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00:02 | Okay, So today we're going to talking about neurons and glia and we'll |
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00:07 | on this for the next couple of . So neurons comprise about 10% and |
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00:14 | comprise about 90% of the total brain population, neurons are like chips. |
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00:23 | the chocolate chip cookie. And I ask is a chocolate chip cookie possible |
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00:32 | chocolate chips. No, but is cookie possible without the dough? Just |
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00:41 | chips. No, it's called So in order to have the brain |
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00:50 | glia which traditionally was referred to supporting structure network. And from greek glia |
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01:00 | the glue kind of gluing the networks to now knowing that glee are actually |
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01:06 | intricately involved in regulating brain function. the neurons are really responsible for the |
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01:14 | of the fast action potentials and the and that transmission in the brain. |
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01:20 | other thing here is the game in brain is mainly in the stain like |
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01:24 | rain and the plane in spain is in the plane and that is as |
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01:32 | recall from previous lectures, you really visualize sells individual neurons unless sustain |
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01:40 | You cannot visualize networks unless sustain But we also discuss a technique and |
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01:46 | contrast technique that does allow you to neurons at least there's so most if |
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01:51 | their processes to a great extent without any stains. And as we talk |
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01:58 | neurons and glia, it's a it's topic that obviously is a review and |
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02:05 | levels because neurons are just like other and neurons will have, the cell |
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02:13 | will have the nucleus will have the machinery and the nucleus it will have |
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02:19 | organelles surrounding it mitochondria which is very , has a lot of energy production |
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02:26 | neurons and in the brain we have desperados you have holly robinson complexes. |
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02:34 | have rough and the plastic ridiculous smooth the plastic ridiculous uh where there is |
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02:41 | of calcium inside the south and inside Solich of free calcium. And the |
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02:46 | of plasma neuroses very tightly regulated because not just in the ion that's also |
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02:51 | messenger inside the south. And there some unique aspects that you're observing here |
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02:57 | the neurons such as for example this Philip and myelin sheets. These white |
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03:06 | myelin installation like that surrounds these And this zone is where the action |
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03:15 | is produced. So all of the is integrated from all of the different |
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03:22 | of the sell by the selma. if the cell is excited enough or |
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03:28 | enough input will generate an output which in the form of an action potential |
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03:33 | gets generate an accent, initial hill , accident initial segment here and then |
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03:40 | travels down the myelin native access once reaches its terminal down the mile undated |
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03:47 | into another neuron. That actual potential gets generated here is the same attitude |
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03:53 | external terminal as it was at the of its initiation near the soma. |
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04:01 | this action potential then results in the polarization of external terminal and release of |
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04:05 | neurotransmitter that neurotransmitter. Well done. synapses will monitor them rise and good |
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04:12 | synaptic projections going onto the selma's and going to be a release of neurotransmitter |
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04:18 | posson optically. These neurons will then receptors and then your expands is also |
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04:26 | a unique feature two neurons and we'll why they are important also uh in |
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04:33 | of developmental mental litigations especially this is that's very basic. You have |
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04:42 | N. A. That gets transcribed RNA are in a gets transported from |
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04:51 | and there's splicing of RNA that takes . And during the splicing you splice |
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05:01 | the in trance. Okay. And leave only the exxons and you create |
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05:09 | messenger RNA. And so you have variants and supplies variants can be both |
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05:14 | and pathological slight variations. And splash is what makes us slightly different and |
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05:21 | brain cells and processing capabilities. problem capabilities of these cells and also |
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05:29 | variants. Could be pathological meaning if message is not sliced correctly could be |
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05:34 | a protein that has a slightly wrong and that protein and the wrong |
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05:41 | This project could be either contributing underlying disease because that protein could be a |
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05:48 | channel that's in the plasma membrane Organelles and the plastic particular ribosomes and five |
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05:57 | complexes uh messenger and a and then proteins that get translated and can either |
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06:04 | santa's olic or free floating or membrane programs and we'll discuss a lot of |
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06:11 | associated proteins because these are membrane receptors receptor channels and voltage gated channels that |
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06:18 | study at the level of the It's a post genomic era. And |
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06:24 | we can utilize these micro racer, micro race that allow us to describe |
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06:34 | have a son of a bird's eye of all of the genes. And |
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06:39 | can have up to 30 or 40,000 that are encoded within this microbrewery. |
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06:47 | you will walk around the campus and will see advertisements for 20 cents per |
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06:55 | pair or a dollar for whatever basis synthetic DNA. And because we know |
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07:03 | code. So we can now lay code inside these wells inside this microchip |
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07:11 | really, really microscopic wells. You to use a microscope visualize them. |
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07:17 | the advantage of that is now you say, Okay, I have 40,000 |
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07:22 | of interest. I'm going to let's say this. 30,000 40,000 |
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07:28 | I'm gonna uninterested in these and I'm to see what this gene expression is |
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07:35 | the development. Let's say how changes in the developed. You can ask |
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07:40 | question, I want to see if is genetic changes in the brain that's |
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07:46 | versus non collective brain that has alzheimer's is not an Alzheimer's disease, you |
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07:54 | use animal models, you can use um tissue of course if it's resected |
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08:02 | the surgery uh potentially from a human it's much harder to obtain those |
