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Hello guys. Oh welcome to the first year lecture. My name is Aka and in a minute we'll get cracking with Charlo who's gonna be giving the lecture today, but we'll just wait three more minutes just to see. Uh just to let a couple more people join and then we'll get cracking. But in the meantime, if you guys want um for the people who are already here, just, just literally right now, we just finished our previous talk about um how to do best in your preclinical years. So if you guys have any questions that you would like myself or sha of you to answer, just put them in the group chat in the chat now. And yeah, we could answer them for you before the talk starts. But other than that, just give us a couple. I just also gonna check, can you guys hear all? OK. Um If one of you can just put it in the group chat that you guys can hear like a thumbs up or something? That would be great. OK, I'm gonna see if you guys come here at seven o'clock. So let's get started. Um So welcome guys. My name is Anushka and I'm the preclinical lead. And this is the first talk of our neuro series guys. Definitely keep in tuned because we've got many, many series coming all the way from Euro to Endo to Cardio, all the way through all the specialities which will be teaching you the preclinical things you need to know for your exams. And today we have a brilliant talk on cells of the nervous system, action potentials and neurotransmitters by Charlo who is a third year medical student from Brighton and Sussex Medical School. So I'll hand over and we can forget. Uh hi everyone. So yeah, just as the N said, I'm a third year medical student and I'm really excited to give this talk to you today. So I'm gonna get straight into it. Um So that's just a little bit about me. Um Yeah, you, you can read all that stuff. I like cakes. So anyone who wants to treat me with cake afterwards, that's fine as well. Um I'm just going to get straight into it. So um as part of my lecture today, I'm going to cover cells of the nervous system, um action potentials, neurotransmitters. And then I've got three F ba type questions at the end. Um just so that we can test our knowledge. So getting straight into it, um cells of the nervous system in the nervous system, we have two kind of key players, the central nervous system and the peripheral nervous system. So in the central nervous system, you'll find neurons that are the main communication cells. They are almost like the brain's messengers which are supported by these cells called glial cells. And you can see examples of those on the diagram there as well. So, astrocytes and oligodendrocytes, for example, which are going to help with nourishment and insulation of the neurons. Um whereas if we look at the PNS, the neurons transmit signals between the body and the CNS. So there are things called ganglias which are small clusters of cell bodies and they process sensory information while the nerves um like bundles of axons send messages to and from the CNS. Um You can also see that I've mentioned Schwann cells in the PNS which assist with the signal transmission by producing myelin, which gives insulation around axons. So if you think about it, the CNS is like your command center and the PNS handles all the other routes of communication. Um So if I look at a really basic neuron structure, um a neuron is a functional unit of the nervous system, which is specialized in transmitting electrical and chemical signals. Essentially, it's a fundamental building block of the nervous system. And if I look at its like components, there's three main parts I would say um the cell body, the dendrites and the axon. So the cell body contains the nucleus and other organelles acting as the neurons control center. Um the dendrites are like those antenna like things at the end. Um And they receive incoming signals from other neurons. And the axon is that long slender extension starting at that point called the axon hillock. Um and that transmits signals away from the cell body. So the axon is surrounded by a myelin sheath which aims to increase the conduction velocity of action potentials traveling through the axon. And we will talk about action potentials in a few slides later at the end of the axon, though you've got axon terminals and terminal branches and they communicate with the next neuron through tiny gaps called synapses. And we will have a look at some synapses as well. Um So neurons can be classified either functionally or structurally. So I'm going to look at the functional classification first. Um And we have three main types. Um you've got sensory neurons and they're like your information gatherers. So they collect data from the body's external and internal environment and send it to the central nervous system. Um Motor neurons on the other hand, are the action takers, they transmit signals from the nervous system to the muscles or glands, the affected organs like we call them and they guide our movements and responses. And then you've got those neurons kind of