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00:01 | Okay, so this is our fourth in this course, and we're going |
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00:09 | continue talking today about neurons and glia not certain if we will get to |
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00:14 | neuronal Numbering addressed are resting membrane But I think as we talk about |
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00:22 | material through the course, hopefully we'll up where we need to be with |
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00:26 | material from mid term one. Now deep that I have is I received |
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00:32 | message from Casa saying that you could a test long in exam. I |
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00:41 | just a blow they very simple general that you would have toe answer and |
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00:48 | would be able to test all of systems and taking the virtual Kosta |
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00:55 | And the suggestion from cost A was you to take it this Friday, |
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01:00 | would be September 4th. So you have to register for today and tomorrow |
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01:07 | take it some time on on I also think that Friday's before Labor |
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01:15 | I'm not sure it's the Rani our plans, but if they're I think |
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01:20 | of you might be traveling by So, um not sure how to |
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01:27 | this. It may be we uh, teach a little Ah, |
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01:33 | all on chat. Uh, right , uh, I guess the question |
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01:39 | , can you would you be willing take a very quick log in test |
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01:45 | Friday, or should we piss opponents next week? Uh, giving you |
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01:52 | time? Teoh, gather all of don't Charlie tools. So see, |
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02:00 | a little illness. Sweetest fun. locating its foreign, it's who? |
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02:07 | front. It's from his friends. , currents. Okay, So what |
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02:15 | do is I will, uh you be able to actually go to Casa |
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02:22 | register for the exam. And I coordinate with Casa today to make sure |
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02:30 | everything will proceed smoothly on Friday for to take us again. You're not |
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02:37 | grated, but this. So this ah purely for you. Test out |
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02:42 | system. Make sure all systems ago that you don't have to stress about |
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02:48 | having a Charlie tool to take the exam on the day of exam. |
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02:55 | right, so we'll receiving this I will communicate, and we'll have |
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03:01 | follow up email to you that all confirming this virtual trial test sample. |
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03:12 | , for which you don't get the you're not getting graded for for for |
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03:16 | Friday. All right, so I know. And one of the key |
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03:23 | off neurons that we discussed. last time with Dendrite. It's and |
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03:30 | particular, the dendritic spines. And talked about dendritic spines is being really |
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03:36 | protrusions, that air coming off the branches in dendritic trees and that these |
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03:43 | and the size of connectivity between neurons so the synapses and the Boston optic |
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03:50 | in particular would be located on dendritic . And all of the information coming |
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03:57 | these spines will be coming from other from other excited, very excited Torrey |
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04:04 | , a turgid cells and synapses so inmates is excited to be neurotransmitters shown |
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04:11 | in green all of the glutamate receptors arm, the down brides and around |
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04:18 | storm off this particular south and the so will be receiving very strong inhibitory |
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04:27 | . And these inhibitory and was mediated Gabba gamma immuno beauty recast it and |
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04:34 | receptors on the image on the right shown in war egx. So everywhere |
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04:40 | see, orange is gamma receptor cities dendritic spines that continue inhibitory receptors, |
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04:49 | air the receptors that will bind inhibitory . And when gabba binds to the |
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04:56 | receptors, cell activity gets inhibit, cells become less active, their activity |
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05:03 | dampened. Uh, when gloomy excites green synapse isn't Boston optic densities. |
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05:12 | cells get deep polarized, the cells more excited, and the cells produce |
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05:18 | actual potential. So they produce more the electrical activity and they release more |
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05:24 | the chemical neurotransmitters onto the other neurons the line. Now, what we |
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05:31 | is that alterations and, uh, dendritic spine densities and the location along |
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05:41 | dendritic tree and interdict shafts. And structure of these finds the morphology of |
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05:49 | fines are very important. And on left you have an image off a |
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05:57 | spine from a normal infant. And the rise you have an image of |
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06:03 | dendritic spine from a mentally retarded in . And as you can see, |
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06:10 | doesn't really expire in some, the are distributed differently, or maybe more |
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06:19 | . In some areas are more dance the other areas that their morphology that |
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06:25 | shape of the them did experience is different on the right is compared to |
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06:29 | left. This is one of the of the sin Jones. So this |
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06:34 | one of the, uh, autism like disorders or a SD Autumn autism |
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06:44 | like disorders and fragile acts. this is a developmental mental red irrigation |
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06:54 | one of the bath Allah, Jeez fragile X as well as the models |
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07:00 | modelling. This autism syndrome like disorder these of normal morphological arrangement off dendritic |
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07:13 | , because structure means function and function and structure and alterations and even the |
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07:22 | will cause during early development alterations in structure of these parents. But once |
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07:28 | structure has been altered, especially if is a long term change such as |
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07:34 | term plasticity change long term depression, some spines over excitability and long term |
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07:41 | ation, as we discussed in the lecture, then, uh, once |
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07:47 | structure has changed, the functionality can permanently as well. And and if |
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07:55 | doesn't change permanently, it may not . It's malleable compared Teoh normal den |
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08:03 | and normal dendritic spines. So a of things to do when the spines |
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08:08 | impaired will be influenced. The synaptic the calcium regulation expression of molecules at |
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08:15 | levels of the dendritic spines and so important. Okay, so for our |
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08:22 | section, we talked about Alzheimer's disease time, and we described the key |
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08:31 | of newer pathology of Alzheimer's disease that adding one more disease now here. |
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08:36 | acts, which is a part of family of the diseases. They're called |
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08:41 | syndrome like disorders, and the neural feature of fragile X is have |
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08:52 | um, dendritic spine morphology and arrangement as well as, uh, |
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09:00 | It's mental interrogation. So this once again, I want to reiterate |
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09:06 | this process of spine development during early spine establishment, which is really establishment |
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09:14 | this sin abscess, is very much on activity. And that's where we |
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09:21 | that this is an activity and environment plasticity. Because duty and environment, |
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09:28 | during the early development, are someone nurturing environment, active environment, stimulation |
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09:40 | different census stimulation of social interactions. are all important things that play into |
