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00:00 | All right, So this is lecture . Okay, this is lecture |
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00:07 | And what you're looking at on the is actually lecture four. And what |
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00:12 | showing to you is that I've actually all of your videos from Blackboard into |
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00:23 | video points. So to go toe into video points you go Thio video |
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00:31 | dot u h dot eu and you your cougar net. I d to |
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00:36 | in. You can see in the hand corner. Here is my cooler |
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00:41 | . Uh, I'm logged down and have the lecturers. Now you have |
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00:47 | lectures here. 23 and four missing because it seems to be corrupt. |
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00:53 | I'm still working and trying to recoup Number one lecture, the very first |
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01:00 | . If I cannot, we may something where I will substitute that |
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01:06 | Then with the lecture from the other with the first lecture so that you |
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01:12 | it if I cannot recruit the number . But now, if you click |
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01:17 | any of these 23 and four, new window opens and that new window |
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01:25 | the is the video and you can the video. You can scroll through |
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01:30 | . It's very friendly format. You remind yourself what you talked about. |
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01:36 | lecture. We went over neuron zahn different neurons look like. And we |
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01:45 | about important things of classifying neurons. we said that to classify neurons |
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01:52 | you need to know several things. there's several things are the morphology of |
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02:00 | cells the location of these cells. so much they're done rights and their |
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02:05 | with us within specific regions and, , whether they're excited, her inhibitors |
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02:13 | what neurotransmitters to release. We talked the fact that the diversity in this |
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02:18 | in the hippocampus and many central nervous circuits, including the cerebral cortex, |
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02:24 | complexity of the cell subtypes stems from inhibitory cell populations. So in this |
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02:32 | we talked about 21 different subtypes of cells and, uh, only really |
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02:39 | subtypes of excited Torrey self shown here blue green colors, we discussed that |
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02:46 | tourists, also the production cells. means that they connect to other distal |
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02:51 | within hippocampus or exit out of the connecting that structure. Thio other brain |
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02:57 | on the distinguishing factor between these south expression off Cal venden CB while you |
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03:06 | only two really different types of these story parameter all cells the same time |
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03:14 | , flanked in this circuit by 21 subtypes of inhibitory cells and there's inhibitory |
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03:21 | have there's almost located in different The yellow triangles represent synapses. They |
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03:27 | their synapses along Different, uh so dendritic access of these excited terry |
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03:35 | But for the most, their control maintained here, local in the |
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03:39 | Some of them like, for basket cell number two and number four |
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03:43 | very similar. And don't distinguish between is Thio essentially have intracellular marker that |
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03:52 | mark the South sports. So one these baskets cells number two expresses prevailed |
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03:56 | in, and Number four expresses a subset of molecule CCK, which is |
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04:01 | cystic island and equal three. The home message and for the test is |
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04:05 | diversity of these cells and how you definitively tell which subtype of the cell |
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04:11 | looking at. So we discuss experiments which you can visualize neurons and brain |
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04:18 | using infrared differential contrast microscopy. And we talked about is what's portrayed here |
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04:26 | to cells and the two cells. being penetrated by Micro Elektra's, the |
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04:33 | micro electrodes, thes glass, micro contained solution, and you can pass |
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04:38 | current. You can change electrical charge plasma membrane, and you can stimulate |
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04:43 | cells, and as you stimulate the , you can give them the same |
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04:48 | , and you will get a different . And this response is the frequency |
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04:52 | the shapes of the action potentials. the recording, you fill these cells |
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04:57 | you could reconstruct the dendrites and the of these cells. Accents are shown |
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05:02 | and widen them. Rides in Black on the left is an inhibitory |
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05:07 | It's the cell on the right is exciting story parameter, also that we |
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05:11 | discussing and the acts on actually comes of the plane of you leaving out |
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05:15 | the hippocampal structures on its way somewhere outside of the field of view. |
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05:21 | finally we cross stained these cells with markers for some out of Staten some |
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05:26 | provide women and B stands for neuro , which is a stain that during |
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05:32 | recordings you inject the south with the through the electrons through the solution and |
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05:37 | electorates, and you recover their full, full morphology. Then you |
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05:40 | a double stained with fluorescence, markers to recover the internal, |
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05:48 | molecular chemical composition of these cells to sure that you identify that Number |
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05:54 | number four, number six or number 21 subtype of the inhibitory sal that |
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05:59 | particularly interested in. So we then on and talked a lot about |
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06:07 | And as we talked about glia, , we discussed several things. But |
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06:16 | , I'm gonna pause the recording a bit and go and a if, |
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06:24 | you recall we talked about different glial And so we talked about astrocytes, |
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06:32 | dander, size micro glial cells. we also mentioned the band normal cells |
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06:37 | fluid, potent, potentially stump. , like legal cells that provide this |
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06:44 | that separates the interstitial fluids of It's around actual cells from the cerebrospinal |
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06:51 | that are in your ventricles. And we talked about a mile and we |
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06:57 | about Meilin Nation dysfunctions and we discussed , uh, disorders one of them |
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07:05 | sclerosis which affect central nervous system. we discuss it d myelin nation off |
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07:16 | neurons can lead Thio really severe not just physical symptoms, but also |
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07:24 | , because de Milo, nation of that connect complex networks in the brain |
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07:29 | involved in many different complex functions not movements of hands and legs, but |
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07:34 | and thinking and memory and such. also discussed Shark Got Married to |
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07:41 | and that was a peripheral mile and dysfunction PMP 22 over expression of that |