in the middle which are interneurons and they are the decision makers, they process and integrate information within the CNS itself and they allow us to think, feel and react. Um But they only exist within the CNS and then neither sensory or motor, they just process signals. Um looking, then at the structural classification, there are a couple of types. Um They, yeah, I've got five categories that I'll talk about. I know there's only four on the slide. Um But you'll see why I've put four and not five in a minute. So the first one I'm going to talk about is multipolar neurons and these have multiple dendrites and a single long axon, they're often found in the CNS. The second type is bipolar neurons and they feature one main dendrite and one axon and they are separated by a cell body typically found in specialized sensory organs like the retina. Um And then you've got your pseudounipolar neurons which have a single process extending from the cell body, primarily serving as sensory neurons and conveying information from the body to the CNS. Um An example of a pseudounipolar neuron is a dorsal root ganglion and that pops up a lot. Um So just kind of like fact check know that one pseudounipolar is a dorsal root ganglion. Um Then there are unipolar neurons and then not on the diagram, but they basically look like a pseudounipolar neuron as well. They have a single process. And lastly, you've got the axoaxonic neurons and they are less common. Um But they play a really important role in modulating communication between other neurons. Um And it is really important to classify at this point, uh to clarify, sorry that all neurons have just one axon. So it's just really the number of dendrites and kind of processes coming off them, which is slightly different, but they all just have the one axon. Um So now looking at glial cells, um so glial cells or neuroglia, some people might call it that are non neuronal cells and they provide various kind of support functions to the nervous system. Um Each has its own unique job in nourishing, protecting and maintaining and the wellbeing of each neuron. So the diagram shows some of the different types of cells. Um they are different to neurons in the sense that they don't have action potentials. They don't form synapses and they are able to divide and actually a lot of the most common sources of tumors within the nervous system, actually derived from the glial cells. Um There are a lot more glial cells than there are neurons. Um And it's actually anywhere between 10 to 50 times more glial cells than neurons. Um Don't quote me on that, but yeah, just get an idea of the ratio, there's a lot more support than actually neurons. Um So I have drawn up this table which kind of breaks down the glial cells on their functions. Um I'm going to talk about each of them in turn. So the microglia, first of all act as the immune system's defenders, their motile cells and they move around cleaning up and breaking down foreign bodies, um similar to other immune cells, they have mesodermal origin, whereas most of the nervous system actually is exodermal. Um But yeah, these are mesodermal uh looking at the next one then. So astrocytes, they nourish and maintain the chemical environment around neurons. Um they kind of look like star shapes on a micrograph and they're only founder than the CNS. Their PNS counterpart is these satellite cells. So um yeah, they basically have the same function. Just one works in the CNS, one works in the PNS. Um oligodendrocytes and Schwann cells both insulate nerve fibers with myelin. Um and that helps to accelerate the signal transmission. Oligodendrocytes are myelin producing cells in the CNS. Whereas Schwann cells are the myelin producing cells of the PNS and kind of one difference between the two of them is that one oligodendrocyte mates, multiple axons. Um whereas only one axon is wrapped up if you like by a Schwann cell. So they both do the same thing, but oligodendrocytes are able to do multiple at the same time. Whereas Schwann cells are a little bit more basic and they only do one axon. So looking now at action potentials, um this is really, really important stuff. It comes up a lot. Um You will definitely have a question if you're doing your on something to do with action potentials. Um So do get your head wrapped around it. I will try and go step by step. But if anyone's got any questions, then again, play in the chat. Um So first thing is electrical synapses. Um So in an electrical synapse, the flow of ions um is passes directly between one neuron and another and that enables kind of swift and synchronized communication between connected cells. Um Electrical synapses are a lot faster than their chemical counterparts despite being a lot simpler in function in structure. Sorry. Um Unlike chemical synapses, though electrical synapses work bidirectionally. Um but they do lack plasticity and that means that the strength of the connection doesn't change. Um Synapses are very small. So you can see about 3.5 nanometers and they're usually bridged by gap