| 00:02 | this is lecture three of neuroscience Tuesday thursday. And for the last two |
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| 00:11 | I introduced the subject matter of covid and infections in the C. |
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| 00:16 | S. Because it was highly It was also something that was quite |
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| 00:22 | as things were unfolding in the last years and they're still unfolding in as |
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| 00:27 | as the long-term consequences on cns infections COVID-19 and artist. So when covid |
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| 00:37 | we were all scared we didn't know exactly it acts in our bodies and |
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| 00:42 | didn't know exactly how it acts in brains. And so I became interested |
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| 00:47 | how do you get a brain infection Covid 19. And obviously if you |
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| 00:54 | enough of the virus in your blood have a heavy viral load in your |
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| 01:02 | . Virus in the blood can reach . N. S. So you |
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| 01:06 | get infected by having a systemic infection your blood but not necessarily in the |
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| 01:11 | . N. S. And there's be a possibility of things crossing from |
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| 01:17 | blood into the brain uh nasal If you see here in this image |
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| 01:25 | have these olfactory nerve endings that are basically at the top or the bottom |
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| 01:33 | your skull on the top of your where you have these tiny openings in |
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| 01:39 | skull. You're looking at the skull from where the brain would be |
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| 01:44 | It's called crystal galley and crib reform here and you can see you have |
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| 01:51 | openings the small ministrations and the actual bone. These olfactory nerve endings will |
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| 02:02 | pass through these openings in the skull your nose. So then it became |
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| 02:09 | question while can you not by inhaling , get these nerve endings infected and |
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| 02:17 | talk about that in a second. that means that the virus doesn't have |
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| 02:21 | be in the blood. The virus enter into your nasal mucous epithelium and |
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| 02:30 | infection there. However, if it the blood, What happens with COVID |
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| 02:39 | ? There's lack of oxygen and there's hypoxia neurons are very sensitive to oxygen |
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| 02:47 | loss of oxygen to neurons causes fairly death in neurons. So neurons are |
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| 02:53 | of oxygen for longer than two they start dying. Unlike other organs |
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| 02:59 | the body and cells, neurons are sensitive to that. Now if you |
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| 03:04 | hypoxia, you also breach what is the blood brain barrier. So in |
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| 03:13 | the blood and the brain we have blood brain barrier. This blood brain |
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| 03:21 | is you have endothelial cells which make the blood vessel walls, you have |
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| 03:27 | that surround it and astra sites and are tight junctions between endothelial cells and |
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| 03:35 | basically don't allow anything into the brain there's a transporter for that substance. |
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| 03:40 | there's something that binds the receptor and transported across the blood brain barrier or |
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| 03:46 | to cross the blood brain barrier. normal physiological conditions. Astrocytes is another |
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| 03:53 | . So astrocytes the glial cells and will rather and processes around the blood |
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| 03:59 | and they'll be checking of what is from the blood into the brain. |
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| 04:06 | if you have hypoxia this blood brain becomes loose essentially If you have infection |
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| 04:14 | inflammation this blood brain barrier becomes loose means now this tight junctions and the |
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| 04:21 | that control things passing from the blood the brain are no longer working |
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| 04:26 | That means things from the blood can more freely enter into the brain. |
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| 04:33 | whenever virus enters into the body whether in the nasal cavity or whether it's |
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| 04:39 | the lungs and other organs, the has to hang on to something that |
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| 04:44 | is an H two receptor that the binds to ace two receptors a a |
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| 04:52 | receptors and they are angiotensin convert converting to receptors that are found in many |
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| 05:01 | organs are kidney, lungs but also the C. N. S. |
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| 05:06 | also in the peripheral nervous system. do these epithelial cells have AIDS to |
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| 05:14 | . Because it would be very easy the virus enters into this mucus layer |
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| 05:18 | you have the nerve endings hanging out the factory uh olfactory receptor neurons. |
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| 05:26 | if there is a stew receptors on nerve endings boom it's very easy then |
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| 05:30 | infected. You allowed the virus to onto something then of course you know |
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| 05:36 | will go inside the salad abuse its machinery and trying to replicate itself. |