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08:09 | And the sample size is usually very . But you can have analysis in |
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08:18 | normal brain and would say brain that a pathology. And the idea here |
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08:24 | that you will then take em RNA wine one and M RNA from brain |
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08:30 | and you will apply it and jeanne reduced expression and brain to will appear |
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08:36 | gene with reduced expression and bray juan appear green gene with equivalent expression and |
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08:43 | in both brains will give you a signal. It's really a fluorescent yellow |
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08:48 | . What is the signal on the slide is essentially if there is a |
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08:53 | of that gene it will have a sequence to the synthetic piece of the |
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08:59 | that you placed inside the well. a lot of it will buy instead |
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09:03 | a like to exactly matching very sophisticated piece. So it matches a lot |
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09:10 | it will bind. So you have over expression and you will compare and |
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09:16 | of the genes will go up and of the genes will go down and |
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09:21 | you will say okay when I look I compare normal brain versus a pathological |
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09:27 | disease. Brain I see that there changes in 2000 genes and say it's |
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09:38 | . Well okay so you've gotten some then you're gonna say okay some of |
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09:43 | genes went up by five times. then I see that 20 genes went |
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09:51 | 20 times. Who said, oh must be important. That wants to |
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09:55 | . The mouse must be somehow contributing disease. Always make this job. |
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10:01 | your mentor tells you that this is genius study in the lab out of |
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10:04 | 20. So you're going to pursue one and that's where you kind of |
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10:08 | to drop your research because the mentors pay for the research too. But |
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10:17 | 24 change Mean that it's most important five whole change. We don't know |
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10:27 | , biological systems. Uh Central nervous is a nonlinear system That poll change |
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10:35 | be extremely important as compared to 25 . We also don't know which change |
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10:40 | place far. Maybe this five ball was there and then the 25 phone |
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10:47 | followed in other genes. So you , you don't get answers to these |
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10:52 | . But then you know, you you read information, let's say you |
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10:57 | honed in on those 20 genes that up 20 times. You read the |
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11:02 | , you read about epilepsy, you , you know, always talks about |
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11:05 | 23 genes. Now you're going to some additional studies in these 23 genes |
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11:11 | find out maybe what part of the they're really over expressed in what sells |
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11:16 | subtypes of cell sage emerged first. what point of pathology? There are |
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11:23 | expressed at the beginning the end after all of these things. But this |
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11:28 | a really good birds eye view of going on on hundreds if not thousands |
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11:35 | genetic changes inside the brain. And is a powerful tool that can be |
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11:39 | in studying the neuropathology as well. under plastic, ridiculous. Um |
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11:47 | protein folding and calcium regulation old You have post translational processing and protein |
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11:56 | . That's what is responsible for when proteins come out and they get sorted |
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12:00 | and go to their final destinations. is very important. So is the |
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12:05 | cycle and you'll have to memorize the cycle. Just kidding because even if |
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12:11 | do you'll forget it and I have do it at some point. I |
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12:15 | it. There's a certain aspects that very important to remember always about the |
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12:22 | production inside the south. And please talk about chemistry professors that I said |
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12:27 | about scratch cycle today. So ATP generating energy and like I said, |
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12:34 | brain is about 3% of the total of the body but it consumes over |
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12:40 | of the total energy. So it's consumes a lot. It's a small |
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12:46 | that sucks a lot of energy. operating outside of the delivery. Um |
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12:51 | operating in a non linear fashion and in stores energy sources protein and sugar |
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12:58 | get turned into hieratic acid Through the process produced 80 p. and carbon |
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13:08 | co. two and this https and important for different processes inside nerves. |
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13:15 | so this is as deep as we're to go into this. But keeping |
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13:20 | mind also reminding you that 80 And like other organ Alice is a |
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13:25 | membrane organelles that has the inner And these very uh unique kind of |
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13:32 | imagination snake like number niss formations that referred to Christie foster lipid Beiler is |
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13:43 | plasma membrane fossil liquid by layer contains audience contains proteins that are channels. |
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13:53 | means that these are the proteins that allow the passage of ion student small |
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14:00 | . Then there are some proteins that trans membrane proteins. That means they |
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14:04 | both extra cellular side of intracellular side are not channels but they may be |
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14:10 | to other proteins inside the south. this is would be an example of |
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14:14 | protein coupled receptors. So in this both of these the this this one |
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14:20 | the middle and this one is a . They can both be receptors of |
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14:25 | . They can both by the chemical them. One of them will conduct |
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14:29 | through it and another one will not anything through it. But instead will |
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14:35 | that message to the interconnected you've heard complex then you have carbohydrates that are |
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14:43 | the south and obviously black of proteus the core of the plasma membrane is |
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14:49 | possible lipid bi layer. We have fatty acid non polar. I drove |
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14:58 | . They're afraid of water tales. the polar hydra filic heads that are |
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15:03 | false statement glycerol and the possible lipid layer is interspersed with the cholesterol |
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15:11 | And so if you were to take lipid molecules and just throw them in |
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15:16 | equally solution that would actually aggregate themselves this Byler and typically form around shape |
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15:23 | mycelium which is essentially the basis behind the organ Alice and even the whole |
