Neurotransmission Lecture PDF

Lecture 17 – Neurotransmission Video 1 Introduction what you can see in this image really is highlighting the two different things that we're going to be talking about today. One is how we are going to propagate an electrical signal along our axon, which we started to talk about a little bit last...

Lecture 17 – Neurotransmission Video 1 Introduction what you can see in this image really is highlighting the two different things that we're going to be talking about today. One is how we are going to propagate an electrical signal along our axon, which we started to talk about a little bit last day when we talked about action potentials and how voltage-gated ion channels work. So one, how you send a signal within a specific neuron is one part of neurotransmission. The other part of neurotransmission is sending the signal from one neuron to another neuron or to a target tissue. So in this image you can see there's incoming messages coming from two different neurons. It's reaching the postsynaptic terminals of each of those neurons. And then we need to somehow get that signal across to this outgoing message neuron. So it's going to gather the signal from different directions and then create a signal that is going to go elsewhere in the body. So we're going to talk about how all of these processes happen today. Slide 2 The first thing that we're going to highlight are how action potentials are propagated along the length of our axon. So if you recall from last day when we talked about voltage gated ion channels, they create action potentials. And what happens is we actually get a series of action potentials happening in succession as we have each voltage-gated channel being triggered along the length of the axon. So essentially what happens is our action potential spreads over the surface of the axon, starting at the trigger zone. So as the sodium flows into the cell during depolarization, the voltage of the adjacent areas of the plasma membrane are affected, and therefore their voltage gated sodium channels will open. So this is a self-propagating system along the membrane. So it's just like our dominoes that we talked about, we just need to flip the first domino and it will knock down all the dominoes in a really long line. When we're talking about a traveling action potential and remember they don't really travel, they're just triggering numerous action potentials spreading along the surface of the axon. That's what we're referring to when we talk about nerve impulses or an electrical signals. So here's our neuron and you can see this is the cell body region and we're going to be getting signals from other neurons in this cell body region. So that's going to be part of what we're talking about today, so what's happening at the synapse level. And that will create the graded potentials that we need and if we have a large enough depolarizing graded potential that it creates change in membrane potential that reaches threshold in the area of the trigger zone, then that's what's going to start the depolarization phase of the very first voltage gated ion channel. So once we get that first voltage-gated ion channel triggered, then that will change the membrane potential all along the rest of the axon as all the other voltage channels go off. So this is what's going to allow that action potential to propagate along the length of the axon. And we're always moving from the cell body towards the pre-synaptic terminals. So once we get to the presynaptic terminals, we need to have some sort of communication with the target tissue. And that communication is going to be via a chemical signal that gets sent from our presynaptic terminals to our postsynaptic membrane. So that's what we're going to be focusing on today. Slide 3 So when we talk about propagation or spreading of action potentials along the length of the axon, it can actually happen in two different ways. One for unmyelinated axons and one for myelinated axons. So in an unmyelinated axon, the spreading or propagation of our action potentials is called continuous conduction. And this is actually what we've been referring to when we talk about the movement of action potentials so far. So an action potential occurs at one spot in the membrane, specifically it starts in the trigger zone, but it can propagate by stimulating adjacent areas. So basically, as the membrane potential changes when the voltage-gated channel opens, it triggers the neighbouring voltage-gated channels to go off. So this is actually called continuous conduction. So again, technically the action potential doesn't move along the axon, just one action potential stimulates another action potential in an adjacent location. One thing we haven't highlighted yet is that action potentials can only spread in one direction. So in a neuron, they're always going to move from the trigger zone down the axon towards the pre-synaptic terminals, they can't ever go in the reverse direction, and I'll explain to you why that is the case. Slide 4 So this is an image highlighting what continuous conduction looks like. So in the axon region of our neuron, it's blown up here and it's cut it open so that we can look at the charge differences on either side of the membrane. So remember in resting membrane potential conditions, the outside is positive, the inside is