We are going to move into the synaptic plasticity. So we have already discussed, in great detail, transmitter release, and postsynaptic sensing magnetism, sensing the transmitters and then to initiate another round of the signal propagation. Well, in this case, on top of this transmitter release and sensing, we are going to discuss synaptic plasticity. What is the synaptic plasticity? Well, the synaptic plasticity that actually the definition is simple, it's just altered the synaptic strengths during the stimulation. If we have a synapse that is the presynaptic big vesicles, right? And this is a postsynaptic receptors. Once the vesicle release the transmitter, and the transmitter will bind to the postsynaptic receptor, and lead to the synaptic response, usually the synaptic potential. Because of the ions will either go through this receptor directly, or indirectly, through the second messenger and then alter the postsynaptic membrane potential. So synapse will have a synaptical response if you trigger the action potential propagate into a nerve terminal and then the postsynaptic will initiate a response, okay? So if you are recording it in the current climate, if you trigger the presypnatic release postsynaptically, it will excite this synapse then you seeing that is a synaptic potential voltage will increase, okay? And what is this synaptic plasticity? The synaptic plasticity is just a change of the synaptic strings, okay? What cause this change? There are many different parameters. For example, the hot topic that a lot of people caring about is doing linear memory, okay? A human, an animal, if they are going through some kind of a learning process, in some special synapse, people believe that before the learning, the synaptic strings is like that. But after learning, the same set of synapse that you will has the bigger response, Okay? So this is called, potentiation, okay? And, depends on the time course how long this order of the synaptic strings last. People can separate the plasticity into short term, long term. And depends whether the string is increased or decreased, people can separate it into potentiation, or depression, okay? And we are going to discuss a little bit about that and how late. Why those synapse have different plasticity? We are also going to discuss one important central singular molecule, which is our old friend, calcium, okay? Remember that we spent quite some effort in the presynaptic terminal talking about how calcium can trigger transmitter release. We have this old friend in the postsynapse side that can alter the synaptic strings so calcium can also play a central role. And a NMDA receptor as a one of the very good example, could serve as a coincident detection to integrate the signals, and NMDA receptors is a calcium-permeable postsynaptic receptors. So you can allow calcium influx through the NMDA receptor to trigger the downstream signal propagation, and lead to the synaptic string's changes. Because calcium can binds to their other senses. For example, some special kinase would be sensitive to calcium or phosphatase. Okay? And then at the end, we are going to just discuss a very small example, D2 example, about not just changing of the synaptic strings. This why we are all discussing about the changing of the synaptic strings, but we are going to discuss about changing of the excitability. That is, if we want to change the neuronal circuitry, we can also just modulate how excitability of the neuron changes. That is, with the same input, if the neuron has higher excitability, for example, has a lot of sodium channel, that will be easier to reactivate. Or has less potassium channel that so that is membrane potential near the resting membrane potential. Then the neuron will be easier to fire action potential even with the same amount of synaptic input, okay? And that can also lead to the changing of the neuronal circuitry, okay? And we are going to use one example. So again, in the central synapse, this is an example of synaptic vesicle in the postsynaptic spine. And in postsynaptic region there is this electro dense material we call, PSD. Postsynaptic density that contain a lot of scaffolding protein and endocrine postsynaptic receptors in reach in this region, okay? If you look closely, there's also this presynaptic density material that people call it. Freedom of comparing this presynaptic membrane with this membrane, it's much more dense. They also contain a lot of scaffolding protein, and other presynaptic materials. That's the reason people call this region the active zone. This is the place that synaptic vesicles are believed to fuse, okay. For example, that we have a lot of SNARE complex that can mediate the fusions. Okay. And the molecular understanding of the postsynaptic density is becoming clearer and clearer. And this is just a illustration of some of the machinery through the biochemical purification max spectrum analysis. So, in a postsynaptic density, we first have some old friend that we talked about. Some glutamate receptors, for example, kainate receptor, ampa receptor in the central synapse, and NMDA receptors, okay? They are sensitive to glutamine, and glutamine binding would lead to the ion channel open and ion flux. And there also you have some adhesion molecule, for example, N-cadherin and neuroligin, some other adhesion molecule. People believe those are the molecules that important for the synaptic assembly, meaning that matching the presynaptic and postsynaptic together, so you have this efficient nerve communication. And in cytoplasm there are a lot of scaffolding proteins, for example, here, this T1, PSD-95. So they can simultaneously interact with some field transmembrane proteins, for example. So they scaffolding them together. So anchoring those transmembrane receptors or adhesion molecule in the postsynaptic site. For example, this PS-95 both interact with NDMA receptor NR2 subunit, and also interact with neuroligin and of C-terminal tips. So there are many other proteins, and they will form this scaffold network, eventually anchoring into the cytoskeleton. Okay? And it's believed that the spine or the generation of new spine actually usually caused by the remodeling of the acting cystoskeleton. And as you can see here, not only this is scaffolding protein, they are also kit kinase 2 complex. These are the calcium sensitive kinase, and as we will discuss, it's believed play an important role in sensing calcium and trigger the plasticity, okay? So the best study synaptic plasticity, in terms of the molecular magnetism, is in hippocampus. And people thoroughly studied different forms of synaptic plasticity in the hippocampus and then they expand into different brain regions. And they found that, indeed, other brain regions will have similar principles. And sometimes they also have some new principles. Okay? So we are going to discuss some examples of how the plasticity, the molecular basis of this LTP in the hippocampus. Before we have this discussion, how the plasticity could occurred? In principal, as I just been drawing here, the increase of the strings of plasticity, for example, potentiation, if it's a long term LTP. There are at least two possibilities. One possibility, if you think about it, is maybe there's an enhancement of presynaptic terminal to release transmitters, okay? The other one, will be a enhancement of the postsynaptic membrane, to sense the sent amount of transmitter readings. And that will be conditions that both of them will increase. Okay? So, indeed, people have already found they are at, depends on the synapse. Both of these types of plasticity occurred and even in a sense set of synapse, different triggering conditions might trigger different forms of plasticity that have different molecular underpinning. Meaning, in some conditions they will be presynaptic. In some condition will be postsynaptic. In some condition it will be both, okay? So it seems to be so complicated and indeed it's complicated and it takes a lot of debate from famous scientists in a field, to finally get to know those conclusions.
