| 00:00 | Yeah, this is Wednesday. Neuroscience 12. And we continue talking about |
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| 00:10 | transmission in my video. And what have in neural transmission, of |
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| 00:18 | is we have the release of uh, into the synaptic cleft. |
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| 00:25 | so you have the fusion of the cycle to the plasma membrane. And |
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| 00:30 | are several very important things that we that need to happen in order for |
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| 00:36 | vesicles release to take place for the release of ethical fusion of neurotransmitter released |
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| 00:43 | take place. And those important things that you have to have deep |
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| 00:50 | so action potential has to arrive at external terminal. When you have deep |
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| 00:57 | , you must have calcium influx. if you had a specific voltage gated |
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| 01:04 | channel blocker that is located and active or if you depleted extra cellular solution |
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| 01:11 | the calcium, this is one of experimental conditions you can deplete extra cellular |
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| 01:17 | and initially, what happens if you have calcium in the solution? You |
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| 01:22 | stop that. The circular release so polarization is necessary. Calcium influx is |
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| 01:30 | . And if you remember, calcium was necessary because the vesicles has a |
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| 01:36 | complex, and that protein complex on vesicles has calcium sensors. And once |
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| 01:41 | is enough calcium, these protein complexes the vest ical and the neuronal membrane |
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| 01:49 | the two membranes and the proximity so they confuse. And unlike in the |
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| 01:55 | junction, which we discussed this very um synapse. So where one synapse |
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| 02:03 | equal 70 million volts of deep polarization the muscle and the contraction of a |
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| 02:09 | in central nervous synapses? First of , the synapses air not that |
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| 02:14 | So single synapse excited to synapse will a deep polarization of about half a |
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| 02:20 | volt and an inhibitory synapse. A polarization off about a half a million |
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| 02:27 | . So we talked about how first all you need a lot of synapses |
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| 02:32 | to 50 synapses in order Excited Terry . In order, thio raise the |
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| 02:38 | potential to the thresholds for action potential , so you'll have to activate a |
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| 02:42 | of synapses. You'll have to release lot of vesicles and then the |
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| 02:46 | N s. You have partial fusion partial particular release your transmitter release or |
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| 02:52 | full fusion and full neurotransmitter release and followed by the psychosis and either processing |
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| 03:00 | the early end of some, just the loading of the protons and loading |
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| 03:05 | the neurotransmitters through the respective transporters and setting up those vesicles filled with the |
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| 03:14 | certain amount quanta of neurotransmitters ready to released again. And so the cycle |
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| 03:20 | recycling neurotransmitters. If the synapse was activated very strongly and a lot of |
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| 03:27 | vesicles were released, neurotransmitters were depleted the process. For the synapse |
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| 03:34 | we build itself to its full activation loaded vesicles will take anywhere between 10 |
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| 03:39 | fif 18 seconds. So we talked all of the processes being in milliseconds |
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| 03:45 | potential synaptic delay or synaptic cleft synaptic delay, a few milliseconds |
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| 03:55 | part synaptic response happening in few But if you jolted the synapse with |
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| 04:00 | laugh of the activity now for in order to restore it to its |
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| 04:06 | efficacy and capacity will take about 10 15 2nd. We talked about a |
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| 04:13 | Colin, uh, neural transmission, in particular, we discussed this, |
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| 04:19 | , typical settle Colleen synthesis degradation We talked about that. It's a |
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| 04:27 | investor race which breaks down Acetylcholine is a target of medications for Alzheimer's |
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| 04:34 | where medications can are also a typical . Race blockers prolonging the an, |
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| 04:42 | the amount of its style. Colin the synaptic cleft. And so you |
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| 04:48 | see that Then the molecules get recycled and reloaded. We synthesized and reloaded |
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| 04:55 | into vesicles from released. So we talked that and the neuro muscular |
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| 05:00 | You have nicotine IQ receptors and the muscle that we discussed. And in |
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| 05:06 | central nervous system you have both nicotine channel receptors for acetylcholine. Acetyl Colin |
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| 05:12 | these receptors and also combined must which are G protein coupled receptors. |
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| 05:18 | most of the cells that are sensitive , Colleen and the CNS will have |
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| 05:24 | combination of both. Of these were , but before we kind of, |
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| 05:30 | um go further in the synaptic Let's go back a couple of slides |
