Hi, everyone welcome to this tutorial on the ionic basis of the action potential. What we're going to talk about today relates once again to one of our core concepts in the field of neuroscience, and that is that neuroscience communicate using both electrical and chemical signals. So today we're going to talk about one of the most important mechanisms within the nervous system for communicating with electrical signals We have some learning objectives for you today. I want you to be able to revisit the Goldman and even the Nernst equations and use those equations to gain an even deeper intuition about the membrane potential of neurons. To actually predict that value given knowledge of the concentration gradients of ions and their relative permeabilities across the neuronal plasma membrane. I want you to be able to describe the ionic basis of the action potential in terms of both the voltage and time depenedent changes in ionic permeablities that occur, that occur across the neuronal plasma membrane. I want you to be able to describe the driving force for current flow across the plasma membrane. Driving force will be an important concept that will help you understand the movement of ions through the ion channels that give rise to the action potential. But also through other kinds of ion channels that are gated not by voltage but by neurotransmitters so that discussions coming up in a few tutorials. Now as you work through these considerations I want you to relate with careful precision the time course of the changes in sodium and potassium conductance. Back to changes in the membrane potential during the course of the action potential. And lastly we'll talk a little bit about what's called the refractory period for the generation of the action potential. So I would want you to be able to characterize and discuss that concept. Okay, well let's begin by reviewing some of our foundational concepts that we introduced last time. And that is that changes in membrane permeability underlie the neuronal action potential. And in order to understand these changes in membrane permeability, let's consider some of the principles that are laid out in figure 2.7. Now recall that during the resting state, there is a little bit of potassium conductance. That is, a little bit of potassium leaks out of the neuron. So the permeability of the neuron at rest for potassium is some small value that's greater than zero. However, the permeability of that resting membrane for sodium is just about nil. So, even though the potassium permeability is small, it's still very much greater than the permeability for sodium. So what this means is that in the resting state the membrane potential is very close to the theoretical limit predicted by the[INAUDIBLE] potential for potasium. Now if we imagine some mechanism that allows for dramatic increase in the permeability of the membrane for sodium. We may find ourselves in a situation where the permeability for sodium is so much greater than the permeability for potassium that the membrane potential becomes predictable. By the Nernst equilbrium potential. Or the Nernst equilibrium equation for sodium. Such that the membrane potential approaches this theoretical value that we can calculate. The Nernst Equilibrium potential for sodium. And this is essentially what happens during the generation of an action potential. The permeability of the membrane goes from being just a little bit leaky for potassium, to now being explosively permeable for sodium. And that will explain the rising phase of the action potential. The falling phase, what we find next, is a bit more complicated. But essentially what we can say is that the permeability for sodium returns back towards zero and meanwhile the membrane restores its resting state where the permability for potassium is considerably greater. Then the negligible, or the nil permeability for sodium. Okay, now in order to review all of this and yet a different mode of learning I would encourage you to consider our, our formal expression for these changes provided by The Goldman Equation. And again, I would remind you that The Goldman Equation allows us to calculate an equillibrium potential when there may be multiple ions that can permeate through the membrane. So this equation includes a permeability term. For each ion that we might be interested in, And it also includes the concentration gradient, which allows us to consider the Goldman equation as an extension of the Nernst equation for permeate ions. Now maybe this more formal approach is less useful to you. That's okay. If that might be you, then I would encourage you to review these basic concepts of electrochemical equilibrium. Using the animation provided on the website that supports our text book. So you can click on the link in your tutorial notes, or navigate to that website following the link on our website. And select animation 2.2 on electrochemical equilibrium. And that will put you in great shape to understand the concepts that we need to consider to explain the ionic basis of the action potential. Well, finally before we get there I'll just remind you that what we talked about last time is that changes in membrane permeability Could have predictable consequences for the change in membrane potential. Now, what we're going to try to explain, beginning in this tutorial, is how is it that changes in membrane potential can impact membrane permeability? Now, much of the work that I'm going to tell you about in this tutorial And the next one that follows is based on the seminal work of two really, just amazing figures in the history of nerve science. Alan Hodg, Hodgkins, and Andrew Huxley. They were both scientists working in England during the time of the second world war, or actually just before it, was when their interests were being peaked by the possibility of recording bioelectrical signals From nervous tissue. And then, World War II intervened. And, well, depending upon who you are, what your family background is, and the circumstances