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07:49 | , which led Thio improper Violin Nation from nerves and proper contraction of muscles |
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07:59 | disfigurement of joints and bones during the . So we distinguish the fact that |
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08:06 | multiple sclerosis is an autoimmune disorder, we view these disorders now. You |
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08:12 | have a list again off several disorders we have already discussed during the |
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08:18 | and we will be adding more information these disorders, such as Alzheimer's |
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08:23 | or will come back and talk some about multiple sclerosis. Or we'll come |
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08:28 | and talk about coded and how it the brain, or how any other |
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08:35 | time that we spent on the neurological . So in your folder, what |
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08:43 | have also, and I'm gonna switch tabs now in your folder for the |
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08:51 | content. I think I showed it your last time. You have supporting |
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08:57 | lecture documents, and under these supporting lecture documents, you will be ableto |
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09:05 | movies and some of these movies that mentioned last time. I'm gonna make |
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09:13 | that you can see it this So what is shown in this |
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09:18 | And if I could just get some confirming that you're seeing the movie See |
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09:25 | ? Yeah. Can't see the chat some reason because, yes, we |
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09:41 | see them. And now you can't it because I switched it off. |
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09:45 | All right, so what we're seeing is ah, radial glial cells. |
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09:49 | you see this line going across Za radial glial cell is this line |
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09:56 | the slightest It's almost like a And you have a neuron and this |
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10:01 | form cytoplasmic continuity and use this radio cells to climb its way after its |
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10:08 | location in the circuit, in the in the brain and start communicating with |
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10:14 | their own. So during early you have formation of neurons only very |
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10:20 | parts of the brain. And then those parts of the brain. Durrance |
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10:24 | quite far distances until they find like discussed, they have to find their |
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10:29 | , their city, their neighborhood and their mailbox. And finally there their |
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10:36 | or an apartment or or anything like . So this is how radial glial |
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10:42 | will help guide neuron Is thio their locations? Uh, so in this |
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10:56 | , you can see that it's actually of neurons that are using these complex |
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11:04 | glia light assess of form side new continuity and use them thio essentially a |
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11:13 | stepping ladder as a rope to drag along to find their right address in |
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11:22 | brain. Their precise position in the the middle. Here, this wife |
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11:28 | circle is an injury to the brain . And what you're going to see |
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11:33 | Aziz. This injury happens. You first see micro glial cells in this |
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11:40 | , reached their processes, stored the of the injury and then slowly start |
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11:46 | physically, not just their processes, their cell must forward the side of |
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11:51 | injury. So this is the and now you can see that all |
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11:54 | the processes this is time lapse. the matter of one or two |
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12:00 | you have a movement of Michael Glia terms off micro meters across the brain |
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12:08 | first started from their processes, and you see advancement of actual Selma's So |
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12:15 | Glial cells will be called in when is an injury. When there's a |
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12:19 | Thio to repair and Michael Glial cells involved in sites of kind release and |
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12:25 | of kind regulations. So these air inflammatory molecules and when you have a |
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12:33 | release, a normal level of pro molecules, that's, uh, just |
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12:38 | normal response of the brain to call on the immune response to call up |
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12:44 | the repair response. But if you abnormal cytokine release, then you can |
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12:51 | uncontrolled inflammation on controlled sponsor of inflammation the brain. And you could have |
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12:58 | to glia micro glee as well as size that we refer Thio Leo |
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13:03 | So there's, uh, Rio system . Now the other thing that we |
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13:09 | important and is you hear about glial cancers on DSO glioblastoma, as are |
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13:20 | common, assess brain cancers, eso proliferation of glial cells, scarring of |
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13:30 | cells and uncle Logical activity in glial can can contribute to all of these |
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13:38 | that could go all right, and don't just affect Leah. They affect |
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13:43 | neuron star, located in the regions are surrounding that air surrounded and supported |
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13:49 | basically, who's synapses are controlled by . The um, migration is controlled |
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13:59 | glia. Synaptic transmission is controlled by , so there's a lot of different |
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14:08 | in the brain to which Leah contribute . This is not a passive support |
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14:16 | . This is a very active system is much needed for normal brain |
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14:26 | The blood brain barrier. It's as you can see. First of |
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14:33 | , you have endothelial cells that form walls of the blood. Vessels that |
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14:39 | separated are linked by tight junctions that a lot of a nutrients and a |
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14:48 | of things that cannot pass through tight . They're surrounded by parasites. Parasites |
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14:54 | then surrounded by Astra glial processes, these air the processes from Astra sides |
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15:02 | place themselves around the blood vessels, they're some of the last post the |
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15:07 | control post for the goods passing in the blood into the brain. So |
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15:13 | brain barrier. There's a lot of that we adjust into the bloodstream that |
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15:17 | get into the brain on. There's lot of things that we ingest. |
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15:22 | can easily get into the blood and into the brain the blood brain barrier |
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15:27 | have to discuss within the context off pharmacological drug development or neuro drug development |
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15:34 | general. Think about a neuro drug is a good neuro drug. It's |
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15:39 | one that passes through the blood brain easily. Why would you worry about |
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15:44 | ? Well, because you don't really euro drugs inside the brain. You |
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15:49 | don't inject drugs into the brain apart oh, Botox, she can inject |
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15:58 | treat migraines. You can inject into parts of the nerves and the brains |
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16:04 | So but so what do we do drugs? We take pills, you |
