The Science of Everything Podcast - Episode 38: Neurons and Synapses

Episode Date: November 29, 2012

A discussion of the neuron, the fundamental cell of the brain and the nervous system, including an overview of its morphology and physiology. I also discuss the generation and propagation of action potentials, including the role of graded potentials, voltage-dependant ion channels, and myelination. The episode concludes with an overview of synapses and the important role of neurotransmitters.

You're listening to The Science of Everything podcast, episode 28, Neurons and Synapses, and I'm your host, James Fodor. In this episode, we're going to look at the structure and function of the neuron, that is brain cells. In particular, we're going to look at the different parts of the neuron and how they fit together, and what their functions are. We'll also look at how action potentials are formed and propagated, including a look at resting potentials, the voltage-dependent ion channels, and graded potentials,

and how these lead to the generation of action potentials. and the propagation of action potentials along the axon. And we'll also, we'll finish off the episode with a quick look at synapses and synaptic transmission and a bit of a look at neurotransmitters. Recommended pre-listing for this episode are mostly episode 10 on the cell. Episode 9 matter and molecules might also be helpful. Also possibly something like episode 15 on chemical bonding may be relevant in some parts, but mostly just a bit of a background knowledge about the main parts of the cell.

which you can find in episode 10. Okay, without further ado, let's get started. So the neuron is one of the key type of cells that makes up the human brain, and the brains of other animals too, and also the nervous system. There are around 100 billion neurons in the human brain, although sources differ a bit on that, but roughly 100 billion, and each of those has maybe about 1,000 connections to other neurons, or 1,000 synaptic connections, as we call them,

So there's a heck of a lot of neural connections inside the human brain, which is what allows for the enormous complexity of conscious thought and language and so forth. A neuron, which is sometimes also called a neuron, spelled with an E or a nerve cell, I'll mostly will refer them as neurons, is an electrically excitable cell that processes and transmits electrical information through both electrical and chemical signaling. Now, as I mentioned before, there are many, many, different types of neurons. Well, depending on how you count them, I've seen counts into the

dozens or even hundreds of them, but they can be categorized in a few main different types or groups, and those are what we'll talk about in a second. But despite these numerous different shapes and types and sizes and so forth, the core elements are quite consistent across the different types of neurons, and so that's what we'll be focusing on. Now, when we're thinking about a neuron, we often describe sort of a stylized neuron, which is an abstraction of the key aspects of of a neuron that applies to most of the different types of neurons in in various ways. So the model that we're going to use to help understand the shape of a neuron is that of essentially a creature with a spiky head and a long tail.

So the head is what we're going to think of as being the cell body or the somer. This contains the cell nucleus, the gold gaparitis, and all the unusual organelles and elements of a standard eukaryotic cell. The cell body is generally you think of as being roughly spherical, and has, as I said, mitochondria nucleus, ribosomes, all the other stuff that are normal eukaryotic cell does. That's the head. The spikes that emanate from the head are called dendrites, which is from the Greek word for tree. So they kind of look like branches with little subbrances coming off,

and then little subbrances coming off those and so forth. What these dendrites are is that there's projections of the cytoplasm that branch outward from the somer, as I said, and they generally get thinner and continues to divide into additional branches. The dendrites don't contain very many organelles. They contain a few mitochondria and some cytoskeleton elements, but that's about it. Mostly they're just projections of the cytoplasm, whose purpose is essentially to pick up information from the outside.

So I think of dendrites as being inputs into the cell body. So that's the head and the spikes. The next part of our idealized neuron is the tail, which is called the axon. Now, most neurons have one axon, although it's possible to have none or more than one, but generally you have one axon. The axon is a long, particularly thick extension of the cytoplasm, thicker than the dendrites usually, which protrudes from a sort of triangular-shaped budding area from the somer, which is called the axon hillock.

So, I mean, the axon hillock is just sort of where the axon starts poking out from the somer. One big difference between the axon and the dendrites is that the axon is generally a lot longer, so many times longer, and it's also generally a lot straighter and smoother. It doesn't have little branches coming out of it like the dendrites do, except for some little ones at the end. There are some what are called axon terminals that branch off from the main axon at the very end of the tail, but for the most part, along the long axon tail, it's fairly straight and long. and the axon is what you can think of as the output.

So the input or the information that goes into the neuron comes through the dendrites. It's processed in the soma and sort of axon hillock area as well. And then the output goes through the axon. Because remember, neurons are information processing cells, and this information is stored and processed in the form of electrical signals. We'll explain to some degree how that works in a little bit. But if there to be information processing, there has to be. some input and some processing area and some output. So the input comes from the dendrites and the output

goes through the axon. Kind of like with a computer, your input goes through the mouse and keyboard mostly, and your output comes through speakers and the monitor. If you didn't have any input or output, you could still have a CPU and RAM and so on doing this stuff internally, but it would essentially be useless because there's nowhere to interact with it. So a neuron is the same in that sense. It needs input and output. Now, most neurons can have hundreds or thousands of dendrites, but generally, as I said, have a single axon. Okay, so now that we've explained the basic morphological features of a neuron, we're going to move on to talk about neuronal function, in other words, how this stuff all works together to process information. I should say right off the bat that it's still not fully understood how neurons process information.