of your family's journey to where you are today you might consider yourself fotunate that, that great war ended as it did. At least those of us in the field of neuroscience are very gratetful for the success of the allied forces because that allowed Hodgkin and Huxley to return in the mid to late 40s to their work understanding the ionic basis of the action potential. This work was recognized by the Nobel Committee in 1963, when together with Sir John Eccles, an Australian scientist, they were awarded the Nobel Prize in Physiology and Medicine. I would encourage you to read about their biographies, including that of Doctor Eccles, at nobelprize.org, where you can also find their Nobel lectures. Well, what Hodgkin and Huxley did as one means of beginning to explore the ionic basis of the action potential was to construct some circuitry that allowed them to do the kinds of experiments that they wanted to conduct. They recognized that in nature. We often have wonderful animal models that allow us to address the questions that we want to ask. In their case, they chose to examine the giant axon that's present in the body of squid. Which were readily accessible to these investigators in their location in the world. Now, in order to study the ionic bases of the action potentials, they wanted to measure ionic currents, but there's a bit of a problem. Because with generation of an action potential, there is a change in membrane permeability that will alter the flux of, Of ionic currents in a way that would make it very difficult to con-, to control and to measure those ionic currents. They devised a circuit called the voltage clamp. And, this voltage clamps circuit is illustrated here from your text book. I don't intend to burden you with the details of this, but I do want you to know that for those of you that are interested, you can read more about this circuit there. Essentially, what this circuit does, is it provides us with an opportunity for measuring. Ionic current, without changing the membrane potential. Hence this term, voltage clamp. We can essentially clamp the voltage of an excitable neuronal membrane to any potential that we wish, and thereby measure. The movement of ions across that membrane as we do these kinds of experiments. So I mention all this to say that we do want to look at a couple of experimental results derived from studies that Hodgkin and Huxley did, as a means of understand the ionic basis of the action potential. So let's begin. Now what we have here in figure three point one from your book is a representation of the kind of data that were available to Hodgkin and Huxley. With the voltage camp, clamp method, they were able to set the membrane potential. Of the squid giant axon to any value that they wished. And here in this experiment, what's being done is a hyperpolarization of the axonal membrane by 65 millivolts. So they're going from a resting value of about 65 millivolts down to about 130 and then they're holding the membrane or clamping it at that potential through some period of time. And they are measuring then the current that can be recorded during this experiment. So what's seen is a sharp transient, which is called capacitive current. This reflects the way charge is redistributed around the membrane. But otherwise nothing significant is happening. So with hyperpolarization there are no significant effects on net current that's flowing into or out of the axon. Now when they passed a de-polarizing current step into this neuron or in other terms when they clamped this neuron at a marked depolarizing level. That is around zero millivolts so they oppose this depolarization step. They saw something quite different and quite remarkable. Following a sharp transient current, what they saw was a transient inward current that, That was followed by a delayed outward current. Now just a word about convention here. In these experiments, inward currents are those carried by positively charged ions into the cell, and our convention is to denote that as negative whereas outward currents are currents carried by positively charged ions that are. Leaving the cell, and this is denoted in positive terms. Now there are other more complicated scenarios that we'll eventually discuss involving negatively charged ions, but for now we can keep it simple. So inward current means positively charged ions are entering the cell, and outward current means positively charged ions are Exciting the cell. Okay, well what we want to be able to do is to understand the underlying changes in ionic fluxes that are explaining these two kinds of currents that were recorded. A transient inward current and a delayed Outward current. And in order to get there Hodgkin and Huxley were able to use both some theory and also some impirical investigation of this system. So the theory comes in the form of the Nernst Equation, so Hodgkin and Huxley knew about the equilibrium potentials for permeate ions even though they weren't sure what those ions were at the time that they began their experiment, they knew that in principle. One could determine or manipulate a ionic species that you think might be permeating the external plasma membrane. And use the Nernst equation to calculate the impact of that permeable ion, given it's known concentration gradiance. Well I'll just remind you then that the nerdist equation is a tool that can be used in studies of this sort, and I'll use that equation to remind you of this concept of equilibrium potential. So remember at equilibrium potential There's no net movement of current. So in an experiment like this we would record a current of zero at electrochemical equilibrium. So again, this is the point where the concentration gradient for a permeate ion is exactly counterbalanced by the electrical gradient that builds up with the movement of that charged ion. Now knowing these two facts it's possible to do experiments then, where we can manipulate the membrane potential of an axon or of a neuron and allow for a prediction on the movement