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16:09 | a pill. And what happens to pillow go straight into the brain right |
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16:15 | from your tongue. It just jumps enters into the brain. That doesn't |
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16:20 | . You swallow the pill. What to the pill goes into the |
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16:24 | Gastric juices, acid starts melting and , and part of it goes into |
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16:31 | digestive system they're part of it gets into the blood. The justice system |
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16:37 | all the way down here, So part of it gets absorbed into |
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16:40 | bloodstream, Then it gets carried through bloodstream. And if it passes through |
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16:45 | blood brain very easily, then a of that drug concentration while, |
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16:51 | penetrate into the brain and having And so quite often you see people |
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17:01 | themselves with neurological drugs or even, example, opiates from pain and having |
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17:07 | completely different side effects. So you're a pill to treat neuropathic pain or |
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17:16 | taking a drug to treat epileptic But the side effects all of a |
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17:23 | are that you have massive constipation. is that? Well, that's because |
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17:29 | drug you're swallowing that drug has a effect. If you're targeting opiate |
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17:36 | if you're targeting Europe attic pain, have to know that with opiate |
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17:42 | we also have ah a a We have a covert 19 pandemic. |
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17:50 | haven't opiate epidemic, and the reason is because we have tens of thousands |
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17:56 | people in this country dying every year opioids overdoses from pharmaceutical opiate overdoses because |
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18:06 | effect of those for opiate is very . Few milligrams and the deadly dose |
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18:11 | opiates is just a few times of does just multiply that few milligrams by |
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18:18 | or five times, and you reach deadly dose and opiate receptors so located |
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18:23 | the brainstem regions that affect vital functions as breathing such as heart trade. |
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18:30 | so, as you're treating the pain of the, uh, opiate addiction |
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18:35 | because it makes you feel good to just takes away the pain, but |
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18:41 | causes massive constipation. That's a systemic as a systemic effect, and them |
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18:47 | treated by another pharmaceutical drug that is designed to treat constipation created by |
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18:57 | Okay, so we have a neuro . Let's say you're treating some |
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19:03 | You're treating some pain. You're treating or or you're treating another disease that |
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19:08 | talking about you're treating, and you massive constipation. Now you need a |
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19:13 | to treat constipation, and that's because that you swallow will have a systemic |
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19:18 | fact if that drug is not effectively through the blood brain barrier, that |
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19:24 | you have to swallow Maura Maura of drug systemically in order for a fraction |
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19:28 | that to pass into the brain toe in fact, so then, you |
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19:33 | , obviously, FDA that safety and studies to make sure that drugs are |
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19:38 | and notifications. But we do have a problem with a lot of drugs |
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19:42 | are safe and applications that are being off the market. Or, like |
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19:45 | mentioned that have very close. The dose is very close to the lethal |
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19:54 | , which makes it very difficult for , especially dozing themselves. Thio avoid |
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20:01 | overdoses on potential mortality, so huge and most neuro pharmacological drugs and have |
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20:09 | take the blood brain barrier into How much of the drug? How |
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20:14 | is it? How well is it into blood brain barrier? And we're |
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20:20 | from nature as well. I think learning from nature. We're going back |
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20:25 | and more so from nature. We're more plant derived medicines, but we |
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20:30 | have to keep in mind that anything we see pharmacological pharmaceutical synthetic usually comes |
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20:36 | a plant derived experience from applying derived that later is being synthesized and So |
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20:44 | think there is slight shift in the drug development or natural plant derived molecules |
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20:51 | than synthetic molecules. Or, if synthetic, maybe that their bio synthetic |
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20:56 | synthesized by either biological, um players as the yeast, for example. |
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21:07 | , so we have this wonderful world glia, and all of the glee |
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21:11 | served different functions that we discussed. today we're moving on to talk about |
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21:16 | member and oppress or resting member in so neuronal number in a trust. |
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21:23 | what is that? It's the fact if you have this recording here set |
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21:31 | , you have this micro electrode and have the ground and the ground is |
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21:38 | zero zero volts. Zero millet Relevant scale for measures off Electrical activity |
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21:47 | neurons is on the order of millet . So if you say that the |
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21:52 | or the outside of the cell is and you have ah amplifier connected to |
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21:56 | volt meter, and you sink this across plasma membrane into plasma membrane, |
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22:03 | volt meter will show immediately, minus miles 55 minus 70 minus 75. |
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22:10 | this is arresting member and potential of cell. This is the number of |
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22:14 | that is created by unequal separation of , with a negative charge is gathered |
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22:20 | the side of Plas Mick inside off cells and the positive charges gathered on |
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22:27 | outside off neuronal membranes. Um, this charge again in, in in |
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22:35 | test this is not to confuse, know? So what is the resting |
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22:38 | and potential? Exactly? Is it 60 or did you say it's minus |
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22:43 | or 65? Or is it minus ? I minus 75. So the |
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22:47 | is that different cell subtypes will have variation in this memory of potential, |
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22:52 | approximately it's about minus 60 to about 70 minus 75 million ball glial cells |
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23:00 | a much lower arresting member and potential minus 90 million balls. What you |
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23:06 | on the right is you have on right and illustration, and we discussed |
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23:11 | the first action potential that was recorded Hodgkin and Huxley. And the action |
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23:17 | the action potential all occurs at the . When you're looking at this membrane |
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23:22 | on the bottom left and you're seeing , blue negative charge and red positive |
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23:29 | . If you insert channels and this discharge very quickly will reshuffle of the |
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23:35 | conditions so the cells receive enough of synaptic input on their down rides. |
