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00:01 | This is lecture 11 of neuroscience and time we talked about differences between amino |
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00:08 | neurotransmitters and we said that those are broadly expressed throughout the brain and the |
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00:13 | and sub cortical areas as well. talked about the means and we said |
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00:17 | the means are very different in the that they are actually expressed in very |
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00:22 | locations with nuclei in the brain and projections from these nuclei are diffused in |
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00:29 | broad reaching so they will innovate a of cortical and sub cortical and peripheral |
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00:36 | as well. But they are different that respect. Also as you'll |
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00:42 | acetylcholine acts through both. I wanna nicotine acetylcholine receptors that are receptor channels |
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00:51 | also binds and acts the most formidable G protein coupled receptors as the dominating |
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00:58 | the cardiac muscle. But other I they're transmitters dopamine and histamine or serotonin |
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01:06 | act only through G protein coupled receptor downstream in the cells. Peptides peptides |
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01:13 | be co expressed with amino acid neurotransmitters to non traditional neurotransmitters that we discussed |
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01:25 | lecture where a. T. A denizen gasses, nitrous oxide, |
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01:42 | monoxide under cannabinoids. We also put academic acid here and we said that |
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02:00 | substances are actually very different because those are lipid soluble and that means that |
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02:07 | not stored in the vesicles gasses or the endocannabinoid or economic acid or economic |
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02:15 | precursor for endocannabinoid inside the body that synthesized and a lot of times that |
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02:22 | act in the retrograde fashion. So the pre synaptic terminal is releasing neurotransmitter |
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02:30 | the synaptic terminal has the receptors for neurotransmitter. Then these molecules and the |
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02:39 | and gasses they act onto the pre terminals from post synaptic areas. So |
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02:46 | act in the retrograde like fashion. would be interrogated, synaptic and vice |
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02:53 | . Synaptic pre synaptic would be retrograde this is for gasses and then the |
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03:04 | and we'll talk about in the cannabinoids more. Uh so you had some |
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03:11 | a few slides back question what's the between uh peptides and neurotransmitters? And |
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03:22 | can see that most of the things happened with neurotransmitters, neurotransmitters synthesis americans |
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03:28 | are released neurotransmitter degradation in the synapse re uptake in the synaptic terminal |
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03:34 | transmitter uploading and the vesicles in the synaptic terminal. It's all taking action |
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03:40 | in this area. However, with peptides, it's a little bit of |
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03:44 | story they synthesized on demand and they're from the resources and the selma's of |
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03:53 | neurons and they synthesized on demand only there's really really high levels of |
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04:00 | So a single action potential that travels the external terminal will cause the neurotransmitter |
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04:06 | here of the secular release. But single action potential or just small activation |
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04:13 | are short activation is not going to on the synthesis of their neuro |
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04:20 | This is sustained levels of activity. levels of activity typically can turn on |
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04:25 | production of these neural peptides Again, can be expressed co expressed with |
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04:31 | But they're cycling is different. Once produced, they're loaded into secret |
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04:38 | And unlike vesicles that are only located specialized synaptic locations with small spaces and |
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04:46 | secretary Granules don't always reach the external , and sometimes the content of the |
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04:54 | Granules can be released the longer external here as it is trying to reach |
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05:01 | terminal. So essentially there is no of uh spatial specificity as much of |
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05:09 | special specificity when you're baptized in the Granules as it is for the bicycles |
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05:15 | are located purely in the synopsis. although the secret or grant also being |
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05:22 | toward the synopsis, there might be release of neuro peptides along the way |
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05:28 | have the differences here in synthesis, and storage of these two types of |
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05:35 | . So neurotransmitters, What they're doing uh filling the vesicles and then vesicles |
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05:44 | organelles there of their own plasma membrane these organ al's this plasma member. |
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05:51 | has the views to the plasma membrane the neuron here and in order for |
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05:59 | fusion to take place take place. things need to happen. two Things |
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06:08 | the Menu. Okay? Or means things have to happen. First of |
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06:17 | , you have to have a deep of action production When that deep polarization |
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06:23 | external terminal, it will open bolt calcium channels and so you will have |
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06:29 | densities of voltage gated calcium channels located at the pre synaptic active zones. |
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06:36 | influx of calcium and interaction with calcium a protein complex on the vesicles is |
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06:43 | with this vesicles fuse the membrane and the neurotransmitter release so deep polarization in |
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06:49 | form of the action potential and influx calcium which happens through voltage gated calcium |
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07:00 | . Once calcium enters inside the this is what the outside of the |
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07:06 | is like. It's actually this hairy with all of these different carbohydrates and |
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07:17 | hanging off of it. And when enters some of these proteins on the |