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15:31 | with the cell membrane and underlying here this uh rather dynamic possible lipid structure |
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15:43 | because it actually rearranges and the molecules are embedded and even trance membrane proteins |
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15:50 | move through that possibility by layer and very fascinating We can move micro meters |
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15:56 | milliseconds. The receptors that are not in synopsis can move into the synopsis |
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16:02 | the membrane. They don't have to be shuttled through the side of plasma |
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16:07 | some way and inserted but they can travel through the membrane at very fast |
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16:13 | and the overall structure of the cell . And if you recall the doing |
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16:20 | that we looked at, they had the different shapes is supported by the |
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16:27 | sadness, chemical elements. So in following slide we look into the sinus |
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16:32 | elements. But you can rearrange the side of skeletal elements and that would |
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16:37 | like rearranging the beams and supporting uh of the wall and moving it into |
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16:47 | different part of the house and now have a different shape to the room |
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16:51 | the house, you rearrange the side skeletal elements and the plasma member and |
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16:56 | the drywall that you put around and you have a different arrangement, different |
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17:00 | house. Always like to show this on fluid mosaic model is pretty basic |
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17:09 | I like it because it just reminds that it's a dynamic structure and we |
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17:15 | should view and understand it is a structure. When we talk about neurons |
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17:20 | the brain, neurons that are very and very dynamic at producing their electrical |
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17:26 | chemical communication. Uh huh. Set and being in the world. It's |
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17:34 | shells history from your team. It's pretty much Yeah. And in my |
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17:46 | and regroup a member naturally settled in because their jails rebuild water as their |
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17:56 | , attracted, doing some cholesterol and few carl hybrids. And you have |
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18:02 | basic structure of the plasma membrane within lipid molecules. We also find different |
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18:11 | which do various things for to sell instance, they receive signals from the |
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18:17 | outside when they transport nutrients in So major proposes the membrane with a |
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18:25 | of different limits carbohydrates approaching and these pronounced stationary. They constantly move within |
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18:36 | structure. We were in changing your . Yeah. The survival of all |
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18:44 | rests on this veil of material. . Suddenly we're just to politics |
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18:55 | So it's a it's a pretty simple but it illustrates exactly the point that |
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19:01 | trying to get at about the fluid the fluid, mosaic marble. It's |
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19:07 | mosaic mosaic of proteins, carbohydrates, of proteins, cholesterol. And it's |
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19:16 | changing mosaic. It's a dynamic Is mosaic, not just because it's |
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19:21 | by fluid, but because it actually changing. When we look at the |
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19:26 | side of skeletal elements, we have subtypes of micro tubules and your filaments |
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19:32 | intermediary filaments of micro filaments. The tubules are the largest set of |
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19:40 | allowing us about 20 nanometers in The neural filaments are the medium size |
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19:46 | of skeletal elements and the micro filaments the smallest ones. And they're comprised |
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19:53 | the acting molecules. Um and these especially active molecules, have the ability |
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20:03 | make longer change. Prelim arised diploma were broken up into shorter change. |
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20:10 | as they do so, they can rearrange themselves underneath the hospital, it'd |
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20:16 | plasma membrane and give the plasma member a different shape and different dynamics for |
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20:22 | fluid mosaic and interactions. If you on the right here. This is |
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20:28 | electron microscope picture that's taken through an that has been sliced through lengthwise. |
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20:37 | if you just took a cucumber instead cutting it in half, you sliced |
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20:42 | alone flies then with you seeing here clearly on the outside edges of the |
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20:50 | of flies and the plasma membrane is sheets of mylan that surround that acts |
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20:57 | and inside the acts on. You , seeing these would look like kind |
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21:01 | like spaghetti ease long, stringy spaghetti looking things. Those are the micro |
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21:08 | . The micro tubules are very important external transport for serving as a highway |
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21:16 | things to be delivered from the soma the peripheral vice versa from the peripheral |
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21:21 | aspects of the cell, into the into the selma. This is an |
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21:28 | of a fibroblast cell and what this illustrates very well is yellow is the |
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21:38 | turbulent molecules is micro tubules. Blue acting micro filaments and purple, staying |
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21:49 | as a nucleus. This is a glass. Al It's a beautiful stain |
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21:54 | shows that surrounding the nucleus immediately surrounding nucleus of the core of the |
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22:02 | If you want to call it the of the house, you have yellow |
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22:09 | on micro tubules and as you go to the outer edges of the cell |
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22:16 | more so outside of the selma using molecules and that just supports the idea |
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22:25 | the smallest sinus chemical elements would be the support for the outer edges and |
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22:33 | determining the outer shape of the plasma and their rearrangement underneath. The possibility |
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22:41 | Beiler will also cause the change in shape of the foster the Tyler at |
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22:48 | plasma membrane. So in this next we start talking about Alzheimer's disease and |
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22:56 | understand why we talk about Alzheimer's disease the context of the sinus chemical |
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23:04 | But in general I had this slide I thought in this presentation but it |
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23:11 | and I use a different slide um I think is on your blackboard |
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23:19 | but I'll make sure it is that want to talk about Alzheimer's disease in |
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23:23 | case the hallmarks pathological hallmarks of Alzheimer's . And this is what I would |
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23:29 | for you all to do this If you're a good student, you're |
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23:34 | notes and you're taking either notes on or you're taking them digitally. During |