negative. But when we have an action potential for at least a brief period of time, the inside will become positive and the outside will become negative. So that's what it is trying to depict in this image. So where we have this darker orange colour that's showing an area of the membrane where an action potential is occurring. So again, what's actually happening here is the voltage gated sodium channels will open, sodium rushes into the cell and brings its positive charge with it. And this is going to happen around the diameter of the axon. As sodium rushes in it creates something known as a local current. So that's the movement of the positive ions into the center of the axon. And then those positive ions are going to be attracted to the negative areas that are just inside the membrane. So they actually diffuse towards those negative areas. And that's what's actually going to trigger the neighbouring voltage gated channel to go off. So then the action potential will occur in the next portion of the membrane. So this would continue along the whole length of the axon. Now if you notice here we have some of these local currents going in the reverse direction as well, but the action potential can't actually move back towards the cell body. The reason for this is because this area of the membrane is still in the absolute refractory period. So the absolute refractory period of the action potential that just occurred is actually preventing the action potentials from reversing in direction. So this is what's actually allowing them to only go forward and not go backward. Essentially, we desensitize the area of the axon because still in a portion of the refractory period. So we can't really stimulate that part of the membrane. So that's what forces it to go in only one direction. So that's continuous conduction. Slide 5 The other type of propagation is what happens in myelinated axons. In myelinated axons, we still have the local currents except instead of stimulating every single portion of the plasma membrane, we go from one node of Ranvier to another and this is known as saltatory conduction. So we still have local currents flowing except now they're flowing between nodes of Ranvier. At the nodes of Ranvier, we have many, many more sodium channels, so they're concentrated in those areas. So that's going to allow us to have a large fast change in membrane potential because we can open many channels at once, large, fast depolarizations that's going to allow the local currents to jump from one node of Ranvier to the next and this is going to make the propagation of our electrical signal or action potentials move much faster along the length of the axon. And that's why myelinated axons transmit signals so much more rapidly than unmyelinated axons. So the flow of the action potentials is much faster because it acts like it's leaping along the axon as opposed to walking. So the analogy I once read was like a grasshopper walking along the floor versus leaping or jumping across the floor, it's much faster to get there with the jumping effect. So in this sense, that's exactly what's happening, we're jumping from node of Ranvier to node of Ranvier. Slide 6 So this is what it looks like. Again, our axon except now we have some myelination via some Schwann cells. So where the Schwann cells are located are known as internodes, and then in between those are our nodes of Ranvier. So where we have the orange that represents where the action potential signal is at that time. So starting with the action potential at the beginning, you can see it's positive on the inside, that's because the sodium is rushing into the cell, except now our local current goes through the entire length of the Schwann cell to the next node of Ranvier, and that will trigger the voltage-gated channels in that area to open. Again, we get another action potential in that area. And it will continue to do this along the length of the axon. We still can't go backwards, we still had the effect of the absolute refractory period to stop our action potentials for moving in the reverse direction, but instead of depolarizing the end higher plasma membrane, we're only depolarizing these little regions at the node of Ranvier. This has a couple of different benefits. One of course is that it makes everything much faster in the way that we're moving the electrical signals. But also it uses less ATP, so it's more energy efficient. So if you'll remember to re- establish resting membrane potential, we need those sodium potassium pumps in, they require ATP. So if we're not depolarizing the entire membrane all the time, There's not as much of the re-establishment of the resting membrane potential, we won't need as much, we'll just need to change it or bring it back to normal at the nodes of Ranvier. So it's much more energy efficient as well as much faster to transmit the signals. So next we're going to watch a quick little animation that helps to visualize these two forms of propagation. Animation No caption file Video 2 Slide 7 In addition to having both saltatory in continuous conduction, there's some other factors that can also affect propagation speed. The first one is axon diameter. Now if you recall, when we talked about the structure of a neuron, we said that the axon diameter is constant along its length, but different neurons can have different