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00:00 | this is mid term to review for and Synaptic transmission communication of 100 billion |
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00:10 | neurons in the brain trillions of You lay out the brain and the |
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00:16 | services like four soccer fields and membrane which is the fabric of our |
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00:23 | These guys here are Monica hall uh Charles Sherington, Camelia gold, you |
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00:29 | course from the past and of the who discovered neural transmission seal Colin by |
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00:35 | the vagus cranial nerve town that goes the cardiac muscle causes the slowing of |
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00:42 | heart rate. An eerie applied the on the naive heart and charlotte saw |
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00:47 | same effect proving chemical neural transmission but also gap junctions, electrical neural |
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00:54 | There's advantages for gap junctions there fast for cells to synchronize and you have |
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01:00 | flux of ions and small molecules. it's secondary messages between the cells and |
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01:06 | you have chemical and electrical neural transmission the synopsis you have access somatic |
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01:15 | accident, sonic and gender didn't ready discussed that acts tectonics and absence. |
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01:20 | don't really affect how to sell the integrative properties but it actually affects out |
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01:26 | properties of the cell where the other actually somatic. An accident riddick, |
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01:33 | affect how the cell is going to that information. Whether it's going to |
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01:37 | an action potential, distinguish between the of typical excitatory around testicle is symmetrical |
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01:44 | inhibit very symmetrical number and differentiations with or vesicles here we talked about that |
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01:51 | things. We talked about the neuro junction. We talked about the employees |
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01:57 | and talked about how the release of cdo Colin will activate. Only nicotine |
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02:02 | receptors is different from the cardiac muscle a skeletal muscle will activate and open |
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02:08 | nicotine acetylcholine receptors will cause very large polarization, employed potential and more than |
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02:15 | million volts and amplitude that deep polarization activate down located here in the genre |
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02:22 | false both educated sodium channels and calcium and generating twitch of a muscle or |
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02:29 | action potential muscular action potential. So high fidelity, very high functioning synapse |
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02:36 | deep polarization At the level of that on here causes a twitch of a |
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02:42 | because of the employee potential or P. being $70 million dollars in |
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02:47 | or larger. So review the neurotransmitter . You have to synthesis transport enzymes |
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02:53 | degrade them and then you have to a whole system plus synaptic aly binding |
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02:59 | ion a tropic and met over tropic systems. We'll come back to this |
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03:06 | but review this that you need deep calcium entry for the exhaust psychosis and |
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03:15 | whole cycle of endo psychosis as Um There is in the synapses in |
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03:27 | cns. There is full and partial . So you should review that uh |
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03:35 | the silicone in signaling. We talked the studio butcher line um and botulinum |
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03:42 | that they interfere with this particular protein binding to the member and protein complex |
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03:49 | therefore with the civil Colin release. this is prison attic person athletically you |
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03:55 | an effect from Taiwan East cobra and will have their effect within the synapses |
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04:04 | affecting a spherical industries. So fast transmission in the brain is mediated in |
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04:11 | cNS, primarily by glutamate excited to synaptic potentials. But the single synapse |
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04:19 | of a single synapse would result in very small deep polarization, about $0.5 |
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04:26 | and a half a million. Also opposed to the neuro muscular junction 70 |
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04:30 | volts one synapse here is $0.5 So you need to have many different |
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04:35 | synapses and continuous neurotransmitter, repeated neurotransmitter in order to reach the threshold for |
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04:41 | action potential generation. Uh inhibition is by Gaba and binding of Gabba gabba |
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04:50 | channels or cause an influx of fluoride I. P. S. |
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04:55 | M. I. P. P. S. A single synapses |
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04:58 | also approximately 0.5 million volts of hyper . I'm gonna tropic courses. Um |
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05:05 | tropic signaling. I am a tropic when the wagon molecule aceto Colin agonist |
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05:14 | step receptor and that receptor is a and metabolic tropic is when that receptor |
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05:21 | not a channel but it has been to ju protean and it can affect |
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05:25 | ionic channels or through membrane attached or numbering attached secondary messenger cascades inside the |
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05:34 | . You will be responsible for acetylcholine . Remember when the seal Colin Colin |
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05:41 | together Kohli Macedo transfers there's a ch till Colin is loaded up in the |
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05:48 | released in the CMS. You have on a tropical single column the subjects |
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05:53 | metabolic tropical single color receptors. So will be different. The function is |
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05:59 | and this is different from the skeletal and this is different from the cardiac |
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06:03 | in particular in the skeletal muscle. only have nicotine in K. |