junctions. Um but there is no signal amplification. So, in fact, the signal weakens upon transmission. And if the post synaptic cell is significantly larger than the presynaptic cell, then the signal actually won't transmit. And the way I can think about it is um in a small presynaptic cell. If you get that same signal and put it into a big postsynaptic cell, the signal kind of just get lost for the amount of area if you like that it needs to work in. Um So that's how I kind of remembered that. Um And of course, it's really important to mention that excitatory signals can't inhibit postsynaptic cells. So an excitatory signal will excite and an inhibitory signal will inhibit. Um So neurons communicate through a process of signal in integration called summation. And this helps to determine whether a signal is strong enough to trigger an action potential or not. Um Temporal summation occurs when multiple signals from the same neuron arrive in rapid succession. And that means that they build up their effects over time. And, and essentially, it's when the input neuron is firing really fast and fast enough so that the receiving neuron can add together its lots of tiny signals and ultimately reach the threshold. Um This happens when the receiving neurons ability to recover from the tiny input and its depolarization, which we'll look at in a minute is slow enough for the next signal to arrive while the receiving neuron has not yet recovered from the first signal. So you can see on the graph there that basically it doesn't allow um the, the, the signal build up on each other. It doesn't recover from the first signal before the second signal is received. Um So yes, the previous signal means that it's slightly depolarized and therefore, it builds that next signal up until it reaches that threshold and fires the action potential. So, in contrast to that spatial summation involves signals from multiple neurons converging onto a single neuron and their strengths are added together. Um So a neuron then determines whether to fire or not based on the ad together of all these tiny signals that it receives from the several other neurons synapsin onto it. Um And that can be both excitatory or inhibitory inputs. So, excitatory and inhibitory inputs will just cancel each other out. Um But yeah, so essentially a spatial summation is lots of neurons converging onto one neuron to give that signal. Whereas a temporal summation is where one neuron fires very quickly onto another neuron to give you that threshold point. Um So yeah, that's summation. And now I'm sure that everyone has seen this graph many, many times before I am going to go through it again, very quickly. Um So you can see on the graph that an actual potential has five ish sections depending on the way you break it down. Um But basically an actual potential is a rapid change in membrane potential that occurs in neurons and muscle cells. Um And I will go through each of these stages in detail, but the complex pattern is basically lots of depolarization and then repolarization and that, that's it really. And we'll see how the neurons do that. So, um at resting membrane potential, um that's typically about the potassium equilibrium potential of about minus 70 millivolts. Um We have these channels called inward rectifier, potassium channels and they are open. So they allow for a steady flow of potassium out of the cell. Um This outward potassium current is pretty much the dominant force in maintaining the cells negative charge. However, when something happens, um and that causes the cells to become less negative and that could be a nearby cell depolarizing or asynaptic transmission. It causes the membrane potential to become less negative um leading to a positive shift known as depolarization. So, when it becomes less negative, that's what we call depolarization. Um And that initiates the rapid depolarization phase. Um And the neuron experiences a rapid change in membrane potential from negative to positive membrane potential. Um And that's the starting point for propagation of the action potential along the neurons exon. Um And that enables the swift transmission of that electrical signal. Um So, the reason for the depolarization is the opening of voltage gated sodium channels, um when sodium rushes into the cell, it is able to briefly overcome the inward potassium rectifier current. Um And the initial depolarization therefore triggers a few sodium channels to open. That means that you've got increased sodium permeability and allows more sodium currents to flow into the cell. The additional sodium influx intensifies the depolarization. It makes it less negative um and creates a positive feedback loop. So as the voltage surpasses the threshold, which is roughly about minus fiftyish, um the neuron commits to firing an action potential um which is all or nothing. So we know that it has to reach that, that threshold to I otherwise it won't. Um So the positive feedback cycle of rising sodium channel conductance and voltage continues until the membrane potential reaches