| 00:02 | This is lecture five of Neuroscience. we started talking about general functions of |
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| 00:07 | cells in this slide. And then went in and started talking about some |
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| 00:11 | the details uh on individual glial So in some of the uh slides |
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| 00:20 | I recommend also they can be used good uh note taking slides. So |
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| 00:28 | you can summarize more information that is the slide. For example, near |
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| 00:33 | oligodendrocytes, you're gonna be able to multiple sclerosis near the uh astrocytes. |
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| 00:39 | already blood brain barrier there. But also later, you're gonna add glutamate |
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| 00:44 | it processes glutamate. So you can these types of slides or you can |
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| 00:49 | your own tables like for example, table that I uh that I showed |
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| 00:57 | on the different uh neuronal subtypes. . So that will, that will |
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| 01:02 | up in a little bit later in slide. I'll show it to you |
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| 01:05 | . OK. So now let's move the radial glia and the radial glia |
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| 01:11 | very important for neuronal migration for the of neurons in the specific places in |
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| 01:17 | brain. They're not born all over brain. Neurons are born in specific |
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| 01:22 | around the ventricles in the brain. from there, they have to migrate |
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| 01:27 | they use radio glia as their They become cytoplasm continuous with radio glial |
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| 01:34 | and crawl along these processes and use to find their final destinations in the |
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| 01:41 | . So I'm not sure if we these videos, but there's a uh |
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| 01:47 | up. Now. Exit. There go. The show. Sometimes they |
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| 01:55 | top three tips on starting an let's say you're struggling. And this |
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| 02:01 | very nicely this this whole migration, migration along radio radio glia also for |
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| 02:10 | cells. Besides his guiding neurons, also can become either glial cells or |
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| 02:15 | can even become neurons. OK. really nice illustration of time lapse of |
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| 02:22 | . There's another link in this lecture that shows neuronal migration also with a |
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| 02:31 | more cells in it. And so can see that there is this neuronal |
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| 02:36 | chain migration that's called, it's a busy traffic area during early development when |
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| 02:42 | neurons have to migrate and find their in the precise destinations in the |
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| 02:50 | Mhm So that's radio guo sounds myelination CNS is provided by oligodendrocytes. Oligodendrocytes |
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| 03:03 | form multiple myelin segments. So they have multiple processes and each process becomes |
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| 03:13 | separate myelin segment on the axon. oligodendrocytes can insulate multiple neurons in the |
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| 03:23 | and each one of their processes is become a myelin segment on an axon |
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| 03:29 | a neuron in the peripheral nervous it's different. So, Schwan cells |
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| 03:36 | Schwan cells, each cell in fact one single unit, one single segment |
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| 03:45 | myelin. So this is Schwann cells the periphery or the peripheral nerves. |
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| 03:52 | , from the spinal cord, when nerves come out, they're now in |
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| 03:56 | periphery. Ok. There's also peripheral that would be coming out of the |
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| 04:02 | stem that we'll talk about like cranial . OK. And they will be |
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| 04:08 | and insulated by Schwan cells. This an example of a optic nerve fiber |
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| 04:15 | has been cross cut and it has wrapped all around it. So, |
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| 04:22 | creation and myelin compaction around the axon mediated by a number of myelin invasive |
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| 04:31 | . Some of them are involved in to cell recognition. So the ligo |
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| 04:37 | has to recognize a neuronal axon or that it wants to wrap around and |
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| 04:42 | proteins will encourage the actual process of . Others will patrol the compaction how |
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| 04:50 | it's compacted. And it's a interplay between these multiple 5 to 7 or |
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| 04:57 | dependent on cells uh of myelin basic that are involved in this process. |
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| 05:04 | between each one of the myelin We have a node of ra |
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| 05:08 | node of ra beer express high levels voltage gated sodium and potassium potassium |
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| 05:15 | And they're going to be the sides action potential once it gets generated at |
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| 05:20 | axon initial segment here, action potentials regenerate in each note of brown beer |
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| 05:26 | they regenerate because they do have such densities of these voltage gated sodium and |
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| 05:32 | channels that you'll understand much better over next two lectures. So we already |
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| 05:38 | epilepsy briefly. We discussed Alzheimer's disease you took some notes on Alzheimer's disease |
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| 05:46 | we'll in fact, come back and about Alzheimer's disease. Again. When |
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| 05:50 | talk about acetylcholine or cholinergic signaling, also talked about fragile X syndrome and |
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| 05:58 | was correlated to dendritic anatomy and dendritic . We discussed it as intellectual |
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| 06:06 | developmental, intellectual disability in each one these disorders. What I'm asking you |
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| 06:13 | do is to think about several I'm asking you to think about cellular |
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| 06:19 | of this disorder. I'm asking you think about the age of onset of |
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| 06:24 | disorder. Fragile acts which is uh disability and developing Children. Uh It's |
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| 06:33 | to genetic mutation, it's very different Alzheimer's disease which has onset and individuals |
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| 06:39 | are 55 or older. So I you to have a general understanding when |
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| 06:44 | , when we're speaking or when somebody gonna ask you about neurological disorders that |
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| 06:50 | are smart. And you can well, there are different things about |
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| 06:55 | disorders. You know, neuroscience we study cellular mechanisms. We also |
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| 07:02 | a little bit about symptomology, but still talking about from descriptive perspectives from |
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| 07:08 | we know we're not really treating But we are trying to understand the |
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| 07:15 | and the treatment paradigms that are available patients that have these different neurological |