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07:25 | are calcium sensors. One of such synaptic stagnant and enter of calcium and |
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07:35 | of calcium by what is now simplified the snare the secular snare protein complex |
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07:44 | T snare, which is trans membrane complex influx of calcium will allow for |
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07:51 | protein protein complex interaction to take place the protein complexes interact with each |
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07:57 | Then there is the fusion of the membrane within their own own membrane. |
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08:04 | there is excess psychosis of the neurotransmitters exocet. Oh sis this patch of |
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08:11 | number in here. This classical it's going anywhere it buds off and gets |
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08:18 | back into prison at terminal endo psychosis this plasma membrane piece here and then |
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08:26 | of this neurotransmitter bicycle with americans many molecules. These are some of the |
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08:39 | that illustrate some of the features of synopsis and pre sign optically what you're |
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08:47 | at here on the lot this electron image and it shows presumed calcium |
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08:53 | There's little dots here and then. see these craters here. This is |
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09:00 | exercise topic or psychologic fusion pore. essentially looking at the best local coming |
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09:10 | and fusing in the membrane and looking the crater so the neurotransmitter is being |
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09:16 | right now. And this is You see also we talked about the state |
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09:23 | membranes and difficult synapses can be 29 . But then you would have these |
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09:29 | areas where the two membranes come close and form the large gap junction, |
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09:35 | little areas like that. And this where you have gap junctions. Those |
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09:40 | the electrical synopsis, not as dominant the brain as the chemical synopsis, |
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09:47 | very important as we talked about for synchronization of neuronal networks or cells in |
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09:55 | , such as cardiac cells. Now modern day, we are also capable |
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10:03 | not only looking at the anatomy of going on but also looking at the |
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10:09 | of the synopsis and in this diagram probably with the activity. I forgot |
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10:16 | mention to you that at some scientists were very interested about the two |
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10:24 | of the plasma numbering and they were what proteins associated with the cytoplasmic |
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10:31 | brussels cellular side remember it and said would during these experiments very quickly freeze |
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10:38 | patch on the membrane. And they put a little needle or a little |
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10:47 | of glass next to the number and would tap it their junk lit if |
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10:51 | were lucky enough, this frozen piece the number and we'll split up the |
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10:56 | foster lipid bilateral faces would split And so there's a face and there |
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11:01 | a p face. And this was studies to try to address what basically |
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11:10 | elements of the membrane are embedded within or other side or on both sides |
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11:16 | both hostility by labs. And as stimulated and we understood that calcium is |
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11:24 | will also wanted to visualize calcium. so there are guys that allow us |
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11:30 | visualize neuronal activity. And if you're at pre synaptic activity, a good |
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11:36 | to study pre synaptic activity would be in calcium. Because pre synaptic li |
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11:43 | require a lot of calcium influx. synaptic lee will have high densities of |
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11:50 | voltage gated calcium channels allowing for using image calcium concentrations with south africa. |
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11:59 | these images that you're seeing are from dyes that are calcium sensitive dyes are |
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12:09 | that are sensitive to different ions. as the concentration of these ions increases |
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12:16 | dyes will change their reflective or absorptive . And those will be picked up |
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12:23 | the imaging cameras on the microscope. when we talked about, for |
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12:29 | non invasive imaging in the clinics, emission tomography pet scans the first uh |
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12:36 | second lecture of this course. This in the clinics but experimentally we can |
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12:42 | measure ions, we can measure So there are dyes that are sensitive |
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12:48 | voltage. Not just a specific but this is what calcium fluctuations look |
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12:54 | pre synaptic aly. And it shows calcium this is taken from neuron to |
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13:01 | . 4th edition of this bug a of images because they show their clearly |
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13:08 | there are these micro domains of See these little peaks here reading indicates |
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13:15 | concentration of calcium, the highest concentration , a steady state or low levels |
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13:22 | calcium concentration. And when this imaging done it was shown that these migrant |
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13:32 | , these little mountains are corresponding the of these calcium micro domains which would |
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13:38 | to vault educated calcium channels are very associated with these pre active. We |
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13:46 | up exiles where the vesicles are A lot of vesicles are actually primed |
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13:51 | ready to go. A lot of vesicles will be hanging out right by |
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13:55 | membrane, ready to fuse and ready the neurotransmitter release. But so when |
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14:06 | neurotransmitter release happens, this is a without deep polarization and neurotransmitter release. |
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14:14 | this and it shows what happens when is a deep polarization and the pre |
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14:19 | terminal during neurotransmitter release. You can clearly see that first of all, |
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14:26 | a massive increase in calcium concentration threesome lee there's also loss of some of |