axon diameters. So essentially, if we have a larger diameter axon, there's more surface area. More surface area means more voltage gated sodium channels can be in the plasma membrane. If there's more channels than we had faster local currents. So it's sort of like concentrating at the nodes of Ranvier, like we said, with saltatory conduction, except in addition to that, if you have a large diameter, you can also have even more voltage gated sodium channels. So larger diameter, faster propagation speeds. If we're comparing different neurons and the amount of myelination they have, so the amount of times the Schwann cells or oligodendrocytes wrap around the axon, if we're heavily myelinated, then were much faster with our propagation speed compared to more lightly myelinated or less times wrapping around for our Schwann cells or oligodendrocytes. The last thing that can affect propagation speed is temperature. So action potentials propagate more slowly when our axon is cool. Like you, this has something to do with the functioning of the gated channels. They are proteins and proteins can be affected by temperature. So the physical changes in the protein structure that happen in order to open the gates are more slowly occurring because of the cool temperature. Slide 8 In terms of the different types of fiber types we have, there are three main types of nerve fibers. Type A have large diameter myelinated axons. These are our fastest nerve fibers and they conduct action potentials from 15 to a 120 meters per second. These are going to be the type of nerve fibers we see in motor neurons that are supplying skeletal muscle, as well as the majority of our sensory neurons. Which does kinda makes sense, if we want to have fast interpretation of sensory information from our environment, we want to have quick skeletal muscle responses, we need to have the fastest nerve fiber type for those types of information. Type B fibers are medium diameter and they're lightly myelinated, so the Schwann cells or oligodendrocytes are not going to wrap around as many times and because they're medium diameter, we're not going to have as many voltage-gated sodium channels around the plasma membrane. So these are going to be a little bit slower, they conduct signals anywhere from three to 15 meters per second, and these tend to be part of the autonomic nervous system. So the autonomic nervous system remember, is going to go to smooth muscle, cardiac muscle, and glands. The last type is Type C, these are our small diameter unmyelinated axons. So these are going to transmit action potentials the slowest of all the types at around two meters per second or less. These are also part of the autonomic nervous system. Now if you think, well, why do we have these really slow ones? Well, many process in the body don't need to happen rapidly. For example, digestion. It's not like we need to send a signal to our digestive tract to rapidly break down our food. So we don't always need to have these fast types of nerve fibers. We can use these unmyelinated small diameter types of nerve fibers in certain situations that it might not require quite as faster response. It's still pretty fast to meters per second would be the length of your body in less than a second, but it's slower compared to what we see for the sensory and motor neurons. So before we move into the synapse, let's pause here and do some practice questions. Video 3 Slide 9 So now that we know how we conduct the action potential along the length of the axon. What happens to the signal when it gets to the end of the axon or the presynaptic terminal? And then how can we send that signal from one neuron to a target tissue, which in this case is another neuron? So how do action potentials in one year on communicate with other neurons? Well this happens at a junction between the cells that allows one to communicate with another and that's called a synapse. So we've talked about synapses already several times, but now we're going to focus on what's happening at the synapse. This is just showing the synapse between our first neuron and the two target neurons. The first neuron in this synapse is called the presynaptic cell, or the presynaptic neuron. The two neurons that are coming after the synapse are called the postsynaptic cells or the postsynaptic neurons. The postsynaptic cells could also be target tissues, for example, skeletal muscle, so any tissue that is receiving a signal can be a postsynaptic cell. In this case, we're just talking about another neuron. There are two types of synapses. Electrical synapses and chemical synapses. We're going to talk about both types of synapses now, but really electrical synapses are not found in the nervous system. These types of synapses are what we find in cardiac muscle and smooth muscle. So they're still used in electrically excitable tissues, but just not neurons. Neurons use chemical synapses. So I just wanted to highlight that for you now. Slide 10 So in an electrical synapse, there's actually a junction between two cells. So in our example here we have some smooth muscle cells. So as you can see, smooth muscle cells are closely packed together and they connect to each other via these little electrical synapses. So we're physically connecting one cell to the neighbouring cell. So what's happening in the image at the