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| 07:23 | So, there's another one here, sclerosis. It's a demyelinating disease. |
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| 07:30 | a disease of demyelination. When myelin lost around axons, axons actually slowly |
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| 07:36 | degenerating and dying also. So, of myelin can lead to loss of |
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| 07:43 | altogether and result in lesions which is or sclerotic lesions in multiple sclerosis. |
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| 07:53 | be found in multiple sites. That's it's multiple sclerosis. Ok. It's |
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| 07:58 | lesions that are in multiple sites in brain. It's oligodendrocytes because we're talking |
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| 08:04 | central nervous system. So we're talking CNS neurons and we're talking about oligodendrocytes |
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| 08:11 | insulation by oligodendrocytes. What kind of is? It? It's an autoimmune |
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| 08:18 | disorder. We talked about fragile for example, and we said that |
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| 08:23 | has a genetic basis. We talked uh uh epilepsy and we actually discussed |
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| 08:33 | within the context of traumatic brain But that's not the only way a |
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| 08:38 | can uh end up having epilepsy, the only uh way and it can |
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| 08:44 | also due to genetic mutations too. this is an autoimmune neurological disorder, |
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| 08:53 | , that means your own immune system attacking something natural that belongs to your |
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| 08:59 | body. In this case, um is targeted by the immune system and |
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| 09:06 | basic proteins. We're not certain why of a sudden the immune cells start |
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| 09:13 | its own, its own body cells causing demyelination and causing exon a loss |
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| 09:20 | eventually neuronal loss or neurodegeneration. There be a genetic predisposition, there could |
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| 09:29 | some triggers. In addition to that predisposition, the genetic predisposition can be |
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| 09:36 | but not necessarily the mutations. The could be infectious factors could provoke and |
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| 09:45 | multiple sclerosis. There is correlation with factors as vitamin D, most of |
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| 09:53 | D sources from the sun, uh you have a dietary intake supplements of |
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| 10:00 | D, that's significant, but you some. So environmental factors contribute to |
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| 10:06 | . The onset ages, twenties to , females are more affected by multiple |
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| 10:13 | . And again, the symptoms of sclerosis symptoms is vision problems, blurred |
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| 10:19 | double vision, muscle weakness and painful spasms, tingling, numbness or pain |
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| 10:25 | the arms, legs, trunk or and clumsiness, mental or physical |
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| 10:31 | mood changes, cognitive dysfunctions. That's lot. Why is it so much |
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| 10:40 | it's multiple sites for these lesions? then what we've learned about the brain |
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| 10:45 | that different parts of the brain are for different functions. So, if |
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| 10:49 | have demyelination along your optic fibers or your visual system, you may likely |
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| 10:58 | patient may likely exhibit blurred or double or difficulty loss of perception of |
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| 11:05 | For example. Now, why do have muscle weakness and muscle spasms? |
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| 11:14 | the demyelination is in CNS, what my skeletal muscles? What what, |
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| 11:21 | contracts my muscle? Well, what uh what tells muscle cell to contract |
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| 11:31 | junction, the spinal cord, where the spinal cord get its own |
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| 11:38 | Yeah, from the, from the and it gets some information we already |
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| 11:43 | about Elon Musk. Remember it's the the motor commands would be, that |
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| 11:49 | be in the motor cortex, for . So what if you have areas |
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| 11:54 | are responsible for motor commands or motor of those commands from motor cortex? |
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| 12:04 | there's several areas that are involved in patterns of, of these commands and |
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| 12:11 | and such. So if there's demyelination , it will have a more significant |
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| 12:17 | and people will not be able to the muscles properly. Why? Because |
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| 12:22 | spinal cord is fine, the Schwan are OK. There's no demyelination in |
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| 12:27 | P MS but your brain gives the , you know, clench your fist |
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| 12:35 | you clench your fist and then it's command relax. But the axons are |
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| 12:43 | , they're demyelinated. And that command relax is not reaching properly. The |
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| 12:50 | cord because there's impaired communication, the are impaired and communication between the S |
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| 12:55 | impaired. So relax, relax, and it cannot do that. And |
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| 13:02 | you know what happens if you have contracted for prolonged period of time, |
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| 13:05 | becomes painful. So, you there's other things the same with cognitive |
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| 13:12 | . It depends where demyelination is. in general, what kind of |
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| 13:16 | Overall, it has on the the body and the mental state of |
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| 13:19 | individual that has multiple sclerosis, treatments a mass or pharmaceutical other treatments and |
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| 13:26 | therapy. Some alternative treatments also. , whenever you look for sources or |
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| 13:34 | disorders, in particular, this is we're talking about, make sure they |
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| 13:39 | from really reliable sources. So in case, I have a link to |
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| 13:45 | DS which stands for National Institute of Disorders and Stroke dot National Institute of |
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| 13:53 | . And it has a lot of information if you click on this link |
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| 13:57 | is written up there and they update . So these lengths, they remain |
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| 14:02 | same, but sometimes they update and new mechanisms for new understanding of the |
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| 14:07 | every ever so often. Another good is uh obviously pub med and peer |
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| 14:18 | publications, articles, original articles and reviewed review articles. And another good |
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| 14:25 | is professional organizations or associations, especially it's a more rare type of neurological |
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| 14:35 | . Uh Sometimes the smaller associations and serve as a great database of all |
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| 14:43 | the resources that are published about uh particular rare disease. So that's another |
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| 14:50 | resource. Uh libraries, you can have access to so much literature through |