an overshoot phase where the voltage surpasses about 30 mis. So, yeah, that's depolarization. And then the next phase is repolarisation. So after the initiation of an action potential, the repolarization phase becomes um yeah, it begins. So it this phase is involved with um the voltage inside of the cell becoming less positive uh or more negative. The it depends on the way you want to think about it but less positive or more negative. Um it is driven by two delayed action events. So the first one is sodium channels, inactivation, reducing the influx of sodium irons into the cell. And the second one is delayed rectifier, potassium channels opening. So that allows an increased efflux of potassium ions making the membrane less positive or more negative. Um So both of these kind of happen at the same time, you kind of just got to think of the sodium going down, potassium going up. Um And these events both kind of play a crucial role in restoring the neuron's resting state and then it prepares itself for the next round of signaling. But what ends up happening um is you get this refractory period. So that's defined as a period of time in which during the neuron becomes incapable of reinitiating an actual potential. So it's kind of like a time out for the neuron. Um during this time, the neuron's membrane readies itself for receiving another stimulus, but it can't respond immediately. Um The refractory period is primarily after the um wait, let me get that right. The refractory period primarily occurs um during after hyperpolarization. Um And that ensures that the neuron signaling maintains precision and prevents overexcitability. Um So, after hyperpolarization um is the next phase, this is when at the end of an action potential, the voltage inside the neuron briefly becomes slightly more negative than at rest. Um this dip is followed by return to the resting membrane potential. So when the voltage drops below about minus 60 the inward rectifier, potassium channels open up again. Um And these channels stay open until the next depolarization. So what they do is they kind of clamp down the voltage closer to the equilibrium potential for potassium and they're responsible then for maintaining the resting potential. Um So the interplay between increased potassium permeability and decreased sodium permeability brings the membrane potential back towards that potassium equilibrium potential. Um And ensures that the neuron is ready for the next wave of signaling. Um So that is basically a quick run through of an action potential. But as we know, action potentials are all or nothing, so they don't give us any information about the size of the stimulus that triggered them. So how would neurons know about the intensity of the synaptic input? Um Well, the answer is in the frequency of the firing. So the more intense the activity, um the higher the firing frequency and it's a really important mechanism um increasing the threshold, lowest firing frequency. Um And you can kind of see that in the figure um and when there's more excitatory synaptic activity, the firing frequency goes up. So interestingly, the duration and size of synaptic currents also play a role, longer smaller currents, create a higher threshold for action potential generation compared to larger currents. And this occurs due to the accommodation of sodium currents which inactivates during slower subthreshold depolarization. So this allows different neurons to respond to stimuli of varying strengths um and make neurons basically more adaptable to different sensory tasks. So whether that could be like light touch or pain, so it's able to differentiate between those a little bit better. So the last little section is about neurotransmitters. Um There is a lot to cover on neurotransmitters. So I've tried to condense it down um to the really key stuff that I think are really important, but it's definitely worth investing a little bit of time into understanding what the different neurotransmitters do, how they synthesized, how they work in the body. Um It's, it's usually one of those things that are quite fundamental. So I would invest a little bit of time to look into these. Um But I will give you a quick overview today. Um So we looked at electrical synapses before we're now going to look at chemical synapses and these are mostly found in the mature CNS. So if we look at their structural classification, um they can be categorized based on the specific connections that they make. Um First of all, we have axoaxonic synapses where the axon of one neuron communicates with the axon of another. And that exerts precise control over the signal transmission. Axoaxonic synapses are modulatory and they change the strength of the signals to alter the release of the neurotransmitters. Um indirectly, then you've got axodendritic synapses where the transmitting neuron axon connects directly with the dendrites of the receiving neurons. And that allows for more extensive and dynamic communication. And then lastly, you've got Axo somatic synapses and they are involved in direct