There's a lot of active research in this area, which I will talk about later on in future episodes, because it's an area that I'm particularly interested in, neural information processing and neural networks and that sort of thing. For the moment, though, we're just going to talk about the basic anatomical and physiological features of neurons and how they conduct, in particular how they conduct action potentials. And this basis will be necessary for future episodes that look at the information processing angle

from a more complex and developed point of view. So we don't fully understand how the information is processed or represented in the structure of electrical signals, but we do know that it is the electrical properties of the neurons that are responsible for the storage and processing of information. So that means that essentially everything that you see, feel, here, think is electrical impulses mixed around and transmitted and processed in various complicated ways that we don't fully understand. But it's all electrical impulses in the brain and the rest of the nervous system. So that's the very vague handwavy explanation of how neurons process information and what they do. But I've been using this term action potential, and I haven't really explained what it is yet.

So that's what we're going to be looking at. That's what we're going to move on to look at now. What is an action potential and how is it produced? An action potential is simply a temporary change in the electrical membrane potential of a cell. Okay, so let's try and break that down and explain what it means. So remember, every cell, neurons included are surrounded by a plasma membrane. Well, in animal cells anyway, we're talking about in animal cells here. Plant cells don't have neurons, so that's not really relevant to them.

And the plasma membrane, just to remind you, is a bilayer of lipid molecules that regulates the transport of molecules and other substances across into and out of the cell. The membrane also has a bunch of protein structures and other structures embedded in it, which, well, perform various tasks. One important thing to realize is that the bi-liplid layer is a very powerful electrical insulator, which means that charged particles can't cross it very well. Essentially, the reason for that is because, if you remember back to some of our past episodes, especially where we talked about the cell and biochemistry basics, the non-polar tails of the phospho-lipped molecules that make up the plasma membrane, the non-polar tails there are not, well, they're not charged,

and they tend to push out charged particles or ions or other charged particles that try and pass through, and so that's why it's a very effective chemical instillator. So suppose that you want to move charged particles or charge molecules in and out of the cell, which, of course, you do sometimes. How do you do that, given that they can't just pass through the cell membrane because these phospholipid molecules are pushing them out? Well, to allow for that, there are various structures, proteins generally, that are embedded in the plasma membrane that permit the transfer of these molecules.

So basically they sort of, you can think of these proteins as being like little holes in the plasma membrane, but they're selective holes, so they only let certain things through, or that they're, one type of them are, for example, gated ion channel, so they're sometimes closed and they're sometimes open, so they only occasionally let charge particles through. Yeah, but the basic idea is that these proteins are sort of a gateway that allows charged particles to move through the plasma membrane. Now, because the plasma membrane is a good insulator, the inside of the cell and the outside of the cell can have different electric potentials, or just think of that as being electric charges. We haven't done much on electricity yet, but we'll get to that. But I think

everyone has, you should have at least the basic idea of what an electric charge is. If the membrane was a good conductor, then that would not be possible. In other words, charge would equalize inside and outside the cell. So the fact that you have these phospholipid molecules preventing the transfer of charge particles is very important to allowing the inside of the cell to have a different charge or electric potential to the outside of the cell. And generally, because the cell contains many proteins and DNA and other structures, which are themselves as a whole, like on aggregate, electrically negative. So they have an overall negative charge.

Whereas outside of the cell, generally, it's roughly neutral. Now, this sort of normal, standard, slight negative charge of roughly 70-millimeter, or negative-millimeter, because it's a negative charge. A volt is just a measurement of electric potential and a millivolts are thousands of that. So it's a relatively small negative charge, but significant enough for its purpose. So this small negative charge of negative 70 millivolts is called the resting membrane potential of the neuron. And it's just resting because, you know, that's the normal situation when nothing particular is happening. You've got a internal charge of negative 70 millivolts.

And remember that's because you've got all these negative proteins and DNA and stuff inside the cell, which is insulated from the outside by the membrane. Now, remember I talked about those proteins that allow ions and other particles to cross the membrane, another charged particles across the membrane. Well, one such protein is called the sodium potassium pump. It's called a pump because literally that's what it does. It pumps ions across the membrane. The sodium potassium pump helps to maintain this resting potential by pumping out positively charged sodium ions.

Now, this sodium potassium pump is particularly important because its function basically is to make sure that the potassium concentration inside the cell stays relatively high, and the sodium concentration inside the cell stays relatively low. But, as we know, chemicals have a tendency to move in the direction of their concentration, well, in the opposite direction to their concentration gradient. That is, they tend to move into areas where they are relatively more sparse. So this means that the cell would not be able to maintain its concentration gradient very easily without the continual operation of the sodium potassium pump,

which pumps potassium ions out of the cell and pulls... Excuse me, which pumps sodium ions outside the cell and pulls potassium ions inside the cell. So there's a constant exchange of sodium for potassium. However, every time three sodiums are pushed out of the cell by the sodium potassium pump, only two potassium are brought in in their stead. sodium and potassium ions are both plus 1, so they're both positive 1 charged.

