Term
| The Concentration of Ions Across the Cellular Membrane Is Different |
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Definition
Neurons are electrically excitable cells that owe their excitability to the unequal distribution of ions across their cellular membrane.
Other concepts:
• Nernst equation
• Goldman equation (or GHK)
• Cable theory
The fact that you have several ions-- if we really want to calculate what the equilibrium potential of a cell would be after the contribution of many ions, then we need to expand the Nernst equation, and we use something called the Goldman-Hodgkin-Katz equation. That is only an expansion of the simpler Nernst equation to take into account many different ions. All of these calculations, by the way, came up from what we call cable theory that is extensively used for signals and systems, but that's a different story. |
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Term
• Summation
• Time constant
• Length constant
• Cable equation |
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Definition
I already mentioned before the concepts of summation, time constant. Now I introduce one which is new that you haven't heard-- is the length constant. All of these-- you don't have to learn them in detail, but it's good to be aware of them, because it is through these mathematical equations that we can explain the electrical properties and behavior of actions and of neurons in general.
What you have here on the right-hand side is an action potential. An action potential is a transient change in the polarity of the cell so that the inside of the cell becomes positive very quickly, and then goes back to being negative. Remember, the inside of the cell is negative with respect to the outside.
So on this axis, you can see that the cell is resting at about minus 70 millivolts, and then events might be happening. Those events, we will learn, are, for instance, post-synaptic potentials which are arriving, some of which might be excitatory, and some which might be inhibitory. The proper definition of excitatory and inhibitory-- and I will repeat this several times-- is not that excitatory is equal to the polarization, because you might depolarize a cell and actually make it more unable to fire.
So the proper definition is that excitatory post-synaptic potential is an increase in the probability of the post-synaptic cell to fire, while inhibitory post-synaptic potential is a decrease in the probability of that cell to fire. To fire means to release an action potential. Action potentials are all or none and types of events.
In other words, a cell cannot fire a quarter of an action potential or a fraction of action potential. Either the actual potential happens or it doesn't happen. And because of this manner in which action potentials happen, many times people equate them to 0's and 1's-- to digital behavior in a computer. And it is, indeed, some sort of digital code. 0's and 1's allows us to represent the occurrence of action potentials. |
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Term
| Neurons Are Connected... Neural Networks |
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Definition
| The point I want to make here is for you to realize that all of these cells are connected, OK? They are connected in the sense that they have synaptic contacts with each other. And I mentioned before-- a pyramidal cell in the cortex might have even more than 10,000 synaptic connections. In the local environment, they might have several, also, very close, nearby cells. |
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Term
| 2 parts of info processing in the CNS |
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Definition
information processing in the central nervous system has two parts. One is that-- and I mentioned it already-- the fact that action potentials are all or none events makes it digital-- makes information processing digital. They either happen or don't happen.
But all of these little fluctuations that we have-- that for many, many, many long years were thought to be just electric signals-- we demonstrated are not quite electric signals, but they do have an impact on the local environment of the action. And this has to do with the dynamics and the characteristics-- the electric characteristics-- of the action. And in the recordings that happen-- doing it both in the soma and the action that was caught-- it was determined that in the local vicinity, these local fluctuations impact the post-synaptic cell to make it simple.
Local signals are a hybrid of analog and digital, while digital signals are still just digital. The reason for that is that there is resistance in the action. Remember, the whole thing is analyzed using cable theory.
So still, when a signal has to go far away, the action potential is the only signal that is able to make it far away. Remember, also-- if it is traveling through a myelinated axon, it might be very fast in doing saltatory conduction from node of Ranvier to node of Ranvier. But in the local environment, the actions usually don't half myelin.
There's a very large amount of action collaterals in pyramidal cells, and all of those synaptic contacts have an impact. The local environment, therefore, communicates with analog and digital signals. |
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Term
| local vs long distance communication |
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Definition
A different way to look at the same type of information is shown in here, and what we have is recordings showing the local field potential and joint multi-unit activity and so on. Making the point, again, that the cell is embedded in a network of many other cells, all of which are communicating with each other.