bottom here is we're blowing up one of these connections between two neighbouring smooth muscle cells and this is what we see. So this represents the plasma membrane of the top cell, and then this represents the plasma membrane of the adjacent cell that's just beneath it. See there's a physical connection between the two cells. There is a small gap between the cells and that's known as a gap junction, but really this is only about two nanometers in distance. So it's not a large space and it's enough that we can take these proteins that are going to attach one cell to the neighbouring cell. So these are tubular proteins and they're known as connexons. They're physically creating a channel or opening from one cells cytosol to the neighbouring cells cytosol. So if you can imagine how this is going to work, if we have some positively charge ions on the inside of this cell, so again, remember the insides of cells at resting membrane potential are typically negative and the outsides of the cells are positive. So imagine that was the resting condition, but then this cell becomes depolarized. So that means an action potential is propagating along the cell membrane. And this happens very much the same as what we saw along an axon in this smooth muscle plasma membrane as well. So the action potentials propagating along the plasma membrane and where the action potential is located, we're getting more positively charged ions, because remember this sodium is rushing into the cell. Once the action potential reaches the area where we have these connexons, the positively charged ions are attracted via a local current to the negatively charged area on the inside of the neighbouring cell. So that's actually going to cause a local current, bringing those positively charged ions through that connects on to the neighbouring cell and essentially those positively charged ions will trigger a voltage-gated channel on the inside of this plasma membrane. So that will allow for the cell up here to have an action potential and then trigger the neighbouring cell by physically moving ions from one cell to the next. So it's triggering now the voltage gated channel here and that's going to create another action potential. In addition, it spreads along the muscle cell and it will go through all the different connexons. So we're going to have the action potential continuing on. You can see there's one connection there, there's another connection there, so it will continue to move along the entire plasma membrane of the muscle cell. So it goes along, but at the same time the ions are moving through and creating action potentials on this side of the plasma membrane as well. So you can see how it's going to quickly spread from one cell to the next. Now this is one of the situations where we actually have action potentials moving in two different directions. But like what we saw with our axon, the action potential is moving away from where it started. So when the axon, it starts at the trigger zone and then it moves along the axon to the presynaptic terminals and it can't go backwards. In this case, it starts at the connexons and then it spreads away from the connexons and it can't go back towards the connexons. So even though it's going into different directions here, it's still actually moving away from where it started. So it's still taking advantage of the fact that it's going to have an absolute refractory period and it can't go backwards towards the connexons. So this is going to continue on the next cells, then going to depolarize and it's going to send the signal to the next cell, to the next cell, to the next cell. So this essentially causes what looks like this. So we get these little local currents and that's going to trigger action potentials in the neighbouring or adjacent cell. This type of synapse is very important for coordinated contractions. Imagine if you just had portions of smooth muscle contracting and other portions don't get triggered, we need to have a nice coordinated response. We're also going to see these types of synapses and cardiac muscle, which again, you can imagine your heart beating, that's a very coordinated process, we need to have all the muscle fibers working together and that's why they use these types of synapses. So we will see this as I said, in cardiac muscle as well as smooth muscle. So that's all we're really going to talk about for electrical synapses right now, we will highlight these again when we start to talk about cardiac muscle if you take term two of the course and we look at the heart. Slide 11 But for what's happening in a neuron, it's a chemical synapse. So remember in our neuron, the end of our neuron is known as the synaptic end bulb, or the presynaptic terminal. So that's where our action potential is going to wind up. So what we're focusing on in the chemical synapse is how we take the action potential that's being sent to the presynaptic terminal, and we turn that into a signal that can get to the neighbouring cell. The neighbouring cell, as I already mentioned, is going to be the postsynaptic cell and in this case, the membrane of that cell is known as the postsynaptic membrane. So again, this could be another neuron cell body, it could be a target tissue, doesn't really matter, but it's the postsynaptic membrane and it's in close association with the presynaptic