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09:48 | Nuremberg pathology and the normal normal anatomy well as a neuropathology off. This |
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09:56 | is, well, US genetic so they can be familial that becomes |
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10:02 | from the family that they can be , which means that they just occur |
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10:09 | , do to the environment. And why so this environment, opportunity and |
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10:14 | could see Jean uh, processes that influence the final structure information of the |
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10:22 | and then further, once the structures activity, I even environment that changes |
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10:29 | change the plasticity of these structures, the synapses, weakening the synapses SARS |
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10:35 | shown on the right this spinal contained Colorado Distomo complex. And that indicates |
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10:43 | the dendritic spine, which is adjacent it's on the Ryan adjacent to the |
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10:48 | tone along the last that this dendritic is an independent by a synthetic |
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10:55 | a zone. By possessing this part so more conflicts. Also, it's |
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11:01 | surprising if in some of the synopsis many synapses would also see um, |
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11:06 | p. A special in the pre side is is one of the energy |
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11:11 | that is necessary for the exercise doses . So, uh, moving on |
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11:19 | neurons if we already talked about certain things about neurons first, we said |
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11:27 | neurons can be roughly divided or are into two major classes and those air |
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11:36 | two year olds and inhibitory neurons. then we said, in with them |
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11:41 | excited inhibitory neurons. And general, over 100 50 different stuff. IVs |
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11:47 | different. So how do we describe neurons and where some of the features |
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11:53 | are common amongst these nerds So most have more functional regions, which is |
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11:59 | inflict region on the top with and have an integrated region. Then you |
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12:05 | to conduct our region and you have output region. The input region is |
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12:09 | that particular neuron receives its temper and component complementary component or input words coming |
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12:17 | So ah, neuron a neuron. model Darren is contacting another your on |
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12:23 | its SoMa, which serves in his units of many synapses. Potentially |
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12:30 | different little neurons contact the soma, then the solar decides whether it's the |
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12:36 | unit and integrates excited during inhibitory Onto this narrow and the overall |
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12:44 | what is happening? The levels of and decides next the computation, whether |
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12:50 | going to produce an action potential, an action potential is going to get |
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12:56 | , and the axle on hillocks which located between the Ronel Soma in the |
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13:01 | segment, the first violin aided segment the axle, then conduct all unit |
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13:07 | a shown here and Blues Mile. she's a wrap around the accents that |
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13:13 | as a conduct I'll units that conducts electrical potential change. That actual potential |
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13:18 | is gets generated. A level of axe. Our killer. It conducts |
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13:23 | but propagated conductivity into his outfit which is a synaptic terminal in this |
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13:31 | , Axe Onal Terminal. And there a secretion o. R or release |
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13:36 | the neurotransmitter. And not, but so in the, uh, second |
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13:45 | from left arrived, you have a neuron, so you have an input |
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13:49 | the skin, so we already know kind of neuron this would be. |
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13:54 | example, we already discussed the anatomy the spinal cord, and we said |
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13:59 | is divided into the door. So car and central motor part, and |
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14:06 | send that the door so sensory since out then picks up the signals |
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14:10 | the periphery. This would be a axe on, then picks up the |
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14:16 | in the river and conducted into the So you have here different arrangement where |
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14:22 | have the peripheral Axum is conduct all . Then you have the dorsal root |
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14:27 | there, the spinal cord that will the integrity of, uh, |
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14:31 | calculation. And further, you will it through the central AC so onto |
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14:36 | neuron. So from the sensor in , um, let's say from the |
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14:40 | through dorsal root ganglia, and you contact the motor neuron and spinal or |
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14:47 | zones. And of course, the neuron will release the neurotransmitters inactivating the |
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14:54 | neurons. Now, motor neurons here contact, uh, other motor |
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15:02 | Or these implantable comes from the sensor can activate a motor neuron and that |
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15:08 | neuron will conduct it's information actual potential gets generating the solar here and well |
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15:16 | neurotransmitter onto the muscle, causing the of the most now local into neurons |
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15:24 | the Interneuron is that don't conduct signals long distances. But you have a |
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15:31 | Interneuron step interconnect with each other, most of the local interference of the |
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15:36 | are inhibited, turned into neurons, in fact, most of that diversity |
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15:41 | the subtypes of the brain comes through diversity of that inhibitor ended. There |
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15:46 | Interneuron PSA Grain. Then you have into neurons. This is a |
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15:53 | but these are some of the rear neurons that will inhibit our engineers That |
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16:00 | project the longer distances on. And you have narrows that actually are contacted |
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16:07 | then you're and a cream cells, they can actually release an influence |
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16:13 | as a constriction of acid elation at level of the capital ary with in |
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16:20 | , despite the fact that you can other neurons and humanitarian excited story that |
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16:26 | can announce contact must also cost muscle that, because, uh that Kabila |
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16:34 | a constriction of acid elation in the , Um, and overall sort of |
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16:40 | apparent crime like secretion from the neurons Korean systems in the way you have |
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16:45 | huge diversity of these sounds, but of them Happy's four functional regions. |
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16:51 | we just discussed here. Okay, now let's look at some of the |
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16:58 | and let's start learning increasingly more so these different cells. So morphological ease |
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17:07 | way in which you distinguish these We want to stop. Classify them |
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17:13 | , what's to stop classifying them into 150 different. Sometimes we have to |
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17:17 | a lot of the information. we have the morphological information that so |
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17:22 | you live, you have ah, polar cells and those. It's also |
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17:27 | a cell body and have one So North Pole only. And you |
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17:33 | accents projecting into dem rights. And projecting in one direction of visa difficult |
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17:40 | neurons, Bipolar or so, such as bipolar. Sell off the |
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17:47 | . We'll have dem drives. Then have so volume will have an accelerant |
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17:53 | Jackson. That's bipolar because it has holes. It has a very clear |
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18:00 | pole, so to speak, which den drives in the Southern Pole, |
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18:03 | is Axl pseudo unit polar cells or cells Again, a retinal cells to |
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18:10 | find them in the olfactory epithelium on someone spinal cord suit early in a |
