So last time we talk about action potentials and a little bit about synaptic transmission as how to the action potential generate. Get into the nerve terminals and trigger transmitteries. And we touch upon a little about about how calcium trigger transmitteries. And let's just refresh what we have been through. And then, in detail discuss the identification and understanding of how transmitters are regulated and how scientists in the past, through different approaches, including causeology, biochemical, and genetic approaches to identify the key molecular components that control transmitter release. And that would be the main focus, okay? So before we touch upon that, let's just go over the outlines for a neuron, a polarizing neuron, to communicate with the downstream target, it requires the transmitter release. But the neuron usually will get excited to generate an action potential, integrate different presynaptic and generate action potential. And the action potential is all or none. Okay? And therefore the neuron uses the frequency coding. There is a different frequency of action potential generation and propagation into terminals. And in the nerve terminals, the arrival of action potential will activate the calcium channel and then trigger a transmitter release. And the transmitter release will subsequently activate a postsynaptic receptors, and this is through the chemical synaptic transmission. And the calcium is playing a key role in triggering the transmitter release. And how do we understand and figure it out calcium is playing such a role? Well, just like many other approaches in different disciplines. Usually the way is through measuring, see and moving, okay? That is to demonstrate calcium can trigger transmitter rays, we can design approaches to block calciums action, okay? For example, you see calcium curators. EGTA or even better fast calcium and specific calcium kealator. A measure that is to use ways to measure calciums action, calcium influx triggered transmitter release and in this case we have measure. Calcium. How do we measure it? If calcium is going through the presynaptic terminal to trigger transmitter release, we can measure the calcium influx through measuring the calcium current. Okay? Because, when you have a positive charged ion going through a membrane, you will generate a current, and so if we can measure the calcium current in a terminal we can measure. Or even better, we can measure the intracellular calcium concentration. Again the prediction will be that once calcium gets into the cells, and if you have optical indicators for calcium and that will respond by increase the forces, for example. So we can measure it in different ways, okay. And this is part of a seeing process, right, using the optical measure for measuring you only achieve the temporary response. Temporal kinetics. You can also achieve the spatial resolution, right? Just purely measure the current in the cell body. Usually, we will not allow you to understand where the calcium influence occurs. So optical tool has that advantage comparing with a lot of commissional matter is, in principal, you can achieve a good spacial and temporal response. And another logic would be move it. That is if calcium in D playing an essential role in triggering transmitter release through the opening of calcium channel. Then we can completely bypass the calcium channel by directly delivering Calcium into the nerve terminals and that if it is sufficient will trigger the transmitter to release. And this will damage the sufficiency. Okay? And again, for that, in the pupal. In history has already tried different methods for example by directly injecting calcium into nerve terminal which work as good as we want. And then there are interdiscipline approaches that people design so called cage calcium that you can use a flash of UV light to repeatedly chemically release or uncaging calcium in the nerve terminal. In the very temporal controlled manner and then you contribute release. Okay so that's the calcium part, and then calcium triggered transmitter release is an inorganic ion that plays a central role. What is its downstream effects? What senses calcium? And how does calcium work with other important molecules? Presumably residing in the synaptic vesical. Or In the post Membrane to cause these two membranes to fuse and how do you identify those components? And after you identify them, how do you demonstrate at which step that they are essential to trigger transmitter release? Either they are essential to transport the vesicle close to the plant's membrane, blocking the plant's membrane or opening of the fusion port by exerting the the fusion interaction, okay? So that would be also essential in understanding the machinery that control the transmitter radius. And so in summary, in a last 50 years work, we have already understand the synapse transmission, the chemical synapse transmission that is the action potential in weight of propagate to a nerve terminal. That triggers the opening of water calcium channel, calcium influx. Somehow magically will [INAUDIBLE] infected protein. Nowadays we know that it's the calcium sensor. That can somehow interact with this banana like structure protein across [INAUDIBLE]. And that together will cause the [INAUDIBLE] to fill with [INAUDIBLE] membrane and transmitter will defuse right across this teeny tiny synaptic [INAUDIBLE], and that actually with a post [INAUDIBLE] receptors. And then receptors will open and then [INAUDIBLE] Depolarize or hyperpolarize the downstream cells. And in our brain, the majority of excitory receptors will be the so-called empire receptors, these glutamate receptors that will open to excite the cell.