terminal and sometimes it makes these little pockets, as you can see. In between these we have a little bit of space, so they're not physically connected there is a bit of space, and that space is known as the synaptic cleft. So this is the area where our chemical signals from our presynaptic neuron are going to be sent to our post-synaptic neuron. So in a chemical synapse, there's no direct transfer of the action potential from the nerve to the neighbouring nerve or the neighbouring target tissue, like we saw in the electrical synapse. In the electrical synapse we're physically connecting them, so the action potential was actually moving from cell to cell to cell to cell. In a chemical synapse, this doesn't happen, there's no direct transfer of that action potential. Instead, we rely on chemical signals and those chemical signals are known as neurotransmitters. So when the pre-synaptic terminal we produce, store and release these neurotransmitters and they're stored within little vesicles called synaptic vesicles. So that's what's being represented here in this image. So here's our action potential, it's coming or it's reaching the presynaptic terminal. In there, we have the synaptic vesicles holding the neurotransmitter. That is then going to release that neurotransmitter into the synaptic cleft and it will bind onto ligand-gated receptors that are located on the postsynaptic membrane. And that will then create the next set of graded potentials, which could or a may not start an action potential in the postsynaptic membrane. So that's basically how it's going to work. Let's break down all the steps of how it occurs. Slide 12 So here we have our same image again, we have our axon, we have our presynaptic terminal, we have the synaptic cleft in the postsynaptic membrane. In addition, it's blown up the receptors or the ion channels that are part of the postsynaptic membrane. So step one, the action potential is going to arrive at the presynaptic terminal. And in the presynaptic terminal we have voltage gated calcium channels. So all along the axon we've had potassium and sodium voltage gated ion channels, but in the presynaptic terminal we switch to calcium voltage-gated channels. So there's still going to open in response to the membrane potential change of the action potential. Except now what's going to move into the cell is calcium instead of sodium. So here we have our voltage gated calcium channel. This is going to then allow the calcium to move into the cell and the process of the calcium moving into the presynaptic terminal is what actually triggers these synaptic vesicles to move towards the synaptic cleft. And what they do is they release the neurotransmitter via exocytosis. If you're unfamiliar with exocytosis, you can read about it in chapter 3 of the textbook, but essentially these little vesicles are membrane-bound and those membranes fuse with the membrane of the presynaptic terminal and eventually release the contents into the synaptic cleft. The contents are our neurotransmitter and that neurotransmitter can then diffuse across the synaptic cleft. So here's our synaptic vesicles, here's our synaptic vesicles fusing with the plasma membrane and the presynaptic terminal that's closest to the synaptic cleft, and it's dumping out the neurotransmitters into the synaptic cleft. From there we can blow it up to our larger image here. Neurotransmitters are then going to bind onto the receptor sites on our ligand-gated channels. In this example, we have sodium ligand-gated ion channels. So when we have our neurotransmitter binding, we open these up and sodium is going to rush into the cell. Again, sodium rushes into the cell with its concentration gradient as well as with its electrical gradient because it's more negative on the inside compared to the outside. So in this case, when sodium rushes into the cell, we're going to get a depolarization response on the postsynaptic membrane. And again, if we can get a large enough graded potential occurring in this region of the postsynaptic membrane, if this is a neuron, and it reaches threshold at the trigger zone, then we can generate an action potential in the next neuron or the postsynaptic neuron. If this was a target tissue like skeletal muscle, than it would create an action potential along the membrane of our skeletal muscle and we'll be talking about how that works a little bit later in this semester. So for now, just know that we can cause a depolarization of the cell. But in addition, we can also cause a hyperpolarization, and we'll talk more about that a little bit later. So let's stop and watch a little animation describing all the steps that are happening at a chemical synapse, and then we'll pause and do some practice questions. Animation No caption file Video 4 Slide 13 Another thing that we need to consider when we're talking about chemical synapses is how we get the neurotransmitter out of the synaptic cleft. So if we constantly left their neurotransmitters in the synaptic cleft, we would always have the ion channels open and we don't want that to happen, we want to be able to turn the signal off as well. So there are three main ways that we remove neurotransmitter from the synaptic cleft after it's been released. The first method involves just simple diffusion. So if you think about what's happening here, the