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18:17 | cells, you know, you polar cells are, uh, cell |
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18:24 | cells. They have peripheral axe song projects the skin and muscle, and |
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18:30 | has essential acts on single process. by for Kate is single acts on |
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18:38 | external terminals that contact spinal cord cells This is our dorsal root ganglion cell |
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18:48 | . It's pseudo unit polar because it a peripheral axum, and it has |
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18:53 | central access. It doesn't have a north done dried south. Excellent, |
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18:59 | instead north. Maximum inside back. subsidiary. The polar cells, those |
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19:05 | mechanic receptors for perception and sensations of Jane pressure projections. They're going to |
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19:14 | spinal cord, as we discussed You have a lot of multipolar salsa |
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19:19 | the brain, three times a multipolar to show that the bottom off this |
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19:24 | two diagrams. Uh, first one motive during a spinal cord. It's |
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19:30 | because it has multiple poor, poor . Accent is pointing one direction, |
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19:36 | then you have done dried, start radial E and have multiple projections in |
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19:42 | directions. Karama Bill Salus in hippocampus Perama, tal cells of the |
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19:47 | We actually mentioned and discussed these prom sauces or the major excited Forest house |
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19:53 | the court. Actual criminal solace. describe a shaped sort of like a |
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19:58 | three dimensional paramour bid on by that and has an ethical 10. Brian |
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20:04 | in the top 10 and has Basil , sir, creating out of the |
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20:09 | of the pyramid. And also the of the pyramid is because we have |
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20:13 | projection off the axe on. So are around. It all sounds |
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20:18 | Very sauce on their campus. On left, The motor neurons are motor |
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20:23 | of the spinal cord. And on right, at the bottom riot is |
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20:27 | of, um, many lure. either Mr many artists. Ah, |
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20:32 | cell is a poor Kenji style of Balham that has again, that's a |
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20:38 | self, and it has an incredibly dendritic tree. So when we talk |
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20:46 | cells having hundreds of thousands of just look at the magnitude and the |
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20:55 | off off this dendritic tree. And imagine the the month of computation that |
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21:05 | cell has to dio in order. , they're in quickly calculate all of |
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21:13 | information from all of its inputs, the more complex cease trees are, |
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21:19 | more studied are the den drives with spines. The more complex is |
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21:26 | computation, But that computation, even Sarah Palin, the potentially cell level |
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21:32 | to happen on the order of milliseconds cerebellum is being some of the fine |
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21:41 | Command Adjustment center, essentially middle name motor commands has to do very quick |
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21:49 | . Very quick calculations or two. you have different times off sin ounces |
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21:57 | where you have different types of polarities and different times of war. Apologies |
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22:02 | describe this cells based on the Um, spinal motor neuron is a |
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22:08 | has about 10,000 synapses. Um, cell can have up 250,000 synopsis or |
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22:17 | ? Nah, just stick em Um, then drilling tree. |
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22:26 | now there's some other classifications based on fact that some parents are very clearly |
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22:33 | neurons that will have spines. And can see these spines and you stay |
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22:37 | the South so you can see this protrusions using a light microscope, and |
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22:42 | will be some several not contain any . And also you can. There's |
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22:48 | other gasification based on spying on our . Me. Um, now what |
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22:53 | It was straight a year is actually fact that one very important way in |
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23:02 | we classifying neurons it's not homely by way they look so morphology. But |
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23:10 | way they're connected. Whether their projections or their local network into the runs |
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23:16 | on the excitability of excited Turney So inhuman, very solves. They're |
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23:22 | different. Shapes are excited yourselves. different shapes of prohibitory yourself, one |
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23:27 | specific markers do they have inside? that's another way in which we would |
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23:32 | , classify them and finally would have action potentials that they produce. Whatever |
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23:39 | sequences of action potentials that they can , we call them firing signatures. |
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23:45 | if you look in the image on right, it's actually the first published |
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23:51 | recording from squid. Giant Axiron is first published actual potential in 1930 I'm |
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23:59 | Hodgkin and Huxley. Imagine how they to do it in 1939. They |
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24:07 | squids, so the squid was not like the one you see in the |
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24:12 | . The swell of the ships but axe on in the screen is pretty |
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24:17 | . About one millimeter in diameter or is something that you can die sacked |
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24:23 | see. With the naked eye and recording. They stuck these accidents with |
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24:31 | and they projected electrical currents. Shown is a fluctuation from minus 17 millet |
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24:39 | approximately, which is minus more like 55 million balls, which is |
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24:46 | Memory potential is very fast situation in water for a couple of milliseconds to |
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24:52 | 40 million volts on the scale and back. Teoh, the resting member |
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24:58 | potential So they would capture that using electrodes, and they would project the |
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25:05 | of the actual potential onto the bacillus . And then they would take the |
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25:11 | camera mounted over the screen of the sculpt, and they would take a |
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25:18 | after action potential that would take a of what the bacillus cope was |
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25:24 | So quite interesting. Way off of things again. We're not Houston. |
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25:31 | is cure codes and digital now. then the author of the article Hoskins |
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25:38 | would send the image would send the paper with the image, and the |
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25:43 | would produce copies of these using print copying machines. And you would get |
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25:49 | publication and mail because there was no or you would go to the library |
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25:55 | read the uh, journal of and you would find information about the |
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26:02 | published interest. Sally Life Recording. the first published action potential humans. |
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26:08 | . You've given how Look at They just recorded this. That's, |
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26:13 | , almost 100 years ago. 80 ago, the first recording of action |
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26:19 | published. So it tells you how when you until 1939 we didn't really |
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26:25 | the way we knew that they produce potentials. There was no way of |
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26:29 | capturing that information you have, which in Arctic needs, that all of |
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26:34 | Hodgkin reflexively on some other false that mold. Now this is one of |
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26:39 | favorite Dia graphs and and in this because it describes and it shows to |
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26:48 | everything that we've been talking about. what you have you want to 21 |
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26:54 | subtypes of cells, in particular different of inhibitory cells or into neurons Inhibitory |
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27:04 | in the structure that we keep talking hippocampus that codes for memory codes memory |