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| 05:36 | let's discuss what happens by Synaptic So we discussed in great detail what |
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| 05:42 | if we sign? Nah, where you have vesicles release physical |
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| 05:47 | we discuss these toxins and remember, discussed, uh, bunch line, |
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| 05:53 | toxin as interfering with the protein, binding complex and stopping the release off |
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| 06:01 | S. The deal. Colleen, talked about black widow venom which also |
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| 06:09 | the cynical and release. Then we about Alfa Bungalow toxin, which affect |
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| 06:16 | synaptic receptors. And we haven't really much about pasta Matic receptors. And |
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| 06:21 | , organa false face or nerve gas that are sarin and some on white |
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| 06:31 | that are also it's Italico Ministries uh, that are toxic and |
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| 06:39 | And they used in warfare and they by terrorist groups a swell. So |
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| 06:44 | , nature is powerful. You have , spider snakes and you in nature |
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| 06:49 | use also part of the human nature creating synthesizing things that air human synthesized |
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| 06:55 | both medicinal purposes in case of Alzheimer's or warfare purposes. In case off |
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| 07:03 | nerve gas is you BSP's E P P stands for excited Terry Pawson optic |
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| 07:11 | . So now we're going to Okay, what happens? And so |
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| 07:14 | us to understand what happens, Boston Let's understand what our favorite I |
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| 07:19 | Assad, neurotransmitters, glutamate and Gabby doing so. What happens when glutamate |
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| 07:27 | released prison optically when glued, Americans process. Kristen optically glutamate will bind |
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| 07:35 | Louis made receptors so their receptors that gated by glue, the main in |
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| 07:42 | potentials. These receptors had a vaulted , both educated, sodium channels |
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| 07:49 | They were gated by voltage and this up. You have binding of glutamate |
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| 07:56 | sodium influx inside the cell and P S P is a small, |
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| 08:01 | polarization. If it's a single only half a million bolt of deep |
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| 08:06 | and few milliseconds in duration. And is what a single synaptic activation here |
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| 08:14 | by binding glue to make molecules to glutamate receptors, allowing the influx of |
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| 08:21 | current and causing this deep polarization. actually, what happens In addition to |
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| 08:27 | , there's also re polarization, which through potassium and potassium, leaving the |
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| 08:33 | through the same channel. And actually, I'm gonna, uh, |
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| 08:38 | this diagram later, as we discuss and Maura about Buddha motor tics signaling |
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| 08:46 | key information here is that sodium is to cause this deep polarization. Austin |
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| 08:53 | glutamate will bind to glutamate receptors and for the influx of sodium. But |
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| 08:57 | you'll see glutamate receptors, unlike voltage sodium channels which were just permissible to |
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| 09:03 | or, unlike gated potassium channels, is just permissible to potassium. You'll |
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| 09:08 | that these glutamate receptor channels air permeable multiple ionic species. We'll discuss that |
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| 09:14 | a little bit. The point here make is little mate. Binding will |
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| 09:18 | influx of sodium, which will cause deep polarization of this number. So |
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| 09:22 | have to activate many, many exciting synapses and different parts of the dendritic |
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| 09:27 | and different parts of the cell. the 10 drives in order for the |
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| 09:32 | membrane for synaptic cell membrane to dipaula and have to reach the threshold for |
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| 09:39 | , um on. Remember that at same time as you're activating excited Terry |
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| 09:45 | so might be nearby and inhibitory synapse an inhibitory synapse. You will have |
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| 09:51 | release of Gabba. And when you GABA, you cause an I, |
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| 09:57 | S P and I PSP stands for cost synaptic potential. This is |
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| 10:04 | Terry part synaptic potential, e p p. And this is inhibitory parts |
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| 10:10 | potential or I p s p. when gaba our favorite, I mean |
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| 10:16 | inhibitory neurotransmitter gets released into the synaptic in this inhibitory synapse, it will |
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| 10:24 | to gather receptors, and it will an influx of a negatively charged |
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| 10:32 | All right, so this is an now entering into the cell. Negative |
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| 10:38 | . Entering into the cell will hyper the plasma member. So if it |
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| 10:43 | a minor 60 it may draw it to minus 65. If you activate |
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| 10:48 | of these inhibitory synapse. Okay. again, the differences in the case |
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| 10:55 | exciting Terry Synapse glue dramaturgical, synapse , ergic signaling glutamate will bind thio |
