Neuronal synapses (chemical)

I think we have a decent idea of how a signal is transmitted along the neuron. We saw that a couple of dendrites, maybe that one and that one and that one, might get excited or triggered. And when we say it gets triggered, we're saying that some type of channel gets opened. That's probably the trigger. That channel allows ions to be released into the cell-- or actually, there are situations where ions can be released out of the cell. It would be inhibitory, but let's take the case where ions are released into the cells in an electrotonic fashion. It changes the charge or the voltage gradient across the membrane and if the combined effects of the change in the voltage gradient is just enough at the axon hillock to meet that threshold, then the sodium channels over here will open up, sodium floods in, and then we have the situation where the voltage becomes very positive. Potassium channels open up to change things again, but by the time we went very positive, then that eletrotonically affects the next sodium pump. But then we have the situation where that will allow sodium ions to flood in and then the signal keeps getting transmitted. Now the next natural question is, what happens at the neuron to neuron junctions? We said that this dendrite gets triggered or gets excited. In most cases, it's getting triggered or excited by another neuron. It could be something else. And over here, when this axon fires, it should be exciting either another cell. It could be a muscle cell or-- in probably most cases of the human body-- it's exciting another neuron. And so how does it do that? So this is the terminal end of the axon. There could be the dendrite of another neuron right here. This is another neuron with its own axon, its own cell. This would trigger the dendrite right there. So the question is, how does that happen? How does the signal go from one neuron's axon to the next neuron's dendrite? It actually always doesn't have to go from axon to dendrite, but that's the most typical. You can actually go from axon to axon, dendrite to dendrite, axon to soma-- but let's just focus on axon to dendrite because that's the most traditional way that neurons transmit information from one to the other. So let's zoom in. Let's zoom in right here. This little box right there, let's zoom at the base, the terminal end of this axon and let's zoom in on this whole area. Then we'll also zoom in-- we're also going to get the dendrite of this next neuron-- and I'm going to rotate it. Actually, I don't even have to rotate it. So to do that, let me draw the terminal end. So let's say the terminal end looks something like this. I'm zoomed in big time. This is the terminal end of the neuron. This is inside the neuron and then the next dendrite-- let me draw it right here. So we've really zoomed in. So this is the dendrite of the next neuron. This is inside the first neuron. So we have this action potential that keeps traveling along. Eventually for maybe right over here-- I don't know if you can zoom in-- which would be over here, the action potential makes the electrical potential or the voltage potential across this membrane just positive enough to trigger this sodium channel. So actually, maybe I'm really close. This channel is this one right here. So then it allows a flood of sodium to enter the cell. And then the the whole thing happens. You have potassium that can then take it out, but by the time this comes in, this positive charge, it can trigger another channel and it could trigger another sodium channel if there's other sodium channels further down, but near the end of the axon there are actually calcium channels. I'll do that in pink. So this is a calcium channel that is traditionally closed. So this is a calcium ion channel. Calcium has a plus 2 charge. It tends to be closed, but it's also voltage gated. When the voltage gets high enough, it's very similar to a sodium voltage gated channel is that if it becomes positive enough near the gate, it will open up and when it opens up, it allows calcium ions to flood into the cell. So the calcium ions, their plus 2 charge, to flood into the cells. Now you're saying, hey Sal, why are calcium ions flooding into the cells? These have positive charge. I just thought you said that the cell is becoming positive because of all the sodium flowing in. Why would this calcium want to flow in? And the reason why it wants to flow in is because the cell also-- just like it pumps out sodium and pumps in potassium, the cell also has calcium ion pumps and the mechanism is nearly identical to what I showed you on the sodium potassium pump, but it just deals with calcium. So you literally have these proteins that are sitting across the membrane. This is a phospobilipid layer membrane. Maybe I'll draw two layers here just so you realize it's a bi-layer membrane. Let me draw it like that. That makes it look a little bit more realistic, although the whole thing is not very realistic. And this is also going to be a bilipid membrane. You get the idea, but let me just do it to make the point clear. So there are also these calcium ion pumps that are also subsets of ATPases, which they're just like the sodium potassium pumps. You give them one ATP and a calcium will bond someplace else and it'll pull apart the phosphate from the ATP and that'll be enough energy to change the confirmation of this protein and it'll push the calcium out. Essentially, what was the calcium will bond and then it'll open up so the calcium can only exit the cell. It's just like the sodium potassium pumps, but it's good to know in the resting state, you have a high concentration of calcium ions out here and it's all driven by ATP. A much higher concentration on the outside than you have on the inside and it's driven by those ion pumps. So once you have this action potential, instead of triggering another sodium gate, it starts triggering calcium gates and these calcium ions flood into the terminal end of this axon. Now, these calcium ions, they bond to other proteins. And before I go to those other proteins, we have to keep in mind what's going on near this junction right here. And I've used the word synapse already-- actually, maybe I haven't. The place where this axon is meeting with this dendrite, this is the synapse. Or you can kind of view it as the touching point or the communication point or the connection point. And this neuron right here, this is called the presynaptic neuron. Let me write that down. It's good to have a little terminology under our belt. This is the post-synaptic neuron. And the space between the two neurons, between this axon and this