connection of the axon to the cell body and that impacts the integration of the incoming signals. So there's quite a lot happening on this slide. So I'm going to just break it down neurotransmitters. First of all are messengers of the nervous system. They are molecules that are synthesized within the neuron and influence the post synaptic neuron or an affected organ. What's interesting is that when we introduce these neurotransmitters from external sources, they most often than not seamless, seamlessly mimic um the natural functions. And they also have a mechanism behind their removal from the synaptic cleft. Um looking at the types of neurotransmitters, they can be broadly classified into amino acids, monoamines, acetylcholine and then neuropeptides. So, amino acid monoamine and acetylcholine are all synthesized in the presynaptic terminal. Um They are stored in synaptic vesicles and are released quickly by a local release in calcium and that's stimulated usually by a brief localized impulses. Um On the other hand, neuropeptides are synthesized in the cell soma and then they are transported to the terminal in secretory Granules. Um And they are released quite slowly um because of a global increase in calcium. Um And you can see there that there's like four little graphs. Um I don't know how relevant they are to other courses for my particular university. They came up a lot. So I would just learn what those mean. It's just basically a summary of the table there. Um So your fast transmitters are your amino acids monoamines and acetylcholine and the slow transmitters are the neuropeptides. And it basically just shows that with low frequency impulses, neuropeptides aren't going to do much. You need that global increase in calcium before you get that build up of neuropeptides functions. So looking first at amino acid neurotransmitters, um we have excitatory neurotransmitters and you can think of those as kind of go signals the green light in our brains inducing depolarization and igniting the firing of a neuron. So glutamate is the central player there and that facilitates rapid exchange of information within the central nervous system. It's in size from key precursors such as glutamine and alpha ketoglutarate. And that is a really regulated process by enzymes. I don't know how much you need to know about the synthesis of amino acids. We were expected to know how the amino acid was inside. So I have included a diagram there. Um just so that you can see it a little bit better if we then look at inhibitory neurotransmitters. These are your stop signals. Um So your red lights, um they hyperpolarize neurons preventing over excitation. Um So Gabaa is the one that's predominantly found in the brain and glycine in the spinal cord and brainstem. And they also undergo this meticulous synthesis. And Gabaa is actually synthesized from glutamate, whereas glycine comes from serine or pine. Um So yeah, then we're gonna look at monoamine neurotransmitters. So first up, we have serotonin, this has loads of roles and you'll hear serotonin pop up in lots of different places, but it's not just about mood regulation, it also influences sleep pain, emotion, appetite, and even some gi function um its synthesized from the amino acid tryptophan and undergoes a series of enzymatic steps which include hydroxylation and decarboxylation. Um to make it, then if we look at dopamine, it's usually known for its involvement in the brain's reward and pleasure systems, but it's more than just the feel good messenger. It also contributes to motor control and decision making. Um So, dopamine synthesis starts with the amino acid tyrosine and involves a sequence of enzymatic reactions. Um And again, that's mainly hydroxylation and the carb oxidation. Um So, yeah, monoamines are usually modulatory new transmitters. So they don't really excite or inhibit, they kind of just regulate things. So, if I now look at the neurotransmitter storage, um they're initially synthesized within the neurons cytoplasm and to prepare for release, they're moved into specialized vesicles by membrane transporters. And these are typically proteins embedded into neuronal membranes. Um The relocation of the neurotransmitter is guided by electrochemical gradients. Um So that is a gradient created by a difference in charge between the inside and outside of the neuron. So that's your electrical side. And a chemical gradient is about the concentration of ions. So your protons and chloride ions inside and outside the neuron. Um membrane transporters actively transport neurotransmitters into the synaptic vesicles against the concentration gradient. And so, because you're working against the concentration gradient, it's a process that requires energy. Um So within the synaptic vesicles, the um the vesicular transporters are found on the membrane of the synaptic vesicles and they actively pump neurotransmitters from the neuron cytoplasm into the vesicle and they use a proton gradient to kind of pack them away. Nice and neat. So protons are actively pumped into the vesicle