from each other by this space. The current of the action

potential cannot pass over the gap and enter into its neighboring neuron. How then does neuron

A communicate with neuron B if there is no way for the information, the current of the action

potential, to get it across that gap? We change it from an electrical signal into something that

can actually get across the gap. In the nervous system, that is achieved by converting the

electrical signal to a chemical signal.

If there is our synapse where that is going to happen, we have the pre-synaptic terminal,

and this is the post-synaptic terminal. Stored in the pre-synaptic terminal are secretory vesicles,

and within the secretory vesicles are chemicals produced by the neuron, called neurotransmitters,

therefore the vesicle that holds the neurotransmitters are called neurotransmitter vesicles. When

the current of the action potential reaches the terminal, what it does is it opens a calcium channel.

The calcium acts as a molecular trigger, it initiates some internal events and the neurotransmitter

vesicle will migrate forward and dock with what is called the active zone, fuse with the active

zone, and be released into the space separated between the two neurons. The brain is a fluid

filled world, this is all fluid between the two neurons, and the chemicals will move by what is

called Brownian motion, simple random molecular movement until they reach the post-synaptic

neuron. On a post-synaptic neuron there is a region called a PSD, post synaptic density, and

included in the PSD are specialized receptors that will bind with the neurotransmitter. The

neurotransmitter will bind with the receptor, and as a consequence, the receptor will generate

some type of change in neuron B, and that could mean changing its electrical state, or cellular

activity. In summary, the action potential comes down the axon, initiates the events in the pre-

synaptic terminal that causes the neurotransmitter vesicle to dock with the active zone; the

neurotransmitter is then to be released, wander across the cleft, bind with receptors, activate

those receptors, and those receptors then affect the activity of the neighboring neuron, changing

the electrical condition of the neuron or the way it is functioning. Remember we said before the

change that causes the neuron to reach threshold takes place at the synapse. One of those

electrical changes could be bringing the neuron to threshold.

You see that we go from electrical to chemical and back to electrical. How then do we

change the chemical signal back into something electrical, for the second neuron involved in the

synapse? This change results from neurotransmitter receptors, and there are two types: ligand

gated ion channels and G-protein coupled receptors. We release the neurotransmitter, it wanders

across, reaches the receptor, and some receptors are actually attached to ion channels, so the

neurotransmitter binds with the receptor, causes the ion channel to open, and ions either move in

or out, depending on the channel type. Imagine that the neurotransmitter binds with the receptor

and allows positive charges to enter—what is going to happen to the neuron as positive charges

enter? It depolarizes. If it depolarizes enough, what is going to happen to the neuron? It will

reach threshold and generate action potential. What if the ion channel opens and positive

charges move out? It becomes hyperpolarized, it becomes more negative and farther away from

threshold, preventing the neuron from having an action potential. That is probably 90% of all the

activity in your brain right now, inhibition, inhibiting all of the things that you are not doing. If I

gave you a pharmacological agent that stopped inhibition in your brain, you would have a

seizure, everything would be activated all at once. Most neurotransmitters cause inhibition, only

a couple of them cause excitation. That is a ligand gated ion channel.

The other type of receptor is what is called a G-protein coupled receptor. In this case, the

neurotransmitter binds with the receptor, but instead of opening an ion channel, it activates a G-

protein, and the G-protein creates a second messenger. The second messenger then alters the

activity of the neuron, it does not directly cause a change in the electrical condition, but rather

changes the way the neuron functions, maybe making it less likely or more likely to have an

action potential, or changing the gene expression of the neuron. Here is the best way to

understand this: think about the generalized states of the nervous system; have you ever been a

little bit depressed? Doesn’t it change the way you see the world in general and all other

activities? Or think about when you are highly motivated, or being in a reduced arousal state like

just about to sleep. Those things are all regulated by G-protein coupled receptors, they do not

cause neurons to have action potentials, but they change their generalized activity. Most

communication in the brain occurs like this, and this is called modulation. Most

neurotransmission is actually modulation, just altering the general activity of the neurons, and

therefore we have a state dependence. Clearly the most obvious one is wakefulness or sleep.

Sleep is an active process, the brain actually has to be doing very specific things to be asleep, it

is not a lack of activity, it is a specific set of activities that causes you to sleep.