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14:33 | spatial specificity and the concentration peaks here calcium. So calcium becomes spatially readily |
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14:42 | throughout the entire pre synaptic area rather being spatially confined to very specific zones |
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14:51 | developers gated calcium channels are located and concentration of calcium can be up to |
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14:58 | micro molar during these kind of uh doing basically deep polarization on particular |
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15:10 | Um For those the gap junctions um for the large in like what like |
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15:17 | causes a larger gap junction and a gap junction. Um Why? Some |
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15:29 | them we don't really know that while have lesser number of gap junctions and |
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15:37 | have more. So there's no no explanation for that. It's not as |
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15:42 | as for example as we know that a lot of voltage gated calcium |
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15:47 | person that there's a lot of voltage sodium channels and potassium channels and runs |
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15:51 | here. But there's not as much understanding and predictability on the spatial |
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15:58 | So the size is uh the gap networks. Now when we talked about |
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16:07 | muscular junction, we said that the potential in the neuro muscular junction, |
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16:18 | neuro muscular junction has include potential and size of that template potential is About |
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16:30 | million malls. So it's massive employee and that's why we said that the |
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16:35 | is always very reliable. There's always to be passed synaptic response, the |
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16:42 | is also very reliable in the sense if there is action potential and motor |
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16:47 | , it will always cause the secular . Now in the central nervous system |
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16:56 | we produce exhibit story post synaptic potentials E. P. S. |
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17:03 | S. Or inhibitory post synaptic potentials . Ps piece. And the single |
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17:12 | can generate an E. P. . B. Or an I. |
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17:16 | . S. B. Of approximately mil of all change. So what |
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17:24 | that tell you? That tells As we spoke from the very |
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17:28 | neurons have to have many excited or activating. Now, neurons also have |
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17:37 | inhibitory synapses projecting onto them and inhibiting activity. So single synapse activation is |
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17:48 | very reliable. What we're talking about If you're at -65 million goals that |
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17:59 | membrane potential And you have the threshold reaction potential of -45 million bowls. |
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18:12 | ? And this is your resting membrane neuronal membrane potential. This is about |
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18:19 | million balls difference. So single synapse to our synapse will cause a deep |
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18:29 | of half mil evolved and it's gonna like this. And if you activate |
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18:37 | may be too excited to the synapses , it will cause a deep realization |
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18:43 | this. You activated 40 or 50 , you may be able to reach |
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18:51 | threshold for actual potential to generate the potential. So you have to have |
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18:57 | of excitatory synopsis in order to cause sufficient deep polarization but not in the |
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19:04 | muscular junction with single synapse causes a of 70 million minutes. And by |
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19:11 | virtue neuro muscular junction synapses are very . That's what I call them. |
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19:16 | fidelity. 121 release of neurotransmitter means twitch of a muscle or contraction of |
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19:23 | muscle, and the central nervous Synopsis are not as reliable because first |
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19:31 | all they produce very small change and need to synchronize and activate 40 50 |
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19:39 | 100 excited third synapses sometimes in order reach the threshold for the action potential |
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19:46 | . But that is not the case the end plate potential. The other |
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19:52 | is central nervous synapses are capable of release of the neuro cosmetic. That |
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20:03 | that when there is fusion of the to the number rain, not all |
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20:08 | the content gets released, only part the content gets released and that doesn't |
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20:15 | in neuromuscular junctions. So again these nervous system synopses are not as reliable |
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20:24 | two reasons is they're not as strong amplitude and single synapse and be polarizing |
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20:32 | their own. And the second reason sometimes you don't get a full fusion |
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20:38 | pull the secular release but you get a partial fusion. So once the |
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20:44 | are loaded they're docked in these areas actor zones you need energy. So |
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20:52 | production of a teepee and other factors facilitate the priming of these vesicles very |
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20:58 | to the areas where you have both calcium generals. And then there's deep |
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21:05 | voltage gated calcium channels will allow influx calcium and binding of calcium to the |
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21:13 | Curtin complex will allow for the membrane fuse. And in some instances there |
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21:21 | not be enough calcium for one reason another, maybe there wasn't enough calcium |
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21:26 | the extra cellular calcium environment. Maybe educated calcium channel was not opening properly |
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21:35 | you get partial fusion for opening and it actually goes back into this position |
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21:45 | back into this position to be dark prime again. So it's called the |
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21:49 | and run. So this is not full commitment here. You don't release |
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21:55 | of the neurotransmitter. You just kiss the membrane and release a little bit |
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22:00 | run in most cases though. And there is sufficient enough calcium levels there |
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22:06 | be full fusion. And that means the poor the fusion poor will open |