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| 14:56 | libraries. I hope you know how use it. If not Google uh |
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| 15:01 | , the first link click on it it will say, hey, do |
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| 15:05 | have a coun that has a little on the corner and have a cos |
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| 15:10 | , do you know how to do ? Everybody, I don't see that |
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| 15:13 | hands. Let's do it together. . Ok. Uh, Libra |
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| 15:32 | Oh, look at that homepage. of Houston libraries. All right. |
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| 15:37 | you think that you have Chad T, and you're good, open |
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| 15:41 | , I, do you know that GP T does not read PUBMED. |
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| 15:47 | not allowed, even if it it has to do it in a |
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| 15:50 | circuit, it does not communicate that to public. So whenever you ask |
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| 15:54 | GP T, hey, what does molecule do that? Does this and |
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| 15:58 | is, this is awesome copy you know, done. No cross |
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| 16:04 | . Uh wrong response D failed. cannot rely on it. There's some |
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| 16:11 | good answers that Chad G BT and that I can give you, but |
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| 16:17 | some really awful answers. It can you and wrong answers and wrong interpretations |
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| 16:22 | things that it kind of are heard the grapevine on Google. But even |
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| 16:28 | you ask open A I or Chad T, please give me a reference |
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| 16:31 | this that you just said, what it gonna tell you? Oh I'm |
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| 16:36 | , some years ago they cut me from reading peer reviewed scientific literature. |
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| 16:42 | it doesn't have that. So you are now at the level where you |
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| 16:47 | need to substantiate and to cross verify of the information that you're receiving, |
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| 16:55 | it's on Google Open A I chat T any other ones, you |
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| 17:01 | if you're creating images, that's another , you know, just being |
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| 17:06 | But if you're doing scientific research, papers presentations don't just solely rely on |
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| 17:15 | . And the other thing is that , you know, there are all |
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| 17:19 | these things like turn it in, it in as working in the I |
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| 17:23 | and to turn it in now. it will soon be able to tell |
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| 17:27 | whether this was created by A I it was created by, by |
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| 17:32 | by humans. And uh right now , if you, for example, |
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| 17:38 | copy and paste something from A uh I can not me but anybody |
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| 17:45 | take what you copied and pasted and it back into A I. And |
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| 17:50 | will say yes, I wrote this it will say I it's, it's |
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| 17:57 | I wrote part of this or it say it's, it's unlikely this was |
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| 18:02 | by uh OK. So what you in also belongs to A I. |
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| 18:08 | this is how their algorithms get And the more complex questions you put |
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| 18:14 | and the more complex answers it gives . And if you have a way |
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| 18:19 | verify those answers, that's when they hundreds of thousands of dollars to people |
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| 18:25 | train the algorithms with really complicated sets questions, cross check and verify really |
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| 18:33 | answers. With real scientific literature or a knowledge base that open A I |
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| 18:39 | IG BT has no access to. this is where you go to uh |
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| 18:46 | , OK? You go to uh and you go to my accounts and |
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| 18:50 | gonna say log in with Google Net identify where you are, where you |
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| 18:59 | your institution. University of Houston. gonna have to enter a passcode. |
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| 19:04 | duo, but if you're logged in can allow you to enter without the |
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| 19:12 | . But it's the same thing you in. Yeah. Now you can |
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| 19:18 | to this databases here. I'm actually this on the lecture. So you |
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| 19:24 | , you can review this on your and there are different databases that you |
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| 19:29 | uh search or new databases. It , of course, what your subject |
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| 19:34 | is, you know, international medieval . That's not necessarily something we're gonna |
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| 19:39 | , we're gonna go to pub OK? And then let's enter a |
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| 19:46 | of interest or anybody has any let's say multiple sclerosis. And it |
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| 20:00 | you that there is 101 11,000, publications with multiple sclerosis in them. |
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| 20:13 | , thanks. That's really helpful. gonna go back to CHA GP |
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| 20:18 | you know. No. So look at this. Mhm The last |
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| 20:28 | years and all of a sudden you're to 20,000 and you're like, oh |
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| 20:33 | , that's still a lot, So let's say you know what? |
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| 20:36 | don't know that much and I really wanna look, let's say five |
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| 20:40 | it's still a lot, 29,000. happened in the last year? I |
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| 20:44 | want the latest literature and you have tabs, these selections, tabs and |
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| 20:49 | filters that you can, uh, you can select as you can |
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| 20:53 | autobiography, bibliography, letter, newspaper, and so on and so |
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| 20:59 | . So you can modify. But if you just do simple things, |
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| 21:03 | click on review, now you're down about 1200 reviews. But then let's |
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| 21:09 | you do the same thing as you with Google, right? When you're |
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| 21:12 | to find something, they will look like I want this jacket and X |
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| 21:18 | and blue and this, you boom, you find it. So |
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| 21:21 | same way, you know, I multiple sclerosis and uh vitamin B and |
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| 21:28 | D and um hippocampus. And Wow. OK. So this was |
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| 21:39 | lot, right? This is quite , but let's say if I erase |
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| 21:44 | and just leave vitamin D 33 results a lot of them are actually |
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| 21:53 | You will see immediately some of them three P MC, three P |
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| 21:56 | That means that the full text with of the figures and everything is |
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| 22:01 | So let's say uh there's some review you found in neural protection of multiple |