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23:41 | of the excited Terry input in the input does not quenched excited for |
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23:45 | But that means to sell Selma's. going to get deep, polarize us |
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23:49 | . Deep polarized. It will produce action potential that the acts on initial |
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23:54 | and the acts on Hillock, which located, ride at the base of |
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23:58 | pyramid here, where the accent is out of the base of the pyramid |
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24:03 | this very fast fluctuation from about minus minus 60 million balls plus 40 million |
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24:10 | and then returning back thio minus 70 back to the resting membrane potential. |
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24:16 | blip is only +123 milliseconds in It's a very, very fast action |
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24:22 | . So the reshuffling of the car first positive car and going in and |
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24:26 | polarizing the south and then positive card leaving is re polarizing the cells, |
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24:34 | we'll discuss the action potential number and in greater detail in the next couple |
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24:42 | lectures. But the reason why oppressed have the separation of charge. That |
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24:49 | poised to react very quickly quickly is we need very quick reactions we need |
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24:57 | neuron is to produce on to react the environment and some of the things |
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25:05 | we do and neurons produce action potentials reflexive, and they're very fast. |
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25:12 | it would be a pity, right you step on the nail, and |
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25:16 | of a sudden you had to contemplate a few minutes whether it's really hurting |
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25:22 | . Whether it's hurting you a you wonder what kind of nail it |
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25:26 | , whether it's rusty nail whether you put your leg and pull you like |
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25:30 | not even going to do that, going to react before you know |
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25:34 | If you step on something sharp and , if you put your hand on |
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25:39 | hard for super cold, you will it immediately. Then you'll think about |
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25:44 | , and even that after some time will feel the pain, then maybe |
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25:48 | itch, but not at the very . So this reflects of behavior is |
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25:54 | where eyes were actual potential, so very fast and where you can have |
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26:00 | of this reflexive behavior that is mediated by a single synapse. So we're |
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26:06 | discuss now this within within the context the knee jerk stretch or patellar tendon |
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26:18 | . Okay, it's it's It's the thing Knee jerk or stretch reflects or |
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26:23 | tendon reflex. So you have this tendon here, and this is a |
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26:28 | arch. It's the simplest kind of badly that we're discussing When you goto |
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26:35 | doctors office for a yearly check up to a neurologist office. What they |
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26:40 | do is they will sit you down they will take a soft knowledge and |
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26:45 | will top on this patellar attendant on knee tendon here. And the response |
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26:53 | that your lower leg, the lower of your leg, is going toe |
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26:59 | up without even thinking. So this it is a stimulus stimulus. You're |
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27:10 | the patella tendon and at the same , also stimulating the muscle spindle off |
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27:16 | quadriceps muscle, which is an extensive . This extensive muscle has the nerve |
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27:22 | from the dorsal root ganglion, sensory . So here what you have to |
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27:28 | is here, I would advise to , as I said at the beginning |
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27:32 | the semester that you should have a for for neurological disorders that you should |
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27:41 | have a table that does something like . That place is sensory cells, |
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27:59 | cells into neurons. And what's the type of cell that you studied, |
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28:03 | criminal cell drama All cells. And should know as much as you can |
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28:10 | these four sub types of cells Rahman sensory motor and into neurons. Sensory |
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28:19 | in here are after parents. So current information from the periphery, from |
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28:25 | muscle spindle activated muscle spindles, some stimulus on the attendant informs that sensory |
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28:33 | , which is a dorsal root ganglion , and that sensory neuron through his |
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28:39 | Axiron will inform the some of the neuron and through Central Act song will |
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28:47 | activate another red neuron, which is motor neuron. So once the sensory |
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28:54 | root ganglion neuron is activated, it release glutamate in the spinal cord |
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29:01 | and it will release glutamate on the on the Denver writes off the multipolar |
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29:07 | neuron cell, which is shown an and that motor neuron cell is an |
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29:13 | Farron going away from the central nervous into the periphery. And the E |
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29:20 | is the motor neuron. The affair are the sensory neurons, dorsal root |
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29:28 | cells to get excited by enough of tapping on the need. They released |
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29:33 | on the modern neuron. These air uniforms ourselves to sensory neurons. The |
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29:39 | neurons are multipolar ourselves, and modern will then releases the title Colleen onto |
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29:47 | muscle cells. So when I said you should outline what these cells |
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29:51 | you can put the censoring around the Unipol, her anatomy. It is |
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29:57 | during your arm. It releases Motor neuron is multipolar anatomy, |
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30:07 | When when? When motor neuron is , it's and it's an e |
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30:12 | Dorsal root ganglion or sensory is an . In this is an E |
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30:16 | When motor neuron is excited, it . That's called Colleen. Okay, |
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30:23 | you put the receptor the neurotransmitters underneath cell that they release. And just |
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30:30 | activating a single synapse here between sensory and motor neuron, you're now telling |
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30:36 | quadriceps extensive muscle to contract. This an illustration where the single synapse and |
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30:43 | are very powerful synapse. Actually, off one motor neuron means a twitch |
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30:49 | a muscle where you activate one motor through a single synapse from dorsal root |
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30:55 | , sensory neuron, and you have contraction of the quadriceps muscle. |
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31:01 | we know that if you just do , the movement off the leg is |
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31:07 | going to be very efficient. And reason for it is because you haven't |
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31:14 | hamstring flexor muscle. And for Thio, extend and contract extensive |
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31:21 | You have to relax the flexor So how do you do that? |
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31:27 | the same dorsal root ganglia and sensory . That same afternoon neuron will carry |
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31:33 | to the motor neuron that contacts extends muscle. But it will also contact |