creating a proton gradient across the vesicular membrane. Um neurotransmitters are loaded into vehicles by exchange um by their exchange with protons. So as the protons enter the vesicle, neurotransmitters are carried along with them. Um And that, as I said, is powered by the proton gradient. Um So looking then at the release and transmission of neurotransmitters, it all begins when an action potential arrives at the axon terminal, the electrical surge depolarizes the presynaptic terminal, prompting the opening of voltage gated calcium channels. As calcium rushes in the concentration within the terminal rapidly increases. And that surge in calcium concentration activates calcium calmodulin dependent kinase two, which is a really important enzyme and it will come up a lot. Um calcium calmodulin dependent protein kinase two. then phosphorylate synapsin. Um that phosphorylation helps the vesicle detach from the cytoskeleton and freeze them up for the next step. So the liberated vesicles then dock into the active zone um with precision thanks to the snare complexes, and those complexes kind of work like molecular zippers. So they bring the physical membranes closer together um and then zip them up. So as the calcium concentration continues to rise, it reaches a critical point um and then it binds to synaptic Tagment. Um and that binding event acts as the kind of ultimate trigger for the fusion of neurotransmitter containing physicals with the cell membrane. And that fusion then um enables the release of the neurotransmitter via exocytosis um into the synaptic cleft where they're ready to kind of influence the postsynaptic cell or neuron. So when the neurotransmitter is released into the synaptic cleft, they seek out and bind to specific receptors on the post synaptic neuron. These receptors are typically proteins precisely tailored to receive these chemical messengers. Um The binding of neurotransmitter to its receptor acts like a key that kind of unlocks a series of events. So it often triggers the opening of opening or closing of ion channels and that regulates the flow of irons across the neuronal membrane. So the flow of ions um leads to a kind of a dynamic alteration in the excitability of the postsynaptic neuron. And depending on whether the receptor is excitatory or inhibitory, the excitability can change and generate what we call an excitatory postsynaptic potential, an epsp or an inhibitory postsynaptic potential. And I PSP um the excitatory postsynaptic potential will make the neuron more likely to fire an action potential. Whereas the inhibitory postsynaptic potential as, as the name suggests, decreases that likelihood. Um And then as the neurotransmitter is complete, transmitting the signal, it becomes really important to actually turn them off and turn that signal off as well to maintain the balance between neural communication. So the termination process varies kind of depending on the neurotransmitter. For amino acids such as glutamate or Gabaa, there are reuptake mechanisms. So transporter proteins on the presynaptic neuron actively retrieve excess neurotransmitter, pulling them back into the neuron for recycling. When you're looking at something like monoamine neurotransmitters like serotonin or dopamine, they also rely on reuptake and have specific transporter proteins like serotonin reuptake transporters or dopamine transporters that recapture these molecules. Um When you're looking at acetylcholine, in particular, it undergoes degradation by acetylcholine esterases. And these are enzymes that are found in the synaptic cleft. Um what they do is they ensure that the signal is basically terminated. Um and the molecule is broken down. So some neurotransmitters are broken down enzymatically. So, neuropeptide neurotransmitters for instance, are typically degraded by enzymes in the synaptic cleft and that stops the signal um simultaneously to all of that, these membranes that previously housed neurotransmitters are recycled through endocytosis and that allows them to be refilled and reused in the future. Um The recycling process does use up energy but it's quite fundamental to keeping neuro communication efficient and I guess sustainable as well. Um So I've kind of given a whistle stop tour of those three topics. Um And I do have some SBA questions now. Um So please feel free to use the chat function um to kind of interact with me. Um So I'll give a few minutes to read the question. Um And then we can see what we think about them. Uh So this is question one, what is the primary function of oligodendrocytes in the central nervous system? So, if you wanna put your answers in the chart, that would be great. So I'm seeing some answers filter in, I'll give it like another minute and then we'll see how many people could, right? OK. So I'm going to go through this. Um Those of you who put c it's correct aytes in the CNS are responsible for producing myelin and those wrap around the axons to give electrical insulation and facilitate the efficient signal transmission. And I have put that slide back