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| 11:02 | receptor channels that will allow the passage sodium and positive charge coming inside the |
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| 11:09 | will cause the deep polarization Excited. Pawson, Apple potential In the inhibitory |
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| 11:16 | release of inhibitory gaba neurotransmitter gabba will to gather receptor channels. These gather |
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| 11:25 | channels will allow the influx off If you recall, there's a lot |
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| 11:30 | sodium chloride on the outside of the , so this receptor channel will specific |
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| 11:36 | chloride and influx of the negatively charged will cause this hyper polarization in the |
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| 11:43 | of I, P S p. now you can imagine that there are |
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| 11:49 | hundreds of thousands of these synapses, of them are generating inhibitory inputs. |
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| 11:55 | nearby generating excited Torrey deep polarization CPS I ps ps. And so if |
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| 12:02 | have enough of the e p s that some AIDS, it will produce |
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| 12:07 | action potential. So first, the p s P. M may be |
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| 12:12 | , but you activate mawr and more . That's how you reach the threshold |
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| 12:20 | action potential Boston optical. Okay, actually gonna, uh So the way |
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| 12:30 | you read this is a time from synaptic action potential. So there was |
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| 12:34 | action potential that happened. And the here, the E p s P |
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| 12:40 | , then if we continue the scale , our goal now is to reach |
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| 12:56 | our goal is to reach the threshold action potential. So let's say that |
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| 13:03 | threshold for action potential is going to somewhere here, right? We're gonna |
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| 13:10 | as minus 45 million goals. So happens when you activate one synapse? |
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| 13:23 | , you will get you will get small, deep polarization that will look |
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| 13:29 | this. Uh huh. If you two synapses, you can get the |
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| 13:40 | , deep polarization. It will essentially some mating. Okay, you're some |
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| 13:47 | the apple itude Until eventually. If have enough off the excited Torrey synopsis |
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| 13:59 | . Guess what happens eventually. each one of these lines representing |
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| 14:09 | uh, Mawr and Mawr synopsis being . Eventually, you will activate enough |
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| 14:20 | to reach the threshold for action And guess what happens at that |
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| 14:25 | And at that point, you generate action potential, which is now going |
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| 14:31 | the charts. And it's now we'll coming coming back from the top someplace |
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| 14:41 | . Mhm on returning again. so this represents an action potential. |
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| 14:53 | ? And this is the just the incomplete action potential, So I'm actually |
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| 15:01 | separate kind of with lines like Okay, But the idea here is |
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| 15:10 | is one synopsis activated. Okay, is too synopsis activator. Uh |
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| 15:19 | This is three synapses activated. This four X sanitary synopsis activated, |
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| 15:30 | Until you reach whatever number of synapses still absence that are activated for you |
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| 15:41 | reach this threshold for action Potential Uh huh. Is this clear that |
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| 15:52 | difference between the Neuromuscular junction is a synapse will reach the threshold for action |
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| 16:00 | But here in the CNN s, have to activate many synapses in order |
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| 16:07 | reach the threshold for action potential and CPS peace will be adding up on |
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| 16:15 | and amplitude. The more synapse issue , you also have to activate synopsis |
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| 16:21 | the same time. Because guess what if you activate one synapse or if |
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| 16:29 | activate five synapses or four synapses, and then four synopsis later. This |
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| 16:37 | the response that you get, so may not reach the action potential threshold |
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| 16:44 | over here. So you have to the synapses have to happen in |
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| 16:54 | At the same time, they have some in space because you have to |
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| 17:00 | many synapse since in space along different spines and along the soma in |
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| 17:10 | And then you have to make sure those synapses in different parts of the |
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| 17:15 | get activated about the same time. if you do get activation from 18 |
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| 17:22 | or 25 synapses, you're you are fact reaching Ah, the threshold |
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| 17:32 | Well, the action potential generation. , the more synapses you activate. |
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| 17:39 | right, so you it's not just it's not that simple that Oh, |
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| 17:46 | just have to activate 20 synapses. have to make sure that these 20 |
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| 17:51 | air activated within a couple of millisecond in order for them to add up |
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| 17:58 | for the membrane potential Post Synaptic this is excited or pasta Synaptic potential |