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| 05:42 | don't have a stew receptors. These neurons but instead the cells that surround |
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| 05:48 | , they're called sustain tacular cells. contain ace two receptor. So it's |
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| 05:52 | likely that infection in this mucus olfactory layers and in between happens by infection |
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| 06:00 | such spectacular cells once a spectacular In fact that there seems to be |
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| 06:05 | least one way in which cell can another way is in this trans cellular |
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| 06:11 | , which we don't understand very well . However, if from such spectacular |
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| 06:16 | you have an infection of the olfactory , you will have one of the |
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| 06:21 | symptoms in the P. M. . Which is loss of smell. |
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| 06:25 | when these olfactory nerve endings get that's when you have a loss of |
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| 06:30 | , which one of the symptoms for 19 not everybody experiences it. But |
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| 06:36 | if you are experiencing anosmia which is of smell is because there's an infection |
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| 06:44 | the level at least the olfactory epithelium not in the higher centers because from |
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| 06:50 | you can climb up further into your . So uh there's a lot of |
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| 06:57 | here and we'll come back and talk this information but what we talked about |
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| 07:03 | the peripheral nervous system when you have infection of these peripheral nerve endings, |
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| 07:08 | have anosmia which is loss of You can also have a goose CIA |
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| 07:16 | is loss of taste. And that if there is an infection of the |
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| 07:20 | nerve endings essentially the process dictates to in the periphery but what if it |
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| 07:27 | up into C. N. If it gets into C. |
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| 07:30 | S. H. Two receptors are on neurons on glia their present and |
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| 07:38 | cells. So once it gets into . N. S. It can |
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| 07:43 | bind onto glial cells, bind onto . And what does it do? |
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| 07:47 | A mild symptom of a C. . S. Covid. 19 infection |
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| 07:54 | headache and vertigo. That is if don't have a bad infection. But |
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| 08:02 | there's a significant infection in the N. S. Covid 19 can |
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| 08:07 | to coagulate sympathies which is basically almost blood vessel disease. It can lead |
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| 08:15 | rupture of blood vessels or stroke and hemorrhaging. It can lead to hemorrhaging |
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| 08:22 | forming of the uh coagulation and hematomas and uh and and hardening of the |
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| 08:30 | and the brain can lead to meningitis is an infection and inflammation of the |
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| 08:39 | can lead to acute necrotic and cephalopod . Since a falopa. Theism brain |
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| 08:49 | with inflammation and necrotic is that it start killing the south will be necrosis |
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| 08:57 | the neurons of neurons and glial So these are very very serious |
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| 09:06 | Heavy viral infections in the C. . S. Uh so when we |
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| 09:13 | back at the end of the semester included additional information. I will not |
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| 09:17 | you responsible to discussing all these other but I did want to introduce the |
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| 09:25 | matter because we're still going through My daughter's school had choose a debate |
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| 09:33 | I think 10 cases in that high from the beginning of the semester and |
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| 09:38 | a small school, just a few students. So it's it's still |
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| 09:43 | That's why it's really important that we're of it that we still uh we |
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| 09:49 | all of the instructions about the symptoms infections and things like that that you |
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| 09:55 | you should follow. And when we back at the end of the semester |
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| 09:58 | will give you more information. And at the end of the semester you |
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| 10:03 | understand a lot more about brain function anatomy. So we're gonna be able |
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| 10:07 | put these new things within the new of understanding and context that you will |
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| 10:16 | . Alright so this is where I it to end lecture to and start |
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| 10:21 | three uh which is positive supported. Lecture three is also our first lecture |
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| 10:31 | neurons and glia About 10% of all the cells and the c. |
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| 10:39 | A. neurons, paglia. Up maybe 10 years ago, 90% of |
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| 10:48 | were studying the 10 the brain the because everybody thought that neurons produce action |
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| 10:56 | they are responsible for chemical neuro transmission really where the exciting things are happening |
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| 11:03 | the more we reveal about glia the what types of lee and their |
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| 11:08 | We realize more and more about glee how intricately and actively it's involved in |