of that ion. And as should be intuitively obvious to you, I think, if you choose to clamp the membrane potential at the equilibrium potential for a permeation, then that ion is no longer going to, going to contribute to the measured current. Because by definition, at equilibrium potential there's no net movement of the ion. Okay, so these are the kinds of considerations that are brought to bear in the following experiment. So now, what is being described, and figure 3.2 from the textbook Is the results of producing an experiment now where there are incremental changes in the voltage clamp setting in the depolarizing direction. So we're starting off at rest, somewhere around 65 millivolts. And we are now applying a depolarizing current step from rest to different values of depolarization. First approaching zero millivolts and then even going beyond zero millivolts. That is making the inside of the cell more positive than the outside of the cell. And what we see is that as we begin to depolarize this membrane from rest, there is indeed a transient inward current followed by a delayed outward current. But notice the magnitude of these currents. With small depolarizations, the currents that are measured are relatively small. With larger depolarizations, like around zero millivolts The transient inward current increases in size as does the delayed outward current. But now look at what happens to the transient inward current as we depolarize to plus 26 millivolts. This transient inward current is getting smaller. But, look at the effect of the delayed outward current, it continues to grow in magntitude. Now, we approach plus 52 millivolts in the experimental data and what we find is, obviously, quite a large growth of the delayed outward current. But notice, the, the transient inward current seems to have gone away completely. We'll come back to that point in just a moment, but now let's move on. If we depolarize the cell even further, again we continue to see growth of the delayed outward current in a relatively monotonic fashion as we change membrane potential in the depolarizing direction. But now look at the point in time where we earlier recognized a transient inward current. What we see is a small inflection in the rise of this outward current. In fact, what appears to be happening is that the transient inward current is no longer inward. But outward. And this might explain this small shoulder effect that we see in the development of this outward current. Okay. Well, these considerations allow us to make. A couple of points. First of all, we see that this transient, inward current appears to be nulled out with membrane potential around 50 millivolts. And then when we go beyond 50 millivolts or, in this result perhaps precisely 52 millivolts. This inward current reverses. It becomes an outward current. The second observation we make here is that the delayed outward current steadily increases with increasing depolarization. Now, we can measure these currents at particular points in time and plot their magnitude as a function of membrane potential. And when we do that we have data that look something like this, which capture again what we've just described. And that is, that with depolarization, the transient inward current grows. But we eventually hit a point of reversal and that delayed inward current becomes an outward current with the crossing of 0 millivolts being somewhere around 50 millivolts in membrane potential magnitude. Now the delayed outward current behaves differently. It continues to grow monotonically with increasing membrane potential. Now, these observations together again provide evidence That this transient inward current reverses near 50 millivolts while the delayed outward current increases steadily. Now, knowing something about the ions that are present in seawater and having some sense of what the ionic contributions might be to the cytoplasm within axons. Knowing something about the Nernst equation, and then having the ability to manipulate some of these empirical parameters in the experiment, allowed Hodgkin and Huxley to identify What are in fact the ions that are carrying these 2 kinds of currents. What they concluded is that the early current is carried by sodium. Now the nuanced equilibrium for sodium happens to be very close to plus 52 millivolts in their experimental. Preparation. That is highly circumstantial evidence supporting this conclusion that the early current is carried by sodium. One way to test that hypothesis would be to change the solution that is bathing the neuron. And if you substitute the solution with one That removes all sodium, the prediction would be that the inward current ought to reverse to become an outward current because even though the normal physiological concentrations of sodium are much greater outside than they were in compare to the inside. If you artificially remove all sodium from outside the cell, there will be a concentration gradient favoring the efflux, or the outward flux, of sodium. And that appears to be what is recorded in this experiment. And then returning back to normal physiological conditions, similar to what we find in sea water, the inward current is once again restored. This conclusion is further supported by experiments using a toxin found in nature, a toxin called tetrodo-toxin. Found in the pufferfish and when that toxin is applied to this axon, what we find is that the transient inward current is blocked. All we're left with is a delayed outward current with the application of tetrodotoxin. So that result provides additional empirical evidence. Supporting the conclusion that the early current is carried by sodium. Now, additional experiments were done using a tetraethyl-ammonium ion, which is now known to block potassium channels. And when that ion channel blocker is applied to this preparation, what we find is that the delayed outward current Is removed. And all that we find is the transient inward current. So this is very good evidence supporting the conclusion