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22:12 | and dilate and will cause the full of the chemical into the synopsis following |
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22:22 | you have to recycle this piece of number. And so this piece in |
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22:26 | membrane gets tagged. There are usually and tags for pieces of the membrane |
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22:32 | basically you are a vesicles that have released the neurotransmitter. We're gonna coach |
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22:39 | with molecules such as Claritin for And then it gets recognized as an |
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22:45 | bicycle that's coated with Claritin and it have two pathways that can go back |
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22:51 | the early end of cell and get and this bigger cattle here and made |
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22:58 | a new bicycle. Or it can filled with protons. In both cases |
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23:07 | gets acidified with high proton gradient inside vesicles. And that high proton gradient |
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23:15 | mechanisms will encourage to upload neurotransmitter neurotransmitter is going to be specific transporters, |
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23:24 | transporters on these membranes that will be with the help of this high protium |
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23:32 | h plus gradients and then re filled are going to be positioned again in |
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23:38 | dark prime positions for the subsequent So this whole process from the release |
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23:47 | the neurotransmitter gets released and the synapse active and is releasing neurotransmitters And for |
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23:55 | synapse to fully reload All of the . I'm not talking about one, |
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24:00 | let's say the synapse had thousands of ready. You got big stimulus, |
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24:07 | got released vesicles non stop for a seconds. It's gonna take about 12 |
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24:14 | for the system to recovering. So finite. There is a certain |
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24:22 | Uh These neurotransmitters. The interesting thing for employee potential. Each vesicles will |
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24:30 | a quanta Of about 2000 to What kind of chemical and neuro muscular |
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24:42 | . Acetylcholine. So a single vertical neuro muscular junction will contain a quanta |
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24:50 | these molecules. 2000 to 4000. see what kind of point it is |
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24:55 | one or 2, 2002 or but it's not 20 and 2000. |
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25:01 | there is basically the reason why the potential will be approximately 70 million |
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25:09 | Because some, some vesicles will contain . Some vesicles will contain 3,421 |
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25:19 | Others will contain 2850 or whatever number exact molecules that get loaded up into |
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25:27 | vessel. So you can also estimate many acetylcholine receptors you can activate because |
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25:36 | I if you recall, I told that it takes to acetylcholine receptor molecules |
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25:41 | open nicotine acetylcholine receptor channel. So have 2000. That means you can |
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25:48 | 1000 channels. And if you think , oh well wait a second, |
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25:53 | I can go back. What I in the first course about conductance is |
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25:57 | conductance. As individual conductance is of channels. And now I can figure |
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26:03 | that if it's 70 million balls and because of the 4000 molecules, it |
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26:07 | it's 2000 channels that are open. much of the middle levels each channel |
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26:15 | , how much of the current each contributes or conductance is. You can |
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26:18 | calculate it and derive it for total . And also individual channel conductance |
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26:24 | The other thing I want to address is look what happens when there's a |
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26:30 | of this bicycle to the plasma What happens to the surface area of |
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26:37 | terminal? It increases and this is , but what if you're binding 100 |
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26:45 | bicycles, you actually significantly increase the area, which increases which property of |
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26:54 | plasma membrane, the capacitance property of plasma membrane, larger surface area and |
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27:00 | surface area. The more charge can stored so momentarily or during the the |
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27:07 | release, the capacitance of the cell up. You can actually measure increases |
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27:14 | capacities of the cell membrane during this release. Now, once it gets |
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27:22 | coast again, the capacities goes back the pre uh vesicular release levels to |
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27:30 | same surface area levels, steady More or less, it's always |
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27:34 | Yeah. So given that that process , what happens if there's any |
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27:45 | any any any point issues with which I mean you have all sorts of |
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28:03 | have all sorts of problems. If can't release vesicles, that means the |
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28:07 | of communicate properly. You cannot recycle . That means the kind of community |
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28:16 | properly if you cannot synthesize. Because I mentioned that those mean systems, |
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28:23 | are responsible for different behaviors, but also are correlated with distinct neurological |
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28:30 | Dopamine neurological disorders are typically motor disorders Parkinson disease, serotonin and improper serotonin |
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28:43 | is typically with psychiatric and mental depression, anxiety, uh eating |
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28:54 | So and it depends then. So if you lose one of these |
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29:00 | in the brain that synthesizes acetylcholine, deprive the whole brain potentially of this |
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29:07 | molecule which plays a very important But it just depends where that |
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29:13 | Uh and it's very common that neurological have to do with post synaptic receptor |
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29:23 | . At least we understand that better the pre synaptic but they're definitely effects |
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29:28 | the pre synaptic side. Especially an to release inhibitory neurotransmitters or enough of |