Neurons have action potentials, cause the release of chemicals, those chemicals change

the activity of the neurons. If the action potential represents one unit of information, and all it

can do is cause chemicals to be released, how do we ensure that the chemical also represents one

unit of information? Imagine going to the ATM, putting your ATM card in, asking for 20

dollars, leaving, and then every other person that came after you also got 20 dollars from your

account. There was one set of instructions that said to dispense 20 dollars, you took your 20, and

then it just kept dispensing 20 until your account was empty. That was not your intention, so you

need an instruction to terminate, you need the instruction to say give me 20 dollars, and only me

20 dollars. If the electrical signal causes the release of chemicals, how do we stop those

chemicals from acting perpetually? We have to inactivate them, and there are a couple different

ways neurotransmitters can be inactivated.

When we release the neurotransmitter, one mechanism is that there is a reuptake

transport, so we can reuptake. SSRI, selective serotonin reuptake inhibitor, is a class of drugs

given to individuals with mood disorder, primarily depression. The actual pharmacologic agent

blocks the reuptake of serotonin, which is a neurotransmitter, and keeps serotonin elevated. One

mechanism is reuptake; another mechanism is enzymatic degradation. Does anyone know what

happens at the neuromuscular junction? Acetylcholine is released from the motor neuron and

causes an action potential in the skeletal muscle. What happens to acetylcholine after it is

released from the motor neuron? It is broken down by an enzyme, acetylcholine estrin.

Another mechanism is what is called biotransformation; instead of breaking it down

enzymatically, we make it into an inactive form, then retake it back up to the neuron and convert

it back to its active form, we just transform it.

The last mechanism is just diffusion; the actual neurotransmitter just wanders away and

leaves the synapse and wanders out into the giant ocean of fluid that is in the brain. These are all

mechanisms to inactivate the neurotransmitter.

Neurons can only have two electrical states, action potential and resting potential. How

do we have all of these amazing functions, if the neuron only exists in two states? Initially

scientists thought, well, the neuron is producing all of these chemicals, maybe it is the chemicals

that create all of these amazing differences—but there are only a handful of chemicals. Have

you ever been really angry with someone? Have you ever been indignant? Do you know what

the difference is between being indignant and being angry? Anger is a generalized state and

indignance is anger when you believe that you are right. When you believe you are right and

you are angry, everything is fair game; anything you say, any way you treat the other person, is

totally correct, because they are wrong and you are right, and therefore you can say anything,

you can humiliate them, you can diminish them to nothing. Is there some magical chemical that

makes you indignant versus angry? No, it is anger while simultaneously activating the brain

circuits that give you the rational senses of right, and then you overlay this rational state with

anger, and then you are indignant.

There are only a handful of chemicals in the nervous system. The neurotransmitters are

categorized. One category is called cholinergic; the cholinergic neurotransmitters are primarily

the chemical called acetylcholine; acetylcholine is found in the neuromuscular junction, the

peripheral nervous system and the vasa forebrain.

Another category is catecholaminergic, things like norepinephrine, dopamine, which are

modulators, so they do not cause neurons to have action potentials, but they change the ability of

the neurons to have action potentials. Epinephrine, which is released from the adrenal medulla,

which increase the contractile strength of cardiac function and therefore reduces ESV, increasing

stroke volume, increasing cardiac output, therefore increasing blood pressure. Epinephrine is

released in the brain, not a major central nervous system chemical. These are inactivated by

reuptake. Norepinephrine’s neurons are in a structure called locus coeruleus, and is involved in

arousal state, meaning awake versus asleep. Dopamine is found in the VTA and also in the

substantia nigra. Parkinson’s disease results when the dopamine neurons in the substantia nigra

degenerate. Dopamine is primarily involved in motivated behavior.

The next category of neurotransmitters are neurons that use the chemical serotonin, called

serotonergic. This is primarily associated with mood and affect; it is inactivated by reuptake,

and the neurons are primarily in a structure called the dorsal raphae. Serotonin is primarily a

modulator.

Chemicals that allow the neuron to have action potential fall into the category of

aminoacid based neurotransmitters. They are aminoacidergic. The primary ones are glutamate,

gaba, and glycine. Glutamate is the primary neurotransmitter that causes action potentials. It

causes what are called EPSP’s, excitatory post-synaptic potentials. When glutamate binds with

its receptor, it depolarizes the post-synaptic neuron. When neuron A causes neuron B to have an

action potential, it is going to be glutamate. Gaba causes what are called IPSP’s, inhibitory post-

synaptic potentials; neuron A hyperpolarizes neuron B, decreasing the probability of neuron B

having an action potential. These are what are called true neurotransmitters; the neurotransmitter

binds with the receptor, the receptor opens an ion channel and directly changes the electrical

state of another neuron. All of the other things we talked about were modulators, no direct

change in electrical state. However, most neurotransmission is not excitation, it is inhibition, it’s

all gaba.