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06:07 | H. So it's only an excited synopsis and in the cns synopsis obviously |
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06:13 | have glutamate synopsis which are excited gabble which inhibitor but a ch through nicotine |
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06:20 | acetylcholine receptors will cause deep polarization and mascara nick or metal tropic acetylcholine receptors |
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06:28 | cause hyper polarization in the same Once a seal Colin is released gets |
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06:33 | down by acidic all necessary to see castle Colin, gets transported back in |
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06:38 | and chatted back into pseudo code. we discussed that medications for Alzheimer's specifically |
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06:43 | sudoku Lunesta races but blocking the breakdown acetylcholine master is a pseudo Colin by |
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06:51 | um that's a local investor race. is an increase in the single Colin |
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06:56 | . And so we discussed that for medication this is a system neurotransmitter system |
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07:02 | is impaired early on in the court to a simple coding system. |
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07:09 | so organophosphates will also do the same if you're this is the nicotine Nicholas |
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07:16 | they have their own agonist nicotine and and they have their own antagonist karate |
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07:20 | antwerpen. Let me check the questions quick if I can open that, |
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07:31 | not letting me, So getting back the second we reviewed that the same |
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07:35 | of principles exists for cattle colony. so we reviewed that uh dopa and |
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07:42 | and then later norepinephrine and epinephrine come tyrosine. Um And we discussed in |
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07:48 | detail in europe and africa actually and between europe and africa uh and came |
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07:57 | and talked about amino acid neuro transmission how all of the cells that are |
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08:02 | cells will contain britannicus and deeper box . And if you do carb oxalate |
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08:08 | you take the C. O. . Group, this is Citigroup away |
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08:12 | basically from glutamate produced Gabba. So one enzymatic reaction away major excitatory cns |
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08:19 | into major inhibitory neurotransmitter. We talked about serotonin and how antidepressant medications and |
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08:30 | medications can control. Also the re of these molecules not just a breakdown |
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08:35 | the synaptic club but also the re of these molecules and how each one |
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08:40 | these neurotransmitter systems, serotonin or cata means and aceto Colin. They're involved |
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08:46 | different functions, different moods, sleep learning control and so on. |
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08:52 | then we talked about in the For under cannabinoids. We discussed that |
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08:56 | is two major under cannabinoids and and a tour of the two Roky donnelly |
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09:01 | glycerol and with the polarization, significant polarization in both inhibitor and excitatory synopsis |
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09:08 | can have increased production enzymatic synthesis of with the influx of calcium and then |
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09:15 | cannabinoids are not stored in the Like all of these southern new york |
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09:19 | were just discussing. Instead they've used through plasma membrane and retrograde fashion. |
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09:25 | target CB one receptors that are located optically and these are g coupled |
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09:30 | So this metal tropic CB one receptors actually regulate calcium channels that will close |
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09:36 | calcium channels and regulate the release of and inhibitory neurotransmitters. So the cannabinoids |
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09:43 | this negative feedback loop the pre synaptic and through a little bit tropic |
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09:49 | control the excitatory glutamate and inhibited the of these balancing excitation and inhibition in |
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09:56 | brain and delta nine THC. A nine tetrahydrocannabinol also actually receive you on |
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10:03 | primarily in the brain. Although there also another subtype of receptors called CB |
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10:08 | . Cannabinoid receptor two in the brain expressed in buia dominated more in the |
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10:14 | and the spleen organs that are associated immune function and immune response interrogates signaling |
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10:22 | the release of neurotransmitter from pre synaptic synaptic retrograde signaling is that neurotransmitter traveling |
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10:28 | post synaptic side and binding to pre receptors. This is also true for |
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10:33 | gasses nitrous oxide and carbon monoxide that in the same fashion. They're also |
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10:39 | soluble not stored in vesicles and have pre synaptic matters oxide carbon monoxide target |
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10:47 | to identify the cells. We use techniques in university chemistry consider hybridization and |
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10:54 | of neurotransmitters as well as another technique we discussed that was. And caging |
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11:01 | the neurotransmitters in the neurotransmitter mimic re just shown here of course. Now |
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11:09 | spatial summation, neurons can have spatial . So several synopsis active at the |
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11:15 | time will cement that signal. And signal from $0.5 million 1.5 million |
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11:23 | If you have 40 50 active excited synopsis, it can reach Now the |
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11:28 | can become large enough to reach minus which is the threshold for action potential |
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11:33 | . If you do temporal summation which a high frequency discharge of the same |
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11:38 | potential pilot spike. Again you also a much larger mps B but doesn't |
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11:45 | the same altitude as does with the summation. That's because there's a slight |