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27:11 | is responsible for memory recall as well semantic memory. It's emotional information |
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27:20 | And what you see is that if looked in the campus, hippocampus actually |
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27:25 | , uh uh three major last stride . Adams triumph. Rommedahl Astride of |
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27:32 | eons, there's one more striking. possible. Larry. It's a very |
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27:37 | , but mostly it's considered an R cortex, which is surprised that |
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27:43 | Three major, dominant leg most of south and, uh, hippocampus will |
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27:50 | relocated and striving for middle. And because there's very high density off your |
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27:55 | the valuable Perama tal cells that will across this wide stratum Pirmin Allen, |
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28:02 | there would be expressed it very high . I don't see if I can |
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28:12 | the question. Yes. Did you a question? Yes, I have |
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28:32 | question. And so what? You're our interest, your arms, What |
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28:39 | showing Very good question. If I correct, that showing is both the |
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28:45 | . Cells of the projection cells and abdominal cells that are projection cells excited |
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28:50 | ourselves have shown here and green, , sort of a bluish colors. |
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28:59 | they're labelled C B plus and C minus. And then you have from |
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29:05 | to ride Teoh this kind of violet one through 21 dozer the inhibitory. |
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29:15 | does that answer your question? So that means the blue cells are |
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29:21 | . Terry on a neurons and then orange and red and violent. No |
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29:27 | of you to be clarifying this. that blue cells are the exciting Torrey |
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29:32 | . Nall sells their projection cells to cells. This beram inal cells that |
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29:37 | labeled here, Stevie Plus and C minus. They will actually project to |
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29:42 | the arrows. The blue arrows going there will project out of the |
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29:47 | so they will project a distant parts the hippocampus. Is these air the |
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29:52 | cells? And these? Were they for yourselves? Now, one through |
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29:56 | there, flanked by the inhibitory Interneuron the inhibitory Interneuron principle that have there |
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30:03 | must located in different players. So can see 12456 1921. They have |
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30:09 | Somis in the Rommedahl earlier, And if you look there, axe |
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30:15 | or their synapses are shown is yellow . So 2341234 will be targeting mostly |
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30:25 | the soem us around the somatic areas the Haram it'll cells. That means |
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30:31 | I have a really significant impact on integrative properties because, uh, |
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30:37 | it'll south. And so most are for integration of the signal. They |
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30:41 | a significant control inhibitory control of These parameter all sauce we're going to |
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30:48 | out into the adjacent networks. So you look, it sounds like five |
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30:53 | six, their synapses distended, projecting that, uh, so much projecting |
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31:00 | onto the applicant will done dries and done hearts. So of course it |
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31:07 | influence the integrative properties. But the that the stronger your synaptic impulses are |
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31:14 | to re cells. In this a stronger and more of the synaptic |
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31:18 | emperors are around the so most of excited resells them or off the insecurities |
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31:24 | off these sounds is going to It was close by them. And |
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31:28 | can see that some of the South 10 11 and 12 they have their |
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31:34 | cops or their sin absence located with very half a co down tries of |
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31:40 | perama tal salt. So, the point of the slide is to |
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31:47 | you that first of all, you see the orientation off. The location |
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31:52 | the so most of the Interneuron is in different parts of the hippocampus that |
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31:58 | synapses project into different parts of the to ourselves, which will communicate the |
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32:04 | of these political left words. You see that there, Dan dries. |
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32:08 | of them are pointing horizontally, and of them were pointing vertically. So |
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32:14 | of these air distinguishing factors and some. The most important factor is |
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32:20 | staining staining for some of the Albelin marker. So you will see |
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32:24 | example three. Beram It'll sells one them. Sayings for CB were just |
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32:30 | and positive and solitude are killed. Negative. The other two are more |
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32:35 | , and they're less densely located in tried already Adam talk and the other |
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32:41 | stratum. Laurean's bottom flair. If look 234 actually old basket cells. |
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32:50 | the difference between 234 obvious is like me. The difference is pretty obvious |
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32:56 | of the solo where the stones are , which lair? But what is |
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33:00 | difference between two and four Morphological e , they live the same. The |
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33:05 | also located in uh uh, striding a dollar two and four. The |
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33:12 | drives are pointing vertically their inhibitory Cielo cops are targeting the same part |
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33:22 | the X sanitary beram. It'll cells salts. So how do you distinguish |
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33:27 | two and four? Well, to from PV, which stands from Peru |
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33:33 | Int and four stands from Basket Sal in big with three and CCK stands |
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33:42 | Callisto Kinda and voltage on da the main channel big look three. |
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33:51 | this is the final way to distinguish that. Some of these very fine |
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33:56 | of these inhibit their Internet arrests. may not be reflected in their morphology |
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34:01 | their sights. Architecture that you have actually cross stain these cells for some |
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34:10 | or genetic markers are some expression Marcus they contained, such as provided |
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34:16 | uh, hope in them Publicist, kind and the That's, um you |
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34:21 | , pressing and so on. So is the definitive fiction morphology, synaptic |
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34:30 | . Uh, would they stain And then this is just still the |
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34:37 | . So finally, for you to tell the difference between the stalls, |
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34:42 | also have to include their action potential so you can imagine two cells that |
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34:50 | next to each other. And I that these cells were different, but |
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34:55 | you have sell also look very but this is one way in which |
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34:59 | performed these experiments on I was doing I post doctoral research. Ah George |
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35:08 | University in Fairfax, Virginia uh, I was studying epilepsy, and I |
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35:17 | interested to see one action potential parents produced by different cells in normal tissues |
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35:25 | how these electrical action potential parents change neuro pathological conditions such as epilepsy and |
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35:35 | models. And what is showing this in the middle is a photo Micrografx |
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35:42 | photographed through a microscope of what we as a whole cell patch. Clamp |
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35:48 | from the last lecture whereby you see lectures on a glass electricity targeting individual |
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35:55 | , some the last on the Both of these neurons get a positive |
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36:01 | . They get positive current that gets through these micro electrodes into the individual |