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| 22:08 | and you click on it and it you all of these choices here on |
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| 22:13 | right. And you can click full , open access, free, full |
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| 22:16 | access. And it gives you different where you can eventually find the PDF |
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| 22:24 | and look at the PDF. Sometimes just want to look at the figure |
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| 22:28 | read about a figure or you can in this html format and do the |
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| 22:33 | . Sometimes, uh, just click the figures and they get enlarged. |
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| 22:39 | you can actually download them and it a lot of stuff. So this |
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| 22:43 | , this is something that uh you really know about all of you and |
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| 22:51 | because cha GP T is not enough it, it has to uh you |
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| 22:57 | , that human intelligence, that that drive or ideas should come from |
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| 23:04 | . But cha GP T can help . Sure. I've used it and |
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| 23:08 | suggests some really cool things I haven't before, but then I don't just |
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| 23:13 | and paste, you know, suggested that I work on it. And |
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| 23:16 | I check with it saying like, this, does it, does that |
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| 23:20 | like it came from you? Is all mine says, no, |
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| 23:22 | you know, all yours keep it they keep it too. So that's |
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| 23:26 | important thing to know. All So now we go back into this |
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| 23:35 | screen hopefully, where are we right ? No. And uh we're talking |
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| 23:48 | a mass and the next disease that talking about is Charcot nude disease or |
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| 23:54 | . And that is P MS demyelination affects mostly the limbs, legs and |
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| 24:01 | . It is a swan cell disease demyelination loss of swan cells. Uh |
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| 24:10 | is a type of uh abnormal growth is non malignant, that is called |
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| 24:19 | . Some of you may have heard glioblastoma, for example, cancer, |
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| 24:24 | . There's also something called schwannoma. when there's too much of the Schwann |
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| 24:30 | going here, you have lots of cells. It's one of the most |
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| 24:35 | inherited neurological disorders. Ok. It's . Uh It is having an onset |
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| 24:48 | typically in adolescence and early adulthood. that's the onset, if you inherit |
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| 24:55 | disease, the onset of that disease be different. It could be in |
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| 24:59 | very early, immediately after birth in first two years of life or sometimes |
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| 25:05 | the lessons. Their symptoms are weakness paralysis, high step gait with frequent |
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| 25:12 | or falling balance problems, foot uh inverted champagne bottle shape where the |
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| 25:21 | are buckled inside and the feet are outside. And the individuals usually have |
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| 25:29 | with gait and they typically, instead forward motion, they do a lateral |
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| 25:33 | when they move themselves forward and Uh loss of muscle bulk, reduced |
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| 25:41 | to feel heat, cold and So we we we probably understand |
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| 25:48 | all of these deformities and atrophies and because there is no signal that's going |
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| 25:58 | axons. It's not activating So now have central nervous system and it says |
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| 26:03 | right hand and this command is being perfectly. It goes to the spinal |
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| 26:09 | where it's supposed to move the right and the spinal cord axons are |
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| 26:14 | It's failing to do that. And you are failing to do the proper |
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| 26:19 | contractions as, as a part of early adulthood, adolescence development, it |
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| 26:25 | deformities in your bones and it can a permanent uh deformity. Uh |
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| 26:31 | that, that, that, that have to deal with. So, |
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| 26:37 | this disease as early as possible, for individuals to be placed in braces |
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| 26:44 | braces will keep them more symmetrical. the bones suggested better. Uh of |
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| 26:50 | , physical therapy activity, but it be very painful, painful contractions of |
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| 26:59 | muscles, muscle cramping nerve pain in periphery. So obviously, these treatments |
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| 27:05 | then be analgesic, treating the pain shaco to disease. Now, um |
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| 27:15 | would a person have decreased sense of exception or reduce the ability to feel |
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| 27:22 | called unto if you recall, the nerves are comprised of the sensory |
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| 27:29 | which is the dorsal component, dorsal ganglion and the ventral component. We'll |
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| 27:36 | that again today and that's a motor . And so the sensory component is |
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| 27:41 | affected by the myelination in the peripheral . Therefore, you don't have as |
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| 27:47 | of a perception of touch or of or app proprioception, which is location |
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| 27:55 | your muscles and parts of your body respect to your joints and tendons and |
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| 28:02 | as it holds you down to the . Ok. So this is oligodendrocytes |
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| 28:08 | swan cells and insulation, myelination and . Next is microglia microglia responsible for |
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| 28:18 | injury or repair. They are the mobile elements in the brain. So |
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| 28:23 | there is injury, when there is , when there is inflammation, there |
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| 28:28 | to be an immune response. And they sort of act like a local |
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| 28:33 | and the brain. But they also upon the immune cells from the blood |
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| 28:38 | enter into the brain like CD four cells to help them maintain what we |
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| 28:44 | the normal or homeostasis, normal dynamic or homeostatic range in the brain. |
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| 28:52 | they're responsible for all of these They have sensors, they send reactive |
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| 28:57 | species R OS, which are essentially sign of inflammation in the area due |
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| 29:03 | infection or injury. Uh It's extracellular , it actually release of cytokines and |
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| 29:14 | cytokines uh typically is a normal response an infection or inflammation and a signal |
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| 29:21 | call up call upon the uh immune . However, if that cytokine release |
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| 29:28 | uncontrollable, you, you heard during on the radio, the cytokine storms |