However, if you're exchanging 3 out for 2 in, that means on net you're losing plus 1 charge out every time this sodium potassium pump operates. In other words, the sodium potassium pump, by spitting out 3 sodiums for every 2 potassium it pulls into the cell, is helping to maintain a negative charge or a negative resting potential inside the cell. Remember that negative 70 millivolts that we talked about. Now, the sodium potassium pump is a form of active transport, it requires energy and essentially happens all the time as long as there's enough energy for it to happen.

There are many other types of proteins or ion channel proteins that regulate the transportation of ions and other substances of course across the cell membrane and the neuron membrane. And one type of them are called voltage dependent ion channels. So the sodium potassium pump is not a voltage dependent ion channel. That's something different. We're now looking at voltage dependent ion channels, which are ion channels that are only open or only open up in response to changes in the electrical potential or think electrical charge near the channel. So most of the time these

voltage-dependent ion channels are closed, but if there's a sufficiently large change in the potential or charge around the ion channel, they can open up. And how does that work? Well, essentially, the electric potential or electric charge change can lead to a change in the confirmation or a change in the shape of the proteins that form the ion channel. And when that happens, the channel can go from being closed. In other words, the proteins are in a shape such that ions cannot get through. The confirmation changes, and they are now in a shape such that the ions can get through. That's how they basically work. You might be thinking, what relevance does all this stuff about sodium potassium ion channels and voltage-dependent ion channels? How does it relate to action

potentials, which is what I said I was explaining? Well, don't worry, we're nearly there. The last piece of the puzzle that we need to understand action potentials are graded potentials. So these graded potentials are different from the resting potentials. the resting membrane potential of the cell, and they're different from the voltage-dependent ion channels. Graded potentials are changes in the resting membrane potential that occur as a result of various external factors. Now, there can be many things that cause graded potentials. A common one is essentially if a neuron is on the receiving end of an action potential from another cell, that flow of electric charge, in a sense, from the first neuron can lead to a change in the electric potential for the second neuron,

which can cause a greater potential. There can be many other things that cause greater potentials as well. Like, for example, photons cause graded potentials in the photoreceptors in our retinas when we see things. Same thing in our ears, when we hear, the mechanical movement of hair cells

in our inner ears caused by our sound waves leads to greater potentials in the neurons in the ear, which then leads to signals being sent to the brain, which we interpret a sound, and so on. So many different things can cause graded potentials, and it just depends upon the particular type of neuron and what type of input the neuron is specialized to receive. But regardless of where they come from,

greater potentials are always temporary changes in the resting potential of neurons. So remember, the resting potential is generally around negative 70 millivolds. Maybe it'll go down to negative 72 milovolts or negative 80 millovolds, or it'll go up to negative 50 millovults, or negative 60 milovolts, or negative 10 milovults even. These are graded potentials. Now, there's two types of greater potentials,

one where the potential becomes more negative. These are called hyper-polarization. because the membrane potential becomes more intense, and so it's hyper, in a sense. The second type is called depolarizations, which occur when the membrane restive potential becomes less negative. So if we went from negative 70 to negative 50, that would be a depolarization.

If we went from negative 70 to negative 80 millivolts, that would be a hyper-polarization. And it just depends upon the nature of the greater potential, basically, whether the greater potential is leading to more negative charge or more positive charge around the membrane area. And also, another thing to remember is these greater potentials are local. I mean, they may be spread across a wide portion of the neurons membrane, but they can also be quite localized to a specific area.

So only voltage-dependent ion channels around that area of the membrane where the graded potential is being felt will be affected by that particular graded potential. So why do we care about these greater potentials? Remember, what we're trying to explain is how an action potential works and how it's propagated. Radial potentials are crucial because they are essentially the cause of the action potential, or they are what gets the action potentials started. Action potential is basically always, there are some exceptions, but generally they start at the axon hillock, which, remember, is the sort of triangular bit that protrudes from the somer and forms the beginning

of the long axon. The axon hillock is where the action potentials begin, and the reason for this is because the axon hillock contains a sufficiently large number of voltage-dependent ion channels. You don't get action potentials in the soma or the dendrites, generally speaking, there are some exceptions, but generally the action potential begins at the axon hillock and then is transmitted across the along the axon, because that is where you have enough voltage-dependent ion channels for the action potential to occur. Greater potentials are what causes the voltage-dependent ion channels to open up in the first place, thereby causing the propagation of the action potential.

So you can think of it like this. some external stimuli can be light or it can be a sound vibration or it can be a neurotransmitters, which will get to in a second, but some external stimuli leads to greater potentials, which leads to the opening of voltage-dependent ion channels, which leads to an action potential. That's the basic sequence of events that we're looking at here in the process of neuronal firing. How in detail, though, do action potentials work? Given the basic overview, and we know they're caused by greater potentials, We know they start at the axon hillock, but how exactly does it work?