there. So we can see that it says oligodendrocytes support and insulate neurons. Um So yeah, it makes them is basically OK. Question number two. So in a lab setting, a researcher investigates the effects of a specific drug on the conduction velocity of an actual potential in neurons. The drug inhibits voltage gated sodium channels. What is the most likely impact of this drug on action potentials? So again, just put your answers in the chat. OK. I'm gonna give the answer now. So the last five seconds to put your answers in. Um So the answer is actually b slower conduction velocity is because of delayed repolarization. So if we remember back inhibition of voltage gated sodium channels would mean that we get less sodium influx. And that means that we delay the depolarization of an action potential. That would mean that we slower the conduction velocity. And so it will take longer for it to propagate longer than you on. So that's this bit here. Basically. Um looking at the sodium coming in and if that's delayed, then we get that delay in repolarization afterwards. Uh So the last question I have is this one here, a patient experiences symptoms of anxiety such as restlessness or excessive worry. The physician prescribes a medicine that enhances the inhibitory actions of the neurotransmitter gaba in the brain. What is the primary mode of action of this medicine or medication? So again, answers in the chat and I will explain them in a second. OK. Um If it inhibits sodium channels doesn't, then does it not mean no sodium can enter the cell at all. Let's go back to that question. Um So it inhibits voltage gated sodium channels. It doesn't mean that it's going to stop them though. It's not closing those channels, it's just slowing them down. So um that means that it'll just take longer for that sodium to come through if that makes sense. I hope that answers your question. Let me know if it doesn't. Um But yeah, that's basically the, the reasoning there for that question. Um Got it. Thank you. So let's go back to this. Any answers for question three. So we've got an answer coming in and we've got different answers coming in. So that's going to be interesting. Any more answers. I'll give it another 30 seconds and then we'll go through it. OK. So the actual answer is D and that's because Gabaa is an inhibitory neurotransmitter. Um And it reduces neuro excitability and anxiety. So, medicines that enhance Gabaa activity um So it enhances the inhibitory actions of Gabaa are referred to as Gabaa agonists and they promote the inhibitory effects of Gabaa. Um More Gabaa means that you've got more inhibition. Um It's a bit of a weird concept to get your head around, which is why I've put this question in. Um But it does not actually lead to more Gaba release, but it means that it binds more. Um So yeah, the answer is actually an enhancing of the Gabaa receptor. There'll be more activity on the receptor side, but the release will be the same. Does that make sense to those people who answer the question there? Fantastic. OK. So I think that's everything from me. Yeah, I just included that slide again there. But yeah, I think that's everything from me. Um I hope that you found that very useful or at least a little bit useful. Um But yeah, please feel free to hit me up with any questions. If there's anything that's burning, I will try and answer them to the best of my ability. Yes. In the last question, let's go back to that last question. Yes. I'm not sure if you're typing or not. Um But if there is a question, let me know. Um I'll be around for another couple of minutes. Um But otherwise Anushka, oh, we've got the pressure coming. Does that mean that the mechanism of action for the medication to enhance it? Yes, it is. So, the mechanism of action is to enhance the inhibitory effect if that makes sense? And that happens at the Gabaa receptor side rather than at the neurotransmitter side. Uh Is that the only way to do so? Uh I'm not sure if I'm really honest. Um I would have to look that up myself. I have no idea. Um As far as we were taught, we were taught just up to this level. So I would stick with this. Um Unless your kind of lectures said something different. Um But yeah, this is as far as we know in the preclinical setting. Thank you for your question though. It's great to have some engagement. Um Great uh uh an initial. Are you there? I don't know if it feels there or not, but any other questions then let me know otherwise. Yeah. Thank you so much for an amazing lecture. Um Yeah, guys, if you have any more questions just uh put them in the chart now. And if not, then I'm sure you can contact me on uh the group chat and you can just let us know if you do have any other questions. But guys just remember to fill in the uh the feedback form, sorry, which will be available to you straight after the session. Um And that way you'll have access to the lecture recordings and the amazing amazing slides. So thank you so much and have a good evening everyone. OK? I think we can call it there then. So see you guys later. Bye-bye.