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| 11:15 | signaling in neuronal signaling, neuronal synaptic enough to genesis formation of new synopsis |
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| 11:22 | so on. So neurons again, of our like chips and the chocolate |
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| 11:26 | cookie and glia is like a dough a lot more of it to support |
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| 11:32 | chocolate chips. But not only that you don't have dough, you have |
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| 11:38 | . If you don't have chocolate you have sugar cookie. I guess |
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| 11:43 | are kind of boring without each So you need both glia and neurons |
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| 11:49 | both are actually active, not just sauce, including leo sauce in this |
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| 11:55 | the game and the brain is mainly the stain. Because we as we |
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| 12:00 | the gross anatomy of the brain in 18th and 19th century. And we |
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| 12:04 | describing the specific areas of the brain the 20th century with cider, architect |
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| 12:11 | methods and different stains is what revealed cider architecture of the brain reveal different |
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| 12:20 | . So we became increasingly more interested the second half of the 20th century |
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| 12:26 | what are the subtypes of neurons and , how they different, how they |
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| 12:31 | around and form these networks. What some of the rules and the way |
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| 12:37 | communicate with each other. What are of the properties that they have and |
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| 12:42 | amongst each other as well. And of the slides that we will look |
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| 12:47 | their quite basic and you already know information from other courses. And there's |
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| 12:53 | things here that are quite specific and some things that you'll remind yourself and |
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| 12:58 | , okay I I realized that I that. So neuron cells like other |
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| 13:04 | that have Selma's that have nucleus that mitochondria have pollen, roberson's golgi apparatus |
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| 13:11 | into plasma, particular rough and the particularly just about like any other |
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| 13:16 | But then we go to this process called axle. And it's not like |
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| 13:21 | other cells, it's quite unique to . These are axles that have myelin |
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| 13:27 | them. The smiling sheets which provides to axon axon initial segment in this |
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| 13:34 | will produce the action potential. And have this installation so that action potential |
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| 13:39 | gets produced at this axon initial segment to the selma and it travels long |
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| 13:46 | , sometimes few micrometers, sometimes 10 , sometimes centimeters in distance. It |
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| 13:52 | reproduce the same fast large electrical external terminal. And that's why you |
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| 13:58 | insulation in certain specific mechanisms by which information gets communicated. The other thing |
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| 14:06 | neurons have dendrites And we already alluded in the last couple of lectures, |
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| 14:11 | have these dendritic spines and these dendritic are the most plastic units, meaning |
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| 14:18 | these dendritic spines can change their shape on activity. There can be elimination |
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| 14:25 | dendritic spines when you're born and your are formed. You have a lot |
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| 14:30 | than riddick spines and synapses that you up when you're adult, you prune |
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| 14:35 | dendritic spines that are not being You prune the synapses that are not |
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| 14:39 | used. You strengthen and potentially enlarge synapses and the pathways that are being |
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| 14:47 | and are being stimulated by external or processing here. So when the axon |
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| 14:54 | action potential it will conduct it all way to external terminal and external |
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| 14:59 | You have the vesicles that are filled neurotransmitter and that electrical potential is necessary |
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| 15:06 | with calcium for these neurotransmitters to be onto the pasta topic. South boston |
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| 15:11 | side. And so most of the in the south will be formed on |
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| 15:15 | almost and underdone drives. But there also some synopsis that will target |
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| 15:22 | This is very basic information of N. A. The genes get |
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| 15:27 | into RNA. A. They get from the nucleus through these nuclear transport |
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| 15:33 | shut outs. I'd like to mention part that after transcription into RNA you |
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| 15:40 | splicing and splicing is really removing the coding regions of the code and splice |
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| 15:50 | create splice variants splice variants. That that there might be a slightly different |
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| 16:00 | . Uh amina acids is slightly different , It gets coded by this messenger |
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| 16:08 | into finished enzyme or finished protein. you think about it, we're splice |
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| 16:14 | of each other. That's what makes a little bit different than our thinking |