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| 29:34 | the TV news, the cytokine then they can become pro inflammatory pro |
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| 29:42 | in this case in the brain. let's watch this video of microglial cells |
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| 29:52 | this instance, what you're seeing is injury. So this is the side |
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| 29:58 | the injury right here. And the thing that you'll see is you will |
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| 30:03 | these processes extending these uh microglia are glowing here. And why they have |
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| 30:08 | specific microglial stain. And they will their processes toward the side of the |
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| 30:14 | and then slowly start moving their sous order to engulf uh a debris or |
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| 30:20 | cell. And this beautiful structure of with the processes that you see at |
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| 30:27 | beginning, once they engulf that for example, a piece of that |
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| 30:32 | , they become a me boy like then they get eaten by astrocytes is |
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| 30:37 | re so as we talk about and don't know who eats astrocytes. So |
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| 30:43 | find out as this story unfolds in . But you can see that very |
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| 30:50 | within minutes, you have all of processes and microglial sous migrating toward the |
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| 31:01 | of the injury and taking care of injury. This this time lapse, |
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| 31:05 | think of several hours this afternoon. that's why we call them the most |
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| 31:11 | units in the brain because they actually through the brain. Uh not just |
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| 31:17 | processes, but also the cmas astrocytes the most abundant w sub type in |
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| 31:23 | brain. Oocytes regulate very much what between neurons and the synaptic transmission between |
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| 31:31 | neurons. You can see here, synoptic neuronal terminal loaded with these green |
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| 31:38 | for neurotransmitters. You have a synoptic and then you have the postsynaptic density |
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| 31:44 | the dendritic spot and surrounding these two , green and dark green or brownish |
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| 31:53 | neurons. Is this blue indicator or process. So, ostracizes very tightly |
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| 32:02 | the synoptic transmission. They control how of the neurotransmitter, glutamate. The |
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| 32:09 | neurotransmitter in the brain is available to , for example. So they control |
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| 32:15 | between these neurons too. If there too much of a certain neurotransmitter or |
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| 32:23 | that increases in concentration locally ostracized, the ability to slurp up those chemicals |
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| 32:32 | these ions because they have such So and extensive processing spatially with very |
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| 32:39 | volume and also interconnections with other astrocyte . They can very quickly spatially buffer |
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| 32:50 | high concentrations that are localized in potassium for example, in a neurotransmitter like |
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| 32:57 | and spatially buffer and distribute them through large volume, their largest trees of |
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| 33:04 | and also interconnections because they're so tightly in the synaptic communication. They're responsible |
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| 33:12 | synaptogenesis or birth of the synopsis synaptic , which is changes in the |
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| 33:20 | the strengthening of the weakening increase of number or decrease of the number of |
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| 33:26 | synopsis, their outgrowth and their So as they're going to be changing |
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| 33:33 | shape during the development, then later the process of plasticity, astrocytes will |
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| 33:40 | this process very closely and will influence . And astrocytes also contribute their fee |
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| 33:50 | blood brain barrier, the blood brain is a barrier between the blood and |
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| 33:56 | brain. What's in the blood doesn't get into the brain. What you |
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| 34:02 | in the blood is very tightly controlled endothelial cells that form the blood vessel |
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| 34:10 | and have the tight junctions in between endothelial cells. So only really small |
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| 34:17 | , only lipophilic or fat-soluble substances or that have their transporters or cot transporters |
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| 34:25 | facilitators that can help them cross through barrier. Only those molecules are allowed |
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| 34:32 | go in. And there's a lot stuff that go goes in from the |
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| 34:36 | into the brain. But so it's , the tide junctions by endothelial |
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| 34:42 | And then second and uh second is astrocytes, the astro astro glial processes |
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| 34:55 | surround them. So they're also a essentially from the brain side of what |
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| 35:03 | enter into the brain. So for most part, it's a great thing |
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| 35:08 | we have this blood brain barrier because example, you can get very easily |
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| 35:14 | infection in your blood, right from anything, just a scratch, |
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| 35:19 | know, you could be fishing and you scratch yourself and you put yourself |
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| 35:24 | the dirty mud here in Texas. then, you know, you, |
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| 35:28 | have pain and it's swollen. So may have a localized infection. You |
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| 35:33 | have some, some infection that crosses your blood too if it's a bigger |
|
| 35:38 | , you know, but that doesn't that it's going to infect the |
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| 35:42 | So the brain is gonna have its protective mechanisms when you consume a lot |
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| 35:46 | something. When you digest something, ? You're drinking something, you |
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| 35:50 | consuming a lot of certain iron or . Not all of that is gonna |
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| 35:55 | of a sudden to go through the in your, in your brain, |
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| 35:59 | gonna get controlled by this blood brain . So, but it also presents |
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| 36:05 | to the development of neuro pharmacological neuro pharmacological preparations. Because how do |
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| 36:13 | uh how do we as humans, individuals consume pharmaceuticals? What happens? |
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| 36:21 | do we do if you, if , if you have a, if |
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| 36:24 | have a migraine, which is you , happening in your CNS, how |
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| 36:29 | you, how do you take the ? Yeah, you ingest it in |
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| 36:33 | mouth and then what happens to Yeah, it goes into your |
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| 36:40 | You swallow it right. You don't on it. There's some tablets you |
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| 36:44 | so quick dissolving tablets. Maybe they absorption through what is called here. |