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29:34 | inhibitor. And our transmitter. Question when does when does the when |
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29:44 | they open up when the action potential ? Okay, so that's that's the |
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29:52 | the voltage opens these channels? You to have a it can be it |
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30:10 | be a lot of times adjustable fusion it can have partial fusion and that's |
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30:16 | that's different from neuro muscular junction, calcium levels and interaction of this podium |
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30:25 | complex that has to uh use. it's a pretty reliable system. It's |
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30:32 | as reliable. I'm not saying it's all the time, you know, |
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30:35 | then every time you would try to know, produce a something complex, |
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30:41 | emotionally, you know, motor you would be failing at it, |
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30:45 | know trying to press a keyboard and can't do it. So so it's |
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30:49 | that it happens often. It's just we have to engage multiple sin |
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30:55 | We have to release multiple vesicles in to reach the threshold and a lot |
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31:01 | them will be fully fused and release full content. But some of them |
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31:05 | have this partial fusion and that's what a central nervous system more complex and |
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31:10 | understanding and not as reliable as neuromuscular it is not to say that it |
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31:16 | not reliable. Mhm. Okay, questions. Now, let's see. |
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31:28 | talk about E. P. P. Since I started talking about |
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31:31 | . P. S. P. . We're gonna come back to the |
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31:33 | diagram. So E. P. . P. S. Again the |
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31:37 | E. S. Synaptic people So when you have the release of |
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31:47 | and glutamate will bind to glutamate for channels that will cause influx of sodium |
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31:52 | other things that will cause this deep . We'll also see that the also |
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32:00 | deepness of compassion and we'll study that . But this is excitatory post synaptic |
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32:05 | . Those are going to be a synapse. E. P. |
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32:10 | P. S. Only on the about half a mil level and change |
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32:15 | the number of potential post synaptic This is pre synaptic PPS PPS. |
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32:24 | synaptic recording a level of depersonalization. synaptic these are graded potentials. So |
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32:32 | can be half a little ball Two balls. Formula balls. They're graded |
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32:38 | size action potentials is all or meaning that once it reaches the threshold |
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32:45 | action potential opens up both of created channels more so more. There's you |
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32:50 | stop an action potential after mindless 45 . If it reaches that level, |
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32:56 | cannot stop the action potential. But E. P. S. |
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32:59 | S. If it goes to minus minus 16 minus it can come back |
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33:05 | the same for I. P. . P. S. So they're |
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33:09 | , they're not all or none like action potentials. I PS PS is |
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33:17 | binding of Gaba to Gaba receptor channels then one there are two subtypes. |
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33:23 | Gaba receptor channel A gaba a will for influx of chloride influx of so |
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33:33 | a positive charge causes deep polarization, of chloride negative charge causes hyper polarization |
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33:42 | the form of inhibitory cost synoptic I PSP. So as the cell |
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33:51 | trying to reach the threshold for action , this cell is not only receiving |
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33:57 | inputs, it's also receiving inhibitory And only that reaches the threshold will |
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34:06 | the action potential. Mm. So cells neurons will have pre synaptic excited |
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34:16 | synaptic inhibitory inputs coming in suddenly have of thousands of them in one |
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34:24 | It can happen at the same time they happen at the same time they |
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34:28 | in time if it happens in the area, the summit in space and |
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34:34 | more they some aids in deep The better chance they have to reach |
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34:41 | threshold to generate the action potential. , these are synaptic potentials. All |
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34:52 | potentials are graded, excited during inhibitory potential is all or none. |
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35:00 | So when we talk about ion a signaling its ligand gated channels, ligand |
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35:09 | to these receptors proteins and these receptor are also channels that allow for the |
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35:16 | of ions in this case chloride. it's ion a tropic versus metabolic |
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35:24 | It's G protein coupled with suffers a , binds to the receptor and causes |
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35:35 | effect on the G protein. It's with this G protein complex activating this |
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35:43 | complex can gain ion channel. So there's no flux through this receptors that |
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35:52 | played in a couple of receptor, no ion flux but it can nearby |
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35:57 | the channels and open nearby channels and talk about that and in the next |
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36:03 | of lectures it can also activate it can activate secondary messengers through this |
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36:13 | tropic signaling. It can activate transcription at the level of the soma and |
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36:20 | nucleus of the cell. So medical signaling is only indirectly. That's what |
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36:30 | , indirectly can affect bionic channels, of ions and can exert intracellular effects |
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36:41 | the cellular cascades and cellular messengers inside cells. Same neurotransmitter, different |
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36:52 | Same. Your consumers are different effects different selves. We'll look at this |
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36:55 | a little bit but this is one our favorite molecules that we are |