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11:50 | if you're activating the same synapse and there's time delay here that allows for |
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11:56 | cps be to start re polarizing rather immediate response From spatially cemented three synopsis |
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12:03 | are activated at the same time and in axons that propagate this action potential |
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12:10 | reproduce it in the salted story conduction each note of Ron beer that there |
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12:16 | a break out of this action potential is the same uplifted at the acts |
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12:20 | initial segment. Ah And that acts terminal And the synapse that's not the |
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12:29 | with inverted cables. But the good is not Meilen eight, it's just |
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12:34 | fully insulated. So that means the is going to escape. And so |
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12:38 | talked about this Lamb. The value the length constant length constant is essentially |
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12:46 | you inject the current which is your the zero value here, injection 100% |
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12:55 | . And then you place electrodes a list and the cable and measure how |
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13:00 | this current decay over distance. And does this current over distance reach 37% |
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13:07 | its maximum. That by definition is voltage. Okay value. The λ |
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13:18 | λ stands for the length constant. how far along this dendrite the signal |
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13:26 | going to travel before it reaches 37% is the length constant. So if |
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13:33 | some reason you have a lot of open and if you haven't done really |
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13:38 | that has very high densities of this lambda maybe Shorter, reaching 37% |
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13:47 | here. But if you have a length constant, that means that signal |
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13:52 | its maximum value will travel a longer here before it reaches its 37% value |
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14:00 | video. So this is synaptic And then for shunting and for inhibitory |
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14:07 | if you have excitatory synapse, it's enough. $0.5 million. $40 million |
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14:12 | may not be enough because you have ambition. If there's no inhibition, |
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14:16 | have excitation and you record from the most of that or part of that |
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14:23 | from that synapses going to reach the . But if you activate inhibition along |
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14:30 | way then you need to have a more excitation. Because if you activate |
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14:34 | not only hyper polarizes the cells but also shuts the currents out of this |
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14:40 | cable and by shunting the currents out the level of the soma and |
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14:47 | Get no deep polarization, No change all. So modulation when we talk |
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14:55 | modulation we talk of course about the protein coupled cascades that are through dental |
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15:02 | potentially cycling KMP protein kindnesses. But come back to the different diagram when |
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15:07 | talk about this again, these are neurotransmitter systems that we discussed when we |
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15:12 | about fast neural transmission. Glutamate and . Of course they have. I |
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15:18 | tropic and metabolic tropic receptors but signaling ion a tropic receptors as fast acetylcholine |
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15:24 | . I wanna tropic and metal tropic receptors but serotonin and catalonians, they |
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15:32 | only through medical tropic signaling and so is different because they are also expressed |
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15:39 | throughout the brain as opposed to the acid neurotransmitters. This is again you're |
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15:45 | pharmacology of aceto colon and the colon the metal but tropic side when you |
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15:51 | a single colon was currently concept. you actually open potassium channel. So |
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15:57 | you activate nicotine receptor, sodium comes and d polarizes the cell. When |
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16:03 | activate metabolic tropic must koranic receptor you this to protein couple protein reaction that |
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16:11 | opens potassium channel potassium leaving will hyper . The song luna made is very |
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16:20 | important to realize that leah is all glutamate signaling and glutamate receptors. Again |
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16:26 | have that ion a tropic and metabolic little interceptors gotta Colombians movement, |
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16:34 | attention and visceral function dopamine. So disorder would be associated with Parkinson's |
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16:41 | attention, visceral function, adrenaline of brain, mood control serotonin also |
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16:49 | So they have overlapping functions as neurotransmitters . But you can see that they |
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16:55 | sub serve. They're kind of a functions in the brain. For the |
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17:03 | . What we looked at is this pull system was classical push pull system |
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17:08 | two metal tropic receptors if you have seat locally and you have nicotine acetylcholine |
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17:15 | acting in opposite way too meta tropic , acetylcholine receptor Then here you have |
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17:25 | subtypes of literal tropic receptors. One beta receptor. Another one is alpha |
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17:31 | receptor in or benefit from binding to receptor stimulates the production of cycle game |
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17:37 | through a dental sightly stimulation and stimulates production of protein kinase assay and putting |
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17:44 | . As for late channels and can channels and keep them open and in |
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17:50 | the same molecule norepinephrine can activate alfa after causing an inhibition of the general |
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17:58 | and decrease in cycling campaign and decrease protein kindness production. So you have |