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| 36:49 | buckle areas beyond the cheek, sublingual the tongue or upper esophageal. Your |
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| 36:55 | esophagus has a lot of uh absorptive for substances. So things that dissolve |
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| 37:01 | quickly. Some hard medications, for , they dissolve very quickly because they |
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| 37:06 | to have immediate effect. They have enter into the bloodstream immediately. But |
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| 37:10 | lot of medications that uh uh individuals and even everyday stuff like Advil and |
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| 37:18 | like that, it doesn't take effect . Sometimes it takes 15 minutes, |
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| 37:23 | it takes longer than that half an before you feel an onset of some |
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| 37:28 | . But we're talking about neuro right. So, what is an |
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| 37:33 | here after it goes into this It drops into your stomach and it |
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| 37:39 | squirted with these gastric juices of about three point something. So it starts |
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| 37:46 | that active ingredient. That might be medication. And then for that active |
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| 37:52 | to enter into your system, it to go through the digestive tract. |
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| 37:58 | , it has to get digested and it gets absorbed, it gets absorbed |
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| 38:02 | the blood. So you may have prescribed the patient 200 mg of an |
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| 38:10 | ingredient, whatever it may be ibuprofen some other active ingredient. It doesn't |
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| 38:16 | that 200 mg of that active ingredient gonna get into the blood. And |
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| 38:23 | if that molecule is large, if molecule is not lipophilic, even |
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| 38:30 | even smaller amount of that is going get from the blood, from your |
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| 38:36 | system, going to the systemic blood enter through the blood brain barrier is |
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| 38:40 | be a fraction of one consumed of one consumes. So most of the |
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| 38:47 | this is how uh neurological disorders are treated is through tablets or pills and |
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| 38:56 | quite ineffective if you think about nasal sprays, which people don't really |
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| 39:01 | to use were creatures of habit. , just swallow a pill and |
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| 39:05 | you know, spraying something in the . It seems a little bit |
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| 39:09 | but that can bypass the digestive system get it directly into the, into |
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| 39:17 | brain. We'll discuss that. When talk about the olfactory system, there's |
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| 39:21 | pathways to get into the brain from nose. What about transdermal? Anybody |
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| 39:27 | of transdermal? Anything transdermal patch is or analgesia? All right. So |
|
| 39:34 | , what does that do that penetrates active it from the skin, from |
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| 39:39 | surface of the skin into the Again, it bypasses the digestion. |
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| 39:45 | doesn't mean it bypasses the metabolism by and uh and uh and kidneys filtering |
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| 39:52 | kidneys and all of that, but enters into the blood. Ok. |
|
| 39:56 | there's more effective ways. And so lot of times when people design uh |
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| 40:03 | , they have to make sure that it is a pill or a tablet |
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| 40:07 | it has either quick dissolving and high rate immediately in the oral cavity or |
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| 40:15 | it bypasses all of that low ph , you know, gets into the |
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| 40:21 | system to the highest proportion possible and through the blood brain there in the |
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| 40:27 | proportion possible because it is nano particularized maybe it is coated with something that's |
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| 40:34 | . Maybe it has something else that for it to be facilitated across the |
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| 40:39 | brain barrier. All right. And this we end our lecture on neurons |
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| 40:45 | glia. So for the rest uh an hour or so, we will |
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| 40:50 | talking about membrane neuronal membrane membrane voltage, voltage gated channels, |
|
| 41:04 | hyper polarization, overshoot, undershoot resting and potential. We're gonna start with |
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| 41:16 | number and potential today. Neuronal membrane or resting membrane potential. What is |
|
| 41:23 | ? So when we were able to to record in for cellular activity and |
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| 41:30 | not what neuralink does. It doesn't the same activity as we talk with |
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| 41:36 | cells that rather picks up activity from of the cells from networks c |
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| 41:41 | Now, if you go inside the and you presume that the outside of |
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| 41:46 | cell is charged, neutral is zero and you just cross this p pa |
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| 41:53 | pi pa through the plasma number into cell, your bolt meter would read |
|
| 41:58 | 65 millivolts. And that's what we resting mene potential. And that is |
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| 42:03 | there is a separation of charge across plasma membrane and the inside side of |
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| 42:08 | plastic side of this possible lipid bilayer negatively charged. So negative charge is |
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| 42:14 | on the inside and positive charge is on the outside of this possible lipid |
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| 42:21 | . Now does that mean that resting and potential is minus 65 millivolts all |
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| 42:27 | time? No, it doesn't mean mm number and potential resting number and |
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| 42:35 | minus 65 millivolts. Let's say here is going to fluctuate in biology. |
|
| 42:46 | you see a flat line, it's good. OK. When you, |
|
| 42:54 | , you watch the uh clinical or movies or series that is a flat |
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| 43:01 | is usually sound associative with that. nothing really stays flat. OK. |
|
| 43:09 | What I mean by that is this and potential. It's going to fluctuate |
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| 43:15 | and down a little bit, which really bad. She's better, it's |
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| 43:21 | to fluctuate. And if it goes direction, OK, it becomes |
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| 43:29 | OK. This is depolarization. And it goes down and goes beyond what |
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| 43:38 | would call the resting membrane for shall this direction was called hyper |
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| 43:46 | OK. I for full resolution. if this membrane potential, the M |
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| 43:57 | of the membrane which is measured in , the voltage of the membrane is |
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| 44:06 | the M MD if it reaches this here, which is minus 45 millivolts |
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| 44:14 | , and we call this value the for action potential generation. So if |
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| 44:20 | plasma membrane depolarizes and reaches this membrane to a level, it will now |
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| 44:32 | a very large, I don't wanna over there, but I think I |
|
| 44:36 | , you know, it produces very action potential. So this is the |
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| 44:44 | potential. Yeah, it actually is want to see if I can erase |