neurotransmitters getting released into the synaptic cleft area. Well some of that neurotransmitter can simply just diffuse away from the synaptic cleft. So this will reduce the concentration of the neurotransmitter and ultimately allow those ion channels that are ligand-gated to close. So that's one way that it can happen. The next way is via something called enzymatic degradation. So in our example here we're using the enzyme acetylcholinesterase. So in this picture here we have our synaptic vesicle and inside the synaptic vesicle is our neurotransmitter, acetylcholine. So acetylcholine is getting released into the synaptic cleft now on the post-synaptic membrane mixed in with the ligand-gated ion channels is an enzyme called acetylcholinesterase, if we're in a synapse for a neuron that releases acetylcholine. So that acetylcholinesterase is basically waiting for any acetylcholine molecules to come by and bind onto it. In fact, that acetylcholine, once it binds onto the acetylcholinesterase, it gets broken down into choline and acetic acid. So essentially we break the acetylcholine into independent molecules and those can no longer bind to our ligand-gated ion channel. So therefore it would allow them to close. And in fact, the acetylcholine esterase is actually so fast at breaking down the acetylcholine, it's almost or race sometimes for the acetylcholine to get to and bind onto the ligand-gated ion channel before the acetylcholinesterase breaks it down. So we need a significant amount of the acetylcholine to be released in order to have an effect on the ligand-gated channels because the acetylcholinesterase is so efficient at breaking it down. Now we are able to recycle some components of the acetylcholine. So the choline gets taken back up into the presynaptic terminal and there it will combine with acetyl-CoA to re-form the acetylcholine along with some CoA molecules. So you don't need to know all the individual steps here, but know that we basically break it down in the synaptic cleft so it can no longer bind on to the ligand- gated receptors and therefore, it will then stop the neurotransmitter from functioning. And then we can recycle it and repackage it so that we can use it again. So that's another way that we can remove neurotransmitter. The last way is via uptake by the same neuron or some neighbouring glial cells. And these are via neurotransmitter transporters. So in this example we have again a synaptic cleft, and in this case our neurotransmitter is norepinephrine. So norepinephrine can either bind onto the ligand-gated ion channel, or it can get taken back up into the presynaptic terminal via a neurotransmitter transporter. So in this case it's simply taking the neurotransmitter back up in the form that it was already in, it's not breaking it down first, it's just pumping it back into the presynaptic terminal, there it can either be repackaged and used again, or it can be broken down into other metabolic intermediates if it's no longer needed. So this is a really simple way of getting rid of the neurotransmitter. We dump it into the synaptic cleft and then we take it back up via specialized transporters that can pump it back into the presynaptic terminal. And one real life example of these neurotransmitter transporters is via the drug called Prozac. Prozac is a drug that's given for a variety of different mental health conditions including depression. Prozac actually is, is a serotonin re-uptake inhibitor. So like norepinephrine, another neurotransmitter is called serotonin and serotonin gets taken back up into the presynaptic terminal via a neurotransmitter transporter. So what happens with Prozac is it blocks the re-uptake of the serotonin, so it's an inhibitor of the re-uptake pump and what that does is it allows the serotonin to stay in the synaptic cleft longer than normal. And what they find is by stimulating the postsynaptic membrane for an extended period of time, it helps reduce depressive symptoms. So that's one way that drugs can interact with some of these neurotransmitter re- uptake transporters. Slide 14 Now if you recall from when I was talking about the chemical synapse, I said that the postsynaptic membrane often will have a depolarizing response. So for example, sodium channels will open and that will cause a depolarization of the post-synaptic membrane. But not always is it a depolarization, sometimes we'll get a hyperpolarization. So what happens on the post-synaptic membrane is what we're talking about here with postsynaptic potentials. So there are two main types of situations that will happen on the post-synaptic membrane. One is something called an excitatory postsynaptic potential or an EPSP. In an EPSP we get a depolarization on the postsynaptic membrane and that response is stimulatory. So that means that we are actually getting closer to reaching threshold if we're in a neuron or we will create a response or contraction in muscles or in glands if that's our target tissue. So the depolarization, if it gets large enough a graded potential, it can cause an action potential in the postsynaptic cell. So in this case, it's showing the graph at the top here really we're just talking about graded potentials again, it's just graded potentials specific to the postsynaptic membrane and that graded potential needs to be large enough to reach threshold