So expression cloning is a powerful way. It has some limitation, but in this case it's a very powerful way for people to identify. It turns out that the glutamate receptors, they clone. Is one of the tetomers, okay. So after cloning and characterizing a glutamate receptor, listase okay, okay, have already saw the crystal structure for the glutamate receptors. So this is one of them. Again they are petromeres. As you can see the glutamate receptor is a transmembrane protein. That four of them will form this ionic pore. But in the extracellular part you have this, ATD domain and LBD domain. The LBD domains are the ligand-binding domain that we combine to glutamate which is shown here. It's difficult to see, but the ATD domain actually can be modulated by a lot of different other sins. For example these theorem, some cofactors can control it, so totally these things can control a glutamate receptor's opening. And if you look at, in detail, how this receptor, so you can see there this pore, that it opens up from the top to the bottom, and this is illustrating. This is the part that has the smallest diameter. So, that is the gate, okay, and then from here that is opens up. And if you look at the glutamate receptors, it's poor. Comparing with the potassium channel that are crystallized by [INAUDIBLE] You can see that even now it's a different family. One is a potassium channel and the other one is an ligand gated receptors. They have pretty closer architecture, indicating that the evolution they might, coming from the same ancestor. That during evolution it gets duplicated and then multiplied and one is sent to the ligand and the other one is sometimes water is sensitive to open the potassium channel. So again, understanding theligand-gated channels, we have to understand how you function in the nerve synapse, in the nervous system. And also identification of the gene and now rich to the structure studies and usually with direction. It's in that order. It's usually very difficult to go from the reverse direction that is first crystalized essentially and it's all. This is a potassium channel this is the ligand-gated receptor. Usually it's much more challenging because nature building those receptors or ion channels not initially for you to crystallize them. They are building it just for function, right? But structure started either crystallization or is trying to lock them in a lowest energy state. That it will be less movement so you can see its static images, but nature building those receptors labeled big dynamic to response to different ligands. So, that's the reason even for identification of those since people takes a lot of engineering efforts to stabilize those receptors to achieve this atomic resolution understand. Okay. And we skipped the LND receptors which is a very unique glutamate receptor. Ligand-gated glutamate receptor, both are gated by glutamate and voltage. There is for example, only when voltage is higher that it will be open. And the reason is that these NMDA receptors in a resting condition in a cell will be blocked by the high concentration of magnesium in the port. And people identified that during the water depolarization this magnesium block will go away. And therefore, the NMDA receptor can be activated. So therefore we have this specialized receptor that is both sensitive to weattage and ligand, and only when there is wattage to remove the mechanism block the voltage depolarization. And to the ligand the glutamate present, the receptor will be open. So people actually have already demonstrated NMDA receptor is very key molecule for linear memory. Because it can work as a coincidence detector, meaning that the two things need to be simultaneous present. Okay, so this is sort of like conditioning. Okay how one link sound verse time to go, right. In a cell, the coinstant detector seems to be a, is a linkage that can link two unrelated things, together. You need to have two of these both present to function, okay. Indeed, the genetic studies by looking out NMDA receptors, or blocking them, have demonstrated that in model organisms, like mice. Then they don't have good learning. It requires this coincidence detector for learning and okay? And that we will discuss in detail next time along with some tools to study neuroscience, the techniques in neuroscience.