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18:04 | one is pushing production of something like and protein kind say another one is |
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18:10 | away from producing more of this. systems that we discussed like norepinephrine or |
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18:17 | or even other systems. And here have a single Colin system here that |
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18:21 | discussed some greater life two cooling system see in green. These are the |
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18:28 | in the cns where you will find so moe's that produces silk Colin and |
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18:36 | else. So if you look at example so this is the magna cellular |
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18:43 | forebrain produces acetylcholine and particular pawn teen the latter and also take mental nuclei |
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18:50 | acetylcholine. What does that mean? acetylcholine axons or a seal Colin is |
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18:57 | going to be found in these two . No, because this diagram illustrates |
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19:04 | better. Just like 40 goal in same as the case for snore and |
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19:10 | the same as the case for certain they have very specific nuclei in the |
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19:14 | that express these molecules. So the famous of these cells that produce is |
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19:20 | calling the producer up enough and the Tony and they live in these very |
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19:26 | areas in the brain stem. But projections out of these nuclear the |
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19:31 | The axons have these projections are So of these massive accidents have come out |
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19:36 | project everywhere. Sub cortical e new and to serve the element into the |
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19:42 | cord. That's where they referred to modular Torrey systems to because they specifically |
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19:50 | synthesizing these nuclei the activity program coupled and glutamate and Gaba. They mean |
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20:00 | neurotransmitters. Classical amino acid neurotransmitters that discussed. They will be expressed all |
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20:07 | . You will find cells that are of litter, mate and hippocampus and |
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20:10 | cortex full of gaba in hippocampus and cortex cerebellum and so on and so |
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20:17 | . So that's a big distinction and between these neurotransmitter systems. So just |
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20:22 | remind you that this process is referred as deep polarization induced suppression of |
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20:28 | This process of under cannabinoid signaling where polarization. If you have a lot |
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20:33 | deep polarization, what other cannabinoids do they suppress the release of neurotransmitter. |
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20:40 | if it's deep polarization and release a neurotransmitter, it will be inhibition. |
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20:48 | polarization induced suppression of an ambition. it's goalabama Tajik will be deep polarization |
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20:54 | suppression of excitation or dse amino acids . Again, they will have their |
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21:02 | transporters for glue to glue. Dramaturgical pharmacology have glutamate that will buy into |
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21:09 | subtypes of receptors that are distinguished based their chemical agonists and antagonists tampon and |
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21:16 | and kind. Um they also have pharmacology so they're bound by different agonists |
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21:24 | blocked by different antagonists that different kinetics glutamate is released it will immediately open |
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21:31 | channels sodium flux uh flux, skin the initial deep polarization And only when |
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21:39 | block is alleviated through deep polarization than channels will open. Them cause a |
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21:44 | influx of sodium and calcium. The of opening how fast or slow ample |
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21:51 | responsible for the early PSP component in for the late selectivity. All of |
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21:58 | NBA channels are permeable to sodium calcium potassium and only some I'm for channels |
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22:05 | permeable to calcium And conductance conductance perspective India channels are much larger conductors. |
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22:13 | PICO seamans they also have their own antagonists and ample key name is blocked |
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22:18 | seeing Q. X. And an 80 s. After some blocked by |
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22:23 | PV. Because in the areas after to detect glutamate. It also actually |
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22:29 | a glycerine as a co factor to function and it has to have a |
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22:36 | polarization person optically. So it has have the pre synaptic component, the |
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22:40 | , not the deep polarization because of is referred to as coincident sector. |
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22:45 | coincidentally detective chris an african possible app and it's not to be confused that |
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22:50 | receptor is a metal with tropic with interceptor because an M. D. |
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22:53 | receptor is just blocked by magnesium. is not do protean couple. So |
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22:59 | India is responsible for the late portion the PSP and has a slower |
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23:03 | And you can see that there's many substances uh such as PCP and even |
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23:09 | that has binding sites on an D. A receptor. In this |
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23:14 | we discuss that if you use a clamp and you record currents. Glutamate |
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23:19 | currents and you block ampara receptors. you see is a normal physiological $1.2 |
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23:27 | magnesium solution of minus 60 million volts barely see any opening of the |
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23:32 | You have to de polarize the number potential to -30 to start seeing the |
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23:37 | of the channels. zero new It's a reversal for an M. |
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23:42 | . A receptor. It's an equilibrium for an M. D. |
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23:45 | Receptor positive 30 you can see more current. So it's rectifying awkwardly produces |