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31:39 | Interneuron, which are living in the cord proper. And these inhibitor into |
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31:45 | will release glycerine. So unlike the into neurons that live in the cerebral |
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31:53 | , in the in the brain, spinal cord Interneuron released lysine, the |
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32:00 | N s inhibitory Interneuron. They released Obama Immuno beauty, Eric Asset. |
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32:08 | , so once glycerine gets released is a different neurotransmitter that is well expressed |
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32:14 | the inhibitor into neurons in the spinal . Once glycerin is released, this |
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32:20 | neuron that is targeting the flexor hamstring is inhibited. Inhibition of this nerve |
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32:28 | for the flexor muscle to relax while extensive muscle properly contracts and you have |
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32:36 | proper movement of the leg upwards. what? What what? What do |
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32:44 | what? There's a lot of things you can start thinking about now. |
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32:48 | of all, you have a monos IQ reflex here. What is the |
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32:52 | in app Pick, that means one involved spinal sensory neurons, the spinal |
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32:57 | motor neuron to contraction of extensive muscle reality, even for the archery |
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33:02 | To be successful, you have to opposing muscles, so it does involve |
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33:08 | than just one set up. The thing is that you have to think |
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33:12 | because the inhibition of the opposing muscle the flexor muscle happens through additional |
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33:20 | Through the inhibitory Interneuron, there's gonna a slide funeral, second delay when |
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33:27 | muscle is completely relaxed. In other , the extensive will start contracting |
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33:32 | and then this is going to fully along for the leg to move |
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33:37 | So it's fall of synaptic for this to be effective, fully effective, |
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33:45 | have to involve more than one And what There are many reflexes in |
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33:50 | body that involve different parts of the . Actually, there are complex |
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33:54 | That's one example is a gag reflex gagging or vomiting reflex, which involves |
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34:02 | of the brain stem, involves, , brain stem nerves and brainstem structures |
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34:10 | cranial nerves. So it za lot complex but understanding with circuit, knowing |
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34:16 | three subtypes of salsa choosing here. Unipol, a sensory African releases |
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34:22 | multipolar, excited Terry and motor neuron at the top. Polian Multipolar inhibitory |
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34:29 | of the spinal cord releases glycerine. , so these 33 candidates here, |
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34:35 | should know really, really well. imagine a situation. You walk in |
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34:40 | doctor's office or neurologist office. They're doing a regular check up, and |
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34:45 | taps on the leg and the leg move, so he has to tap |
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34:50 | the light harder. He sees the moving, and then it's going back |
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34:55 | away, just moving a little, not moving enough that it requires. |
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35:01 | it requires a lot off stimulus. you are now in the field and |
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35:11 | have to pretend your doctor What is hypothesis? Anybody can chime in or |
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35:20 | their hand. What would you say wrong in the circuit? If you |
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35:25 | thio, give such strong stimulus and just seeing a little bit of |
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35:32 | Anybody you can take a Gus, don't know. I'm just looking at |
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35:40 | SAARC it. Why does it need lot off input? Maybe the censoring |
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35:46 | own is not working well enough, it seems to be starting to move |
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35:52 | legs. So it's it's carrying the , right? That's starting to move |
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35:58 | lag. But then it doesn't What's what's going on? Maybe the |
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36:02 | is decreased. So if you decrease , what happens if you take? |
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36:09 | if there's no inhibition off the flexor , what happens? Can quadra such |
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36:16 | efficiently and move the leg? Now start moving the leg and will stop |
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36:21 | you can say, Well, so there are other tests and neurologists |
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36:26 | , uh, general practitioner so much and me on these kind of observations |
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36:33 | by testing, you know, the of the eye. Whether you trace |
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36:36 | eyes, whether you can focus in odd whether your hotel attendant is |
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36:41 | All of these things are starting to people if there is some dysfunctions. |
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36:46 | a sort of a rudimentary, crude of testing at the system. Of |
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36:51 | , then you'd have to go through casts and look for, um, |
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36:56 | , um, nor sophisticated testing his potential around out. No, it's |
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37:05 | It's a good way of saying actual that's run out, and it actually |
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37:10 | potentials run away to e. Guess you're saying is, uh, then |
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37:17 | would say no, it's a little . Maybe what you're thinking is something |
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37:22 | tetanus. So when the muscle is active, active, active and kind |
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37:26 | a locks up goes flaccid from too activity, a piece are all or |
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37:33 | . If it goes, it goes . Yes, but yes. But |
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37:40 | if you have a dysfunction at the off the motor neuron receptors? |
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37:46 | if the glutamate receptors are not functioning so yes, you're correct. If |
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37:50 | activated, you produce an action You're seeing a movement. There is |
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37:54 | action potential that happens in place. a matter of fact, with |
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37:57 | There is neural transmission. It's a of fact. Maybe there is increased |
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38:02 | or sensitivity off inhibitory circuits. Maybe is desensitization of sensory neuron to so |
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38:10 | the stimulus needs to be much stronger orderto initiate that action potential. Great |
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38:16 | , Arts Mhm. All right, no, these cells know what they |
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38:23 | that currency parents neurotransmitters to release and know that parameter will sell. This |
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38:28 | excited to resell on the C. s and they have a campus and |
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38:32 | cortex that we discussed and know the into neurons in the cortex. Also |
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38:37 | they were released gabba and they're also and come in different shapes. So |
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38:43 | go back and talk about some basic . Maybe it's basic for some of |
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38:47 | and hopefully not through basic. But have water were made up of |
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38:52 | Our brains are made up of water our brain styles air floating in this |
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38:58 | well, they're not floating. Some them can move micro glial cells, |
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39:02 | they are in this acquis environment. , uh, water oxygen attracts extra |