So let me describe the process in a bit more detail now. So, again, we start with some incident-graded potentials, that is, localized changes in the potential of the cell membrane. These can be caused by, as I've already pointed, as I've already said, numerous external factors. For the moment, we'll just think about them as being caused by neurotransmitters, for example, that have been received and open up ion channels in the post-synaptic cell, and cause the formation of graded potentials. Now, greater potentials only are they only localized,

so they only apply to a particular area of the cell, maybe a particular dendrite or a particular part of the somer, where the change in the concentration of ions has occurred. However, we know that electrical charge tends to move in the direction of lower potential. That is, if you've got a concentration of positive charge in a particular area, then, and the rest of the cell is relatively negative charge, then this positive charge is going to diffuse throughout the negatively charged cell,

moving in the direction that it's attracted by the negative charge. So whenever we have greater potentials, and generally these will be positively charged, because remember the resting potential is negative 70 millivolts, and the greater potentials will generally push the localized potential a bit above that. So this relatively positively charged area of the cell, the ions there, positive ions, gradually diffuse out throughout the rest of the cell,

and particularly to neighboring membrane regions. Now, if the greater potential, is relatively small, then these will just sort of fizzle out and the cell will gradually return to equilibrium and nothing much happens. However, some of these positive charges, these, for example, potassium ions or sodium ions, may diffuse, diffuse just means sort of float in that general direction, may diffuse in the direction of the Axon Hillock. And what we may have is multiple graded potentials occurring at the same time, perhaps from different dendrites or different regions of the soma. If enough of these graded potentials diffuse to the axon hillock,

we may have a change in the potential of the axon hillock area, of the, you know, the membranes surrounding the axon hillock, the change in their potential there may be sufficient to move above the threshold level of depolarization, which, as we said before, was around negative 55 millibolts in a lot of mammalian axons. If the sum of the graded potentials, uh, that reach the axon hillock is less than 55 millivots, maybe it goes from negative 70 to negative 60 or negative 70 to negative 65. It doesn't do anything.

Only if it reaches the threshold level of depolarization does an action potential occur. So this is crucial. Degraded potentials that diffuse and reach the axon hillock have to sum, because they add up with each other. You know, you've got some ions from one source, some ions from another source.

If they add up to a sufficient level of charge or of electric potential such that the threshold level of depolarization is reached, then an action potential will occur. And how does the action potential occur? Well, it occurs with the opening of the voltage-gated ion channels. Remember those? The voltage-gated ion channels open up at the threshold level of depolarization. Only if that level of depolarization is reached,

does the conformational change in the proteins at the voltage-gated ion channels occur, and therefore the ion channels open up allowing sodium and potassium ions to travel through. If you don't get that threshold level of depolarization, the voltage-gated ion channels don't open up because their proteins don't change shape, and therefore the ions are not allowed to travel into the cell, and therefore nothing happens. The charge, the graded potential charge, will just diffuse throughout the cell and eventually return, the levels of polarization will return to their base levels. However, if we do reach the level of depolarization, then the voltage-gated iron channels open up. Now there's actually two

types of voltage gated iron channels that are most relevant. Sodium and potassium. So both of these channels, the sodium and potassium, are sensitive to the level of voltage and they'll both open up if you reach the threshold level of depolarisation, but the sodium opens first. And what happens is the sodium

iron channels open and sodium rushes into the cell along its concentration gradient. Because remember that the sodium potassium pump that I talked about earlier, that's constantly pumping sodium out of the cell and potassium into the cell. Because the sodium potassium pump is constantly pumping sodium out of the cell, the concentration of sodium in the cell is relatively low. When these sodium voltage-gated ion channels

open, therefore the sodium ions rush into the cell down along their concentration gradient. Now, sodium ions are positively charged, and so this massive influx of, well, you know, comparatively massive, influx of sodium ions causes a further substantial depolarization of the cell membrane around the axon hillock. Remember, this is only occurring around the axon hillock area, not throughout the rest of the cell. Sodium ions continue to enter the cell until a membrane potential of around 40 milovolts is reached. So that's a membrane potential at around the axon hillock. That's quite substantially above the negative 70 milovolts we started with. When this positive 40 millavolt level is reached, the sodium ion channel closes and becomes temporarily

inactivated. This is called the refractory period, which means it's incapable of opening again. for some period of time. It's quite a short period of time in milliseconds, I think. During this short refractory period, it's not possible for the sodium ion channels to open up again, regardless of the level of stimulation they receive. So you could pump up the level of depolarization to plus 5,000 millivolts, and still the sodium ion channels wouldn't open. And one of the reasons for this is to prevent sort of repeated or continuous firing of a neuron, because since the sodium channels can only open for a certain period of time and then have to close for a certain period of time before they can't up it again, you have a maximum limit of the rate at which neurons can fire.

Around the same time as the sodium ion channels are beginning to close, the potassium ion channels, again, these are also voltage-gated ion channels, begin to open. And this allows positively charged potassium ions to flow out of the cell. So, just to be clear, both calcium and potassium, sorry, both sodium and potassium ions, are positively charged, they're plus one. But the sodium potassium pump is pumping potassium ions into the cell, and so therefore the potassium concentration inside the cell is relatively high, whereas for sodium it's relatively low. So that means when the potassium ion channels open, instead of flowing into the cell like they did for sodium, the potassium ions are going to flow

out of the cell, because the concentration inside the cell is quite high. So now we've got positively charged ions flowing out of the cell, and that's going to lead to a reduction in the membrane potential around the axon hillock. And so we go from the maximum membrane potential of around plus 40 millivolds down to even below the resting potential around to like negative 80 or negative 90 millivolds. So this is called an overshoot or a hyper-polarization because the polarization has actually increased relative to the, it's become more negative relative to the resting level. This hyper-polarization or overshoot is relatively short. It doesn't last very long.