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23:43 | course of the semester, we will about six, maybe seven, maybe |
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23:49 | neurological disorders. And when we talk these disorders today, for example, |
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23:54 | will talk about Alzheimer's disease and we certain aspects of Alzheimer's disease today. |
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24:03 | at the same time, uh we come back to Alzheimer's disease when we're |
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24:11 | a single cooling signaling and synaptic So what I usually recommend is that |
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24:18 | we have a notebook, you dedicate page or in the back of the |
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24:24 | , you basically dedicate uh you basically a page. You dedicate a page |
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24:45 | each of these neurological disorders and you do it at the end of your |
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24:49 | or you can dedicate a new digital for or you can just dedicate one |
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24:56 | as you go through your notes. I recommend to set it aside because |
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25:01 | keep coming back and talking about these throughout the semester as we learn new |
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25:07 | in neuroscience in general. But today going to start developing some of the |
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25:12 | or maybe some of the language that's basic, but maybe you haven't thought |
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25:17 | before and some of the language that's clinical. I would say to that |
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25:23 | you haven't thought about it before. . So let's start with. This |
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25:30 | I've asked this question yesterday in class I came completely prepared. I |
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25:36 | how prevalent this Alzheimer's disease? And is Alzheimer's disease? Alzheimer's disease is |
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25:41 | form of dementia as a neurodegenerative That means that neurons degenerate is a |
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25:50 | disorder? Also because it's a neurological is a disorder of the brain. |
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25:57 | I said, what is the Sea of Alzheimer's disease. So this |
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26:07 | the first term prevalence of the And what is the prevalence of the |
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26:11 | ? How common is the disease? commonly does this disease occur? Have |
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26:15 | thought of how common the South Do you have any friends in class |
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26:22 | have Alzheimer's disease? Do you have grandparents or their friends that have Alzheimer's |
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26:30 | ? So now you start thinking well what age is this? A is |
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26:36 | a disease of the young. Is a disease of the middle ages. |
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26:40 | a aging? It's correlated with Is this part of normal aging to |
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26:48 | losing memory and good demented and have disease. No, maybe to lose |
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26:54 | skills, certain agility, certain aspects members. Okay. But what we're |
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27:00 | to talk today about is something that to severe pathology in the brain. |
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27:04 | , so far it's problems. And asked that question in class yesterday and |
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27:10 | had a very good student and she looking it up immediately as I was |
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27:15 | me and she said In the ages 71% of all, 70 years of |
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27:20 | of older Think she said it's about or 15%. So here is your |
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27:28 | of your answer. What happens at age? Are you more likely to |
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27:34 | Alzheimer's if you live to 19? the answer is yes, That number |
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27:39 | up very rapidly out. But I exactly know what it is. And |
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27:44 | not asking you to to remember this the exam. And I'm asking you |
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27:50 | think about the concept with prevalence. is the disease prevalence? The disease |
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27:56 | starts increasing after 50 years of there's a curve that's enough for curve |
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28:01 | the older you get, the more you are to develop Alzheimer's disease. |
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28:05 | over 90 years of age is it very, very problem becomes in tens |
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28:12 | the percentages. So now. Is it? Uh, only in |
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28:22 | United States. Yeah. And why I ask that? Because there's a |
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28:30 | of certain disease in one geographical Ethnic Cultural Location vs Another one. |
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28:39 | could be a higher incidence of epilepsy certain countries and low incidence of |
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28:45 | It's in other countries, nations, people that use some of the foods |
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28:52 | that are inherently anti inflammatory. A of the political see, research has |
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28:59 | to why there's lesser prevalence c of incidents and opulence incidents in India is |
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29:06 | under reported. Is there something going ? It's probably both. But curcumin |
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29:12 | is being researched as a potential dietary . It is normal for for local |
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29:21 | that actually could be beneficial, preventative reducing a certain disease. Okay, |
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29:30 | , uh symptoms of the disease? is a symptom And what are some |
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29:37 | the Alzheimer's symptoms? So the difficulty hasn't put Russia and Alzheimer's |
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29:46 | You have a progression of the distance the early symptoms of the disease could |
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29:51 | loss of short term memory. Disorientation anxiety. Mhm. And so when |
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29:58 | come into the doctor's office, you say I have a clock in my |
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30:03 | . My neurons are dying. I feel it. I have a pain |
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30:08 | my hand. That's my symptoms. know, I I can't hear anything |
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30:13 | my right ear. That's a symptom not a cause so early Alzheimer's symptoms |
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30:20 | mild alzheimer's symptoms is, like I , memory loss, anxiety, disorientation |
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30:25 | them. What happens later? You the formation of a pathology and the |
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30:33 | becomes more with progressive, becomes worse worse pathologies of that thing and that |
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30:42 | causes the progression of the disease and understand why in one second we'll come |
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30:50 | to more severe symptoms. But let's about what is technology. You want |
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30:56 | get down to the underlying causes of symptoms, right? So if somebody |
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31:06 | forgetting or somebody has anxiety or depression is also part of the Alzheimer's disease |
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31:15 | you lose touch with the society and ability to interact with people which isolates |
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31:21 | further On the pathology level, there two important hallmarks at the cellular |
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31:30 | One of them is the formation of amyloid plaques. We also refer to |
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31:34 | as beta amyloid plaques or senile plaques Alzheimer's flax isn't that aggregates proteins that |