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39:09 | and has negative charge. Hydrogen has positive charge the hell biker Vaillant bombs |
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39:16 | other Poland molecules dissolved in water. I on such as chloride, |
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39:21 | potassium, calcium dissolve, are surrounded waters and a lot of fans, |
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39:27 | also call these clouds of hydration, clouds of waters of hydration that that |
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39:33 | attracted by the charge of these ions surround the ions, my aunts, |
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39:42 | and molecules that having that electrical charge ions form ionic bonds, such as |
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39:48 | Seoul, sodium chloride. Difference in number of protons and electrons is if |
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39:53 | ionic balance. You're charged. You Mondale and ions and die. They |
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|
39:58 | Somalia. Vaillant Um, cat It's positive and a plus. Die |
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40:06 | Catan is positive. Calcium two plus I m is negative. Ion chloride |
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40:14 | one plasma membrane we already discussed is of all, it's a possible IPIC |
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40:20 | air. But more importantly, we about the fact that it's a possible |
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40:25 | bile air that is dynamic, So have the movement off the proteins inside |
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40:32 | foster lipid bi lair. You equally have the movement off ions across plasma |
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40:41 | . So the most important ions that discussing as they relate to the resting |
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40:46 | of potential of sodium and the Potassium K plus chloride and calcium. |
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40:52 | plots. You can see that there unequal distribution of these islands across plasma |
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41:01 | in parenthesis. Here you have the of these ions that are measured in |
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41:07 | Mueller. So there's 18 million Mueller on the side of plastic intracellular |
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41:13 | and there's 145 million Mueller sodium on cellular side potassium. There's 135 million |
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41:22 | on the inside of the cell, inside of the cells are dominated by |
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41:27 | high. On outside, there's only million Mueller potassium. There's a lot |
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41:34 | chloride on the outside, extra cellular and little chloride on the inside of |
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|
41:40 | south. Only seven million moment for . There's only 0.1 Micro Moeller. |
|
|
41:47 | is an exception. Calcium 0.1 micro on the inside, often neurons and |
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|
41:55 | million Moeller on the outside. for calcium, actually, there |
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42:01 | ah, highest, uh, this in concentration between the inside and the |
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42:11 | of the South. Um, and very important. There is not that |
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42:17 | calcium that is freely floating inside the . Most of the calcium stored inside |
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42:21 | intracellular calcium stores, such as more two plasmid particular Um, word is |
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42:27 | up by calcium bounding proteins by calcium proteins and other molecules, so calcium |
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42:37 | is a very kindly regulated inside the . But calcium has a very strong |
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42:43 | drive because of the difference in the radiant to be driven inside the south |
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42:50 | calcium. Too much calcium could be dangerous. So that's why calcium intracellular |
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|
42:55 | controlled. If there's too much calcium the South, you can have calcium |
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43:00 | toxicity or toxic activity in the cells cell death Do thio Abnormal levels of |
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|
43:09 | eso well, Do you have all these individual channels for sodium, |
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43:16 | Florida and calcium islands You also and Ionic Pump and Ionic Pump. |
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43:21 | these channels that work partly down the ingredient, bionic comp works against |
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43:29 | Great answer. It uses energy. teepee converts it into a D. |
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43:34 | , and it transports sodium from inside outside. Despite the fact that there |
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43:39 | a lot of sodium on the outside the self, and likewise, there's |
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|
43:43 | lot of potassium on the inside of cell, but the pump will use |
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43:47 | teepee and little transport potassium molecules into inside off the south. Alright, |
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|
43:56 | remind ourselves about the building. Basic blocks of nature. Those air, |
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|
44:03 | amino assets that bound get bound up polyta tied bonds, and you have |
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|
44:09 | central amino acids and non essential amino know that essential amino acids are |
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|
44:16 | You don't have them, so you to seek them out in nature. |
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|
44:20 | sources plant in animal sources to provide with these essential amino acids and |
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44:28 | tied bonds structures and allow for the of chains of these amino acids. |
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44:34 | as you create these chains of amino that are bound up by Paula Peptide |
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44:40 | by peptide bonds, you then can them into data sheets. You can |
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44:45 | them into Alfa Helix system from the structure to the secondary structure. The |
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|
44:51 | a helix is may become a single membrane segment. There's four trans membrane |
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|
44:57 | shown here in one sub unit, this one membrane sub unit becomes one |
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|
45:02 | the five. Subunits have come together comprise a trance membrane Rodion Channel. |
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45:09 | it starts out from these building blocks joining bricks together in tow, ropes |
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45:18 | amino acids, twisting them together, folding, putting them into the sub |
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45:24 | , joining the sub units together. , secondary, treasure and Co ordinary |
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45:29 | . One. This is how things Belden these house. And when we |
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45:35 | about ion channels, ion channels are selective. So we said that there |
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45:41 | a sodium channel that there's a potassium , that there's a calcium channel. |
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|
45:47 | look here on the right. This a sodium channel. Sodium channel is |
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45:55 | permeable or sodium. So these channels the inner luminous the inner most parts |
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|
46:02 | these channels that they're highlighted here. limit of the channels they are |
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|
46:08 | the function of like molecular seething because not just a chemical Grady int, |
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46:16 | its chemical interactions and electrical interactions that within the loom in itself. The |
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46:22 | what ions pass through this channel when comes in from the outside up the |
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46:31 | from the extra cellular space again it's by water. That water is the |
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46:38 | molecules traveling into more narrow part of channel. These waters to increasingly more |
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|
46:43 | stripped. And there is a very microsecond interaction between sodium and the amino |
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|
46:54 | residue, negatively charged amino acid residues are located in this normal, enormous |
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47:00 | of the channel. And by this interaction, there is a propulsion of |
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|