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| 44:56 | . Yeah, the A P no, the A P like action |
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| 45:03 | can you erase it magic? All . So this is our action |
|
| 45:12 | So, depolarization, hyper polarization. if you reach this, this happens |
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| 45:17 | all or none even called potential. that's where the hodgkin and ox |
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| 45:22 | And that's why we call neurons suid because they have a separation of charge |
|
| 45:28 | they can also produce a very fast potential that's on the water of one |
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| 45:31 | two milliseconds and the duration of the potential. So, action potentials, |
|
| 45:38 | are they so fast is because we to react to things very fast. |
|
| 45:44 | one of the examples and still like back to the circuit that we already |
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| 45:50 | about is if you have a nauseous , or if you, for |
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| 45:54 | step on something that is sharp, going to have a reflex and you |
|
| 45:59 | immediately move your foot away. In words, you're not gonna stand and |
|
| 46:05 | , but I feel that there's something in my foot, it might be |
|
| 46:10 | blood dripping. Should I make a and step off of it? So |
|
| 46:14 | is not for, you know, of an intellectual contemplation, it's reflexive |
|
| 46:19 | , it's very fast and reflexive behavior a good example of where you need |
|
| 46:26 | V circuits and quite simple circuits to that reflexive behavior. Of course, |
|
| 46:31 | we stepped off the sharp object, will be conscious of that, you |
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| 46:35 | perceive it, you'll understand what's going . You'll execute a much more complex |
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| 46:39 | of going to the first aid kit putting a band aid and then getting |
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| 46:44 | medical help if you need to and on and so forth. Also, |
|
| 46:48 | brain neurons are very fast and the we process information is very fast. |
|
| 46:53 | these are the fastest cells in our . And neurons, neurons can fire |
|
| 46:58 | to 600 spikes. A 2nd, action potentials. A second, the |
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| 47:04 | is 1000 milliseconds. So some of neurons are extremely, extremely fast and |
|
| 47:11 | just for moving the legs reflexively, also processing the information that comes |
|
| 47:16 | There's for example, information that comes at 20,000 Hertz 20,000 oscillations per |
|
| 47:26 | And we have the ability in our , the hair cells to respond to |
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| 47:31 | 20,000 stim part stimulus. So in other words, we we we have |
|
| 47:37 | have very fast circuits. This is circuit, an example of circuit that |
|
| 47:43 | already know to a certain extent. this is simple reflex also referred to |
|
| 47:51 | knee jerk stretch or patella tendon And this is quite often if you |
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| 47:56 | for even an annual checkup at a neurologist's office, they will ask you |
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| 48:01 | sit down like it's pictured here and will tap with a mallet right here |
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| 48:07 | the tendon right here. OK. patella tendon and the response of this |
|
| 48:14 | tap is going to be an extension the leg. OK. So the |
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| 48:19 | extends and this is one of the to check for basic neuron, neuronal |
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| 48:26 | function, reflexes, condition and state the spinal cord as properly responsible or |
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| 48:33 | properly responsive as this patella tendon stretch . So what happens is when you |
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| 48:40 | the stimulus, the stimulus get sensed picked up by the sensor or of |
|
| 48:46 | gang cells, there are pseudo unit cells that have a peripheral axon that |
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| 48:52 | into the muscle and senses the muscle contraction and vibration. So, muscle |
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| 48:59 | in this case, on the extensor quadriceps, and it sends that information |
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| 49:05 | the clump to the ganglion that is here, sends that information. And |
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| 49:10 | the central axon of the pseudo unipolar delivers excited for information. So it's |
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| 49:19 | excitatory. It excites motor neurons, central axon will excite motor neurons and |
|
| 49:25 | with one synapse, monosynaptic connection exciting motor neuron by releasing glutamate on |
|
| 49:33 | this motor neuron will be excited and will now release acetylcholine motor neuron is |
|
| 49:39 | multipolar cell. In the spinal it has a long axon that becomes |
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| 49:44 | part of the same nerve here and innervates the muscle and causes the release |
|
| 49:49 | acetyl colon. It's also only excited syn only excited to a transmitter there |
|
| 49:55 | causes contraction of this muscle. So with one sat sensory to motor |
|
| 50:01 | you can cause contraction of the However, for the reflex to be |
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| 50:06 | and for the movement of the this pick up to be proper. |
|
| 50:11 | have opposing muscle which is hamstring, muscle. So every muscle major skeletal |
|
| 50:18 | has an opposing muscle. When you biceps, your triceps relaxes when you |
|
| 50:25 | triceps, your biceps is extended and relax. Ok? And that's if |
|
| 50:30 | wanted to contract biceps, but your wouldn't relax, you wouldn't be able |
|
| 50:35 | properly only partially, maybe contract the . And so in order for this |
|
| 50:41 | and the kick up to be good proper, there's another involvement of another |
|
| 50:47 | here, the same sensory neuron activates inhibitory interneuron of the spinal cord. |
|
| 50:55 | inhibitor and interneuron of the spinal cord glycine and also gaba releases a couple |
|
| 51:04 | inhibitory neurotransmitters and those inhibitor nerve Now make sure that this motor neuron |
|
| 51:12 | innervates the opposing muscle, the hamstring is not active. Therefore, the |
|
| 51:19 | is relaxed. So it has to the opposing muscle and it does that |
|
| 51:24 | the inhibitor interneurons. So remember when talk about classification of the cells, |
|
| 51:30 | talk about several things, whether they're or local interneurons. Here's an example |
|
| 51:36 | an inhibitor interneuron. It does its locally within the spinal cord circuit. |
|
| 51:42 | does not project out of the spinal motor neurons, they project out of |
|
| 51:47 | spinal cord and innervate the muscles. . Yeah, an image that we |
|
| 51:52 | last lecture where uh the neuron uh a green and orange group leva Andre |
|
| 52:00 | that um and those were the was that like at a moment? |
|
| 52:05 | my question really is um were there of one than the other? And |
|
| 52:10 | at that moment, uh So it's very good question because when you talk |
|
| 52:19 | uh this is neuromuscular junction and neuromuscular , this is only excited target. |
|
| 52:28 | it's a little bit different from the that we talked about. Uh It's |
|
| 52:34 | one versus the other in a really circuit. One first immediately followed by |
|
| 52:40 | . So this may initiate to contract as this initiated to contract just 100 |
|
| 52:46 | , 200 milliseconds later, this gets because this is called a synoptic. |
|
| 52:50 | there will be some delay. This immediately to motor neuron. This through |
|
| 52:55 | neuron is gonna have some delay. it is going to relax this muscle |
|
| 53:01 | a slight delay. I'm not sure that completely answers your question. |
|
| 53:06 | maybe another way to view this question what if somebody is stimulating the patella |
|
| 53:15 | and it doesn't kick up. So can refer to a neurologist or a |
|
| 53:22 | something, maybe the sensor neuron is working. But what if they're seeing |
|
| 53:30 | when they're tapping that this is trying contract, but this is not |
|
| 53:36 | That gives an indication, you maybe there isn't enough inhibition or maybe |
|
| 53:43 | connections from the sensory to inhibitor neurons from inhibitor neurons to motor neurons are |
|
| 53:49 | . So of course, that won't the question just by tapping on |
|
| 53:52 | on your, on your knee to this reflex. But uh now last |
|
| 54:00 | when I showed the slide and I , look at all of these exciting |
|
| 54:04 | synopsis and neurons receiving house to integrate of the information. Right? |
|
| 54:10 | the muscle only receives excitation. So doesn't, it doesn't, it's just |
|