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31:42 | abnormal aggregates in the brain. They calcify and they start ruining the local |
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31:49 | of the network. If the accents located close to these flags and accident |
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31:56 | segment and acts on Philip will be and won't be able to produce action |
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32:03 | . So on the outside of the you have the formation of the |
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32:09 | But those plaques on the outside obviously pitching and intruding on physically. The |
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32:18 | form in certain parts of the brain the campus, certain parts of the |
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32:23 | . In early Alzheimer's pathology where some platform then they migrate throughout the whole |
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32:31 | . That's another weird thing is that kind of like think they throughout the |
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32:34 | brain and at advanced stages of the will have a massive invasion throughout the |
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32:41 | . Uh these amyloid or senile flags the south. You have another pathological |
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32:50 | hallmark, which is Nurofen brutally So remember I showed you the |
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32:57 | These, I said that those are tubules. So the spaghetti is and |
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33:01 | micro tubules are being used for delivering to and from the cells. So |
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33:12 | . You go back to this presentation , you have molecules and you have |
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33:26 | klasnic transport and you have those micro and other side of skeletal elements that |
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33:32 | to be precisely arranged in order for micro tubular highways to try to transport |
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33:38 | in the correct way At the slow , which is 1-10 mm a |
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33:43 | Fast acts of plasma transport, which about a meter. Day. Uh |
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33:49 | millimeters today versus a meter. There have two types of transport, interrogate |
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33:56 | and retrograde transport interrogate transport. You have these little engine proteins like arms |
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34:02 | the cartoon like fashion that will pass it needs to be uh protein or |
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34:09 | from the selma interrogators from the soma the peru for And then on the |
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34:17 | hand, down in the middle of class, I'm sorry, I'm |
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34:20 | I can't stay here. Can you outside please? You have the same |
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34:27 | ? Okay, sorry, no Um I leave the door opens. |
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34:35 | guess it invites some guests to try use the computer because if they see |
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34:41 | there's a hallway student and having seen anyways interrogate transport, I just got |
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34:50 | tangled up and retrograde transport, retrograde . You'll have the dining and molecules |
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34:58 | will go the opposite direction from the into the sun. So now going |
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35:06 | to the Alzheimer's technology when you have side of skeletal elements and the tangle |
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35:13 | that ruins the transport of goodies inside south of communication within the stuff. |
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35:20 | you can say the tangles are affecting inter cellular early and then to cellular |
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35:28 | and transportation. And the plaques are extra cellular and intracellular communication and connectivity |
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35:39 | the networks and the plain wool Uh and unfortunately, you cannot really |
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35:47 | the early pathology of Alzheimer's disease and cannot really visualize the plaques or some |
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35:53 | markers that are associated that you can up and the person is either susceptible |
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35:59 | is developed. The flax and the diagnosis for Alzheimer's disease comes postmortem. |
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36:07 | a pathologist can look at the brain in severe advanced stages of the |
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36:16 | the brain would be written by the and tangles. The cells will be |
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36:23 | neurons and accents will stop communicating and the signals and at the gross anatomical |
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36:31 | you will see a shrinkage and loss gray matter in particular but also white |
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36:38 | gray matter is the loss of them bodies And then some of the white |
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36:44 | fibers that still remain. There is there are more original and the violence |
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36:50 | remains around them so you can still it. But this is the advanced |
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36:56 | Alzheimer's disease. Brain on the right to normal brain structure here as the |
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37:04 | uh So this is severe pathology. happens when you have these flags and |
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37:14 | all over your brain? It's not that you're disoriented. Then you get |
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37:21 | blue alert saying an elderly personal after and they haven't been seen for a |
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37:26 | . It's usually they went to grocery the spatial disorientation, the campaign in |
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37:30 | home. It's time disorientation. So it's you know, if it's a |
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37:36 | somebody thinks at six a.m. And six And wondering why everything is closed and |
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37:41 | all the people are, It happens and then it gets worse. Brain |
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37:48 | communicate things don't register short term memory going first, then it starts affecting |
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37:54 | term memory. Then you start losing ability to be lucid in this |
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38:00 | You're almost like stuck in your own that cannot interpret things from the outside |
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38:06 | and then it starts shutting down vital , eating, swallowing, drinking, |
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38:16 | , breathing and you're done. So is this is the real real nasty |
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38:25 | . And then you will say okay that was the therapy so everybody you |
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38:30 | anxious enough can you stop all There's no cure for Alzheimer's disease. |
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38:34 | only therapies that will slow down the of Alzheimer's disease. But there is |
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38:41 | character. So what does that That means that you can only hope |
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38:49 | the person lives longer and when somebody Alzheimer's disease, they may also have |
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38:55 | comorbidities. That's another thing in the capital. What's the co morbidity? |
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39:01 | you have Alzheimer's in your 70 some old you're 50 more times likely to |
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|
39:07 | epilepsy. That's a co morbidity. not always get affected the main |
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|
39:13 | Alzheimer's disease or comorbidities epilepsy. Can person die from epilepsy? Yes it's |
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39:19 | morbidity because co morbidity is usually uh the progression of not only disease but |
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39:28 | shortened the lifestyle. Uh huh. inability to move your motor function because |
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39:36 | impacted your motor centers, the plaques you fall and you break your |
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39:41 | So now you have all sorts of breakage problems and uh bone problems. |