47:06 | sodium, again guided in part by diffusion all forces into the inside off |
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|
47:12 | cell, where, on the inside of the channel again sodium, gets |
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|
47:17 | by water and gets propelled onto the of flies. Mick side of the |
|
|
47:24 | . So if you look at the muscular junction, that's a tall Colin |
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|
47:30 | junctions between neurons and muscle between motor and muscle, where you have release |
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|
47:36 | That's a title Colleen single acetylcholine receptor can conduct AH 100 million ions a |
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|
47:45 | . I stands for current. The I R. I sense recurrence of |
|
|
47:51 | lot of charge. A million islands second gets conducted. That's a lot |
|
|
47:56 | charge, as opposed to an a a T P pump on a k |
|
|
48:01 | . T P ace, which can deliver 100 ions per second. It's |
|
|
48:06 | slow mom that works against concentration ingredient energy and maintaining this, uh, |
|
|
48:17 | , concentration and balance across plasma numbering sodium and potassium islands. So channels |
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|
48:24 | selected bionic filters. In this sodium gets stripped off the waters of |
|
|
48:30 | by amino acid residues and enters But if it was a potassium |
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|
48:37 | it would be larger in diameter and would be trapped and send back |
|
|
48:43 | That should bring an interesting question. that mean that because potassium is larger |
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|
48:49 | diameter, it would require a larger and therefore smaller down in our |
|
|
48:55 | On such a sodium minds can also through potassium channel, and the answer |
|
|
49:02 | no. There is a lot more it. We're not talking about channels |
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|
49:07 | are specific to sodium channels that are to potassium. There are protein channels |
|
|
49:12 | glutamate receptor protein channels that actually passed , potassium and calcium through through its |
|
|
49:20 | lumens. But there's other things that here. Size does matter, but |
|
|
49:27 | is not the only thing, because smaller ions actually have higher attracting |
|
|
49:34 | so they have larger clause of hydration them. So there is another interaction |
|
|
49:41 | , and you have this very specific here with amino acid residue that is |
|
|
49:47 | to sodium channel. And you will this negative amino acid residue in the |
|
|
49:52 | channels Well, but it's different, then the interaction is different. The |
|
|
49:57 | of it is different. You will have a positive amino acid residue for |
|
|
50:02 | . Channels for negative islands passes so size is important. But |
|
|
50:10 | it's not just that it's molecular. evening. It's electrostatic forces that are |
|
|
50:17 | this, helping the diffusion all forces the aisles across. Alright, so |
|
|
50:23 | law if you remember. If you , you will know E equals |
|
|
50:31 | These voltage that stands for volts and relevant scales for neurons is Mila |
|
|
50:36 | Iet's current is measured in amperes and . Relevant scales are million and Paris |
|
|
50:46 | micro and pears are is resistance, is measured in arms. So the |
|
|
50:53 | the larger the surface area, the the structure of the cell, the |
|
|
51:00 | resistance it has but sells a very and therefore the resistance and neurons is |
|
|
51:05 | in mega homes. You also have , which is the opposite. It's |
|
|
51:12 | inverse of resistance, and it's measured Siemens for us, The relevant scales |
|
|
51:18 | and Nano Seaman's for the conducting of and individual channels. So the equals |
|
|
51:23 | R G is one over are. I is equal GV. Everybody sees |
|
|
51:32 | so arms law will come back to and we'll have Thio use a |
|
|
51:37 | But let's talk about how this diffusion charge happens across plasma number, |
|
|
51:42 | And if you're looking at just the Grady Int, that's very simple. |
|
|
51:46 | have a lot of sodium and Florida the left. You have a plasma |
|
|
51:49 | in the middle. There's no There's no Ionic flow in certain channels |
|
|
51:54 | open the channel. Sodium in Florida slow down its concentration radiant until there's |
|
|
51:59 | amount of sodium in Florida across plasma . So this is just simple concentration |
|
|
52:07 | . But we also know that Ionic is not just influenced by chemistry, |
|
|
52:13 | it's also influenced by electricity and electrical . We know that on voltage drives |
|
|
52:21 | through channels of voltage can repel on can attract, so sodium cat ions |
|
|
52:28 | gonna be attracted to negative charge are be attracted if you're looking at |
|
|
52:33 | um uh, battery, and you imagine that you have a battery across |
|
|
52:41 | membrane and this battery with attract the and the cathode will attract cat |
|
|
52:48 | and the positive and an out will an islands. And the reason you |
|
|
52:54 | have the separation of charge across And that's the reason that gives rise |
|
|
53:00 | difference in electrical potential that you're measuring minus 65 mil of alters. The |
|
|
53:06 | is this. Negative charges accumulated, the inside the end voltage on the |
|
|
53:12 | , minus voltage on the outside. is minus 65. Outside is zero |
|
|
53:18 | your member and potential the membrane or M address. The membrane potential is |
|
|
53:25 | . Thio inside of the cell is the negative on the inside of the |
|
|
53:30 | , which is approximately negative. 65 17 syllables. Remember the basic things |
|
|
53:37 | current flows in the direction of net of positive charge. That means Anna's |
|
|
53:42 | opposite and katanas move same as current . And if you reduce the |
|
|
53:49 | if the inside of the cell becomes negative, less negative charges on the |
|
|
53:54 | you have reduction in charge separation between and outside of the South, which |
|
|
53:59 | called deep polarization But if you accumulate of the negative charge on the inside |
|
|
54:04 | the South, you have an increase separation of charge. There's more negative |
|
|
54:09 | now, and this is called hyper . Now each ion has in a |
|
|
54:16 | , um, potential because each ion not only driven by the, |
|
|
54:23 | chemical radiant but also by the electrical int. So Equilibrium potential or e |
|
|
54:32 | . I also will use it as reversal potential. So I mentioned equilibrium |
|
|
54:38 | , and I also mentioned reversal potential ionic. It's a potential it which |
|
|
54:45 | diffusion. Allfirst's is chemical radiant forces electrical forces to charge are equal on |
|
|
54:54 | to each other in strength. And is no Nana Janek movement across plasma |
|
|
55:00 | . So let's look at what scenario talking about here you have inside of |
|
|
55:04 | cell and you have potassium ions, lot of potassium ions illustrated on the |
|
|
55:10 | by their large K plus, and can see that accumulation of the |
|
|
55:15 | If you have a plasma membrane with channel and you have a potassium |
|
|
55:21 | you will have the flow potassium across channel onto the other side down. |
|
|
55:27 | concentration ingredient where there is little potassium the right small K. Plus, |
|
|
55:32 | have other ions, or you have molecules that are negatively charged on the |
|
|
55:37 | and outside of the cell that cannot . So just, for example, |
|
|
55:41 | charged ions and the proteins and the of the plasma membrane, the cannot |
|
|
55:47 | through the plasma membrane. Not all them. But what happens after some |
|
|
55:52 | ? As potassium flows down his concentration , it actually stops flowing before it |
|
|
55:59 | the same concentration of both sides and from the right side. Why is |
|
|
56:05 | ? Because, as potassium flows to right side, positive charge again, |
|
|
56:10 | that the charge separation and charge accumulation happening across plasma membrane. So if |
|
|
56:17 | look in the diagram on the what you're seeing is a lot of |
|
|
56:21 | charge. On the side of Solich , ah stuck onto the membrane. |
|
|
56:26 | lot of positive charge of extrasolar side onto the membrane, but the inside |
|
|
56:31 | the selling the side of Saul or environment. They're equal, their charge |
|
|
56:38 | . The charge plus and minus are , So the only separation and accumulation |
|
|
56:43 | across the plasma membrane. So as potassium flows across plasma membrane, the |
|
|
56:49 | charge now starts accumulating on the other of the possible number. And guess |
|
|
56:53 | happens that positive charges. A repellent is our repellent to positive ions coming |
|
|
57:01 | that repulsion. That electrical repulsion is electrical force. Now that electrical force |
|
|
57:07 | counter acting the chemical force, it against the chemical Grady and saying, |
|
|
57:13 | , you're not gonna put more I'm already positively charged on the |
|
|
57:17 | I don't care. There is a more potassium will left on the inside |
|
|
57:20 | the cell. Not more of it going out now. The electrical force |
|
|
57:26 | equal in size to the chemical um, driving for us when those |
|
|
57:31 | forces are equal to each other. when you have a number and potential |
|
|
57:37 | a potential at which there is no ionic flow across this channel or across |
|
|
57:44 | membrane or potential behind Um, so is ah, Ionic reversal potential for |
|
|
57:53 | . There's Ionic of Russell potential from , and we can calculate these ionic |
|
|
57:58 | and there is a formula by which calculate. But let's look at this |
|
|
58:03 | number and then small ionic number It's a small amount of concentration. |
|
|
58:08 | can cause large voltage fluctuation. So you have an open channel reshuffling very |
|
|
58:15 | , we shop Lincoln cause you know of tens of millet balls in the |
|
|