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| 16:18 | our perceptions and this is a normal to have splice variants as a normal |
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| 16:26 | variance. But if the splicing process when you're throwing out note coding |
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| 16:32 | you're really like rebuilding this code. you have a mistake someplace there and |
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| 16:39 | if that mistake again is related to or two, a few amino assets |
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| 16:44 | sequence a few amino assets that can in a pathological condition. So a |
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| 16:50 | of what we're gonna talk about is and protein channels. The messenger RNA |
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| 16:56 | code for these proteins and protein And if you have slight impairments and |
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| 17:03 | of these protein channels you have upset of the protein channels. You have |
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| 17:07 | neuronal function which can lead to pathological . Some of the proteins that we |
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| 17:15 | discuss. Most of the proteins that discuss our membrane associated uh some of |
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| 17:21 | proteins that we'll talk about are freely . So most of the membrane associated |
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| 17:27 | will talk about our receptor channels and protein coupled receptors that are responsible for |
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| 17:34 | and medical tropic signaling in the I'd like to remind everyone about this |
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| 17:42 | . I like the slide because last introduced to you there are so many |
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| 17:48 | levels of thinking about the brain and . There's so many different views you |
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| 17:54 | have. You can have a single view and just focusing on where that |
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| 17:59 | molecule was located. You can trace cells, you can look at structures |
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| 18:07 | networks. You can look at the brain activity in the whole brain. |
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| 18:12 | can look at gene mutations and we living in the post genomic error. |
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| 18:19 | this is a useful technique if you example want to compare normal brain versus |
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| 18:24 | disease brain like an epileptic brain. you want to understand more of a |
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| 18:30 | eye view as I say, or of a holistic view of gene fluctuations |
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| 18:36 | epileptic brain. So when these techniques out about 20 years ago or |
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| 18:42 | they were very novel. Now you micro race that are pretty common. |
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| 18:48 | race will contain up to 30,000 little in them each. Well will contain |
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| 18:53 | little piece of synthetic D. A. That you have put the |
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| 18:59 | synthesized. So you know what is to bind to. We can think |
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| 19:03 | this as a very sophisticated little piece velcro in there. And so if |
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| 19:07 | a matching sequence to this piece of it will bind and will stay |
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| 19:13 | It will indicate that there's more of gene for example or whatever is in |
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| 19:18 | in this well versus the other. now you can take brain one and |
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| 19:23 | to you can put brain one in vial and label it in red brain |
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| 19:30 | label it in green. You apply it to D. N. |
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| 19:34 | micro ray jeans with reduced expression in to will show up in red because |
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| 19:41 | have a different diets. Usually fluorescent will reduce expression in brain one will |
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| 19:46 | up in green jeans that are no between brain one and brain to will |
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| 19:53 | in yellow. So you will okay great. But isn't that gonna |
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| 19:58 | me so much information on hundreds of potentially that went up in their levels |
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| 20:06 | expression and epileptic brain and maybe hundreds genes that went down what is |
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| 20:14 | So if you're studying epilepsy, you're gonna go back to the pub mad |
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| 20:19 | , searches your mentor the papers that in front of you on the adaptive |
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| 20:23 | and you're gonna say, what are genes on the epilepsy and you're gonna |
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| 20:28 | . Well, you know, I see 200 genes that one top an |
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| 20:32 | brain but it seems like these 20 ones that are associated with genetic mutations |
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| 20:39 | and apple etc. So I'm gonna into these 20 genes. More clothes |
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| 20:44 | , do you follow the genes that up regulated or down regulated? What |
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| 20:50 | more important? Is it more important you make a lot more of something |
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| 20:56 | that you don't make enough of I don't know. And these functions |
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| 21:00 | the genes could be very different? gene that went out could be down |
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| 21:04 | something, Okay, so so we don't know. Then you go, |
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| 21:10 | , you talk to your mentor and , we're going to study these two |
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| 21:13 | because I just wrote a grant honor need data. Have you know my |
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| 21:19 | and these two genes. And so you're a Monica hall you say okay |