Now we have neurons, we understand a little bit of how they generate electrical signals,

we understand how they communicate with each other chemically. Now we want to talk about

how neurons are all constructed together to create the nervous system. Brain functioning,

although it requires those electrical events and chemical signally, functioning is not derived

directly from those activities.

We have individual neurons that have their own properties, and they confer limited

function. What you

Very little of what you are doing, and what you perceive in your nervous system,

emerges from action potentials nor chemicals. The neurons are organized into circuits, neurons

connected with each other creating circuits. The idea is that I can create all kinds of

functionality. If you know anything about circuit boards and electric circuits, you only need a

limited number of different types of electrical components to create a lot of different functions.

Here is a simple example: I have three neurons in a circuit, neuron A activates neuron B, neuron

B inhibits neuron C. If A is active and then activates B, what happens to the activity of C? It

goes down. Another example where I have three neurons in a circuit: A activates B and B

activates C, what happens to the activity of C when A is activated? It goes up. Just by changing

one component of a circuit, I changed the function completely.

We have circuits, and circuits exist in structures, multiple circuits within a single

structure. Structures are organized into systems, multiple structures linked together. Systems

work collectively to give rise to what is called emergence. Your higher brain function never

results from individual neurons and has little contribution from the individual circuits. The

highest brain functions come from emergence, the collective activity of multiple brain structures

at the same time. That is why if you alter brain functioning, even in the most minor way, a lot of

our high cognitive functions change dramatically, because they are not one structure doing

something like, for example, creating memory. Memory is no where, you cannot find memory, it

is not in a physical structure and you cannot find physical evidence of it, it is an emergent

property. Your working memory, what you are presently consciously aware of is an emergent

state that results from the collective activity of the brain.

In summary, we have individual neurons that reside in circuits; the circuits are in

structures, the structures are linked together to form systems, and the systems work collectively

to give rise to emergence. One other property of the nervous system that affects all of these

levels is called plasticity. Brain function is plastic. Prior experience changes future functioning;

that is why you are what you are. You are the sum of all prior experience that has subtly

changed your nervous system to make you the way you are. Imagine yourself when you were 14

or 15, and imagine the way you interacted with your parents, you were dead sure and absolutely

positive your parents were too stupid to understand the world, because they weren’t you, and

they couldn’t understand you, and you thought for sure that they were dumb stumps. Five years

later, you look back and say aw crap, they were right. You will be the same way ten years from

now, you are sure of yourself, you are confident, you are navigating through this world, ten years

from now you will look back and say, aw crap. What is happening is summing across your life,

all of the changes, you are subtly becoming who you will be, it is all plastic. You would not help

but being the 14 year old you were, because you were absolutely confident and sure, it not some

failing or flaw, it is simply a state of the nervous system at that point, and you just try not to

make serious mistakes when you are young, because you are not capable of making good

choices.

Now we want to talk a little bit about the brain itself, how it is organized, and its parts.

When we look at the nervous system, there are two basic parts, the central nervous system and

the peripheral nervous system. The central nervous system is the brain and the spinal cord and

the peripheral nervous system is the connections between the central nervous system and organs

and muscles and also between sensory structures and the brain.

The human brain has three natural divisions. There is the cerebral hemispheres, the

cerebellum, and the brain stem. The brain is a bilateral structure: you have two hemispheres, two

cerebellums, and two brain stems; they are all connected together, they are fused and do not look

separate, but you have two.

Let us start looking at the individual parts of the brain by first looking at the cerebral

hemispheres. The hemispheres are divided into different functional regions

The surface of the brain is highly convoluted, with lots of folds and grooves in between.

The elevated regions are called gyrus, and the grooves are called sulcus. We can divide the brain

up into different functional regions. The most anterior part of the brain is called the frontal lobe,

and the division that separates the frontal lobe from the rest of the brain is called the central

sulcus. Behind the central sulcus is the parietal lobe, and the parietal lobe is separated from the

occipital lobe by the occipital-parietal sulcus. The more inferior region is called the temporal

lobe, and that is separated from the superior parts of the brain by the silvian fissure, also called

the lateral sulcus.