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36:08 | . Cell on the left responds by a very high frequency terrain of action |
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36:17 | . So you see these spikes and going up. Each one of these |
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36:21 | is an action potential. The cell the right receives the exact same impotence |
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36:26 | cell on the left, but it a much slower and different shave action |
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36:33 | So these are what we call no action Potential firing signatures. The one |
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36:40 | the last is very much representative off firing inhibitory Interneuron, since it was |
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36:48 | the right, is representative off excited and slow of firing the Ramelow |
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36:56 | So during the experiment, especially if doing interest annular also recording In this |
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37:04 | , we're doing also recording the The environment that you have inside the |
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37:10 | actually represents the same cytoplasmic environment. even if you touch or if you |
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37:16 | a small window to the south through electrode, the style is viable. |
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37:22 | can survive for a couple of And you're pretending that you're just on |
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37:27 | of that south through this electric with side of plastic. And during the |
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37:34 | , he in this, uh, solution you also have a guy euro |
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37:41 | die is referring to or by a , and I So that's another dying |
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37:47 | adult to your less try. You golgi stain. You have missile |
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37:59 | I'm writing it down because he's a exam. Questions you have. What |
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38:04 | stains that we talked about Anybody remembers , missile bios, iten When Euro |
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38:15 | is another one, but we're talking now. We also talked about horseradish |
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38:22 | days. Do you remember that H p horseradish peroxide ezam viruses used for |
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38:29 | purposes. Okay, so these are of the great questions to know that |
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38:35 | between these different stains and dyes or reminding Tobias Iten is used during the |
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38:42 | recording its place to sign the electrodes it diffuses into the cells during the |
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38:50 | recordings. When you do after the is, you recover the tissue in |
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38:56 | exposing tissue, you expose the stain by using immuno histological techniques, you |
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39:04 | that no biting and that allows you also label the entire process is an |
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39:12 | morphology off the South from which you recorded. So this looks very |
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39:18 | These drawings of the sounds that were by me in this case using a |
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39:24 | version of camera lucid up microscope still a glance mirror system, uh, |
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39:33 | a system called Neural lucida and I the cells after the experiment and in |
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39:43 | you see the down drives of the and and yellow. You see the |
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39:48 | on the South's and following that this the end of the experiment, that |
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39:54 | tissue with more exposed to neural biden I also cross stained it with markers |
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40:01 | some at a Staten and provide algae and neuro via Tim. So that |
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40:08 | me, for example, this salad shown here at the bottom and purple |
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40:12 | has a narrow says some. It for somatic standing, and the East |
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40:17 | your abiding. That means this was and I recorded, and it hasn't |
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40:23 | marker for some at a Staten. my cell. Then I recorded from |
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40:28 | , has a fluorescent marker for some of Staten. This cell turned out |
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40:33 | be number seven cell allow allow themselves these horizontal like, Dent writes, |
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40:41 | it has an ax on that goes the very topical regions of the genetic |
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40:47 | . So I was just a big of B so a themselves, and |
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40:51 | kept bashing and recording from them and whether there were some Sonata Staten positive |
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40:58 | reconstructing the anatomy. So this type experiment, if you record any biological |
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41:06 | or euro uh, neurological activity, a seizure activity from individual south and |
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41:13 | know they're firing signatures. You know exact location of their exact morphology of |
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41:19 | styles that you recorded from and, know, the internal markets. Then |
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41:24 | can definitively say that this Waas Elam which stands for Koreans local awesome, |
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41:31 | local area because it projects it's accents strangle orients s O to ask the |
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41:38 | , distract him like an awesome malakal at the very apex off. What |
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41:44 | be the A packs off the down off the parameters cells excited to |
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41:49 | And there would be a sin ass on through the optical den dries of |
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41:53 | parameter all cells modulating the distal activity the distant inputs onto these parameters cells |
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42:00 | it hasn't done drives alarms style at bottom into neuron that projects Ah, |
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42:06 | , projects a result. Lino Parietal on the right has the axe on |
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42:10 | comes toward you and exits out of tissue is going out on its |
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42:15 | projecting out of the fields of Okay, so I think that maybe |
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42:22 | some questions. Okay, great. this is a good way for |
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42:28 | Teoh National information or abaya attempt or your side 10 is, uh is |
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42:37 | stain in the electrodes? No TV for car valve, you men. |
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42:47 | is a calcium binding protein. see, what else are I also |
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42:58 | a question. OK, Did you to raise a hand and I can |
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43:04 | . Okay. So here, um going back to the the layout |
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43:09 | like, the neurons and bug slide this one. So the cusp stands |
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43:18 | the and turnarounds. Not like inhibitory . Okay? Yeah, the |
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43:27 | the yellow god triangle. Like I them cups the you know, kind |
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|
43:32 | ah, triangular. There are the synapses and visitor, perhaps drive. |
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43:41 | for the fact is that most of excited Terry cells living there and have |
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43:48 | so most in this struggle Permodalan the so later that basically shows you what's |
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43:56 | these different into numerous where along the dried or so more axel wearily would |
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44:03 | targeting and projecting inhibitory synapses onto BCE care themselves. That has to do |
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44:11 | with with a lot of what the integrates and decides to send onto the |
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44:17 | networks. And it has to do a lot of input. Some of |
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44:21 | empezar coming in distantly, some of implicit coming in approximately so distantly with |
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44:28 | fire away in first there would be into the distilled and rights and proximal |
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44:34 | we call the ones that are close the solar. Keeping in mind that |
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44:39 | will make that decision. So most the fast and strongest integration and the |
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44:48 | some of the most influential decision makers the synapses that are located around the |
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44:54 | approximately around the soma. But we call this Paris somatic regions. Does |
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|
45:00 | answer your question? Um, but okay, So the top did |
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45:07 | say it was called apple? And the bottom called Near the stratum orients |
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45:12 | , Those of basil down rights. also you will have the arrows pointing |
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45:19 | those air, the accents coming So they depicted. And in the |
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45:24 | of the criminal sauces, just showing they're projecting their not showing the synapses |