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| 21:23 | will do the work on micro race these two genes. But I'm also |
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| 21:27 | in the third gene. Can I I do some work on that |
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| 21:30 | Nobody's looking at it. So again can pursue the the hot five, |
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| 21:36 | know, genes that are involved in are being studied now the last five |
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| 21:41 | or you can go for something nobody about. It's like in life. |
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| 21:46 | know you can jump on a trend be a part of something or you |
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| 21:49 | fight the current and get nowhere or will turn around and say oh my |
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| 21:56 | this person is fighting the current but all the way at the top there |
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| 22:00 | . So just depends the same as science. So how do you pursue |
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| 22:05 | ? Intelligent thinking, hypothesis driven I have to come up with a |
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| 22:13 | . This gene goes up therefore something . The hypothesis should have directionality. |
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| 22:18 | something goes up, something is also go up, something goes up, |
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| 22:22 | is gonna go down. So this how you pursue this work. But |
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| 22:27 | gives you a good understanding of what happening on a whole brain level, |
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| 22:32 | in certain conditions and when we go some other organ Alice issue have smooth |
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| 22:38 | plasmid particular um which does the same as another cells involved in protein folding |
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| 22:44 | you have calcium regulation. So you internal calcium stores. You can call |
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| 22:49 | the release of internal calcium to golgi . There's gonna be post translational processing |
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| 22:55 | protein sorting, membrane bound versus freely them Brain. Uh really floating protein |
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| 23:04 | . And as I mentioned, the is only about 5% of the total |
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| 23:08 | mass but it consumes over 20% of total body energy. So that means |
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| 23:13 | lot of energy metabolism that we're doing out of equilibrium and non linearly driven |
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| 23:22 | feed the brain, so to Uh And the energy comes in the |
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| 23:28 | of a Tps. They have dietary energy sources protein sugar fat to do |
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| 23:34 | to peru vic acid oxidation information of . T. P. And |
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| 23:39 | 02. You have the sources of . And so neurons will have a |
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| 23:44 | of a teepee and certain parts of will have a lot of energy source |
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| 23:48 | . T. P. So for this Omagh's and then dendritic spines because |
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| 23:53 | talked about dendritic spines being somewhat biochemical . They have mitochondria in energy source |
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| 23:59 | then external terminals because you need to the vesicles and recycle the vesicles also |
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| 24:06 | higher levels of E. T. . So it's distributed strategically throughout neuron |
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| 24:12 | it needs these sources of energy. mouse of course cells and how the |
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| 24:19 | doctrine proponents were correct neurons are discrete that had their own phosphor lipid bi |
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| 24:27 | membrane that surrounds them. This phosphor bi layer is comprised of the hydro |
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| 24:34 | Killeen phosphate literal group, which is head and the hydrophobic fatty acid tails |
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| 24:42 | hydrophobic. Once they are afraid of will co join together and forming this |
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| 24:48 | layer and the hydro filic heads will exposed to either the extra cellular environment |
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| 24:55 | the side of plastic environment. plasma membranes of course, will have |
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| 25:00 | membrane proteins, membrane attached proteins, , cholesterol is embedded in their |
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| 25:08 | carbohydrates and underneath the structure of this membrane is supported by side of skeletal |
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| 25:17 | and this plasma membrane is not The south and the structure of the |
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| 25:25 | are not like a concrete. The membrane constantly moves around and they could |
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| 25:31 | reorganization within plasma membrane of these different that are embedded. They can be |
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| 25:38 | in. They could be taken out the number and they can also travel |
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| 25:42 | the number and quite far and quite . So the plasma membrane is really |
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| 25:49 | a fluid dynamic model and for that dynamic bottle, I'd like to show |
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| 25:58 | movie here machinery of the inner It's very quiet between the living machinery |
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| 26:08 | the inner cell and the harsh conditions the outside world stands the cell's plasma |
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| 26:15 | as crucial as this barrier is. surprisingly flexible, push it and watch |
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| 26:22 | move poke hard enough and it might and begin to regroup. The lipid |
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| 26:29 | of the membrane naturally assemble in a layer because their tails repel water as |