If you wanted to assign functionality to the different regions, the frontal lobe is primarily

movement and higher cognitive functioning, what you are doing right now; the parietal lobe is

primarily somatic sensation, all of the stimuli that you can detect with the receptors in your skin

is processed by your parietal lobe. The occipital lobe is primarily vision and the temporal lobe is

auditory function as well as speech formation and recognition.

Day 2

If we section the brain and look at its internal anatomy, the first thing that is really

conspicuous when you do is that you will see that most of the actual cell bodies of the neurons

are right on the surface. When you think about the volume of the brain, cell bodies are primarily

found on the surface and are organized in layers. The cell bodies have a grayish color to them

and the axons that are usually covered by an insulting material called myelin have a white

appearance. The purpose of the myelin is to make things go faster. Yesterday we talked about

propogation of action potentials and we said we start an action potential here, its current goes in

various directions and engages to next segment and starts another action potential in the next

segment; and action potentials take time, they take 1-2 milliseconds, but what if we could get rid

of the action potentials? Then we could make things go faster. The purpose of having myelin is

to eliminate most of the action potentials so that the action potential goes down the axon much

more rapidly. What happens is that the action potential starts here, its current goes passively

under the myelin, starts another action potential here, its current passively goes under the myelin,

starts another here. This way you do not need as many action potentials and the current gets to

the end of the axon much more rapidly.

When you look at the brain, you see gray on the surface and white in the middle, because

all of the connections are made as the axons pass through the core of the brain and then reemerge

at various areas to make contact with the cell bodies in the cortex. Let us say a neuron in your

occipital lobe wants to communicate with a neuron is your parietal lobe, it will send its axon in

and will reemerge in the appropriate cortical area. Let us say the parietal lobe then wants to

communicate with a region that controls motor activity, it will send its axon and reemerge in the

frontal lobe. The internal volume of the brain is primarily to allow axons to travel through the

brain and then reemerge to make functional connections with neurons that are located in other

cortical areas.

The white patter is not just a tangle of axons, there are purposeful pathways that connect

one region to another. Our brain is organized with cell bodies on the surface and organized in

layers, that is cortex, and then our axons are bundled together, so our axons could go from

structure A to B, all of the axons going from one place to another would be a track. Or A, B, and

C all going to D, this would be a bundle, and if the bundle crosses from left to right, it is called a

commesure. The biggest commesure in the brain is the corpus collosum. The white matter is

organized in tracks if going from one structure to another, bundles if they happen to share the

same physical pathway, and commesures if they cross the midline, going from one side to the

other side.

Not all of the cerebral hemisphere is cortex, some of it is subcortical. There are a lot of

subcortical areas, but the most important subcortical area is something called the diencephalon

which gives rise to the thalamus, the hypothalamus, and the epithalamus. The thalamus is many

individual collections of neurons. When all of the cell bodies are clustered together, not in

layers, one term for that is a nucleus. The nucleus is a really big grouping. A small grouping

would be called a locus. A big grouping with boundaries with ambiguous boundaries, that would

be a substantia. In the thalamus it is primarily nuclei. The thalamus is a major relay area. For

example, if your retina receives visual information, it does not send that information directly to

the cortex, it sends it to the thalamus first and then the thalamus then sends it to the appropriate

cortical areas. The thalamus you can think of as a relay that is constructed out of many

collections of nuclei.

For the hypothalamus, we talked about one of its functions already, controlling the

endocrine system. The hypothalamus made hormones that were either directly released from the

posterior pituitary or indirectly controlled the anterior pituitary. It is also involved in other

functions like controlling visceral function, controlling internal states, things like hunger and

thirst, regulating circadian rhythme. It is also involved in primitive emotion, anger, territorial

aggression.

The last part of the diencephalon is the epithalamus which is the pineal gland, which

makes melatonin. The other part is called the corroid plexus, which makes CSF, cerebral-spinal

fluid. I would find CSF in the ventricular system, which is the fluid skeleton of the brain. The

entire brain and spinal cord are surrounded by this fluid filled system and inside are the secretory

cells called the corroid plexus that pressurizes the internal part of the brain and gives it its

physical structure. The CSF exits the ventricular system and fills the suberacnoid space of the

maninges. The entire brain is surrounded by a fluid filled sac. If this is the surface of the brain,

there is a region called the suberacnoid space that is full of CSF, so it cushions the brain. If you

accelerate your head your brain does not go bashing into the frontal bone.

You can think of the brain as three functionally different regions