that the late current is indeed carried by potassium ions. Okay. Well I think we are ready to move on in our consideration of these data and I want to introduce an additional concept that I think helps us come a little bit closer to the underline biological mechanism that explains the ionic basis of the action potential and this concept that I want us to think about Is conductance. Now, we're familiar with Ohm's law from our study of physics. Right? And so Ohm's law is v equals i r, or voltage equals current times resistance. Well this concept of conductance, while it has more of a formal expression. For our purposes we can represent conductance by the lowercase letter g, and simply state that it's comparable to the inverse of resistance. So it's possible, then, to rewrite Ohm's Law in terms of current. And what we can state, then, is that measured current is proportional to the conductance for that permeant ion times the voltage. Now this voltage term is interesting. This voltage term provides the driving force for the current that we can record that is passing through a neuronal membrane. But in order for that current to actually flow not only must there be a driving force but there also has to be some means by which that ion can pass through the membrane. Which is to say, there needs to be conductance. So I want you to appreciate, using this version of ohm's law, that current flow really requires two kinds of functions. There needs to be conductance greater than zero, and there needs to be some voltage that creates a driving force term. And so rather than saying that the voltage needs to be greater than then 0 of what we need to express is that the voltage must be greater or different from the nuanced equilibrium potential for the permiant ion. Okay. So this allows us now to return to our experimental situation where we changed membrane potential and recorded current but now we get to introduce. This version of Ohm's Law that helps us understand the movement of ions in terms of the conductance of the membrane for the permeant ion. So again, what we have here is a current which can be measured experimentally. We know something about the membrane potential of the neuron and, given the concentration gradient of, of the[UNKNOWN] ion, we know it's Ernst equilibrium potential. So the driving force term then becomes, the difference Between the membrane potential at any point in time and the nernst equilibrium potential for the permeant ion. So what would happen then, if the membrane potential is exactly the nernst equilibrium potential for the permeable ion? Under that situation, the driving force is equal to zero. And no net current is going to flow. This is one way to establish electrochemical equilibrium for a permeant ion. That is, it's possible with the patch-client method to set the membrane potential exactly to the nerve's equilibrium potential for the ion in question. Well, this formulation should make it obvious that there is another way in which to have no net current flow for an ion. And that is when conductance is equal to zero. That is when there's no means by which an ion can cross a membrane. There may be a driving force, but if there's no conductance then the measured flow of that current is going to be zero. Okay, well these are some theoretical ways of considering the experimental results obtained by Hodgkin and Huxley and what's shown now in the lower part of figure three point three are the same Data. Except now, the measured ionic current is expressed in terms of the conductance that is associated with the transient current and the delayed outward current. Now having confidence that, that In that transient current is carried by sodium, and the delayed current is carried by potassium. So what we can now do is express these current fluxes in terms of conductances for sodium and potassium. So let's look at these one at a time. When we look at the conductance change for sodium with depolarization, what we see is a very sharp and steep rise in sodium conductance that happens with increasing depolarization. So it should be obvious then that the sodium conductance is voltage dependent. But look what's going on here, even with a sustained depolarization, this conductance, that quickly rises well above zero, falls back towards zero. Even though we continue to clamp the axon membrane to some value, as indicated here in the figure. So this tells us that this conductance is not only voltage-dependent but it's also time-dependent. Actually, the same conclusions can be made with respect to the potassium conductants, but in a different way. What we see is with increasing depolarization there is a growth to this potassium conductance. So like the sodium conductants, there's evidence for voltage dependency. But notice The growth is gradual, and the onset of this conductance is slow relatively compared to the onset of the sodium conductance. So there's an element of time dependency that we see for the potassium conductance. Now, that conductance does not fall back down sharply the way we saw for the sodium conductance. Rather, the time dependency is in the relatively gradual onset of this rise in potassium conductance that we see. So nevertheless, both conductances are time dependent. But the time dependency seems to suggest that there may be different molecular Mechanisms that mediate those time dependencies. Okay. Let's return now to the sodium conductance and make an additional point about this rapid fall in sodium conductance. That we see after the rapid rise. So, we actually have a term for this, we call this, inactivation. Now, as we'll see in the next tutorial, inactivation is not exactly the same mechanism as simply closing. An ion channel. So we're going to want to understand that point in the next tutorial, but for now, I'll just highlight the fact that the sodium conductance inactivates. And what we mean by that is this rapid fall in conductance that follows the rapid rise. Now notice, the potassium conductance does not inactivate. So