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| 18:05 | Posson optical. You have to Polarize the self strong enough in order |
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| 18:10 | reach a threshold. We're action potential one one vesicles one quanta to two |
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| 18:20 | packet 33 Quanta packet 44 Qantas synapses activated. Okay, you synapses being |
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| 18:28 | your transmitter of obstacles They all something deep polarization is that then have toe |
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| 18:35 | count in time and space. Uh we we talked about in reality, |
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| 18:47 | know, numbering for town troll. this line out. It's gonna look |
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| 18:51 | something like this and deep polarization. inhibitory inputs come in deep Polarization, |
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| 18:56 | inputs coming deep polarization. Okay, firing in action with them. |
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| 19:01 | So you can call this a a , you know where positive what do |
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| 19:07 | the flag shows us excited tourist synopsis they're being inhibited, excited or synopsis |
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| 19:13 | an inhibitory synapses responding excited tourist synapses inhibitory synapses until there is enough excitation |
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| 19:20 | Dr Teoh, the threshold of the of potential activation actual production resumed the |
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| 19:28 | E P s PS, PS, , it's chloride influx, and we'll |
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| 19:33 | about those two types off inhibitory signaling get into more detail on this is |
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| 19:41 | different. So you see in both the cases and glutamate and GABA and |
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| 19:46 | . Glutamate will bind to glutamate and it's a channel. Allow passage |
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| 19:52 | sodium gabba will bind to gabble receptors allow the passage of chloride causing the |
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| 19:58 | polarization. So this kind of a is referred to as direct signaling, |
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| 20:04 | I on a tropic versus metal ba signaling Minimal tropic signaling is you have |
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| 20:13 | transmitter. It's a little bit blurred binds, and this neurotransmitter can be |
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| 20:18 | subtle Colin neurotransmitter that binds to must Seattle colon or SAPTA. On |
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| 20:25 | most Quranic receptor is not a so this green receptor, which is |
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| 20:33 | must Quranic acetylcholine receptor, is not channel. It's not like a nicotine |
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| 20:38 | . Still, Colin Receptor, the , is on a tropic must. |
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| 20:43 | is not over tropic, so when activate this receptor, let's say most |
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| 20:49 | IQ or little Bo Tropic receptor. is linked to G protein complex that |
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| 20:55 | associated with this resaca and your transmitter to G protein coupled receptor will then |
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| 21:03 | this G pro dam. Uh, catalytic subunits of it will get |
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| 21:10 | And these g protein couple protein G protein complexes are member and associate |
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| 21:19 | . And once one of these subunits the G protein gets activated can slide |
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| 21:24 | on the adjacent very close Thio, it exists on the piece of the |
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| 21:29 | brain and the fact what we call G protein gated ion channel. |
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| 21:36 | this is a channel, so this will be conducting islands and G protein |
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| 21:45 | receptors and neurotransmitter activation can either These channels will close these channels. |
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| 21:51 | depends very much on the neurotransmitter, it depends on the subtypes of medical |
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| 21:58 | receptors. So when we look at norepinephrine, we're gonna talk about the |
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| 22:03 | and Beta medical tropic subtypes of these . Right now we're distinguishing between I |
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| 22:09 | a tropic and medical Tropic. So function of G Brodin activation is regulating |
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| 22:17 | ion flow through the nearby G protein ion channel. So this channel is |
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| 22:23 | gated by G protein and not neurotransmitter , but by another protein. |
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| 22:31 | now we know three types of channels types of gating voltage gating, voltage |
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| 22:38 | and channel opens or closes. LaGon . No transmitters bind like luda, |
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| 22:45 | and allow the flocks off ions. , well, g protein Gaeta |
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| 22:52 | So activation of this G pro dam interaction of this program with another receptor |
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| 22:59 | is another way of gaining these channels medical tropics, signaling you can have |
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| 23:10 | not just in the fact on the channels, but you can also affect |
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| 23:15 | enzymes. Can remembering associated enzymes can influence the production of secondary messengers, |
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| 23:23 | go downstream into cellular early and can fact the signaling inside the South and |
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| 23:28 | even the fact that transcription factors at level off the nucleus. Uh, |
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| 23:36 | there's many different of the secondary Messenger and enzymes will get activated as well |
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| 23:42 | you protein gated ion channels. What says, same neurotransmitter. Different. |
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| 23:49 | fact in the same cell, same , different effect in the same |