Soon enough to that, you return back to the resting potential level. And so once we've had the potassium ions flowing out of the cell for a little while, the potassium ion channels also close, and again they have their refractory period, and then both of the voltage-gated ion channels have closed, and the sodium-ion pumps, the sodium potassium pumps return to their work of gradually restoring the concentrations of these ions to their regular equilibrium levels. And therefore, this cell eventually returns to its resting potential level of negative 70 millivolds.

This entire process only takes a few milliseconds, so it's very rapid. And so after a few milliseconds, you return to your original resting potential, and then you can have potentially another action potential. You can have action potentials occurring as rapidly as you like, subject to the restriction, as we said before, that there is a refractory period for the 30-mile channels, which prevents them from opening again immediately after having closed.

So there is an upper limit on how fast you can fire action potentials. So remember, in order to get an action potential, we need the local membrane potential of the axon hillock area to reach above around negative 55 millivols. For that to happen, we need to have sufficient graded potentials coming from the somer and the dendrites and possibly other sources too in order to build up this total amount of necessary a necessary potential.

So it usually takes a good number of individual graded potential signals to produce an action potential. You know, just a single input from one dendrites, probably not going to be enough. You're probably going to need a bunch of dendrites to all contribute greater potentials in order to reach the threshold. However, once you've reached a threshold, you get an action potential. There's no such thing

as a strong action potential or a big action potential. You can have fast and slow action potentials in the sense that you can have many in a given period of time or only a few, but a given action potential is the same. So there are binary all or none phenomenon, as I think I said before. So remember, the action potential itself is binary, all or none, but the greater potentials that produce the actual potential

or lead to it are not. So you can have lots of greater potentials, only a few greater potentials. And the only relevance of how many greater potentials you have is do you reach threshold level? Yes or no. There are two ways you can reach threshold level, essentially, spatial and temporal summation.

Spatial summation basically means you've got lots of dendrites or other sources contributing greater potentials at the same time. Temporal summation means you've got greater potentials coming in at slightly different but overlapping times and so during the overlap period you have enough membrane potential to reach threshold. In practice of course there's no hard and faster things between spatial and temporal summation but it's just too useful ways of thinking about it. Generally because the greater potentials diffuse passively along the cell or the cell membrane, dendrites further away from the axon hillock will contribute,

their greater potentials will be weaker by the time they reach the axon hillock than dendrites that are closer. However, I did read up that apparently there's some recent work that shows that perhaps dendrites that are located further away from the axon hillock may actually produce stronger graded potentials, thereby compensating for their greater distance, but I don't know how solid that is, but it may well be a case that it differs between different types of neurons.

But anyway, the basic point to understand is that the number of greater potentials, the strength of those greater potentials, and the sort of distance that those greater potentials have had to travel by the time they reach the Axon Hillock all contribute to the total size of the greater potential that the Axon Hillock receives, and therefore, essentially, the probability that you'll reach threshold level and thereby produce an action potential. Another thing that's important to realize is that the process of generating an action potential does not actually require any energy, or not significant amounts of energy anyway, because the the sodium and the potassium ion channels,

well, they open up in response to voltage changes, but the flow of ions that they lead to is a purely passive flow. In other words, the potassium and sodium ions are both just flowing along their concentration gradients. That doesn't require any energy. That's called passive transport, basically. They just move along their concentration gradient. What takes the energy is actually the sodium potassium pump,

which is maintaining those differential concentrations in the first place. So, in a sense, it's not the action potential itself that takes energy, it's maintaining the resting potential which leads to the ability to have action potentials which takes up most of the energy. Okay, so we've explained, I hope, in reasonably clear terms, how an action potential begins and what determines whether it begins,

you know, whether you reach threshold polarization. But that only explains how an action potential begins at the axon hillock. How is it actually transmitted along the axon? Because remember, the whole point of the axon is that it transmits the signal of the action potential along the axon and then towards whatever the target of the axon is, usually it's another neuron. How is that propagation achieved? Well, basically, the action potential doesn't really move along the axon.

What actually happens is it's constantly regenerated at the different points of the membrane along the axon. That is, the initial action potential is simply triggered by an opening of the voltage-dependent ion channels. Well, when the voltage-dependent ion channels open, you've got an influx of positive charge, you know the membrane potential increases up to positive 40molts. But then we've got all these positive charges around the membrane area of the axon hillock. Well, those positive charges are going to diffuse away from this membrane area and move into surrounding areas. Now, the axon hillock, there's basically two directions. There's the axon direction.

I'm going to call that forward, you know, along the axon, and there's back towards the somer, which I'm going to call backwards. Now, the positive charges, the sodium miles in particular, are going to move in both. directions. They're just going to diffuse away towards the more negatively charged regions of the cell. However, when they move backwards, that doesn't really do anything, because remember, there aren't any or not significant numbers of voltage-dependent ion channels around the soma or the dendrites. So backwards-traveling positive charges don't really do anything. Forward-traveling positive charges, however, do do something because the forward moving charges,

which move into the axon area, as opposed to the axon. Hillock, they're now actually moving down the axon, the membrane around the axon does contain enough voltage-dependent ion channels. So as these positive charges are diffusing down the axon, they're increasing the membrane potential of that region of the axonal membrane, because they're positively charged, so that increases the membrane potential. And again, if enough of these positive charges diffuse into down that region of the axon, then you're going to reach threshold potential, and the voltage-gated iron channels around that area of the axon open up.