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45:29 | cups yellow cups for the excited to because they are not there in the |
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45:35 | there Another network project on the are they so? And also the |
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|
45:40 | arrows are sorry. I have a of questions for on this example, |
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45:46 | arrows are showing that some of these are connecting onto other nearby regions off |
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|
45:55 | hippocampus. But you will not be for that detail of the information. |
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46:01 | let me clarify what you will have take away from the slide is that |
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46:06 | have, ah, incredible diversity Ah, new rods that diversity. |
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|
46:13 | this structure that we're looking at hippocampus in fact, even in the corn |
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|
46:17 | of diversity stems from the diversity in human very Selves. The function of |
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46:23 | local and heavens air into your answer control these excited to resells local, |
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46:30 | , the diversity of these inhibitor In order for us to some classify |
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|
46:36 | , we need to know their We need to know their 100 external |
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46:42 | that we need to know the firing and the internal staining markets. Then |
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46:48 | can identify individual sub process of these that these individuals, some classes of |
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46:54 | South by projecting on to different parts the criminal sauce, will influence with |
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|
47:00 | prominent all cell network. With this hippocampus network, well, community to |
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47:07 | distant leopards. Because thes perama, cells are not as diverse. They're |
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47:12 | to resells, but they're important because will project information that they will contact |
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47:18 | just on that works outside of the so that starting with the take on |
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|
47:23 | , it don't have to memorized 21 sometimes of cells. You don't have |
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47:29 | memorize all of the markers You asked TV and I think I responded. |
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47:37 | is around human. Uh, I responded twice. Uh, if |
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47:44 | want to know, CB stands for cold end in, um and, |
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47:53 | , when you wouldn't I wouldn't ask that detail. I think the take |
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47:56 | message here is a diversity of the , how you sub classify them and |
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48:02 | these inhibit the endurance of fact. projection. Vermont's. Okay, So |
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48:11 | we have these signatures and this is interesting slide that I like. And |
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48:16 | the slide depicts is depict a patch the new quacks and it shows |
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48:24 | lot of cells in this network in new cortical network and is just attach |
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|
48:30 | Palestine micro meters. So maybe it's cells across its ah 100 times 10 |
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48:37 | meters, maybe only once than to a patch of the cortex, and |
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|
48:42 | has shown here is the diversity off cortical neurons. The diversity off there |
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48:52 | behaviors in this case that the patterns the signatures of the action potential |
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|
48:59 | So you can be in the small and you can imbed electro nor patch |
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49:05 | to the any number off these And these cells can be excited to |
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49:12 | , or they can be inhibitory But these cells will have a different |
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49:19 | to the same stimulus. So the on the laughter called the D |
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|
49:26 | which stands for delayed stuttering ignorance, legs stuttering. There is the so |
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49:32 | because when they receive a positive influx car for stimulation, they respond by |
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|
49:41 | , I'm dropped an intermittent trains of potentials. So if Franken Illustrated would |
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49:48 | like, oh, the polarization signal well on. And so they're called |
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50:00 | if you give them more current, positive and put that delay decreases as |
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|
50:05 | can see here, and the delay be decreasing. But there would still |
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50:10 | stuttering. Then there are cells, example, at the bottom laughed that |
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|
50:18 | our BST, but these ah bursting type of cells. And what it |
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50:25 | is that when it receives the same as the cell in the top |
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50:29 | instead of having a delayed response in flat electrical line, been with trains |
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50:36 | actual potential started stuttering mug, it produced a Sinus sword like waves in |
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|
50:43 | member and potential in the changes in member of potential and produces bursts of |
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|
50:49 | potentials that a pretty uniform and repetitive of infertility. Then there are cells |
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|
50:56 | produce, uh, just continuous This would be the sound that |
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|
51:02 | uh, shown on the top arrived N a. C stance broke classico |
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|
51:08 | accommodating self. And that means that a little current and produces low frequency |
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|
51:13 | action potentials with more, Kern produces high frequencies of action. But that |
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|
51:18 | not the case with all of the in general. The number of action |
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|
51:24 | of the frequency of these action potentials the amplitude of the stimulus, the |
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|
51:30 | of the him. So this is way in which neurons encode information and |
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|
51:36 | information. Important information, strong lots of action potentials, I frequency |
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|
51:43 | firing of action potentials. Not important . Weak, impotent, out, |
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|
51:48 | few action for 10 songs. And let the rest until I get input |
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|
51:53 | in Austin abscess. And it's strong for me to get the polarizing to |
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|
51:57 | a that strain of actual potential. just illustrates it behind an incredible electrical |
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52:05 | off these neurons and neocortex in If a campus was just sentenced as |
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52:11 | example, but you will find an diversity off Salles neuron all across cortical |
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|
52:20 | , Needham Quarter call and CNN s how you can really start thinking about |
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52:27 | action potential trains to be snow and to each other is that these subtypes |
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52:33 | cells is different. 150 different sometimes sows is Interneuron so that we looked |
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|
52:39 | 21 different subtypes of Interneuron. what they do is they have their |
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|
52:46 | dialect is the same language that they the same, the same language off |
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52:51 | action potential also off the deep But it's 100 50 different dialects. |
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52:58 | 100 50 different ways off, integrating information as a neuro and producing 100 |
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|
53:07 | different patterns, signature patterns, and this is what we know so far |
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|
53:14 | the brain and the overall activity. off the individual activity off. Uh |
|
|
53:23 | . Off these networks. So off individual activity off the cells, that |
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|
53:29 | really a collected and combined activity. , far many different subtypes of the |
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|
53:36 | speaking the same language, different In order for the language to be |
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|
53:42 | , they have to synchronize. They to start talking in unison to be |
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|
53:48 | . My distant left works and they to produce a symphony. The harmony |
|
|
53:54 | is, uh these oscillations of people on hyper polarization, Czar excitation in |
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|
54:03 | tradition. So we have. incredibly complex networks have one language, |
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|
54:10 | different dialects. In a way, can also perceive it as a Morse |
|
|
54:15 | . The cell on the top left , did it that is, and |
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|
54:24 | cell in the bottom rice be It's like more skulled, right? |