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| 23:59 | different the fact in the same cell you can have the release of the |
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| 24:04 | Colleen neurotransmitter. Okay, you recall steel Colleen. Sorry. Right |
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| 24:17 | Andi. If it binds to nick acetylcholine receptors, it will be |
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| 24:24 | story to this post synaptic sell. if advance Thio must carry nickel metal |
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| 24:29 | tropic mascara nick acetylcholine receptors or do couple receptor, it will have an |
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| 24:35 | effect on the South. So same . Two different facts on the same |
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| 24:44 | . And that depends on the proximity the expression, densities and levels of |
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| 24:48 | individual receptors. And some of them be dominating in certain synapses like |
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| 24:53 | Okada's dominating and other synapses like What's ? Same neurotransmitter different the facts on |
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| 25:02 | cells. That means that you can the same neurotransmitter. But in one |
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| 25:11 | that neurotransmitter might activate enzyme A and cell. It may activate enzyme be |
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| 25:22 | the same receptor, and that will a different effect on different cells because |
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| 25:30 | cells will have a different enzymes and secondary messengers, different G protein coupled |
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| 25:40 | and different mental ba tropic receptors and G protein couple. So that's what |
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| 25:48 | two things mean? Same neurotransmitter. affect them. The same salads, |
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| 25:52 | game salad. Same cell and same transmitter. Different. The fact in |
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| 25:56 | cells. Hi. So we now this sucker. Really? Well, |
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| 26:03 | that is gonna be quite a few about, um, acetyl Colleen. |
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| 26:12 | . Course it will be found not in the CNN s. Not in |
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| 26:16 | Justin motor neurons. And are Muscular all peripheral nervous system. Pretty |
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| 26:22 | Janek. And the parasympathetic endings. swell. And then the C n |
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| 26:28 | . You know, think of these systems. And the cycling is pretty |
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| 26:33 | toe all of the neurotransmitter systems, serving ah different function and is associated |
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| 26:40 | with, with certain impairments, a Alzheimer's disease. So let's look a |
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| 26:48 | bit deeper into this. Cullen Arctic . Pharmacology. Whoa, Euro |
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| 26:58 | Go tell this to your friends What did you learn today? I |
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| 27:02 | know. What about you neuro You blow their socks off. So |
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| 27:10 | is your A pharmacology is how different agents, or how different neurotransmitters or |
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| 27:19 | derivatives function in the brain. So here we're talking about Colin ergic neural |
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| 27:34 | because we're talking about seal Colleen binding nicotine nick receptors. And you can |
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| 27:40 | that this nicotine receptors has shown this receptors. And the reason why they're |
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| 27:46 | nicotine IQ is because nicotine well, in the continent with subjects. |
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| 27:51 | I don't know that. Yes, . In your brains, nicotine binds |
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| 27:58 | nicotine, Nick acetylcholine receptors, but doesn't mind to most Karina Casino Colin |
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| 28:06 | Very interesting and activates Colin Arctic Uh huh. Activities going arctic |
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| 28:17 | But we have impairments and Colin ergic in certain neurological disorders. Does that |
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| 28:25 | nicotine can help? Does that mean can raise boss synaptic signaling off this |
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| 28:38 | ? Now, this is different. medications will look at as a tactical |
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| 28:44 | . Inhibitors were raising the level off central Colleen in the synaptic cleft. |
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| 28:50 | this case, you're activating parts synaptic , and you're activating nicotine Nick past |
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| 28:56 | Receptive. There's another substance. Must that must. Corinne will not bind |
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| 29:05 | nicotine receptors, but it will buy must carry nick receptors. And that's |
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| 29:09 | they're called must Karen IQ receptors. nicotine binds in the continent, acetylcholine |
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| 29:16 | , it will activate. It will that receptor channel it has a positive |
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| 29:26 | . So does a Seattle. Colin a positive sign. Positive sign indicates |
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| 29:35 | A Seattle Colin will open nicotine receptor . Acetyl Colin will activate Mouskouri nick |
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| 29:43 | and downstream G pro dam activation. is an agonist binding of nicotine to |
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| 29:55 | receptors Will open up nicotine Nicholas after binding of Musker in to most Koranic |
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| 30:05 | will activate the G protein and So agonists ah, molecules that open |
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| 30:15 | channels or activate receptor channels. now antagonists each one of these nicotine |
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| 30:27 | and muscular nick receptors they have their respected antagonistic cure. Are comes from |