in order to achieve an action potential in the second post-synaptic cell. The other type of potential that we can have is an inhibitory postsynaptic potential or an IPSP. In this case, we have a hyperpolarization response and that response is inhibitory. So essentially in this case, remember when we talked about hyperpolarization of cells, this would happen if we open, say, a potassium channel or we opened a chloride channel, these are both hyperpolarizing responses. And when we have a hyperpolarization of the postsynaptic membrane, that is going to cause an inhibitory response because we're actually getting farther away from threshold. So essentially, by getting farther away from threshold, we decrease the ability to produce an action potential in the post- synaptic nerve. Now, why would we want to do this? Thinking about our thalamus, for example, all of the sensory information that's synapsing in the thalamus before it reaches the brain, not all of that do we want up to go onto the cerebrum, we do want to block some of the sensory information so that not every single bit of sensory information gets interpreted. So one way that we can stop signals from continuing on is by using inhibitory post-synaptic potentials. And the way that we would do that would be to open either a ligand gated potassium channel or a ligand-gated chloride channel, because both of those will cause a hyperpolarizing response. Slide 15 So in addition to forming either an EPSP or an IPSP, we can also get a summation response on the postsynaptic membrane. And again, this makes sense, we talked about summation happening in graded potentials and really what we're creating with these EPSPs and IPSPs is a graded potential. So several neurotransmitters signals can be added together on the post-synaptic membrane and that will cause summation. Summation can be either spacial or temporal. Now what does this mean? When we think about spatial summation, essentially what this represents is several different axons coming to the same cell body and releasing neurotransmitter independently of each other. So if we have one neuron releasing neurotransmitter and a separate neuron releasing neurotransmitter. Those two graded potentials can add together and potentially will reach threshold at that trigger zone. So spatial summation is when we're adding independent graded potentials together that are coming from different neurons. So that spatial summation, the other type is temporal summation. So if you recall when we talked about summation, if we have two signals coming very close together in time, we can also add those signals together. So we have two action potentials reaching the cell body very close together in time. So imagine you're releasing a lot of neurotransmitter and then you're releasing more neurotransmitter to those ligand-gated ion channels before it's had a chance to close yet and the membrane potential to come back down to normal. We're adding those graded potentials together and again, if there's a large enough graded potential that it causes us to reach threshold at the trigger zone, then it will create an action potential in the postsynaptic neuron. Now often what's happening is we're going to get both temporal situations and spatial summations happening together at the same time. Now if we want to add to the complexity of this, the signals that reach the postsynaptic membrane can also be a combination of IPSPs and EPSPs if we're using spatial summation. Slide 16 So how would this look? So in this example, we have several neurons coming to one cell body. Some of these neurons are having EPSPs are excitatory responses. Some of the neurons are having inhibitory responses. In the example here we have an excitatory response also with temporal summation. So we're mixing all of these things together. So how do we know if we're going to get a large enough potential change to reach threshold at the trigger zone? Well essentially, if we have an excitatory response, an inhibitory response, they kind of cancel each other out. Now, in actuality, it's not just as simple as that because some changes in membrane potential might be slightly larger with one neurotransmitter than with another neurotransmitter. But for the sake of what this is trying to show, assume that we're sort of canceling these things out and then therefore we would be left with this excitatory response that has temporal summation. So that might be enough to get us to threshold and that would then create an action potential in that triggers zone. So it's really about which response is largest in which can cancel out the others; that will determine what happens in that postsynaptic cell. Conclusion So that's what we're going to end this online lecture. Today we talked about the different ways that we can propagate an action potential along the axon. Continuous conduction versus saltatory conduction. We also talked about some of the factors that can affect the speed of propagation. Then we looked at synapses, we looked at electrical synapses, and we also looked at chemical synapses. We followed by looking at how we get rid of neurotransmitter from the synaptic cleft. And we looked at what happens on the post-synaptic membrane, either excitatory postsynaptic potentials or inhibitory postsynaptic potentials. So that finishes our look at electrical signals.