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39:49 | the central is also co morbidity, of social interactions. You can do |
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39:54 | as co ability to try not to to anybody for two months. I |
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39:58 | understand who you talking to or every seeing a person and thinking that that |
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40:04 | is a new person but it's actually same person we've been seeing. So |
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40:11 | stops the progression of the disease and of the therapy right now targets a |
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40:16 | Colin system for the energetic system and a single clothing inside the synopsis. |
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|
40:26 | you will say ah so there is there. Yes. So these flags |
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40:31 | kill a single Cobain producing neurons in brain. And that seems to be |
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40:36 | of the major targets in early to onset of Alzheimer's disease is the death |
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40:42 | these neurons in the brain that produced single goal and not all the neurons |
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40:47 | the brain produced a set of You understand which ones? And that's |
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40:52 | I asked you to leave some space we will talk about Alzheimer's medications when |
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40:57 | in the second section, when we about a set of Comey neural transmission |
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41:01 | you'll be able to add on to . And it's really for you because |
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41:06 | not just to answer the exam it's for you at the end of |
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41:10 | semester to look at that page that start at the beginning of the semester |
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|
41:14 | say, okay, God, I this, this, this, |
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41:17 | And we even reviewed this and then added more things to. All |
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|
41:23 | And yesterday also had a very interesting in the classroom where one of the |
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41:31 | have worked with dementia and Alzheimer's patients shared some of his personal experiences and |
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|
41:40 | mental stimulation, mental agility, social , social interactions are incredibly important for |
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|
41:48 | people and I tell you that because very difficult right now with covid where |
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41:54 | of the older people or you could they were shut off from their families |
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|
42:00 | a really strong impact, you know ? Because it had a really strong |
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|
42:05 | on the past if you have a or if you have somebody a dog |
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42:11 | the family, that dog was with owner for a whole year. All |
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|
42:15 | a sudden that owners started going back the restaurants again, going back to |
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|
42:19 | job, dogs are freaking out to a lot of anxiety. So when |
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42:23 | talk about dogs, so think think about, you know, |
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42:28 | think about lack of social interaction, sensations, all of these things that |
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|
42:35 | really very important. So stimulate your in your families. That's how I |
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42:42 | , you know, with, with everything that you can social interactions |
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|
42:48 | mental agility things. And there's some interesting study of nuns that were somewhat |
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42:58 | from the outside world. They didn't their own social circle small circle and |
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43:04 | were very interactive and they were reading journals every day and they had book |
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43:11 | not stop and they had all of discussions and prayer groups and stuff like |
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|
43:16 | , had a very, very little instead of Alzheimer's disease. So it |
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|
43:22 | to show you that the continuing mental , not only after you get your |
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|
43:29 | , but also when you're getting old important, just as important in making |
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|
43:33 | go to the gym. It's just important an elderly age to pick up |
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|
43:39 | tried to do a sudoku because it be really good for your brain. |
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|
43:44 | keeping up this activity is keeping up technology which is important. You know |
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|
43:51 | that didn't learn how to use they didn't just not learn how to |
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|
43:55 | email, that kind of a lost connection that everybody else younger and the |
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44:01 | has and it goes to the, know to the heart of not just |
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44:08 | connection and email but an actual interaction is lost too. Have a |
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|
44:14 | So even when we know about Alzheimer's it? Yeah, History of |
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|
44:23 | Okay, I agree anywhere. so more susceptible parts of the |
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|
44:29 | it's not that it's occurring only in prefrontal cortex is plaques at the bond |
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44:34 | will be scattered throughout your diplomatic but cortex in certain parts of the prefrontal |
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|
44:41 | will contain those problematic there as And this seems to be a susceptible |
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44:46 | of the brain that is more susceptible the pathology that goes earlier on as |
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|
44:54 | to other other parts of the Hippocampus for example is very susceptible than |
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|
45:00 | short term memory loss. So you argue that that is also part of |
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|
45:03 | brain that shows early Alzheimer's pathology. platform ation is their prevalence in campus |
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|
45:12 | well. And in fact there are that show that from hippocampus through interregional |
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|
45:17 | and other types of vortexes and near temple of with this migration to displace |
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|
45:22 | these plaques. So it's a very question because there are deaf. Oh |
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45:27 | parts of the brain that are more . These pathologies and kind of a |
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|
45:32 | out earlier as opposed to right. you'll you'll see when we talk about |
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|
45:38 | little cooling and cold energy projections and see where they're located. Maybe it |
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45:42 | make more sensitive to the prefrontal Yeah, you're welcome. So damned |
|
|
45:50 | . And dendritic spines. It's something unique. We have axons accidents can |
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|
45:54 | collaterals. That means that they can . And then axon will also have |
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|
46:00 | terminal or Bhutan Bhutan and present means a kind of a fancy language and |
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46:07 | and french bhutan's button synapse in passing that an accent can leave a synapse |
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46:14 | then continue on with the main Uh So little shop and then terminate |
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46:19 | else with more synopsis at the external . Yeah, mitochondria which is also |
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|
46:26 | important there for vesicular release on The axon initial segment generates the action |
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46:35 | gets regenerated the axa donnell nodes of gear and then there's a deep polarization |
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|
46:43 | this pre synaptic terminal. This influx calcium and fusion of the synaptic vesicles |
|
|