there's no inactivation of the potassium conductance. Now there are certain types of potassium conductances that can be found in certain neurons that do in fact inactivate much like the sodium conductance, but not this conductance. Not in this axional membrane from which these experiments are derived. Okay I think we're ready to put all this together now and have. A computational model that explains the action potential. So, what we have here is a precise alignment of the voltage and time dependent changes in sodium and potassium conductance. Relative to the action potential. And I want you to spend a little bit of time thinking about this figure, figure 3.8. And considering the alignment of these conductance changes with what we see in membrane potential. And the conclusion of such a thought process is that the action potential is indeed explained by the voltage and time dependent changes in the permeability of the neuronal membrane to potassium and to sodium. Now let's look first at the sodium conductance and how it's aligned to the action potential. There is a sharp rise in sodium conductance that occurs in time, with the rise in Membrane potential during what we call the rising phase of the action potential. In fact, the rising phase is explained by this rapid increase in sodium conductance. Now, we haven't explained yet how that itself got started. But we'll come to that in the next tutorial. For now, I'll simply state that some external stimulus was applied to this experimental situation. Or, if we can imagine, a real neuron or a real axon in a real brain, some stimulus in the form of incoming electrical signaling activity, potentially can depolarize that cell and produce this explosive increase in sodium conductance. That explains the rising phase of the action potential. But, again, let's notice that the increase in sodium conductance is short lived. Soon thereafter, there's this falling phase, which we call inactivation of the sodium conductants. And in terms of the membrane potential that can be recorded, this is called the falling phase of the action potential. So we have the rising phase on the up slope, and now the falling phase on the down slope. Now this sodium channel on activation. I know I'm getting ahead of myself just a little bit with respect to the tutorial notes, but it does allow us to explain an important phenomenon called the refractory period. So there's a period of time during which it's not possible to generate another action potential And that's called the absolute refractory period. That's happening during this time of sodium channel inactivation. Because in order to generate another action potential, these sodium conductances need to be reset back to zero. So this inactivation Has to be removed in order for another action potential to fire. So the period of time during which the sodium channels are progressing through their inactivation state, is in fact the period of time that we call the absolute refractory period. Alright, so let's now turn to the potassium conductance. The potassium conductance is delayed relative to the onset of the sodium conductance. But it's also sustained for a longer period of time. And this sustained conductance for Potassium. Allows potassium to flow out of the cell, and that means positive charge is leaving the inside of the cell. This delayed outward current, or delayed potassium efflux, contributes now to the falling phase of the action potential. And notice that at the conclusion of the falling phase of the action potential, the membrane potential actually undershoots the resting membrane level by just a small degree. So this is called the undershoot. And it is explained by the ongoing efflux of potassium ions. Now, when we first considered the ionic basis of the action potential in principle, it was sufficient to say that the resting membrane potential is. Approximated by the Nernst equilibrium potential for potassium. Now, we can state that that's not exactly the case. The Nernst equilibrium potential for potassium is actually much closer to the nadir of this undershoot. The actual resting membrane potential, I'll call it v rest, in this case is about minus 65 millivolts, not quite where the[UNKNOWN] equilibrium potential for potassium would be because there are other complications, other Ionic fluxes that we haven't taken the time to consider and, and that's okay. We can simply state that the resting membrane is not an ideal membrane permeable only to potassium. If it were, then Vrest would be precisely Ek. But these is a small offset and that allows us to explain This undershoot. Now, we've been emphasizing the time dependencies of these conductances. I don't want to overlook their voltage dependencies. So as the action potential is its falling phase and undershoot phase This membrane is now becoming hyperpolarized relative to rest. And as it does so, the potassium conductance trails back down towards it's starting point. So as the membrane is hyperpolarizing. Returning towards rest and then undershooting rest, the potassium conductance is shutting down. Okay. Well these considerations allow us to consider just a couple of other aspects. Of action potential behavior that are worth noting. We've talked some about this concept of threshold. Now, I think, we can approach this in a bit more of a formal way. We know that there is some thing like a threshold. We saw that a couple of tutorials ago, where when exceeded there is a Runaway positive feedback cycle, where membrane depolarization leads to increased sodium permeability. So sodium rushes into the cell and that leads to even further depolarization. This is the rising phase of the action potential. Well, that's accomplished when we stimulaate the axon or when the axon And the neuron receives stimulation from some other source, such that the threshold for generating this positive feedback cycle is exceeded. So we might call that a super threshold depolarization. Now we can also move the cell in the depolarizing direction away from