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| 26:35 | heads attracted, throw in some cholesterol a few carbohydrates. And you have |
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| 26:41 | basic structure of a plasma membrane within lipid molecules. We also find different |
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| 26:50 | which do various things for the For instance, they receive signals from |
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| 26:56 | world outside or they transport nutrients and . So nature composes the membrane with |
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| 27:03 | combination or mosaic of different lipids, and proteins and these molecules are not |
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| 27:13 | . They constantly move within the fluidly changing their positions. The survival |
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| 27:22 | all life rests on this veil of . A supple membrane, just two |
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| 27:30 | thick. This kind of a rearrangement is illustrated here with mechanical touch. |
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| 27:39 | something that happens we will talk about you have side of skeletal elements underneath |
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| 27:45 | that support the structure. Side of elements are also dynamic and they can |
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| 27:50 | their shape and their structure and as change their shape and structure, you |
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| 27:54 | see that some parts of the It can actually collapse if there is |
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| 27:58 | support underneath that. All right. so you have these rearrangements that |
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| 28:05 | It's not that the cells get although there is McCann oh receptors and |
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| 28:10 | that are responsive responsive to mechanical But this rearrangement that happens and this |
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| 28:18 | that you see. It's just a of the normal processes too. So |
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| 28:23 | because you have all of these different , it's actually fluid mosaic because these |
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| 28:29 | change and rearrange themselves. And you have this plasticity and fluidity in the |
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| 28:35 | plasma membrane itself to reshape its possible bi layer arrangements as well. The |
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| 28:52 | of skeletal elements that we're discussing. three micro tubules, neuro filaments and |
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| 29:00 | filaments. Micro filaments are the smallest of skeletal elements of their comprised of |
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| 29:06 | molecules. And if you remember from your previous biology courses, these elements |
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| 29:13 | prelim arise and form longer chains or can deepen memorize or the chains, |
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| 29:18 | chains can be broken up into shorter . What does that mean? That |
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| 29:24 | that the underlying structure beside the skeletal could be changed, can be |
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| 29:30 | If you change the structure then you change the shape of the plasma |
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| 29:36 | So action will be the smallest and have the micro tubules which are the |
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| 29:42 | side of skeletal elements here. You an electron microscope picture. So remember |
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| 29:48 | microscope has really high resolution of about nanometer and it's a cross section through |
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| 29:55 | axon. What you're seeing here is the axle, the smiling and it |
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| 30:02 | like wines going through here. And because milan will wrap itself around in |
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| 30:10 | and the cnR size will wrap around sheets. And so these are the |
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| 30:17 | of myelin that you see on the . But if you look on the |
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| 30:21 | of the axon, you will see other lines. They look like kind |
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| 30:26 | like tubes almost like little blood vessels here. And those are micro |
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| 30:32 | And so apart from the structure and shape of the membrane that the side |
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| 30:39 | skeleton and support, they are very in involved in the acts of plasma |
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| 30:46 | cellular transport. And it's very important you have again, a normal |
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| 30:53 | normal alignment of what we call the tubular highways because if you cross over |
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| 30:59 | entangle them, there's gonna be a jam and everybody's gonna be standing still |
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| 31:05 | 23 hours until the tow trucks show and clean up. And that's what |
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| 31:10 | happen if you have abnormal structures or in these side of skeletal elements. |
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| 31:17 | picture illustrates very nicely that the larger that are shown that purple is the |
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| 31:25 | in yellow. You have tubular lint turbulent or micro tubules of the largest |
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| 31:33 | , turbulence and accent for micro filaments in blue. And what this illustrates |
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| 31:41 | the larger elements and micro tubules and prevalent and there are more surrounding of |
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| 31:48 | core of the cell in the You can think of it as that |
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| 31:53 | like the core the foundation of the and these smaller elements acting elements are |
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| 32:00 | much located in the periphery. So ability to dynamically memorize deep elim |
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| 32:07 | change the shape and the architecture of side of skeletal elements? The smaller |