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| 30:37 | little poisoned frog in South America that spooked by some indigenous tribes on |
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| 30:50 | Thio for hunting purposes on these little arrowheads, Cure are is an antagonist |
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| 31:00 | of purity. Nicotine receptor shuts it and activates at. Europeans will not |
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| 31:10 | to nicotine IQ, but it will Thomas Koranic, and it will decrease |
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| 31:15 | activation of G protein complex. So cure are a and attribute are |
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| 31:25 | There are antagonists because Carrara will close channel on a trip in will inactivate |
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| 31:31 | G protein complexes associated with this Uh huh. And in the |
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| 31:38 | you are both Would you have in skeletal muscles you have the continent |
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| 31:48 | Eso it. Zettel ! Colin is excited. Torrey Neuromuscular Junction is Onley |
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| 31:56 | , Terry Junction it on. Lee one neurotransmitter acetylcholine to skeletal muscles Onley |
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| 32:05 | Torrey that produces a positive A fact polarization through the continent. Receptor |
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| 32:13 | What receptors are expressed in the Why is it that the heartbeat slow |
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| 32:21 | a little? Colin is, uh , uh, in the presence of |
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| 32:26 | silicone at European is an antagonist. , uh, and C n s |
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| 32:37 | these muscle systems we're talking about seeing will contain both nicotine nick and muscular |
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| 32:42 | receptor. Which one wins again? depends a statistical and will get released |
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| 32:48 | the synapse us both they will compete each other actually on. But they |
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| 32:55 | also have a different the fact physiologically these cells. Mhm. So what |
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| 33:05 | other systems but catacomb amine cata cola ? What is it? Why do |
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| 33:16 | need to know about it? the thing is that it's it's a |
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| 33:21 | important system. And if we look the components of the system and in |
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| 33:26 | , how Cata Cola means air synthesized tire ASEAN, dire ASEAN hydraulic |
|
| 33:34 | You put a hydroxyl group here. , age and you turn it into |
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| 33:40 | d hydroxy thin, ill Allah which is l dopa. Anybody knows |
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| 33:46 | l dopa. L dopa is, , one of the classical medications for |
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| 33:57 | disorders for schizophrenia to increase the dopamine because I explained to you that the |
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| 34:05 | on a dysfunction is associated with Parkinson's . But dopamine receptor dysfunction is associated |
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| 34:13 | schizophrenia. Now L dopa will use . A dick, our box. |
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| 34:19 | . Well, dick, our box will take the c o h group |
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| 34:24 | and we'll turn it into dopamine. dopamine through dopamine, beta hydroxy |
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| 34:34 | We'll add another wage here we'll turn into nor upon Afrin into the adrenaline |
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| 34:40 | off the brain and Ventola mean and transfer race will turn norepinephrine will add |
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| 34:48 | CH three group here. Okay, in N h to now and H |
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| 34:54 | a three into open afrah and the thing. The same pattern will exist |
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| 35:00 | year for kind of cola. Means well meaning that there will be loading |
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| 35:06 | Cata cola means into the vesicles release Cata column into the synaptic cleft |
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| 35:13 | Reimportation off the Cata cola means through sodium co transporter reloading again through the |
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| 35:20 | back into the category. Levine's, , bicycles. Okay, eso amphetamines |
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| 35:30 | cocaine will block the re uptake of Cola. Means this is This |
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| 35:40 | in contrast, Thio Alzheimers Medications Alzheimers will target a single Colin system, |
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| 35:47 | it will increase the availability of a Colleen and the synoptic left. When |
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| 35:54 | talking about Cata Cola Means and we're about drugs of abuse or just |
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| 36:00 | there is a blockage off re uptake Cata Cola means. And if you're |
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| 36:07 | about norepinephrine and happen, Ephron the the adrenaline's off the brain is essentially |
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| 36:15 | the signaling off these adrenaline like molecules the synopsis by blocking the re uptake |
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| 36:23 | back into the pre synaptic cleft. , do we share? What is |
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| 36:36 | mayo doing on the on the That's such a great question. Maybe |
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| 36:45 | should make this into a home or . Okay, But I m m |
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| 36:54 | . L will break down the enzyme will break down Cata Colla means so |
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| 37:06 | are m a O inhibitors that are common commonly uses anti anti depressants. |
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| 37:16 | let me leave this sort of a a little bit of a home or |
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| 37:20 | for you guys. Thio do some on M A L. And maybe |
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| 37:25 | will even realize how it's maybe so as a prescription medication and being |
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| 37:35 | Aziz prescription medication. Let's talk a bit more about I mean acid |