rest and not hit threshold for firing an action potential. That would be what we might call the subthreshold depolarization. So what's the difference? What's the difference between a depolarization that achieves threshold and one that doesn't? Well the difference is whether that depolarization crosses threshold, and threshold therefore can be defined as the membrane potential when the sodium current is Exaclty equal to the potassium current. That is, it's a tipping point, where just as much potassium is able to leave the cell as sodium entering the cell. Now, because the sodium conductance opens so much more quickly than the potassium conductance, Depolarizations of a sufficient magnitude are certain to trigger an action potential. Because we know that it's possible for so much more sodium to enter the cell than potassium leaving the cell that we're driving this cycle past threshold and generating the rising phase of the action potential. Another way to conceptualize this is to consider the regenerative nature of the action potential. We've been talking about this vast positive cycle where sodium is entering the cell, leading to further de-polarization and the opening of even more sodium-permeability channels that increase sodium current and further de-polarize the membrane. Until the point at which that conductance begins to inactivate. So this is a picture of exceeding threshold and running this fast positive cycle. But we also have a slower negative cycle, and this is set into motion as the membrane begins to depolarize and the permeability channels for potassium begin to open up more slowly, but as they do Potassium channels are opening, potassium is leaving the cell, and this leads to more of a negative feedback promoting the repolarization and eventually the undershoot of the membrane potential. Now, it's interesting is it not, that the negative cycle is slow. And the positive cycle is fast. This, this temporal dependency ensures that the action potential can be an explosive event. That is, the rising phase can happen unimpeded by this more slow negative phase. However, the negative phase eventually does dominate Yes the sodium conduct-ants is beginning to en-activate but the potassium conduct-ants will drive the membrane back to resting levels and even below rest to undershoot. So the slow negative cycle. Seems to be nature's way of ensuring a rapid signaling event that is an action potential of a short duration. Now there are action potentials in nature that can be longer because other ion channels are involved, but our Canonical action potential that we find in axons and neurons is of this sort: a sharp rising phase followed by a sharp falling phase, with an undershoot. Now, this slow negative cycle also allows us to explain the rest of the refractory period. I mentioned that the absolute refractory period is when sodium conductances are in their inactive state, and it's not possible to trigger a second action potential until that inactivation state is removed. However, there is a relative refractory period that will be present As long as we continue to have this slow negative cycle turning away, which is to say the membrane potential is an undershoot. Now during that time it is possible to trigger a second action potential because this sodium permeability channels are ready to fire again. However with undershoot they're Is, therefor, a need for a slightly stronger stimulus that can overcome that undershoot and bring the membrane potential to threshold in order to fire an action potential. That's why this refractory period is said to be. Relative. Well, together then, this fast positive cycle, this slow negative cycle, allows us to understand the shape and the duration of the action potential, and it also raises some interesting philosophical points, I think. It suggest that there is a limit to the speed of processing in the nervous system. And that limit is defined by the width of the action potential. Of course that limit is actually an aggregate of the billions of action potentials that are happening all the time in neural circuits and neural systems. But in principle, there is a limit to what can be defined as the moment. In fact, the aggregate consequence of this action potential width, is that our brain is perpetually living in the past. We are processing right now information that just happened. A few tens, or perhaps even hundreds of milliseconds ago. No, I'm not talking about memory. I'm talking about the brain working on the incoming flow of information. And because of the width of the action potential, and as we'll see in a few sessions, the delay that comes with synaptic transmission, it takes some time to elaborate our thoughts and our perceptions and our emotions. So from that standpoint, we would seem to be at something of a disadvantage, living in a world in real time knowing that our brain is living perhaps a few hundreds of milliseconds in the past. But. Brains are wonderful organs. One of the best things they can do is predict the future. If fact, our brains are constantly updating our model about the future, so that we can anticipate the actions that happen in real time in the world. So even though the width of the action potential imposes a bit of a delay. In our neural processing we make up for that delay by being able to predict behavior in the future. Well, enough of that philosophy for the moment. I think we're ready to wrap this up. And I'll leave you with a study question. Which you can find at the bottom of your tutorial and you can find it online in our next slide. So, consider this regenerative nature of the action potential This fast positive cycle and the slower negative cycle. But I want you to think about, why is the action potential a spike? That's sometimes the term that neurophysiologists use to describe the action potential. Which of these factors listed below do you think is the best explanation for the short duration of a typical neuronal action potential? Okay. I'll see you with the next tutorial.