46:49 | release of the neurotransmitter into the synaptic boston ap typically will have densities when |
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|
46:56 | refer to earliest prostatic densities of the that are chemical or wagon gated channels |
|
|
47:03 | lot of times that will be juxtaposed sitting on the fast synaptic membrane And |
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|
47:08 | this distance between the pre synaptic and map it is called the synaptic cleft |
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|
47:13 | the whole process of demobilisation message neurotransmitter release binding of that. They're |
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|
47:20 | receptor and subsequent response, electrical and response. And the problematic cell is |
|
|
47:27 | to as synaptic transmission. We will synaptic transmission in great detail in the |
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|
47:35 | section of this course. Now some the stains and this transport that we |
|
|
47:42 | interrogate and retrograde transport can also be advantage by the stains and for us |
|
|
47:48 | study and to understand the connectivity of projections from the periphery into the central |
|
|
47:54 | or from the central parts into the . So you want to know with |
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|
48:00 | piece of the brain of this patch the muscle or skin is connected to |
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|
48:05 | salads and so you would use something horse riders. Barack's days and you |
|
|
48:10 | inject it into this patch right here neurons that have their accidents will absorb |
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|
48:17 | peroxide days and it is being transported . So from the periphery from these |
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48:24 | terminals it will deliver to die into soma into these neurons here. So |
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|
48:32 | will know that this patch, like said at the brain of this pack |
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48:35 | the skin is connected to this network neurons here. It's a useful tool |
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|
48:41 | use and staining uh science modern day and neuroscience takes advantage of the viruses |
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|
48:49 | well. We had a herpes virus rabies virus that also get to the |
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|
48:58 | or to the central parts and to selma's through retrograde transport. We will |
|
|
49:04 | about shingles later in the course when talk about Samantha sensory system which essentially |
|
|
49:09 | a herpes zoster virus which has the to do both. It has the |
|
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49:14 | to go until era grade from the into the periphery in and retrograde. |
|
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49:21 | gets into the body from retrograde and dormant. And then it reappears again |
|
|
49:29 | terra great from the centre into the . So now then drives are very |
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|
49:36 | and good experience are very important. you saw. They have different shapes |
|
|
49:41 | they described in different shapes. They their own Paula ribosomes conflict system. |
|
|
49:50 | and mitochondria. And these dendritic spines suggests that the critic spines are can |
|
|
49:58 | biochemically independent from the dendritic shaft and the selma they can actually then translate |
|
|
50:06 | elements and certain proteins at the level the dendritic spine independently or turning on |
|
|
50:13 | off the genetic machinery at the level the selma. And obviously the spine |
|
|
50:19 | juxtaposed to the sex onal terminal. a second disease that we introduced |
|
|
50:30 | And this disease is autism spectrum disorders in particular fragile tax so fragile like |
|
|
50:40 | fragile glass X. X. So autism spectrum disorders underneath. Autumn |
|
|
50:50 | disorders is an umbrella of many different . And we're not going to discuss |
|
|
50:57 | likes to the same great extent that talked about Alzheimer's and we'll talk some |
|
|
51:03 | multiple sclerosis and we'll talk some more multiple sclerosis. But it's very important |
|
|
51:08 | understand that the precise formation I've been expired. The precise sub cellular arrangement |
|
|
51:20 | densities along the dendritic shop and precise of these funds equals normal function and |
|
|
51:30 | fragile acts and in developmental mental This is an image of a mentally |
|
|
51:38 | and in funds and it's done And one very obvious striking difference immediately |
|
|
51:45 | not in the dendritic shaft but in structure and densities of the genuine expanse |
|
|
51:52 | see that some of them are very expressed here and there's a whole so |
|
|
51:57 | is no continuity and there's a scattered expression of these super alligators, |
|
|
52:08 | And what is the this is the , the inability to learn. So |
|
|
52:18 | retardation comorbidities such as epilepsy and seizures also be present and fragile X. |
|
|
52:24 | Children. So having these invent experience very important. The good expanses where |
|
|
52:32 | synapses are formed. We have synaptic if you have this abnormal organization that |
|
|
52:42 | that you're not processing information properly. inputs that are coming in cannot be |
|
|
52:49 | properly. Therefore the information either the of the internal information from intellectual or |
|
|
52:58 | capabilities inside the brain are quite just like this image of the dendritic |
|
|
53:05 | is distorted. Image of a normal X. Pine shaft. In addition |
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|
53:13 | as I mentioned will receive excitatory Glutamate which is excited to a neurotransmitter |
|
|
53:20 | the brain. Blue R stands for receptors. And anywhere you see Green |
|
|
53:26 | is sustained for glutamate receptors. And means that anywhere you see a dot |
|
|
53:32 | a pump tape there is a synapse an excited terry senator. And in |
|
|
53:40 | these spines are not only targeted by tourists. Synopsis neurons have both excitatory |
|
|
53:48 | inhibitory inputs. And Gava synopsis and receptor shows an orange. Are they |
|
|
53:57 | their receptors? Yeah. So you see everywhere that's in green is excited |
|
|
54:04 | synopsis and everywhere you see Orange here inhibitors announces and they have to make |
|
|
54:14 | inputs and communications with wisdom. Good . And we cannot do it when |
|
|
54:20 | have abnormal anatomy after the good experience you have lack of dendritic spines or |
|
|
54:28 | densities of those spines. So neuron to integrate information from hundreds of thousands |
|
|
54:36 | excited third hundreds of thousands of the synopsis. It does. That process |
|
|
54:43 | is very fast. It's a fast and single neuron can make a decision |
|
|
54:50 | milliseconds networks and make decisions within milliseconds this is when I mentioned last lecture |
|
|
54:59 | artificial intelligence, Why artificial networks are in how the brain networks learn. |
|
|
55:06 | is our brain that works are really at certain things processing each one of |
|
|
55:12 | neurons is like a mini computer. process is thousands of inputs within |
|
|
55:20 | What our brains not very good The electronic networks are good at. |
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|
55:25 | it's we're good because we can start stop whatever we want to do and |
|
|
55:30 | can switch into a different mode. can switch into different processing ballot. |
|
|
55:36 | that takes time. The computers cannot start and stop themselves unless you program |
|
|
55:43 | to start and stop. But what you do when you close one software |
|
|
55:48 | you open another one. It opens right up right now for humans you |
|
|
55:54 | to be an equivalent. You have finish taking no stand up and play |
|
|
56:01 | . You have to do it with click and you did not really. |
|
|
56:07 | it's a lot of wetware that we that's involved in switching that went way |
|
|
56:14 | takes time. It takes emotional takes motivational component to switch it. There's |
|
|
56:22 | sympathetic system that yes, the big is coming at you you react and |
|
|
56:27 | going to take time to stand there think about it. So there's certain |
|
|
56:32 | you know that our conscious certain aspects are reflective but a fast in this |
|
|
56:38 | that we're talking about in the processing properties of the networks and then other |
|
|
56:43 | that disadvantage to the digital world that have. The networks that can turn |
|
|
56:49 | and turn on and off. But networks are very sophisticated. You've been |
|
|
56:55 | audiophiles house that has an audiophile equipment up, has to be amplifiers |
|
|
57:02 | It's usually the process of turning on 67 buttons waiting for things to warm |
|
|
57:07 | until finally the music comes out of speakers and it's not that simple. |
|
|
57:13 | just things to think about and things start taking notes on. Uh most |
|
|
57:20 | the neurons uh not just about this but about neurological disorders. We may |
|
|
57:26 | return to talk about fragile X syndrome we may talk about autism spectrum disorders |
|
|
57:31 | sometimes we bring up things and sometimes talk about things that something happens like |
|
|
57:38 | happens in this world. Uh and know, we have to watch the |
|
|