It's complicated, and this is why it's so difficult for us to understand many of the aspects of communication in the nervous system. But in here, you have, again, a depiction of what I just described-- the fact that locally, you have a hybrid, digital, and analog. And distally, communication, again, is just based on action potential traveling-- so digital. And this brings us to the end of this part for neurophysiology. |
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Term
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Definition
Myelin increases conduction velocity by: 1. Increasingtheaxondiameter:
Why?
Remember: τ = R*C
Myelin increases R and decreases C, but R is the winner!—which increases τ... but, the main player is increase in λ because increased Rm increases λ
2. Insulatingtheaxon:
(Increases R); prevent leak of current
Now, if we were to think of actions in the myelin and so on in terms of their capacitance, as if they were a capacitor, then they have the time constant is equal to the resistance times the capacitance of that plate. Now, I don't want to get into a lot of the details, the mathematical details, of this, because it's basically irrelevant for you. But it's important that you understand basically what is going on. And what is going on is that myelin is able to increase the resistance. That is very clear. Because if you wrap around the axom some myelin, then you have increased the resistance, resistance to ions moving across the membrane.
But you have also increased tau. In tau, it's also increasing the length constant. The length constant that I mentioned before has to do with the time that it takes for the changes to occur. In the case of a capacitor, the tau it's time to charge. And length is in terms of space. It's the same concept but in space. |
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Term
Concepts:
• Nodes of Ranvier
• Saltatory conduction |
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Definition
| Myelin also insulates the axon. So it prevents the leakage of current, which is good for saltatory conduction. What you have in this schematic here is a depiction of what textbooks usually show. And they show myelin in this manner. And then they always show the nodes of Ranvier as the little areas where the axon is able to have exchange of ions. Because then it's like leaving one space that is not covered by this wrapping. |
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Definition
What you have next is an immunohistochemical demonstration of the presence of myelin. Myelin might not be present in every single part of the axon data. A lot of axon collaterals which are unmyelinated for local environment information processing, and then in here, using, by the way, the ferret prefrontal cortex, you can see in red using immunohistochemical for basic myelin protein, the wrapping begins on the axon. These little green, very thin axon is coming into the corpus callosum. And as it's reaching into the corpus callosum, it now gets wrapped in myelin.
Here you have another example of the same type of thing. So these things have been thoroughly studied, of course, because of their importance in communication between cells. |
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Definition
Remember also, and we mentioned this before, there are differences between the peripheral nervous system and the central nervous system. In the periphery, you have Schwann cells being able to wrap myelin around neurons. In the central nervous system, oligodendrocytes are the ones who do that.
When we look in electron micrograms, electron microscopy is used to look at the details inside of cells. Because light, regular light, microscopy doesn't have the resolution to be able to look, for instance, things that are nanometers in length. So when we look using electron micrographs, these very black, very dark wrappings around actions constitute myelin. Here you have another example in the peripheral nervous system. They are essentially just like you wrap paper or plastic around. So in a cross-cut section, they look like that. |
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Definition
If we go to a node of Ranvier-- this is a typical textbook example. What they are doing here in different colors is showing you the different types of value and channels which are involved. In here you have sodium 1.6 type of channel, which is very beautifully depicted in green. And then next to it, you have potassium channels. And then you might have other channels. And they show you in this diagram the different types of channels that are being detected at the level of the nodes of Ranvier. In here, this part that I hope you are able to see, it's the actual myelin sheet that is coming to an end here and then it begins again.