Positive charge flow in, then those positive charges start. start diffusing further down the axon, thereby raising the membrane potential of that section of the axon, thereby leading to the opening of those arm-gated channels, and then leading to the inflow of positive charges, and then so on. And this just keeps propagating down the axon until it reaches the end. You might think that this process would sort of go on forever, because when a given section of the axon reaches threshold, its voltage-gated iron channels open up, the positive charges flow in, and then they start to propagate out, as I said, in both directions, both up and down the axon. However, remember that refractory period that we talked about

when the sodium ion channels can't open up just after they, so the sodium ion channels open up, and then there's a period just after they close when they can't open again, regardless of how positive the membrane potential gets. That's crucial to preventing the action potential from just continually firing, because otherwise the action potential would sort of propagate forwards and backwards along the axon as well. And then it would propagate forwards and backwards from every position, and we'd just sort of maintain active forever. And, yeah, that wouldn't really work.

You basically just have seizures all the time if that happened, an overflow of electrical activity. So that wouldn't be very good. So this refractory period prevents that from happening because essentially acts as a wall that prevents the actual potential from traveling backwards up the axon. Sorry, backwards down the axon. It only travels forwards along the axon.

So that's very important to understand. Now, I just said that, action potentials propagate themselves along the membrane of the axon, essentially just recreating themselves at every point as the voltage gated iron channels open in response to the local membrane potential exceeding threshold, and then that change, and then the positive charges so introduced diffuse along the axon, thereby polarizing that area of membrane and thereby opening those iron channels and so on. That's a constant regeneration process that must occur at all points along the membrane down the axon. That's not actually how, most neurons work, especially in invertebrates, you know, like humans and other mammals. The reason is because that process that I just outlined of the continual propagation, it just takes too damn long. It's too slow. The speed at which you can transmit this electrical signal down the axon essentially depends upon how fast you can get the positive charges to go down, because all you need to get the signal down the end of the axon is enough positive charges

to get from the start to the end of the axon and thereby transmit the signal and leading to a reach of threshold polarization at the very end of the axon. But if you're constantly regenerating the action potential along the axonal membrane, essentially what's happening is you're constantly leaking out positive charges at every point, the leaking out of the particular the potassium charges. Remember when the potassium voltage-gated ion channels open, the positively charged potassium ions leave the cell and actually reduce its potential. And so this process of leaking out the positive charge and then reintroducing it again at the next point along in the membrane as those sodium voltage-gated ion channels open is very slow.

I mean, it's not slow, but it's in terms of milliseconds, but it's slow in a biological sense. And that can mean the difference between life and depth. It can mean the difference between being able to react to seeing a potential predator and quickly send a signal to your legs to get the heck out of there. and not being able to do that fast enough before you become eaten. So this is actually a big deal, the ability not to... The ability to be able to send signals down the axons more rapidly than this constant propagation along the side of the membrane would allow. One way around that is just to make the axons thicker, like really fat,

essentially because that reduces the resistance. Again, we'll talk about that when we get to electrical circuits about why fat or whys have less resistance, but that's the basic same idea in the axon. Fatter axons produce less resistance to the flow of current, so allow the current to travel more rapidly. But fat axons require, well, more energy to produce and to maintain, and also they take up more space. And so that method of just making the axons really fat is not especially effective. If the human brain relied on really fat axons to do its processing instead of the alternate method, myelination, which I'll get to in a second, then our brains would have to be like a hundred times bigger, and good luck getting that through the,

canal. So most invertebrates don't have myelinated axons. Remember, that's the way we get around this speed problem. They have mostly unmyelinated axons. That's the basic bear form where the, the signal is just continually regenerated along the membrane. However, that would be too slow for the really important stuff, like running away from predators. And so they also have some really fat axons. So the squid, for example, has mostly these, well, it has unmyelinated axons, mostly thin ones, but a few really fat unmyelinated axons for the crucial things. And these really fat unmyelinated axons are actually very useful, because we can use them, we basically use them to understand how axons work,

because they're much easier to study, because they're so much bigger. However, I've been using this word myelination as the way that humans and mammals and other animals get around this problem of slow action potential transmission. What does this mean? Well, myelination is essentially insulation. It's myelin are these deposits of fat basically, or lipids, that sort of twist around the axon, thereby providing insulation, which prevents the leakage out of positive charge, particularly these potassium ions, which normally leave through the voltage-cated ion channels. While when the axon is myelinated, they're not able to do so.