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23:52 | and prefers to conduct current awkwardly. this is non physiological really because most |
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23:57 | the cells will live in this dynamic of -80 -92 -30 mil levels in |
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24:06 | conditions. Now if you remove magnesium the solution and you use the same |
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24:12 | clamp and you release glutamate and you ample block and you're recording an MD |
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24:17 | , you will see the opening of NBA channels and this proves that if |
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24:21 | remove magnesium blog eliminate will activate an channel. So in the absence of |
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24:27 | or decrease of magnesium and NBA channels going to be a lot more responsive |
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24:32 | glutamate. They're going to be open zero magnesium condition can cause massive hyper |
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24:39 | and the brains leading to seizures Apple apps. Too much excitation, |
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24:43 | much glutamate causing roommate toxicity potential. two, I'd pause that we discussed |
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24:51 | for the fast Tampa early component and level and NBA component. So if |
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24:58 | voltage clamp minus Sadie and you stimulate intimate with this line is and then |
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25:05 | take a measurement of how much current is minus 80. For the early |
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25:11 | you will see that emperor receptors show have a linear I. V. |
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25:17 | . Um and the reversal at zero vault. And if you measure this |
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25:23 | current and the peak of late you will see that at -80 million |
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25:27 | . This would be the circles here are filled circles. The filled circles |
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25:32 | showing that at -80 -6070. You have much of the current compared to |
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25:38 | Ham put -80 -60 and so Only at about minus 40 or so |
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25:45 | India current becomes significant. It's non versus zero in on the walls and |
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25:51 | is rectifying in this outward direction. course the positive charge flow in the |
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25:58 | direction. So if you use an , a current blocker which is a |
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26:04 | and it shouldn't. The fact that component, what you do is you |
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26:08 | an early measurement and one of these early component with a P. |
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26:14 | In it and early component without a in it. It doesn't change anything |
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26:18 | the early component. This a PV a specific block of an NBA |
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26:23 | And if you measure late current in presence of a PV which will see |
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26:27 | these open circles and these open circles near flat line here telling you that |
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26:34 | is no only current left because you it and there is no more current |
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26:41 | you would see. And so the current the NMDA currents of the PSB |
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26:46 | illustrated here in blue collar and this the blue current that would be blocked |
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26:52 | the presence of a PV and would this open circle plots. I hope |
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26:57 | explained a few questions that were there . This is a interesting talk about |
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27:05 | Q. R calcium. Yes for , arginine calcium, no single amino |
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27:12 | substitution can influence whether the sample channel permeable to calcium at early stages. |
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27:19 | an M. D. A receptor expressed or what you call a silent |
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27:22 | and then there's specific subunit shifts in . D. A receptor is is |
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27:27 | the development or to do any of signaling in India receptors in their silence |
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27:34 | absence because nothing is going to dip glass remembering in the absence of ampara |
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27:39 | only an NBA receptors that are affected at the very early age and then |
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27:44 | down for receptors come into play. is of course changes with age and |
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27:50 | , ample receptors can move in and of the synapses in the fast way |
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27:54 | significant plasticity. LDP s test for term plasticity that is mediated by the |
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28:00 | GIC and envy and Amber's transmission for but tropical intimate we discussed. This |
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28:06 | really important that way that if you metal properly receptors you convert P. |
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28:12 | . P. Two through Prospal ibc membrane bond. So literal which can |
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28:19 | the protein kinase C. And the of this pathway into production of the |
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28:24 | triphosphate and activation of the I. . Three receptor on the smooth and |
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28:30 | , particularly inducing an inter cellular calcium for calcium is not only an ion |
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28:36 | also a secondary messenger. Gaba ergic . Gaba binding Gaba a receptor in |
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28:45 | will cause the influx of chloride and or hyper polarization dampening of activity in |
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28:52 | brain. So activation of Gava increases tradition or dampens activity in the |
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28:58 | It's also aside for ethanol, benzodiazepine barbiturate nurse. Terror binding Gaba A |
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29:05 | Gaba receptors. Gaba a receptors uh you bind Gabba to them, chloride |
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29:13 | is gotta be receptors. They are through g protein complex to calcium. |
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29:19 | can block calcium influx and potassium channels they can open potassium channels and cause |
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29:27 | influx. So we discussed this important here and this is just in general |
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29:35 | everything together. You can have a synapse and if you have significant influx |