So this area of the node of Ranvier is full of ions. Now, surprisingly-- and I want to mention this just in case you read it in the literature-- there are ion channels underneath the sheets of myelin. And it's not clear why they would be there or if they represent some pathological condition. But in many instances, in actions that are behaving normally, there are still ion channels embedded in the membrane underneath the myelin. And of course, they cannot activate because the myelin prevents them from getting active. |
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Definition
| Following, there is another example on our own studies in which you see all these little green dots where it's stained for KV1.6 channels. In red, you have myelin. And you have dots because they are localized on the nodes of Ranvier. That's very different, and I will give an example for on how channels or these types of proteins look like in other types of membrane, like in the soma. |
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Definition
| In here, this is an example from ferret somatosensory cortex. Again, [? four ?] potassium channels-- KV1.6 and the nodes of Ranvier. And you can see an action bundle, because you can follow. Now we reverse the colors. And in red, you have the channels. And they look punctate. They look like dots because, again, they are the nodes of Ranvier. What you have here is several actions traveling together. And then it's very beautiful, actually, when we have a large field to be able to localize the nodes of Ranvier and see all these little dots that represent the channel that we might be looking at. |
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Definition
And as I said, it's different from the localization and the look that they acquire when they are, for instance, at the soma. These are KCNQ2 types of channels embedded in the membrane of the soma. This is also from the somatosensory cortex of the ferret. And then, what is nice here is that you can actually see the overall shape of the different somata, the different neurons that we are looking at.
You may also be able to determine, although this is more difficult, that there are some cells that do not express the channels. That brings us to an important point. There is a very particular type of distributions for channels of different kinds. Not only in different cell types, but even within the same cell, they might be unevenly distributed. You may have a particular type of channel around the soma then different channels in the axon initial segment and the axon [INAUDIBLE] and so on. You may have different channels in the axon and in the dendrites.
So the distribution of these channels in the different compartments of a neuron is what gives the different characteristics to the neuron. It gives them their differential ability to have electrical behavior. Otherwise, if all of them were the same, all of the cells will have equal electrophysical characteristics, which is not the case. And again, the importance of that is that these different electrophysiological characteristics provide the different cells with a different capacity to do information processing. |
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Definition
I want to also mention something that might be obvious to some of you and maybe not to some others. Being presynaptic and postsynaptic-- all cells are both presynaptic and postsynaptic, and it is just when we talk relative to each other. The cell which is sending information to the next cell is the presynaptic sending to the postsynaptic. But the postsynaptic cell might be the presynaptic one with respect to many others. And it may also be sending some information back to the cell where it received information from.
So the concept of presynaptic and postsynaptic is a relative concept. It has to do with the relationship between the two cells at any moment in time as to how they are behaving with respect to each other. Here also you have metabotropic and ionotropic receptors. And I also mentioned that before in terms of the speed with which they work. Remember, metabotropic [? might ?] subserve them later. Cascades are events that happen via a second messenger [? mechanism. ?] They are slow. While ionotropic are fast because they open to different ions. And how these ions bring their charge and make changes in the postsynaptic potential is what will give rise to either excitatory or inhibitory potentials. |
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Definition
Here you have the same diagram, a little bit more complicated, in trying to make the point that in this complex environment in which you have a soup of many different ions, some of them may not activate some of the receptors. Because they are, again, selective. They might be selective for a very particular type of ion.
What happens inside is complex. Many, many different things happen. The ions are of different sizes. They are of different charges. So the complexity of the events that are happening in here is quite high in terms of, for instance, as being able to model using computers all of these events. These things are difficult to model. |
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Definition
Because I did not want to forget one particular very important type of synapse, I put it on the lower part, the lower right hand side here. And it's what we call the neuromuscular junction. Neuromuscular junction is the junction, is the synapse, between an axon terminal directly into a muscle, via what we call the plate in the motor end plate. So communication initiated by neurons can go to other neurons. But it can also for the case of motor neurons go directly to the end plate and have an effect on skeletal muscle fibers. This is what allows a ferret information model commands to do.