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| 37:42 | This was again. You're not gonna responsible for knowing for having to know |
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| 37:48 | different, uh, enzymes. Dicker , Lis Smith transfer races, hydroxy |
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| 37:54 | . This is to illustrate that just step in dramatic reaction brings you from |
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| 38:00 | , but to dopamine, from norepinephrine from epinephrine, Annapurna from And |
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| 38:04 | are complex chemical women systems that have lot of influence and different activities in |
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| 38:11 | brains. If we talk about amino neurotransmitters, this is what's really fascinating |
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| 38:18 | me. Is that glutamate? This glutamate and talk. This is glycerine |
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| 38:22 | this is Gabba. The difference between eight and GABA is just deke our |
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| 38:28 | elation. So if you Deacon box late glutamate c o h you take |
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| 38:34 | o h. And now you have positive charge on NH three. Now |
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| 38:38 | becomes Gabba. So one and dramatic by the atomic acid dick Our box |
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| 38:45 | turns the major excited to a neurotransmitter the brain and to a major inhibitor |
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| 38:50 | transmitter. Right. So knowing that of the inter neurons are inhibitory, |
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| 38:58 | of the inter neurons that are inhibitory will express gabba will contain God will |
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| 39:05 | the glue atomic acid deco box Okay, so there's this this this |
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| 39:10 | interesting Cool. The 11 step reaction the major excited Terry neurotransmitter into the |
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| 39:18 | inhibitory neurotransmitter, you know, then always here again is really to |
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| 39:25 | And you can see that serotonin is , molecule that will control mood |
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| 39:33 | sleep, learning. Actually, sleep , appetite and learning are all very |
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| 39:42 | correlated. You don't sleep in a mood. You know that mood? |
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| 39:46 | have weird eating, uh, You have weird eating habits in a |
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| 39:53 | mood. You don't learn very well your tired because you don't sleep. |
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| 39:59 | , serotonin is synthesized from trip to . You have trip to find hydroxy |
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| 40:05 | and then that turns it into five trip to fan. And, |
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| 40:14 | we consume trip to fan. That's month. Coming up on Thanksgiving will |
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| 40:21 | consuming trip Defend being relaxed if you for your universe person. Now from |
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| 40:29 | high five hydroxy trip to Fan, have five htp decoder box Elise and |
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| 40:34 | turn it into five htp, which serotonin. So serotonin will have the |
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| 40:40 | Matic receptors will get released into the cleft will get re up taken back |
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| 40:46 | the present optic terminal. And this you have Prozac here on, and |
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| 40:54 | is, uh, antidepressant. But Prozac does it blocks the re uptake |
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| 41:01 | serotonin essentially increasing the serotonin. And not the cleft. So in a |
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| 41:07 | , mood improving your mood are making one happier or less depressed. And |
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| 41:16 | obviously it's a prescription pharmaceutical medication and cannabinoids and we can have a noise |
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| 41:27 | very, very different from everything that learned so far. Because we've learned |
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| 41:32 | newer transmitter, vesicles and neurotransmitter vesicles and then the breaking down of these |
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| 41:40 | , or re optic of these neurotransmitters reloading into the vesicles. But with |
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| 41:46 | CA nominal Lloyd's it's very different with cannabinoids You have pre synaptic deep polarization |
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| 41:55 | . This pre synaptic deep polarization will Posten optic deep polarization. So vesicles |
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| 42:02 | binding of the vest ical binding off or GABA and the cannabinoids are active |
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| 42:10 | both systems and inhibitory system and the Terry Sistemas Well, um, with |
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| 42:20 | . So you have the release here either glutamate or GABA? No. |
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| 42:29 | when you have the release of glutamate GABA, you will have activity, |
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| 42:34 | activity, posson optically and this post activity will actually caused the calcium |
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| 42:44 | And calcium and flocks will promote the of the center cannabinoids. And actually |
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| 42:52 | this this diagram this is pretty poor I don't like it very much. |
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| 42:57 | much better diagrams that that I think have and maybe I'll show it to |
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| 43:02 | . It's over the end of the . But just understand that just at |
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| 43:05 | in the cannabinoids air now produced Austin and they actually crossed through the plasma |
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| 43:13 | , their lipid soluble. So they the plasma membranes and then the travel |
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| 43:19 | gravely, because cannabinoid receptors of the under cannabinoids buying inside our bodies and |
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| 43:26 | CA nominated receptors a measurable tropic the G protein coupled receptors. And |