And so they just, instead of leaking out and slowing up the whole action potential process, they just speed down along. the axon because they can't go out the sides, it's insulated, so they just go straight down the middle. Now, the way myelination works is that you don't just myelinate the entire axon continuously straight down. What happens is that it's myelinated in sections. The sections are interspersed by sort of short, small gaps between the myelin sheaths, which, as they're called, and these little gaps are called the nodes of Ranvier. I think that's how you pronounce it. At these little un-milinated gaps here, you regenerate the action potential as usual. So basically what happens is that the positive charges that are introduced in the cell by the initial, the very, the initial action potential

that occurs at the Axon Hillock, these shoot down the myelinated sections until they reach an un-milinated node of run via. Then they open up the voltage gated ion channels, both the first the sodium and then potassium, and you regenerate the action potential, as described before, and then that introduces a new bunch of positive charges, which then shoot further down the axon, just speeding down the myelinated section until again they reach a new unmylonated note of run via and so on. And so what the myelination does is it doesn't stop the regeneration process that occurs in unmylanated axons. It just means that it doesn't have to happen every point along the membrane. It just happens at selected points along the membrane interspersed

by the myelinated sections. So these myelinated axons can transmit axiometeals about a hundred times faster than unmyelinated axons. And so that can, as I said before, present a significant advantage in terms of reaction time and thinking time. And in fact, when humans are born, and even as they develop as children, they're large regions of the brain, especially the frontal cortex region of the brain that is responsible for a lot of conscious thought and higher cognitive processes are not myelinated or not completely myelinated. And this is thought to be one reason why children, even adolescents, do not have essentially the full cognitive capacity of a fully grown adult and can make, therefore, rash decisions in some cases.

In fact, I've seen research that shows that myelination is not completed until the early or even mid-20s, in other words, well beyond the age of 18. So it takes a long time for myelination to completely finish in all sections of the brain, and it's very important. for essentially reaching peak cognitive capacity because you've got to get these signals transferring as fast as possible. There's one last thing we need to explain. We've explained greater potentials. We've explained action potentials, and we've explained how they propagate along axons, and we've explained myelination, the process of speeding up this action potential transmission. What we haven't explained yet is what the whole point of this action potential is. We know that the axon is the output part of a neuron, that it sends a signal outward,

and the signal is transmitted along the action potential, along the axon via the action potential. but how does the signal go from the end of the action potential to the next neuron, or possibly a muscle cell or whatever else, is at the end there? How do you actually transmit the signal onto something else? And that is where the synapse comes in. Now, the synapse is essentially just the junction between, well, in this case we'll talk about one neuron and another. A synapse doesn't have to be between two neurons.

It can be, you can have a synapse between a neuron and a muscle cell, for example. In this case, we'll think about it as between two neurons. So you've got a presynaptic neuron, which is the initial one, which is sending in the action potential, and the post-synaptic neuron, which is the one that's receiving that as input. And you remember those little spines that I said existed, the little protuberances out of the end of the axon? Well, basically what those do, that these are called terminal buttons, and they connect on to dendrites of the postsynaptic neuron. So the presynaptic neurons axon is connected to dendrites, or possibly soma, but generally dendrites.

have a post-synaptic neuron. And so the output from one neuron becomes the input for the next neuron. That's how information processing happens in neural networks, in networks of these neurons, because one neuron's output becomes another neuron's input, and then this given neuron receives many inputs from different presynaptic neurons, and then it processes those, and then produces as an output,

and so on the process goes. And you can get very complicated information processing systems through the setup. but we'll talk more about those in a later episode. How does the synapse actually work? How does the action potential in the presynaptic neuron get transmitted into a graded potential? Because it doesn't go straight to an action potential. Remember, the dendrites of the post-synaptic neuron don't have action potentials. You go to a graded potential in these dendrites.

But how do we get from the action potential in the presynaptic neuron to the greater potentials in the post-synaptic neuron? And the answer essentially is neurotransmitters. You may have heard of neurotransmitters before. dopamine, gabber are some common ones. There are many neurotransmitters, and we'll do a whole episode on those later. But for the moment, we just need to understand that neurotransmitters are... They're just special molecules that are released by the presynaptic neuron

and bind to ion channels on the post-synaptic neuron, the membrane of the post-synaptic neuron, thereby opening these ion channels and allowing ions to flow in. So it's essentially a very similar process, as we've discussed before. These neurotransmitters bind to the ion channels on the post-synaptic neuron. These ion channels open up as a result of a conformational change in the protein that's caused by the binding on of the neurotransmitter. Therefore, we get a flow-in of ions into the post-synaptic neuron,

and therefore this generates a graded membrane potential. And if enough of these graded membrane potentials occur and enough of the potential diffuses to the post-synaptic axon hillock, then we'll get another action potential in the post-snapting neuron. That's not guaranteed by the synaptic process. The synaptic process only produces greater potentials. Whether or not the postsynaptic neuron will actually produce its own action potential depends upon whether there are enough greater potentials in the post-synaptic neuron.

For the moment, we're just interested in this single one greater potential produced by this one synapse we're thinking about. The terminal buttons, or the very end of the axon of the pre-snaptic neuron, doesn't actually physically touch the dendrite or whatever part of the same. seller might be, of the post-synaptic neuron. There's a small gap between them, and this small gap here is referred to as the synaptic cleft, although sometimes it's just referred to as a synapse itself, but more properly the synapse is the regions of the pre- and post-synaptic neurons, plus the synaptic cleft in between them. So there's actually a gap there, and what happens is when the action potential reaches the end of the pre-synaptic neuron, this triggers the