dendrite, this is called the synaptic cleft. It's a really small space in the terms of-- so what we're going to deal with in this video is a chemical synapse. In general, when people talk about synapses, they're talking about chemical synapses. There also are electrical synapses, but I won't go into detail on those. This is kind of the most traditional one that people talk about. So your synaptic cleft in chemical synapses is about 20 nanometers, which is really small. If you think about the average width of a cell as about 10 to 100 microns-- this micron is 10 to the minus 6. This is 20 times 10 to the minus 9 meters. So this is a very small distance and it makes sense because look how big the cells look next to this small distance. So it's a very small distance and you have-- on the presynaptic neuron near the terminal end, you have these vesicles. Remember what vesicles were. These are just membrane bound things inside of the cell. So you have these vesicles. They also have their phospobilipid layers, their little membranes. So you have these vesicles so these are just-- you can kind of view them as containers. I'll just draw one more just like that. And they can train these molecules called neurotransmitters and I'll draw the neurotransmitters in green. So they have these molecules called neurotransmitters in them. You've probably heard the word before. In fact, a lot of drugs that people use for depression or other things related to our mental state, they affect neurotransmitters. I won't go into detail there, but they contain these neurotransmitters. And when the calcium channels-- they're voltage gated-- when it becomes a little more positive, they open calcium floods in and what the calcium does is, it bonds to these proteins that have docked these vesciles. So these little vesicles, they're docked to the presynpatic membrane or to this axon terminal membrane right there. These proteins are actually called SNARE proteins. It's an acronym, but it's also a good word because they've literally snared the vesicles to this membrane. So that's what these proteins are. And when these calcium ions flood in, they bond to these proteins, they attach to these proteins, and they change the confirmation of the proteins just enough that these proteins bring these vesicles closer to the membrane and also kind of pull apart the two membranes so that the membranes merge. Let me do a zoom in of that just to make it clear what's going on. So after they've bonded-- this is kind of before the calcium comes in, bonds to those SNARE proteins, then the SNARE protein will bring the vesicle ultra-close to the presynaptic membrane. So that's the vesicle and then the presynaptic membrane will look like this and then you have your SNARE proteins. And I'm not obviously drawing it exactly how it looks in the cell, but it'll give you the idea of what's going on. Your SNARE proteins have essentially pulled the things together and have pulled them apart so that these two membranes merge. And then the main side effect-- the reason why all this is happening-- is it allows those neurotransmitters to be dumped into the synaptic cleft. So those neurotransmitters that were inside of our vesicle then get dumped into the synaptic cleft. This process right here is called exocytosis. It's exiting the cytoplasm, you could say, of the presynaptic neuron. These neurotransmitters-- and you've probably heard the specific names of many of these-- serotonin, dopamine, epinephrine-- which is also adrenaline, but that's also a hormone, but it also acts as a neurotransmitter. Norepinephrine, also both a hormone and a neurotransmitter. So these are words that you've probably heard before. But anyway, these enter into the synaptic cleft and then they bond on the surface of the membrane of the post-synaptic neuron or this dendrite. Let's say they bond here, they bond here, and they bond here. So they bond on special proteins on this membrane surface, but the main effect of that is, that will trigger ion channels. So let's say that this neuron is exciting this dendrite. So when these neurotransmitters bond on this membrane, maybe sodium channels open up. So maybe that will cause a sodium channel to open up. So instead of being voltage gated, it's neurotransmitter gated. So this will cause a sodium channel to open up and then sodium will flow in and then, just like we said before, if we go to the original one, that's like this getting excited, it'll become a little bit positive and then if it's enough positive, it'll electrotonically increase the potential at this point on the axon hillock and then we'll have another neuron-- in this case, this neuron being stimulated. So that's essentially how it happens. It actually could be inhibitory. You could imagine if this, instead of triggering a sodium ion channel, if it triggered a potassium ion channel. If it triggered a potassium ion channel, potassium ion's concentration gradient will make it want to go outside of the cell. So positive things are going to leave the cell if it's potassium. Remember, I used triangles for potassium. And so if positive things leave the cell, then if you go further down the neuron, it'll become less positive and so it'll be even harder for the action potential to start up because it'll need even more positive someplace else to make the threshold gradient. I hope I'm not confusing you when I say that. So this connection, the way I first described it, it's exciting. When this guy gets excited from an action potential, calcium floods in. It makes these vesicles dump their contents in the synaptic cleft and then that will make other sodium gates open up and then that will stimulate this neuron, but if it makes potassium gates open up, then it will inhibit it-- and that's how, frankly, these synapses work. I was about to say there's millions of synapses, but that'd be incorrect. There's trillions of synapses. The best estimate of the number of synapses in our cerebral cortex is 100 to 500 trillion synapses just in the cerebral cortex. The reason why we can have so many is that one neuron can actually form many, many, many, many synapses. I mean, you can imagine if this original drawing of a cell, you might have a synapse here, a synapse here, a synapse there. You could have hundreds or thousands of synapses even, into one neuron or going out of one neuron. This might be a synapse with one neuron, another one, another one, another one. So you'd have many, many, many, many, many connections. And so synapses are really what give us the complexity of what probably make us tick in terms of our human mind and all of that. But anyway, hopefully you found this useful.