When we cut the nerve or there is damage or lesions to the nerves that go to the muscle, you impair the ability of the muscles to react. Because it's not able to receive information anymore from the nervous system. Now, to keep things very, very simple, I'm going to repeat again things that I have said before. In terms of synapses, we take the same approach that we took with the neurotransmitters. I told you earlier to think of glutamate as the main excitatory neurotransmitter; GABA, which means gamma-aminobutyric acid as the main inhibitory neurotransmitter; the rest you may think of as neuromodulators.
Remember the idea of the accelerator and the brakes. For everything to work correctly, you want to be able to both accelerate, but you also need to put the brakes. GABA is the brake. Glutamate is the acceleration. And then the fine tuning of all of this is provided by the neuromodulators.
The synapses, we take exactly the same approach, if the synapse is excitatory or inhibitory or modulatory. So those are synapses, that involve glutamate are excitatory synapses. Those that involve GABA are inhibitory synapses. And the last are neuromodulatory synapses.
Now let's pay attention to some of the main things that happened for the conversion of the electric signal which is traveling in the shape of an axon potential in the presynaptic terminal to get converted into a chemical signal and then back into an electric signal in the postsynaptic cell. The arrival of the action potential, the presynaptic signal, depolarizes the membrane. And this causes the opening of calcium channels. Calcium [INAUDIBLE] inside of the cell and is responsible for the beginning of a cascade of events that will result in the release of neurotransmitter.
The transmitter then goes through the postsynaptic cell and docks into those specialized channels that we have been talking about and those receptors and the opens ion channels. Those ions will get into the postsynaptic cell and are responsible for initiating either excitatory or inhibitory postsynaptic potentials. If there are enough of them in time and in space-- that is, enough excitatory potentials-- they might reach threshold, and then the postsynaptic cell is then able to fire an axon potential. |
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Definition
I want to show you, again, one example from electron microscopy used to make another point. There are anatomical differences between excitatory synapses and inhibitory synapses. Among these differences, for instance, the fact that for the case of the excitatory synapse, they contain big, round vesicles. They are closely packed. And they are what we call asymmetric synapses. They synaptic cleft is on the order of about 20 nanometers. That means the distance-- synaptic cleft is the distance between the presynaptic and the postsynaptic membranes.
Now, inhibitory synapses usually contain small pleomorphic vesicles. They are loosely packed, and they have a symmetric cleft, which is of a different distance, about 12 nanometers. And here you have examples-- an example, again, of myelin wrapping around. You can see microtubules. You can see this beginning of the wrapping around of the myelin called the mesaxon. And here you have an axon. And here you have a spine. No need to get into more details. |
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Term
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Definition
the tripartite synapse
Let me now tell you something important about the tripartite synapse without going into a humongous amount of detail. This is, again, just to make you aware that although when we present information to you, we like to summarize everything and present it as a very simple thing, in reality, things are much more complicated-- very, very complex systems. One of these complications occurs with the content of the tripartite synapse that I have depicted both here using electron micrograph and as well on the side with the diagram.
Suffice it to say, what you have in most cases is not only a presynaptic and a postsynaptic cell. You also have glia in both. Now, the importance of the glia that I presented in the introductory lecture, as you're doing maintenance and so on, might be extremely important actually for not only maintenance but might have any impact on the way in which neurons might be able to communicate with each other. The reason is that they are active participants. They may be active participants in that communication between two neurons. In here, they are located in a very particular place on the side of the synapse. And because they are able to take glutamate, for instance-- this astrocyte is able to take glutamate to transport glutamate in or out as well less calcium and many other substances. They have a direct effect on how the behavior of this communication is occurring.
So again, without going into a humongous amount of details, remember, glial cells might be very active in the neural communication-- not only because they provide support and they provide the scaffold and so on, but because through their ability to move in and out of different substances, including neurotransmitters that get a spill from the synaptic cleft, they might release that back and have an effect. They might take it in and so on. They have an effect on active communication. And this brings us to the end of this very short lecture on neurophysiology. |
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