opening of calcium voltage-gated ion channels at the end of the post-snaptychic neuron. Now, remember, careful here, these calcium-voltage-gated ion channels are completely different to the sodium and potassium ones that generate the action potential itself. So it's a different thing, although it's still a voltage-gated ion channel, so the basic idea is the same, but it's a different ion that's involved here. And so voltage-gated ion channels open up in the pre-synaptic neuron. Calcium ions flow in there, and this increase in the concentration of calcium leads to a bunch of vesicles. You remember, vesicles are just little membrane-bound containers,

essentially, that holds some substance in a cell. These vesicles, which were previously just sitting around in the pre-synaptic neuron terminal button area, just sort of waiting around for the action potential to arrive. Once it does arrive, the voltage-gated calcium ion channels open up, the calcium diffuses in, and this acts as a signal for these vesicles to merge with the actual outer membrane of the presynaptic neuron, and when they do so, that effectively

opens up the vesicle, and the contents of the vesicle are dumped out in the presynaptic cleft. What do these vesicles contain? They contain the neurotransmitters. So the neurotransmitters are already there. They're stored in these vesicles in the very end of the presynaptic neurons' axon, or axon terminal buttons, and they're just sitting there waiting for the calcium concentration to increase sufficiently. This calcium concentration won't increase sufficiently unless you have an action potential arrive, which triggers the opening of the voltage-gated ion channels that allow calcium to enter the cell, thereby causing the synaptic vesicles to fuse with the membrane of the presynaptic neuron, thereby dumping out their neurotransmitic contents

into the synaptic cleft. And a lot of the neurotransmitter molecules just sort of float around and diffuse and don't really do anything, but some of them will bind, just sort of by chance, basically, you know, they're just moving around, diffusing throughout the synaptic, through out the synaptic cleft. Some of them will bind to the receptors on the post-synaptic neuron. And those that do trigger a conformational change in the proteins of these receptors, thereby leading to the opening of voltage gated arm channels on the post-synaptic neuron. And these will be the usual potassium and or sodium voltage-gated ion channels that we talked about before. So, just to avoid confusion, the calcium-voltage-gated ion channels are only in the pre-synaptic

neuron, and they don't transmit any electrical signal themselves. All they do is open up to allow the concentration of calcium in the pre-synaptic neuron to increase sufficiently for the synaptic vesicles to dump out their load of neurotransmitters. That's all they do. The calcium itself is not responsible for a transmission. of electric charge or a change in membrane potential. Now, there are actually two types of graded potentials that we can get in the post-synaptic neuron.

Excitatory potentials, which increase the potentials. So remember, the resting potential of the post-synaptic neuron starts at negative 70 millivolts. Excitory potentials increase it above that, so make it less negative. Get it closer to threshold. And there's also inhibitory potentials, which further reduce the potential below resting level. makes it less likely you'll get to threshold. And it's quite possible that the post-synaptic neuron will have a whole bunch of synaptic connections, some of which will be producing an inhibitory greater potential, some of which will be producing an excitatory

greater potential at any given time. And basically all that happens is that you just sum all these up as they, well, they diffuse to the axon-hillick, and at the axon-hillick area, you sum up the contribution of all the positive and negative contributions, and you just see if you've reached threshold. If you reach threshold, then the post-synaptic neuron fires an action potential of its If you don't reach threshold, threshold, then it doesn't. So these inhibitory potentials, by the way, are caused generally by potassium chlorine ion channels, and chlorine is negatively charged. So if you bring chlorine into the cell, it further reduces the negative charge of this cell.

So that's how you can have that inhibitory potential, which further reduces the charge. Once a neurotransmitter has binded to a receptor molecule on the post-synaptic membrane, another neurotransmitter can't bind to that again and open it again. Like once the ion channel is open, it's open. Eventually the neurotransmitter is usually reabsorbed by the presynaptic cell, or sometimes it's broken down and metabolically, metabolically broken down and transformed into energy for some other part of the body to use. But often it's just taken up again and repackaged in these vesicles

and sort of then sits around waiting in the presnaptic neuron for another action potential to come along. But there are sometimes cases or ways of pre-snapections. preventing this re-uptake of neurotransmitters. And one example of this basic idea applied to practice is the class of drugs or compounds that are called selective serotonin re-uptake inhibitors. These are used in very common, many common antidepressants,

including, for example, Prozac, that is a selective serotonin re-uptake inhibitor. What it does is it inhibits, so stops or reduces, the re-uptake, that is the re-uptake by the presynaptic neuron, of serotonin, which is a neurotransmitter. And so if you're inhibiting the re-uptake of serotonin, then there's more serotonin sitting around in the synaptic cleft. Therefore, more serotonin sitting around in the synaptic cleft means you're going to get more binding to the transmitter receptors

on the post-synaptic neuron, and therefore more graded potentials on the post-synaptic neuron. And therefore, more likely that the post-synaptic neuron will produce an action potential because you've increased the number of greater potential, so more likely you'll reach threshold. So, hopefully that was not too complicated. at it again, I'll be posting some useful diagrams and images of neurons and synops and so on on the Facebook page shortly to help you get a visual idea of what all this stuff looks like. If you enjoy the podcast, please help to spread the word by encouraging friends, family, or

random strangers to listen. If you could also visit iTunes and post a favorable review and rating on the podcast page, that would be much appreciated because it all helps to increase the visibility of the show. Thanks for listening. and I'll talk to you next time.