|
|
54:33 | can decide for it. This is digital of action potentials. Is the |
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|
54:38 | code anything that happens underneath action These deep polarization is that don't generate |
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|
54:44 | potential changes of the number and potential do not generate action potentials. You |
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|
54:51 | view it as an analog. Two neurons in the way have two |
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|
54:55 | of operation. An alarm, other mode that decides whether two fine, |
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|
55:00 | potential or not, and the actual which is all or non event. |
|
|
55:06 | , in a way it's kind of a digital note 0 to 15 the |
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55:10 | potential. That means the release of at the synapse and either fluctuations that |
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|
55:18 | not produce action potentials do not resolve deep polarisation of release of the |
|
|
55:25 | Okay, so this is Ah, . When I was doing the postdoctoral |
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|
55:34 | that I was telling you and Julia George Mason University and you can see |
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|
55:42 | I am sin angled for electrodes underneath dishes are actually was the doing of |
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|
55:50 | quadruple recording from from brain tissue here these arms year shown in black, |
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|
56:00 | , one of them on the Burly. There's a micro electrodes |
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|
56:06 | so we have a very, very way, digitally and manually, also |
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56:12 | to manipulate using these electrodes and move in precise position onto individual cells. |
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|
56:19 | very sophisticated holders were sophisticated equipment, when you run out of very sophisticated |
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|
56:27 | . Some far, right? You see I had Teoh adopt a |
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56:32 | It was loosened. The laboratory loner , hold one of my electricity was |
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|
56:37 | . Thio more distantly located amplifier. this is the way that we in |
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|
56:43 | you can record concurrent activity interest Alya from the sauces. Is it? |
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|
56:48 | in? Was you Jim monitor? the electrical activity? Or in a |
|
|
56:53 | , you can say this is a in which you can, uh, |
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|
56:59 | is the way in which you um, listen, Dune Teoh dialect |
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|
57:06 | these different cells. Ah, some them are, uh, really, |
|
|
57:13 | interesting experiments that revolve around these. very technically complex experiments. But there |
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|
57:19 | a lot of fun to do as was a graduate student KOSDAQ and Little |
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|
57:23 | some graduate students here at the University Houston as well. But when push |
|
|
57:30 | to shove and you're really determined, need to do staff, you |
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|
57:33 | look for expensive pieces of equipment. look for last steady solutions. Teoh |
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|
57:39 | the most data that you can. the game and the brain is also |
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|
57:44 | data on glia. Now that we you know about the morphology of |
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|
57:51 | So I understand that they produce these , different electrical recordings. They have |
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|
57:59 | languages dialect. Now let's talk about glioma functions of prettiest mast. And |
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58:08 | their name originally means glue or glia means glue. For a long |
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58:16 | , it was thought that glee I served the supportive and insulated function to |
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|
58:21 | and that sort of about it. that is not the case. You |
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|
58:27 | very different sub dives off my of that are responsible for different things. |
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|
58:35 | responsible for cleanup for damage repair and of the grill sauce Michael glial |
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|
58:41 | actus scavenger cells of the cleanup local . Now they're also Astor sized are |
|
|
58:50 | for nurturance, mirror and I on and housekeeping chores. So they really |
|
|
58:58 | housekeeping choices really regulating synaptic transmission, , radio glial cells. They guide |
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|
59:05 | migration and process out girls on Real stars can also service neuronal real |
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|
59:17 | . So the actually real cells that precursors to what is going to become |
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|
59:23 | final subtype of glial cells or in , Leo sauce release growth factors, |
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|
59:31 | those are very important for maintaining and the slow growth off the brains to |
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|
59:37 | the support of the brain. Synapses plasticity, Astra size real sauce are |
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|
59:44 | part of the world brain barrier, they're part of the filter essentially, |
|
|
59:49 | decides what crosses between the blood into brain. Most importantly, they're not |
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|
59:57 | their act if they actively control soon Genesis synapse numbers synapse function, Synapse |
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|
60:06 | , which is snapped. The Genesis synaptic plasticity. So a lot of |
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60:11 | growth the factors control synaptic plasticity. Glee also are responsible for release off |
|
|
60:21 | inflammatory sytem kinds, doing year about side to kind storms or inflammatory |
|
|
60:29 | Information. In the brain. It usually abnormal control off site, a |
|
|
60:35 | release and inflammation that stems from that the brain. But glia. Unlike |
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|
60:43 | , Deunan produce action potentials. They on produce action potentials, and instead |
|
|
60:50 | communicate with these slow or calcium right? Somehow, no. So |
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|
61:00 | talk about different real sense. Let's about first that insulation and protection In |
|
|
61:05 | peripheral nervous system. You have Schwann again. We have central nervous |
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|
61:11 | Emperor forever system. So we have cells that Miley and accidents in the |
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|
61:17 | nervous system. The Schwann so is single segment of the Mylar axle. |
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|
61:24 | in between the smile and Jackson's, have knows of ranveer. They're separating |
|
|
61:31 | now the bottom you have Central Nervous , or CNS and and C N |
|
|
61:38 | . You have a little Denver sites down. Besides, unlike Schwann sauce |
|
|
61:44 | the PNS in the CIA, NASA dander sides have multiple arms that come |
|
|
61:50 | these 1000. Each one of these of processes becomes a separate segment, |
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|
61:57 | a separate segment violence sheets segment and one only go down beside produces many |
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|
62:06 | , and it can produce many segments many accidents of different neuron. And |
|
|
62:14 | one of the distinct wind, just distinct issues between the mile a nation |
|
|
62:20 | the PMS versus the CNN. So the, uh, last, what |
|
|
62:29 | have is a picture of the top them. Exercise or exercise fill most |
|
|
62:36 | the space in the brain that is occupied. My neurosis of blood vessels |
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|
62:41 | Astra size will have most space, they will have very complex asked acidic |
|
|
62:46 | and there will be sending a lot the Kallstrom signal Studi streets of siphoning |
|
|
62:53 | neurotransmitters. And I asked you in of these trees are very much actively |
|
|
62:59 | in control. What? Bring Barry control off synaptic transmission. So, |
|
|
63:07 | , neurotransmitter level so as well as in the brain in the centre |
|
|
63:12 | Now, if we're talking about my nation off, you take him from |
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|
63:16 | bottom last. Do you have an off a very different cell, of |
|
|
63:20 | , which is illegal. Dunder side it Underside again is wraps around and |
|
|
63:27 | d smile and she's that air separated knows of run, veer, note |
|
|
63:32 | run There is a side where the potential is gonna get regenerated so that |
|
|
63:37 | same action potential, the same amplitude action potential that was produced with the |
|
|
63:42 | of the soma is also regenerated. each note of are here so that |
|
|
63:48 | amplitude of the actual patricians preserved all way to the synaptic terminal to the |
|
|
63:55 | terminal to where the action potential will neurotransmitter classical fusion and neurotransmitter leads. |
|
|
64:04 | , if you have violent nation there is several, uh, Prodi |
|
|
64:13 | that are involved in violent compaction because can imagine. It's a pretty sophisticated |
|
|
64:20 | of one cell's membrane of processes wrapping around that, the one growing and |
|
|
64:27 | around that'll. So you have Ah, seven more related Prodi Insee |
|
|
64:35 | , basic prone audience of control. live action and examples of these are |
|
|
64:42 | an associative black, a protean mag is responsible for salads, sell recognition |
|
|
64:49 | initiation of my elimination. So these Brody is will serve a different function |
|
|
64:55 | the case of mag is really initiating myelin ation process living not a style |
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65:02 | recognising another cell Uh, you can problems. And in my island nation |
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65:11 | , and, uh, of inflammation and De Milo nation will cause |