| 54:14 | synopsis, one receptor, one So it's much more simple than neuromuscular |
|
| 54:21 | . So it either is active or . Active is contraction and active is |
|
| 54:28 | . So here, of course, have excited neuron and contex inhibitor, |
|
| 54:35 | and inhibitor neuron and excited term. at the level of the muscle. |
|
| 54:39 | within these circuits, there might be inhibitor interconnections here locally. But at |
|
| 54:45 | level of the muscle, it's very contract with acetylcholine or no acetylcholine |
|
| 54:54 | Now, uh this is something about interneurons and these inhibitor interneurons, they |
|
| 55:02 | glycine and they utilize GVA. So are the major inhibitor neurotransmitters. And |
|
| 55:11 | a long time, it was thought Glycine, it was the only neurotransmitter |
|
| 55:17 | is used by inhibitory into neurons. spinal cord, this is different from |
|
| 55:30 | inhibitory into neurons in the hippocampus that looked at. It's a different |
|
| 55:40 | And also here they release glycine and in the spinal cord. But there's |
|
| 55:47 | variety, morphological variety of these inhibitor in the spinal cord and the dialects |
|
| 55:55 | they see which is their firing patterns the action potentials, their, their |
|
| 56:00 | patterns. She is a probably a link again. Yeah, it links |
|
| 56:09 | to the links you to this figure here and you can uh read the |
|
| 56:16 | legend. So you can always use links in uh in our lectures. |
|
| 56:22 | am I? Hm. Mhm. me pause this. Oh, such |
|
| 57:04 | nice guy. I'll put that table you and uh you can memorize them |
|
| 57:12 | me. OK? And it has major cell so that we talked about |
|
| 57:19 | camp motor nerves to your g spinal , motor nerves. So you'll notice |
|
| 57:25 | um when you go to your uh you will notice that uh you |
|
| 57:33 | , your exams are gonna be 40 . They're gonna have about 40 |
|
| 57:39 | approximate number of questions, but they're be worth uh 100 points. So |
|
| 57:45 | exam is worth 100 points. And the way that I ask these |
|
| 57:52 | is that the questions will not have weight and question like this could be |
|
| 57:59 | matching question that's worth 5 to 7 of the whole exam because I will |
|
| 58:04 | you to 12345 cells to match with two or more properties. So it |
|
| 58:12 | contain uh questions that are worth five , six points a point and a |
|
| 58:19 | , easy, true and false Do you like this course or |
|
| 58:24 | True? One point just kidding. it's gonna be easier questions. Uh |
|
| 58:30 | there's more difficult questions and more time questions and it was more important to |
|
| 58:36 | . So the other thing you can is you can copy this and paste |
|
| 58:40 | , create your own table, add own notes into it. So you |
|
| 58:44 | use the images. I like the and the slides that have images to |
|
| 58:48 | them because that's how I remember But I also learn the best when |
|
| 58:53 | draw something out and take the So I if I just label |
|
| 58:59 | it's it's pretty good. But if draw it out myself like a neuron |
|
| 59:04 | this thing, then it really, me, it really sticks in and |
|
| 59:08 | has their own different way of Some people like the text and the |
|
| 59:12 | and the description. So um now when we talk about neuronal |
|
| 59:18 | we talk about the cast of chemicals some of these things, the next |
|
| 59:23 | slides might be pretty basic to many you water. H2o oxygen attracts electrons |
|
| 59:30 | negative charge. Hydrogen has positive Oh How like they own bonds. |
|
| 59:35 | polar molecules dissolve in water. So like sodium chloride, they will be |
|
| 59:42 | in water, they will be surrounded certain what we call clouds of hydration |
|
| 59:47 | waters of hydration. Uh The ions atoms and molecules that have a net |
|
| 59:54 | charge. They're held bionic bonds to minus and A plus difference in the |
|
| 60:00 | of protons in electrons is what gives charge of the valency monovalent and A |
|
| 60:07 | divalent C A calcium two plus cion and A plus anion negative chloride |
|
| 60:17 | Those are some basic things about the of chemicals. Neuronal membrane pressed again |
|
| 60:24 | this minus 65 millivolts. And what can see is the molecules are dissolved |
|
| 60:30 | water and they're surrounded, like I , with these spheres of hydration and |
|
| 60:35 | sphere of hydration can be larger or . That kind of it depends on |
|
| 60:39 | size of an ion, the valency that ion and it will determine the |
|
| 60:46 | by of water that it surrounds Now, ions cannot cross through plasma |
|
| 60:53 | . Uh They cannot just cross in the phospholipid bilayer. So you can |
|
| 60:59 | that you have of course, uh compounds and hydrophobic compound. So, |
|
| 61:07 | compound is something that dissolves in water soluble salt, sodium chloride. |
|
| 61:14 | because it has an electrical charge versus compounds, which is something like oil |
|
| 61:22 | is not dissolved in water. It's even electrical charge. Lipids are hydrophobic |
|
| 61:29 | they contribute to the resting and action . But in general, these |
|
| 61:34 | they cannot cross through the phospholipid And so, in order to cross |
|
| 61:40 | phospholipid bilayer, they need channels and are built from the building blocks of |
|
| 61:49 | that are amino acids. And these acids connect to each other through peptide |
|
| 61:56 | . And then you have essential amino that you have to source from your |
|
| 62:01 | food intakes, grains, uh supplements and so on. And then the |
|
| 62:09 | that we synthesize inside our bodies and amino acids are gonna be used as |
|
| 62:15 | blocks of bricks that have a primary and the strings that become secondary, |
|
| 62:21 | can get bomb into alpha elix or can get laid in what was called |
|
| 62:26 | sheets. Then they a single transmembrane here. Typically like this alpha |
|
| 62:35 | there's gonna be multiple alpha helix that one sub unit, which is tertiary |
|
| 62:41 | of the protein. And then you the coordinator structure which is multiple sub |
|
| 62:47 | uh coming together and forming the receptor . And that's why you have to |
|
| 62:53 | all of the amino acids. That's you have to eat well because essential |
|
| 62:59 | come from food. So go get quinoa. Uh It has a lot |
|
| 63:04 | uh uh a large number of essential acids. Uh It's pretty good |
|
| 63:10 | If you haven't tried it, channel , you have polar R groups, |
|
| 63:15 | polar R groups. Channel proteins are selective. So they have selectivity for |
|
| 63:21 | ions. These ion channels can be or open, they can be opened |
|
| 63:29 | by voltage. So they gated by , they can be opened by |
|
| 63:33 | So they're Ln gated, typically receptor and they can also be mechanically |
|
| 63:40 | So when there's a mechanical pressure on membrane or on the actual protein, |
|
| 63:45 | channels will be reacting and opening to . So you have amino acid residue |
|
| 63:53 | these channels that will be interacting with as the ions cross through the channels |
|
| 63:59 | the plasma membrane. OK. And addition to the ionic channels, you |
|
| 64:06 | have ion pumps and those are formed membrane spanning proteins that utilize a lot |
|
| 64:13 | energy A TP and they work against gradient. So you'll learn in the |
|
| 64:19 | lecture that we have a lot of chloride on the outside of the |
|
| 64:24 | And this pump is going to put sodiums on the outside of the cell |
|
| 64:29 | concentration gradient to do that against the gradient. It will utilize a TP |
|
| 64:34 | in the reverse direction, it's going bring in potassium two molecules of potassium |
|
| 64:40 | the cytosol which contains high concentrations of . Therefore, again working against concentration |
|
| 64:47 | using a TP. So it's very the source of A TP, the |
|
| 64:52 | of energy. In fact, I learned recently this very interesting information that |
|
| 64:59 | you work out, we already talked the fact how much your brain consumes |
|
| 65:05 | brain is about 1.5 to 2.5% of total body weight. It consumes over |
|
| 65:12 | of the total body energy all of intake into the into the body digestive |
|
| 65:19 | , the brain, the blood, of the energy, 20%. So |
|
| 65:22 | a lot of energy. And now I've learned is that when you work |
|
| 65:28 | , there's a lot of lactate that built up and turns out that although |
|
| 65:33 | lactate is in the body, So it's, it's from the |
|
| 65:36 | it's from the muscles, about 11% it gets processed in the brain. |
|
| 65:43 | that lactate in the brain gets turned at P and glutamate. So when |
|
| 65:52 | say like, oh, I can better after working out, it actually |
|
| 65:57 | an interesting understanding how the body workout about 10% of that to benefit the |
|
| 66:05 | of the brain and potentially activity, activity of the brain as well. |
|
| 66:11 | that's uh something that's emerging in, the most recent news in the metabolism |
|
| 66:17 | and interactions between astrocytes and neurons. . I'm gonna end here today. |
|
| 66:23 | gonna finish and continue talking about some the biophysics, the next couple of |
|
| 66:30 | and then you will know so much action potential more than you wanted to |
|
| 66:39 | . Have a great weekend. I'll everyone here on |
|
