So this one cartoon here, for the research actually then, it will takes really quite a lot to get these pictures. It will take a few decades actually really to complete this story. So for example, if this channel is really true important for the transaction, then you can do a study. Then you'd look at this channel, see what will happen. And indeed we would do the study, and then the knockout, the CNG channel, and then do a kind of essay. This essay is called EOG recording. EOG is kind of for feel the potential recording record from many, many neurons, okay. Is not a single neuron recording. And take a look, this is the olfactory epithelium, right? Where the olfactory sensory neuron locate. And then if you insert an electrode to this region, then you can pick up the electric signal from those neurons. And so with that, if those neurons stimulated by some chemicals for example, you can puff some odorant chemicals to this region. If this alternate can stimulate those neurons, those neurons will depolarize through the G protein cascade, especially the CNG channel opening. Okay? Then you can recall here. Then you will see those electric signals. If you knockout the channel. what do you expect, actually, there's nothing, okay? Flat, indeed the is the recording. You can take a look. This is actually a knockout trace. Knockout recording is the red one. White tap is the blue one. So if you use different chemicals stimulate the nodes, you can get different signals. Some small, some large, some actually nothing will happen. But here only show all those actually responding ones. But when you knock out the channel, essentially, the nose cannot smell anything, okay? Then you give your evidence. Indeed the CNG channel actually is important, is critical in the transaction of the odor and its information. And also, actually, people then, for example, they can knock out the adenyl cyclase type three. The AC3. They got this similar answer. If you knock out the G protein, you got a similar thing. Okay? So this actually indeed happened in the field, already were done by different groups to knock out different component. And it take really a long time to achieve that understanding. When a chemical stimulation happen to the cell, the cell will be activated, depolarized. So for the signaling it will be critical. If the signaling can be fashioned to be shut of as we mentioned before, the photoreceptor, right? Photoreceptor. When you have activation, then you have the inactivation, right? What happened? What is the inactivation steps for the photo-transduction? [FOREIGN] >> [FOREIGN] >> Okay. >> [FOREIGN] >> Okay. [FOREIGN] >> [FOREIGN] >> [FOREIGN] [FOREIGN] Rhodopsin activated by photon. And then rhodopsin will activate a G-protein, transducin. Then transducin activate. We have with the G-alpha binded to the GTP, isolated from, dissociated from, the beta gamma subunit, binded to the PDE. Right? Those proteins activation. And then later in the activation, each protein should be activated. Rhodopsin, activation by what kind of procedure? Steps. Phosphorylation and resting binding, right? This should be very clear actually if you learn this kind of signaling, cascade. Because GPCR, typically all GPCR use this type of signaling, cascade. Activation, phosphorylation, and resting binding. And then also maybe have similar decay to the protein active [FOREIGN]. For the G protein deactivation, reactivation, what's the steps? The GTP hydrolize to GDP by the intrinsic GTPase activity of the G alpha, with the help of some other protein, such as adenosine, those proteins. Okay, so here, the same thing should happen to the olfactory system. Each set of steps, you need, actually, when you activate it, then you need actually shut off those proteins, okay? For example, the receptor, you have the ONN binding activate this receptor, and the receptor of the ONN unbind. And then you activated G protein, the DTP changes to the DDP then activation. As your cycles three also need activation. So we also talk about it in the photo receptor. We also have the negative feedback, right? The negative feedback may need by the calcium steps, right. So here the same thing, what happened to the olfactory system. Mainly actually I will see the calcium coming, the first thing actually is amplify this signal. And at the same time this calcium actually will bind to the calmodulin. Calmodulin will do the same thing as in the photo receptor, will inhibit the CNG channel, okay? And also calmodulin can activate a calmodulin kinase to phosphorylate adenocyclase to inhibit the synthesizing of cAMP. And also, possible here, I didn't put it there that route down. That is actually, calmodulin also can active the PDE, the phosphodiesterase. [FOREIGN] Now calmodulin can also activate the PDE. [FOREIGN]. The same thing happened here. This calcium meeting the negative feedback is to counteract. [FOREIGN] The odorant response. [FOREIGN] Olfactory adaptation. [FOREIGN] >> [FOREIGN] >> [FOREIGN] Okay, yep. There's actually a experience of the olfactory adaptation. [FOREIGN] If you go to a restaurant [FOREIGN] Means you adapt. Olfactory adaptation have actually can achieve by different ways, okay. One is actually a sensory neuron. For example, this calcium mediated signaling can counteract the olfactory detection. [FOREIGN] This is actually a key step in the olfactory adaptation. Why is the, the key step is the olfactory sensory neuron. And also, actually, even if the olfactory sensory neuron not completely adapted the signal still goes to the brain. Our brain has a mechanism to adapt, okay? [FOREIGN] a network adaptation. By neural circuitry. And you can achieve the olfactory adaptation. This is not so well-studied. But actually some labs including our lab, actually, we actually pursue this direction. The network olfactory adaptation. This is the olfactory sensory neuron. We talk about signaling and some as a related issue. It is quite a long time in the field. That is actually how factory sensory neurons detect those chemicals. Because actually we have really extraordinary ability to detect thousands, even maybe tens of thousands different type of chemicals. You can smell them. [FOREIGN] this ability actually always puzzled the researcher. How can we achieve the ability? Now, in the visual system we detect the colors using three kinds of visial pigment, red, green and blue. [FOREIGN] So your olfactory system, how does it work? [FOREIGN] So these questions always puzzle the field, okay? So how do you solve this problem, if you are interested in these questions? Apparently, we are talking about this step, the receptor. We need to clone these receptors out, right? [FOREIGN]