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65:17 | significant problems. We're not really gonna about, um, injections. And |
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65:23 | for my life is But we will PMP two is another perform island |
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65:29 | which is apparent. Charcot Marie tooth . Sorry, this isn't yellow, |
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65:33 | you can see very clearly. But the name of the disease. Charcot |
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65:38 | Tooth disease and on the right with shown is a fact that deem island |
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65:48 | is one of the features of another disorder that you should add to your |
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65:53 | . And that is multiples. Um de Milo, Nation of accents |
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66:00 | multiple sclerosis happens. And the It happens to the central nervous system |
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66:07 | the central nervous system. In the of the mass, in the central |
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66:13 | system, you have the mile a off different axles. And therefore, |
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66:20 | you think of multiple sclerosis depending on region of the brain that is most |
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66:25 | by deem island nation, you will a stronger impact on that particular |
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66:31 | So if it is the, loan corn tax, where you have |
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66:36 | Milo nation you may experienced significant motor may experience, uh, treacherous. |
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66:45 | it is in certain parts of the that controls emotions or memory, you |
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66:52 | experience memory loss. You may experience bows and emotional mood swings. Show |
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67:00 | sclerosis does not just affect the and this is one of the features |
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67:05 | multiple sclerosis is tremors. So what know about the masses that you can |
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67:13 | or mass, but causing a mutation chromosome 18 was one of the |
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67:18 | And when you cause a mutation and um, 18 you vote tremors and |
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67:26 | sometimes convulsions, muscular convulsions, in the these animals and wish you |
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67:33 | a genetic you saving mutation, which need to have to paddle wheels. |
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67:38 | it's really a chromosome. Any It's a recessive a mutation, |
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67:45 | recess of fina top that is necessary order. Teoh Evoke was called a |
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67:51 | ver tomorrow shiver miles model off multiple . So in Schumer, muting of |
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68:00 | riding with the shown is a normal with cross sections of accents showing these |
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68:06 | think black rains throw blast rings and of my ligation around the accents. |
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68:14 | in the middle thought of Micrografx, see shiver, immune, mint and |
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68:20 | meat that has this chromosome 18 mutation than have very scant, very abnormal |
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68:27 | island nation of the accidents. You partially rescue the FINA time, and |
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68:35 | can partially of rescue a shiver. these minds will literally be shivering and |
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68:43 | sometimes convulsing to Now if you transplant animal not normal, gene, it |
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68:51 | actually improve. My nomination wants to . So again. Sorry. So |
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68:56 | partially rebuild the myelin nation. If do essentially a genetic manipulation here, |
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69:06 | genetic trance faction. Uh, these transgenic mice, of course, that |
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69:11 | probably familiar with them, So in case, it's, ah, it's |
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69:15 | mutation of That's a knocking about ob that causes the stretch mechanic miles that |
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69:20 | the sugar amounts and then partially be with trance factor Gene. So, |
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69:28 | , as a multiple sclerosis, by way, is very important. You |
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69:33 | adding that information is an auto immune , so multiple sclerosis is upon immune |
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69:41 | . That means that your own body recognizing for some reason starts recognising its |
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69:48 | milon. This is a foreign invader stars destroying its own mile, so |
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69:55 | an auto immune disorder. Um, other common disorder that you see with |
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70:02 | dysfunctions is shark off marry tooth. this case, you were talking about |
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70:08 | protean PMP, which is perfect. my eliminating pretty and PMP 22 and |
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70:16 | have too much. There's too much the genetic expression of that. P |
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70:22 | . V 22 eyes actually duplication Geum Promise own 17 on, and |
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70:31 | can measure that on the writer have test tubes basically that the charges of |
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70:37 | charts showing that PMP too as being , and that there is a much |
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70:44 | expression of promise on the team that associated with the PMP to there's a |
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70:51 | than high expression of that protein replication the gene and high expression of that |
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70:57 | due to duplication of Eugene. And a developmental condition that causes impaired gait |
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71:04 | bodily deformities. So, uh, is no cure for sure cannot marry |
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71:11 | . What happens because this abnormal Meilin off the peripheral baby with normal this |
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71:21 | talking about peripheral Milon program and, opposed Teoh and Mass, which is |
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71:27 | in this in the CNS. In case, this is in the |
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71:30 | So we're talking about Schlamme cells that's starts apparent mile the nation when it |
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71:37 | to his abnormal stimulation of muscles. if you have a normal stimulation of |
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71:43 | , bones develop and grow. There deformities in the bone structure that caused |
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71:49 | bodily deformities very commonly in the lower in the legs and causes impaired gait |
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71:58 | the solution really, as if you about the genes application and you detect |
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72:03 | on the Charlotte married to disease than can place the developing individual into the |
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72:11 | to perfect printed T essentially prevent the information to prevent the boned information. |
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72:19 | Teoh hopefully help with the gate because lot of the individual civil have |
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72:25 | um in problem gains, swinging from side to the other side and carrying |
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72:32 | legs and a very, very uncomfortable . Eso The more we can figure |
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72:37 | about early interventions and recovered from this . Obviously there's now medications, but |
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72:44 | braces and with rehabilitation and physical Uh, this is this is really |
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72:52 | . This is ah, good summary that I'm gonna leave with today's |
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72:58 | Actually, we're gonna offline. All this sausage were discussing. So we've |
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73:04 | about illegal down her sides on illegal . Besides, our Meilin aging cells |
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73:09 | the central nervous system, where you see different legs or processes of these |
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73:15 | under size will be responsible in forming individual violence segment on multiple girls you |
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73:23 | ostracised or ostracised on the right here shown in contacting the synapses of endurance |
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73:30 | well as the Camp Hillary's Teoh. indicates that ostracised are involved in |
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73:36 | brain barrier and regulation. What comes the blood as well as in regulation |
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73:41 | synaptic transmission. My googly also said smallest south in the network and they're |
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73:48 | most mobile cells in the network. Michael Glial cells get activated during |
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73:54 | They get activated during a physical injury doing information, and they actually can |
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74:02 | across brain tissue. So if, , I manage, what I'll do |
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74:09 | I'll try Teoh find a movie about with real cells for years. Just |
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74:16 | me one |
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