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37:02 | seed alkaline and so you understand a about acetylcholine and I'll ask you a |
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37:08 | of questions about acetylcholine, acetylcholine is natural agonist for ion a tropic |
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37:15 | Acetylcholine receptor channels and formidable tropic masculinity in coupled receptors you don't make |
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37:28 | Acetylcholine is a natural agonist. When receptors nicotine is an agonist for the |
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37:36 | casino calling the sentence must korean. substance in nature is a natural agonist |
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37:44 | . What is an agonist agonist is that opens the channel or encourage the |
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37:50 | channel activity in the case of indirect antagonist is something that blocks and closes |
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37:57 | channel. So we already know about antagonist. We know about the voltage |
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38:03 | sodium channel antagonist called tetrodotoxin that was in in puffer fish and newts and |
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38:13 | . So your area is actually another poison from little tropical frogs and curare |
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38:24 | an antagonist to nicotine suckers. And is another chemical that is an antagonist |
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38:32 | most clinical research. So they're not distinguished based on uh on their own |
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38:41 | tropic versus metal tropic, they have distinct neuro pharmacology. So now you're |
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38:48 | neuro pharmacologists, that's when you're starting understand what substances bind to what |
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38:54 | what effect it has on our channels downstream on the south the mechanisms of |
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39:00 | of different drugs, endogenous molecules and uh pharmaceutical pharmacological agents. So these |
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39:11 | the major receptors. Now acetylcholine has be synthesized and acetylcholine gets synthesized when |
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39:21 | molecule and the way come together and , this is calling the citadel |
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39:31 | But if you remember get together and and you know that this is a |
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39:37 | everyone. And this is coding molecule synthesized, it's transported here loaded up |
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39:48 | new bicycle. And then when there a proper signal signal coding molecules can |
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39:53 | released here into the synaptic. Once released into the synaptic flat they will |
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40:02 | a clinic and acetylcholine receptors in the . So you have both types on |
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40:07 | tropical metal tropic a ch receptors in cns but also there will be |
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40:15 | So there is a degradation enzyme as call it nestor race that breaks down |
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40:23 | societal covina Siegel cohen asteroids breaks it into Colin and acetic acid call IAN |
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40:32 | transported back pre synaptic aly into the where it comes together with a single |
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40:40 | and chats to make cola molecules and the cycle. So motor neurons will |
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40:55 | a little cold in but in neuro junction you only have nicotine in a |
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40:59 | code in the suffers all quick angry and parasympathetic nerve endings will have acetylcholine |
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41:08 | the brain. We have acetylcholine in specific nucleus and that acetylcholine specific nucleus |
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41:15 | target academic and masculine acetylcholine. So talked about Alzheimer's disease in the first |
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41:24 | of the course when we looked at hallmarks pathological hallmarks of Alzheimer's disease And |
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41:29 | remind you we talked about intracellular Nurofen, broccoli tangles and we talked |
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41:36 | extra cellular plaques. Beta amyloid plaques some of the cellular features hallmarks of |
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41:45 | pathology. We also talked about how are gross anatomical changes and significant loss |
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41:53 | nervous tissue, especially gray matter in C. N. S. In |
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41:58 | advanced stages of Alzheimer's disease and we about a little bit of the |
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42:04 | how Alzheimer's disease is prevalent. Is prevalent in the older population. |
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42:13 | talked about symptomology of memory loss but other significant things that happen with the |
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42:23 | and progression of the severity of this leading to eventually to death. Now |
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42:29 | turns out that acetylcholine and the seed cells are very susceptible and get damaged |
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42:42 | on in the Alzheimer's disease. So is an important molecule for cognitive function |
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42:51 | for memory formations and most of the in the market for Alzheimer's disease. |
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42:59 | hot now with come symptomology mechanisms therapy we're talking about neural pharmacology. So |
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43:09 | start talking about therapy treatment of diseases this case Alzheimer's disease. The most |
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43:16 | drugs on the market are a single to race inhibitors. So think about |
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43:23 | . If you take out a seal Esther race, what do you do |
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43:28 | settle coleene? Do you make more call in? Do you affect the |
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43:37 | of the you cut down on the on the breakdown of the pseudo |
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43:49 | Right. And when you reduce the when you block the subtle cola |
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43:56 | What you do is you increase the or you can call it bio |
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44:03 | how much of that molecule is You increase the availability of that a |
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44:09 | colony number synapse. You give this a chance to linger longer in the |
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44:16 | here. So you don't have enough acetylcholine and most of it will bind |
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44:22 | the receptors to have an effect rather being degraded and recycled. Yeah. |
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44:30 | what happens? It's like uh yeah that that can happen but typically not |
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44:43 | Alzheimer's medications and the doses that are used that's not a very common thing |
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44:50 | restoration universe. Um Most of the problems with overdosing is with opioids with |
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44:58 | medications. Uh Here there's another issue . And let me tell you |