58:20 | over milliseconds. Net Ionic differences at membrane number two and that ionic difference |
|
|
58:27 | charge accumulation and charge separations across plasma . If you go on the inside |
|
|
58:34 | the cell is neutral. The Ionic Force What we call the driving force |
|
|
58:41 | actually the difference between the member and on the reversal potential for that specific |
|
|
58:48 | . That means that if member and is very far away from the value |
|
|
58:54 | the reversal potential or for the Librium for ion, it will have a |
|
|
59:00 | driving force. And we'll address that we come back on Tuesday, because |
|
|
59:04 | requires a separate diagram to explain what force really is. Number four. |
|
|
59:10 | Ionic concentrations is known. We can Ionic reversal potentials for each ions that |
|
|
59:17 | is right. So when we come , first of all, we're gonna |
|
|
59:23 | about sodium, and you can see there's nothing different here for potassium, |
|
|
59:29 | is, that is different for The same way of sodium is positive |
|
|
59:33 | the outside and is going to start on the inside of the south |
|
|
59:37 | There's going to be accumulation of positive on the inside of the South, |
|
|
59:42 | with sodium positive violence, despite the that there is still larger chemical concentration |
|
|
59:47 | sodium on the right side, them of himself. Okay, but now |
|
|
59:51 | is no Net Ionic charge, and is the liberal potential facility. A |
|
|
59:56 | Mhm. So we know that we calculate these ionic reversal potentials or ionic |
|
|
60:04 | potentials because we know the concentrations off inside the cells. So when I |
|
|
60:12 | showing you earlier in a 18 and said 18 million Mueller and the inside |
|
|
60:17 | 45 on the outside next to there is a cual Israel potential for |
|
|
60:22 | and the liberal potential sodium values. 56. Next in potassium is equilibrium |
|
|
60:30 | for potassium negative 102 chloride negative Calcium equilibrium potential positive. 125. |
|
|
60:41 | is Mila. Val's not in Miller Moeller These air the concentration Grady |
|
|
60:48 | that we talked about the chemical Grady INTs what you have. E |
|
|
60:53 | a E, k E C L E C A r Equilibrium potentials or |
|
|
60:58 | potentials for these individual ions, and table on top right actually illustrates that |
|
|
61:06 | have a huge ratio disparity that we , especially for calcium ions. As |
|
|
61:15 | can see, there's 10,000 times more ions from the outside of the cell |
|
|
61:19 | compared to the inside. It's 20 more potassium on the inside. There's |
|
|
61:26 | times more sodium on the outside, the outside solution off our brain neurons |
|
|
61:32 | sold to sodium fluoride. But this , for example, and other animals |
|
|
61:40 | depends on the environment like squid, have about 400 million molar sodium chloride |
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61:46 | they live in a very salty environment . So our environments and part dictate |
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61:52 | the environments and then are created inside bodies for the South, such as |
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61:57 | cells. So what you have now the stable is you have each |
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62:05 | You have a concentration of that. , on the inside versus outside, |
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62:09 | a approximate ratio of that high on vs inside and you have a |
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62:15 | um, potentials that are measured at temperature 37 degrees south centigrade on. |
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62:22 | can see that they have all very values. So when we, |
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62:29 | come back in the following lecture will look at the nurse equation, we're |
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62:35 | out of time today to go through Ernst equation and for me to explain |
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62:39 | and good enough detail. So we come back and we'll talk about it |
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62:44 | Tuesday. We're not gonna have our office hours today or discussion because we |
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62:53 | don't have much material to review. , I wanted Thio again remind you |
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63:00 | for graduate students, I will send separate email about the meeting next week |
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63:07 | if you have difficulties with Casa, let me know what those difficulties |
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63:12 | Whether you contacted Casa's support and let let me know as soon as you |
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63:19 | , the might be a possibility that will allow you to re log in |
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63:24 | test out the system one more Potentially today. So please send me |
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63:29 | email about that. Please check that can log on to the video |
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63:34 | Uhh video points dot u h dot d u to make sure that you |
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63:40 | access your materials. When you get video points, you'll actually see two |
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63:45 | 43 15 63 15. They're two that I'm giving the semester. So |
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63:52 | lectures start with Tuesday Thursday. You'll Tuesday Thursday in front of the lecture |
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63:58 | so that you know you're looking at particular electric. Uh, so you |
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64:05 | the chat Thio, see what we dio or see if you have any |
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64:18 | with cell death due to too much , be do thio over excitation. |
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64:26 | , if there is too much excitability the brain and you will have a |
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64:33 | of calcium activity. But you can imagine one thing is I mentioned to |
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64:40 | that Astra sites will control local rises calcium concentrations. So if those calcium |
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64:49 | air inside the South, cell has deal with it. If the calcium |
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64:53 | outside the cell, which will drive mawr calcium on the inside of the |
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64:58 | , right, then you can think glial dysfunction because glia will should be |
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65:03 | up this extra calcium and siphoning it its network. But if it's not |
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65:08 | so, then it can become even detrimental. To the South, there |
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65:13 | , ah, programmed cell death that get turned on by a callous UMA's |
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65:19 | , calcium excited toxicity. It's called excited toxicity because usually excitation and toxicity |
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65:28 | related to excite hitori cells being Do you have an approximate date and |
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65:36 | ? The rest of the electric videos be applauded. Right now you have |
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65:40 | videos that are already on video So if you are still looking |
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65:46 | Blackboard thistle is old news. You to look at video points. There's |
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65:53 | lectures there. The first lecture I at the beginning off the class is |
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65:59 | . I'm trying to fix it. I cannot fix the first lecture, |
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66:03 | upload the first lecture from the other that I'm teaching this semester on. |
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66:09 | very similar. Maybe some nuances will missed, but it's very similar to |
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66:15 | . So if I cannot rebuild, will upload the other one. After |
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66:21 | , they should be six videos right? Not all. You should |
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66:27 | the syllabus and noticed that this is five. So after today, there |
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66:35 | be five. But if one of is malfunctioning, you will have four |
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66:42 | I can fix number five. I that answers the question. All |
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66:47 | Great. Thanks. Awesome. Thanks being here. Let's try to start |
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66:55 | our videos. I think everybody is , ah, acclimated to being online |
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67:01 | talking online. And don't be Turn on your videos. Next |
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67:07 | At the beginning of the course, don't have toe record. Uh, |
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67:11 | we interact at the beginning of the with each other that z one of |
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67:17 | issues. Thank you for being Have a great weekend on email me |
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67:22 | you have any issues. Otherwise, will see you next Tuesday Day |
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