57:45 | joe Rogan, he's taking some taliban anti warming solution of the two |
|
|
57:53 | you know, should look into his , see what happens to him, |
|
|
57:57 | know, and if something happens and talk about, is there something going |
|
|
58:02 | there? Yeah, that's okay. making sure you guys the lab, |
|
|
58:09 | other distractions apart from me. So continue a little bit. We'll discuss |
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|
58:15 | fact that most neurons have four functional . You can have a model neuron |
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|
58:22 | an input here and put can come sensory neuron from the skin, leather |
|
|
58:28 | neuron, local interneuron projection into neuroendocrine sauce and you understand what we |
|
|
58:34 | , what we mean by all of and the subsequent slides uh the input |
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|
58:40 | . This is where that input The integrated region is usually the |
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|
58:46 | the conduct. I'll region is the that are my pollinated and the output |
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|
58:51 | is where the excellent terminals are with release synoptic neurotransmitter. And you can |
|
|
58:58 | an output in the form of secretion genetic neuron into muscles. You can |
|
|
59:03 | a Vassar dilating bastard constricting aspects from onto the capillary as well. And |
|
|
59:08 | this case more of a para crime neuro endocrine secretion that could affect the |
|
|
59:14 | signaling throughout the body as well. so the brain turns out has over |
|
|
59:21 | different subtypes of neurons. And once understood what different parts of the brain |
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|
59:27 | doing we now started to wanting to what are the different subtypes of cells |
|
|
59:32 | doing. And first of all how we classify these different 100 50 cent |
|
|
59:37 | of cells based on what the first comes to mind is appearance more |
|
|
59:42 | They love different and polarity and morphology polarity. You have unit polar South |
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|
59:49 | one poll, one poll just from North Pole. That's all. So |
|
|
59:55 | polar. South characteristic characteristic invertebrates. branches service acts on and receptive sides |
|
|
60:05 | cell two polls North pole and south and there's a sensory cells. We'll |
|
|
60:11 | about bipolar cells in the retina. we study retinol anatomy you'll find a |
|
|
60:17 | epithelium in the spinal cord. This a pseudo uniform yourself, pseudo uni |
|
|
60:24 | because it has the north and the pole. This is the same matters |
|
|
60:30 | sensor dorsal root ganglion cell. It one peripheral accident that goes into the |
|
|
60:37 | and one central acts on that goes the spinal cord. That's what pseudo |
|
|
60:44 | know, Poland because it kind it just has one poll Done right |
|
|
60:48 | be the 2nd fall. Most of south and most of the neurons in |
|
|
60:54 | brain are multipolar. And here's an of a motor neuron of spinal |
|
|
61:01 | the parameter cell of the neocortex or hippocampus or this beautiful Preqin gee cell |
|
|
61:08 | was originally drawn by ramon alcohol using mirror system camera lucida. So this |
|
|
61:16 | an extensive Three of the cerebellum for cell and it shows you the difference |
|
|
61:22 | the synapses, spinal motor neuron can upwards to 10,000. Synopsis And broke |
|
|
61:28 | the cells can have almost 150,000. a very complex puzzle. This this |
|
|
61:37 | ship microchip has to solve quite quickly that to other interconnected units of the |
|
|
61:46 | . There's other ways of classifying Not all of the neurons will have |
|
|
61:51 | spines, some of them will be spiny. That's another kind of a |
|
|
61:56 | classification projections and connectivity. Some of south will project long distances, a |
|
|
62:04 | range in there called projection. Their projection cells, others in control activity |
|
|
62:09 | the local network and they're called excitability. They can be glutamate releasing |
|
|
62:18 | . So the excitatory cells, they raise the activity in the brain activity |
|
|
62:23 | . Or they can be inhibitory. will be releasing gaba which is gamma |
|
|
62:28 | butyric acid and there will be dampening inhibiting the activity in the brain and |
|
|
62:34 | down the neuronal activity. But ultimately have to look also with the cell |
|
|
62:44 | . Each cell is different because it a slightly different. Each subtype of |
|
|
62:48 | is different because it expresses a slightly subtypes subset of the genes that code |
|
|
62:55 | the same in each cell we sell express slightly different part of that |
|
|
63:01 | And because it does so it may producing specific cell markers such as neurotransmitters |
|
|
63:07 | neuropathy as it expresses. And that help us distinguish, sell some that |
|
|
63:12 | dopamine, others have produced several others that produced in europe Captain Y |
|
|
63:18 | so on. Action potentials. This the first photograph of the first published |
|
|
63:25 | for cellular recording action potential reporting about and Huxley And the first action potential |
|
|
63:34 | reported in 1939. And this is picture from the silla scope showing this |
|
|
63:41 | about 100 million balls and size the taking place over just a few milliseconds |
|
|
63:48 | time. And that's important because different subtypes out of those different looking |
|
|
63:57 | they're not only gonna look different, not only going to express different substantive |
|
|
64:02 | and proteins and neurotransmitters and chemicals but also going to speak their own |
|
|
64:09 | So you have the same language which an action potential Continak but there's 150 |
|
|
64:17 | , 150 languages And 150 subtypes of express themselves, electrical it through this |
|
|
64:27 | of actual potential firing in different Wow this tried. I'm just gonna |
|
|
64:36 | you briefly and I'm gonna end with today because I realized that I started |
|
|
64:41 | and I actually gone through quite a of material today. This is a |
|
|
64:46 | that will come back to the following but I will briefly introduce to you |
|
|
64:51 | this is a part of the hippocampal . Hippocampus is a part of the |
|
|
64:56 | that is famed the most studied in and it has three dominant layers ready |
|
|
65:03 | , tour amidala and orients layer and region of the brain is very important |
|
|
65:10 | memory formation, recall of memory for orientation and special member and also involved |
|
|
65:17 | emotional aspects of the brain process. what's very interesting and a striking example |
|
|
65:26 | this very well studied circuit in the is that these cells and green are |
|
|
65:33 | . It'll excited to ourselves that released and the only difference between them really |
|
|
65:40 | not in morphology but that some of produced Calvin's NCB and honest are negative |
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65:46 | Calvin, you don't have sleeping but diversity and we'll get to the diversity |
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65:53 | how the diverse set of inhibitor cells is responsible for diverse rhythmic activity in |
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66:00 | brain. The diversity and local processing from the inhibitory interference inhibitor there into |
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66:09 | because their accents are going to stay control activity in these local networks. |
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66:16 | there's 21 different subtypes. 21 different genetic expressions and dialects that are being |
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66:25 | to these excitatory cells and these excited of projection cells. That means that |
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66:32 | these inhibitory cells and other excited yourselves communicate information to this excitatory network, |
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66:38 | . once they train that once they all of these languages added the output |
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66:43 | going to come from the projection cells forming another interconnected part of the hippocampus |
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66:49 | not interconnected region of the brain. something of importance is going around. |
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66:53 | putting that signal out and projecting that . So we'll stop here reminder that |
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67:03 | you don't have a class on I'm equalizing you with the monday and |
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67:09 | class sections. So have a long doesn't mean you don't have to come |
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67:16 | either classes but you don't have this on Tuesday, enjoy your weekend be |
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67:23 | . Uh and texas has tremendous Uh So I will urge you just |
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67:31 | listening from some personal stories on delta of how quickly it spreads. And |
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67:38 | of my friends that were vaccinated I'm very cautious after those stories and |
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67:44 | what I said enjoy the great texas |
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