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45:06 | you're losing acetylcholine synthesis and you lost neurons. Do you think this medication |
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45:14 | going to be effective? If there's more subtle choline you're gonna put inhibitor |
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45:27 | it's inhibiting inhibitor but there's no So again, most of the mechanisms |
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45:38 | action of the Alzheimer's medications drivers will as the top kill unnecessary inhibitor |
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45:44 | Since Call Industries inhibitors, you'll even commercials on T. V. |
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45:48 | C. I. N. Sin. Are you any sin medications |
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45:52 | for some older individual medications and things that? How long did the Civic |
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46:00 | last if you're using? Oh that depends on the dose is it depends |
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46:05 | the state of the disease, depends the brand of the medication your neurologist |
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46:12 | to you. But it's a They're quite an effective. It's a |
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46:21 | huge, huge multibillion dollar industry that drugs can slow down the progression of |
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46:27 | disease. there's no cure. So not therapy to cure Alzheimer's disease, |
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46:33 | no cure for Alzheimer's disease. We slow down the progression of this |
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46:39 | but we need other alternatives, we other things. And so I always |
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46:47 | to my students in this course, guys have to figure out other |
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46:52 | just eat acetylcholine and just eat You know, why can't you just |
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46:58 | it if your brain doesn't make You know, we first tried to |
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47:02 | laugh at it and you're like, well maybe there's something to do with |
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47:07 | precursors. You know, if I synthesize this molecule, maybe maybe I |
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47:14 | somehow artificially stimulate the precursors and and maybe there's a little bit of a |
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47:21 | golden chat left in there. So start strategizing and thinking different things, |
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47:28 | know? What about receptors? The is not that I didn't say the |
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47:33 | is not that eventually there isn't going be a receptor because if the receptors |
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47:39 | serving a function that has no chemical it is being bound to a lot |
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47:45 | receptors can buy many chemicals so they still be there. So I didn't |
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47:49 | the receptors are all gone. So can't we have a substance that mimics |
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47:57 | in the brain, how are you take that in your mouth, then |
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48:03 | on your gut, it's gonna affect of this little building receptors all over |
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48:08 | body, all over your muscles, that effective? So you have to |
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48:14 | the blood brain barrier right? Whatever put in your mouth has to cross |
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48:19 | blood brain barrier. Nasal sprays. talking about COVID-19 infections through the openings |
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48:28 | the skull. Yeah very effective way delivering drugs. Yeah nasal spray of |
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48:38 | Siegel calling safe like analog in the lobe that that that that binds up |
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48:45 | the receptors so the future is yours all of these ideas and much better |
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48:53 | you guys can put to practice and new drugs because we need we need |
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48:59 | a it's a terrible disease because the is alive but they're not there you |
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49:04 | . So every disease is really terrible it's a huge burden on others. |
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49:13 | let's talk a little bit more about pharmacology uh poisoning neurotransmitter release. It's |
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49:20 | be a book of special interests spiders, snakes and you. I |
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49:28 | just listening to a program on NPR lady said she was hiking and fell |
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49:35 | by the pond someplace in the mountains woke up like surrounded by frogs like |
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49:40 | of frogs came out of the pond the person that was interviewing. Well |
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49:45 | not so bad. It could have snakes. Talk about spider snakes and |
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49:52 | because a lot of these little creatures very potent toxic molecules toxic to |
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50:05 | So ah black widow spiders can be bite of the spider can be |
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50:18 | And a lot of these natural substances interact with the neurotransmitter release. Uh |
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50:27 | studio butcher Lionel for example, anybody about botulism, heard about botulism. |
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50:35 | uh it's a disease that is not prevalent and and developed advanced countries. |
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50:41 | if you have bad canned food that gone bad, there are Australian botulinum |
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50:53 | to try and start producing a bunch lines on toxins and you can get |
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50:59 | can get food poisoning. You can be deadly in some cases and you're |
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51:06 | invited to a Botox party. So not eating bad canned food, you |
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51:14 | get much a line of toxins in controlled medical spa, beauty fashion or |
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51:22 | an FDA approved pharmacological treatment. So turns out that Botox is an abbreviation |
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51:35 | much a lot of the toxin. not stated on the beauty magazines that |
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51:41 | a toxin that is being injected Botox spun, right, you get service |
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51:47 | of champagne, relax in the chair a friday and get some injections down |
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51:52 | your areas of interest on the face . And what it does is a |
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52:00 | of uh people would leave Botox parties they would also put fillers on their |
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52:09 | . So that looks really big. in addition to being blue it may |
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52:15 | be able to move, it looks well and speak very well, pronouncing |
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52:21 | and that's because what Botox does It interacts with the Seattle Colin bicycle |