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| 43:33 | you protein coupled receptors will shut down of these. You, Prodi and |
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| 43:39 | will shut down the influx of And when it shuts down the influx |
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| 43:43 | calcium, it will reduce the release even glutamate or GABA. And so |
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| 43:51 | is this whole loop here. First all, it can be thought of |
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| 43:56 | a negative feedback loop. If there a lot of excited her activity. |
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| 44:00 | there are a lot of inhibitor there will be on demand production of |
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| 44:05 | cannabinoids that will cross really through plasma . They would travelers and on the |
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| 44:11 | that will target cannabinoid receptors. One want activation of cannabinoid receptor, which |
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| 44:18 | a medical tropic receptor, will cause of g protein which will then shut |
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| 44:23 | calcium channel. So this negative feedback a lot of activity. I'm gonna |
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| 44:28 | you down a lot of exciting activity gonna control and shut you down. |
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| 44:33 | Endo cannabinoids regulate both excited or in inhibitory neuro transmission and the synapses. |
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| 44:40 | this is called retrograde signaling because it's from Boston attic side back into the |
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| 44:46 | synaptic terminal where the cannabinoid receptors are . This is called negative feedback |
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| 44:52 | because mawr activation results and reducing the In technical terms, this is referred |
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| 45:00 | as deep polarization induced suppression off in bishop. Uh huh. That's what |
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| 45:12 | stands for the Assize stands for deep and do suppression of inhibition. We |
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| 45:22 | have d S e, which is polarization induced suppression off excitation or D |
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| 45:38 | e. Uh huh. And so these under cannabinoids have their own degrading |
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| 45:46 | and they will be degraded as So they have synthesizing enzymes. And |
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| 45:51 | on the activity levels, the center system will get mawr less engaged. |
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| 45:56 | highest levels of activity, traumatic incidents the brain seizures, hyper excitability injury |
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| 46:07 | the brain and inflammation will turn on production of other contaminants. And they |
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| 46:12 | act through both neurons as well as . And so will discuss mawr of |
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| 46:18 | . What then, of the The two and the economic noise that |
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| 46:22 | are referring to hear our Ananda mind to our condone oil glycerol or to |
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| 46:28 | G. These air the too well cannabinoids. And for cannabinoid receptors, |
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| 46:35 | have cannabinoid receptor one CB one on receptor to C B two, which |
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| 46:42 | not shown here. But I will , uh, show it to you |
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| 46:49 | in the semester. On the very . The molecule that is shown here |
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| 46:54 | Delta nine THC Delta nine. THC tetrahydrocannabinol. It stands for tetrahydrocannabinol. |
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| 47:14 | is a Fido Can Avalon mhm. these guys and and a mine and |
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| 47:27 | e g r endo cannabinoids. So guys have produced inside the body. |
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| 47:42 | , They're produced inside the body and is a fighter cannabinoid that is produced |
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| 47:49 | cannabis plant. Its veto that dreams comes from a plant is exogenous and |
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| 47:57 | is inside the body Exogenous so endo acetylcholine system is a single column. |
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| 48:04 | is nicotine, and the cannabinoids are tetrahydrocannabinol, THC and over 100 |
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| 48:14 | Final cannabinoids are exogenous naba noise and of the discussion when it comes thio |
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| 48:26 | or it's derogatory Name marijuana. Delta nine THC is the cycle tropic |
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| 48:39 | not only psychoactive but psychotropic molecule, it acts by binding to CB one |
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| 48:46 | . So Endo, cannabinoids and THC to see the wondrous after some control |
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| 48:52 | transmission in both excited Torey and inhibitory . And so this is very a |
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| 49:02 | of very interesting information, and you grow. Maura, Maura, this |
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| 49:07 | The last thing that has shown here gas is such as an address |
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| 49:12 | Our carbon monoxide will also act as messengers, meeting that they will get |
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| 49:19 | hostin optically just like a looking They'll also go through plasma membranes not |
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| 49:25 | in vesicles and their respective receptors or oxide and carbon monoxide. A located |
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| 49:33 | synaptic Aly. That's where they will to travel retrograde. We just like |
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| 49:37 | cannabinoids to regulate the receptors. Pre , all mhm, Mhm. All |
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| 49:45 | , don't forget that next week is quest. So attendance next week is |
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| 49:55 | . Have a good rest of the . Good weekend and I will see |
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| 49:58 | next |
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