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29:40 | calcium you can activate calcium kinds tune Gaba b receptors are located both. |
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29:49 | optically and passing optically. So gabby Prison optically will block calcium influx and |
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29:56 | neurotransmitter release is simulated in a way The CB one receptor function. And |
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30:03 | ethically Gaba receptors can open potassium channels cause hyper polarization. So Gabba |
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30:12 | if this Gaba synapses are located here synapses through Gaba receptor, a receptor |
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30:19 | will cause influx of chloride causing the I PSP inhibitory synaptic potential and the |
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30:26 | hyper polarization through opening of the potassium through the gabba. Be metaphor tropic |
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30:33 | and prison optically if this ambient gaba over here it can block further gabble |
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30:40 | . So you have an auto receptor and if you have a lot of |
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30:44 | that spills over into an adjacent excitatory , it can also control the release |
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30:49 | glutamate by activated pre synaptic gaba receptors the grid. Um antarctic synopsis. |
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30:57 | So you can see again that this intricate interactions here between Gaba a baby |
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31:06 | , potassium calcium channels in an D. A. Receptor is this |
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31:09 | a great questions for labeling diagram or for the exam. This is an |
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31:17 | again where if you stimulate synopsis that excited to input. So this is |
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31:21 | stimulus you will first produce E. . S. P. And if |
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31:25 | synopsis are flying to surrounded or innovated inhibitory synapses boom. Gaba A will |
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31:32 | the C. P. S. . Causing an influx of chloride trying |
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31:36 | drive the number of potential to the potential fluoride which is 1 70 million |
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31:42 | followed by the activation of the Gaba receptor and opening of the potassium channel |
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31:47 | the flux of the potassium trying to the potassium at Louisville potential of -19 |
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31:53 | walls to grab a beer uh through activation and opening of the potassium |
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31:59 | And if you if you block Gaba receptor antagonist is by curriculum. If |
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32:06 | block this gabba a response and you in one and two it's exact same |
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32:14 | . But you can see that if have inhibition excitation is followed by inhibition |
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32:19 | of controls and checks excitation and And if you don't if you block |
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32:26 | with Baekje column you can see this excitatory de polarizing plateau potential that you |
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32:32 | produce themselves. So a little bit the structure of the G protein coupled |
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32:39 | is seven trans member and spanning alpha and a variety of different mineral tropic |
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32:47 | signaling from Seattle Colleen, Gaba, , dopamine, norepinephrine and couple of |
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32:54 | at peace at peace. Not only the energy molecule and also as a |
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32:58 | and receptors. And we discussed also caffeine as two dentists and recep recep |
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33:07 | Yeah there were dentists and receptors as . Uh This is transmitted gated channel |
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33:15 | . So of course it's different from G protein coupled structure here you have |
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33:22 | little cold in receptor in particular as sub units. Each one of these |
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33:28 | four trans member incitement someone threw them what is notable here is different combinations |
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33:35 | these subunits that cause a variety of of gobble and gobble B receptors and |
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33:41 | of the interesting things is nicotine nick critical stuff. The afternoon nicotine |
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33:46 | agonist carrera entre pena's antagonists um you to know I'm an M. |
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33:52 | A. Of course afternoon the Gabba D. And you should know by |
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33:56 | is the antagonist of Gaba a alpha sorry A TPM dennison receptors, a |
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34:05 | dennison is an agonist will discuss that TPS and agonist agonist for different type |
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34:10 | denison receptor called P two X receptor it's still in the dentist and receptor |
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34:17 | they 80 p. stands for a and triphosphate. And there you have |
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34:24 | as an antagonist for denison. So have these things that are dennison is |
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34:33 | , what it does is uh increases signaling and a dentist and dampens glutamate |
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34:40 | . So in the evening time of levels go up and dampen glutamate release |
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34:46 | brain activity quieted down and let inhibition more active and caffeine does the opposite |
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34:55 | increases gonna make released through a dentist receptors through G protein coupled system. |
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35:01 | is the amplification that you can And also different divergence convergence redundancy parallel |
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35:08 | that you would see in this neurochemical and after our prolonged discussions in your |
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35:16 | and you already had a quiz on there will be more questions on the |
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35:22 | and there's a lot of good labeling that is going to come from the |
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35:27 | . And as I said, I'm going to do necessarily a review of |
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35:31 | CMS because we just finished talking about in the last couple of days. |
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35:36 | I would be happy to take any you may have. And other than |
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35:42 | , I'm gonna leave it here with recording today. Good luck on your |
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