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52:31 | and the seed locally in release onto muscles. So why would you do |
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52:37 | ? And why do people do it beauty reasons as we age? And |
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52:42 | muscles move and remove the skin and skin changes because of the sun and |
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52:50 | and things like that. And you wrinkles. A lot of people don't |
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52:56 | wrinkles and when you block the secular and the stimulation of the muscles, |
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53:02 | actually relaxes some of the wrinkles. people look more beautiful, more attractive |
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53:12 | is a different thing phillips. You're injecting, filling the space with something |
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53:16 | fluid that stays there for a The Botox. You're blocking neurotransmitter release |
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53:22 | one of the consequences would be that cannot move your muscles as well as |
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53:28 | speaking following the injections. So when go and get a dental work done |
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53:36 | you have a local anesthesia. Sometimes also will have difficulty chewing right |
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53:41 | But this is a little different. this is now you block the neural |
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53:48 | and you relax the muscles essentially from and therefore you relax the wrinkles. |
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53:57 | beauty focuses. Now there's also another of Botox and that's an FDA approved |
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54:08 | injections to treat migrates. Um so a wide commute of all of the |
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54:21 | of applications that you can come up one molecule first to discover it and |
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54:29 | bad canned food and you get poisoned then you discover the mechanism of action |
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54:37 | that budget line on toxin that it with acetylcholine release. Then you discover |
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54:45 | it specifically interacts with the protein protein in the physical er release. Then |
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54:52 | start using it for beauty purposes and you discover that it may have an |
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54:58 | which people are using it for beauty . A lot of people have come |
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55:02 | to get Botox or so it would my migraine. There's people that do |
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55:07 | , they still have migraines and other . So there was a little bit |
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55:10 | a notice there and then there were that came out and sure enough it's |
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55:14 | approved medication approved treatment. And so many different substances in nature that will |
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55:23 | with pre synaptic also with post synaptic receptors. It can target the release |
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55:33 | Macedo calling. It can target the synaptic receptors and block post synaptic academic |
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55:42 | masculine and acetylcholine receptors. And in to these medical things, humans also |
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55:53 | molecules and these molecules and apostates are acting the same way. Organophosphates are |
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56:05 | seed Alcala nestor race inhibitors. So phosphates are used in some agricultural applications |
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56:18 | organophosphates and humans always when they make things there's bad guys that make bad |
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56:26 | or good guys that make bad things accident and bad guys continue using those |
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56:31 | things. So organophosphates are nerve siren. So mon and nerve gasses |
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56:43 | being used by shady governments and terrorist around the world, There was a |
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56:49 | incident in Tokyo Metro in the 90s Nerve gas was released and killed poisoned |
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56:57 | . I believe there were nerve gasses were being used in the lost conflict |
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57:04 | takeover of syria as well. So there's still stockpiles of these biological and |
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57:14 | weapons. Now, what is so ? And maybe that was the |
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57:22 | How do you overdose from that What is so dangerous and why would |
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57:26 | nerve gas kill you? Because that's whole unnecessary inhibitors should help you with |
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57:30 | Alzheimer's disease. However, those receptors involved in the continuing receptors are involved |
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57:38 | the contraction of the diaphragm to breathe exposure to nerve gasses. Nerve gasses |
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57:45 | used in, when the United States into Afghanistan went on into Iraq. |
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57:52 | were used in Fallujah, one of big areas that were used to. |
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57:56 | how do they kill you? They block the breathing and shut down the |
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58:03 | . So it's not necessarily that they you because they block your receptors in |
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58:09 | brain, but it can also start seizures and uh again, these are |
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58:19 | interesting parallels where you have nature that hurt you, you can take advantage |
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58:27 | that nature and turn it into a treatment you can turn it into from |
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58:32 | collage vehicle drug, you can also it into a weapon and when you |
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58:37 | it into a weapon, these mechanisms action that you have in the brain |
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58:44 | , acetylcholine and the receptors person actually you have it will also be inside |
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58:49 | the body. Therefore the effect of lot of the substances, especially volatile |
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58:54 | such as gasses will be a systemic not just on the brain but on |
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58:59 | whole on the whole body the whole system. So let me see what's |
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59:09 | next area that we're about to get . A subtle Colin uh agonists, |
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59:17 | . And we're gonna review other category serotonin and the cannabinoids, glutamate, |
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59:26 | neurotransmitters, labeling and some other good . So we're gonna leave this information |
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59:31 | next week. I think it's sufficient information for this week for everybody uh |
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59:38 | so have a good weekend and I'll you next week. Yeah. Sorry |
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59:47 | didn't get the last |
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