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| 32:12 | can influence the overall shape of the membrane on the outer boundaries specially have |
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| 32:19 | slide here. But I don't like slide. So use a different |
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| 32:24 | Which will I will make sure you also have it on your on your |
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| 32:33 | , we're going to introduce a couple uh Pathologies today already. We talked |
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| 32:40 | COVID-19 infections. This is a pathology we talked about symptomology loss of |
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| 32:47 | loss of taste is a symptomology, is the symptomology. And we'll talk |
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| 32:53 | Alzheimer's disease and we'll talk about Alzheimer's today. And we'll also come back |
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| 32:57 | talk about Alzheimer's disease later in the . So today we'll describe certain things |
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| 33:03 | Alzheimer's disease when we talk about neural and energetic networks in the brain will |
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| 33:08 | back and talk about Alzheimer's disease we'll talk about therapies for Alzheimer's |
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| 33:14 | And in general, in this you're gonna develop a little bit of |
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| 33:18 | I call a clinical language that you start thinking about when you see a |
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| 33:24 | ? What what is the disease? is the definition of this disease? |
|
| 33:29 | are some of the other things that associated with this disease? Why am |
|
| 33:33 | talking about Alzheimer's disease in relation to skeletal elements. For example, what |
|
| 33:40 | Alzheimer's disease. When you hear alzheimer's think it's a developmental disorder? Do |
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| 33:48 | think it's a middle aged disorder? think it's a a dementia That happens |
|
| 33:56 | 50 years of older? You don't of Children with Alzheimer's disease? |
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| 34:01 | So the prevalence C or the onset the disease is a part of the |
|
| 34:05 | , part of the clinical language What year or when is the disease |
|
| 34:14 | prevalent? C could be how many ? One in 1000 or 5000 and |
|
| 34:21 | from this disease? Oh then when think of Alzheimer's disease, what comes |
|
| 34:28 | mind when you think of symptoms? , somebody came into the doctor's office |
|
| 34:36 | said I can't move my leg. think I have Alzheimer's or is it |
|
| 34:43 | coming in saying you know I feel anxious, I can't remember the names |
|
| 34:48 | my close ones. I'm forgetting things easily confusing the time of the |
|
| 34:53 | That's typically the early symptomology of Alzheimer's is loss of short term memory and |
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| 35:01 | anxious because you're not remembering things. then there's progression of the disease. |
|
| 35:06 | the disease can start out with short memory loss and it can end with |
|
| 35:13 | ? Uh What are the pathology? is the pathology? What is the |
|
| 35:19 | pathology? What is the brain pathology the disease? Not the mechanisms of |
|
| 35:24 | . Not how the disease forms. what do we see in pathology? |
|
| 35:28 | so there are typical hallmarks of Alzheimer's . One of them is an extra |
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| 35:34 | formation of beta amyloid plaques. abnormal aggregation of the proteins here calcification |
|
| 35:42 | then finally inflammation surrounding these flax. these flax will affect neuronal function. |
|
| 35:49 | least flax are located close to accent segments, accident, initial segments will |
|
| 35:56 | of producing action productions. It means will start failing and communicating with each |
|
| 36:01 | properly and these plaques will form, also hear maybe senile plaques or dementia |
|
| 36:08 | . So these are beta amyloid plaques will form outside of the seats. |
|
| 36:13 | happens on the inside of the south Nurofen morally tangles and neural liberally |
|
| 36:20 | What do they do, neuro And they're tangled up and that starts |
|
| 36:26 | the side of skeletal elements inside inside skeletal transport, plasma transport, cellular |
|
| 36:34 | . What do you have inside the ? Now you have traffic jams. |
|
| 36:40 | you have this micro tubular highways. you have entanglements? You have inflammation |
|
| 36:45 | the cell. Things are not being . You have impairment of transport inside |
|
| 36:51 | cell and on the outside of the you have inability preneurs to communicate with |
|
| 36:59 | other and failure action potential production. are the typical hallmarks that you will |
|
| 37:05 | that, you know, it's something the scientists hope to diagnose early |
|
| 37:10 | Uh the blood markers are the final markers are the genetic markers that that |
|
| 37:17 | that say that you will have much predisposition for this disease versus a person |
|
| 37:22 | has a different subset of of So um quite often Alzheimer's disease definitively |
|
| 37:32 | diagnosed postmortem after death by looking at person's brain by seeing the plaques. |
|
| 37:40 | we don't really have a great way light up the plaques and image them |
|
| 37:45 | it's really advanced stage of Alzheimer's disease postmortem and severe Alzheimer's disease, you |
|
| 37:53 | see brains that looked like this that have significantly shrunken and there's a significant |
|
| 38:01 | of degree matter. Green matter are den rides and the, so most |
|
| 38:07 | the cells wide matter are the accents the cells. So there seems to |
|
| 38:14 | like highways that are more rigid and that are left in neurons and their |
|
| 38:20 | and synaptic communications are now gone. if the early onset and symptomology of |
|
| 38:29 | disease is not remembering things, feeling , confusing the time of the |
|
| 38:36 | advanced stages of the disease lead to . Because if you have neuro degeneration |
|
| 38:42 | memory areas, well you forgot something ? You don't have memory potentials. |
|
| 38:49 | have neuro degeneration in areas of the that are responsible for vital functions like |
|
| 38:54 | the brain stem for example, or functions of taking care of yourself. |
|
| 39:02 | functions. So you're not capable of that. Your brain is not capable |
|
| 39:08 | swallowing, feeding yourself and eventually maybe even breathing and driving the heart which |
|
| 39:17 | brain stem responsible for this vital water . So uh this is introduction to |
|
| 39:26 | disease. And we'll talk about several in this course and we will come |
|
| 39:30 | and talk about Alzheimer's disease and the that are being used for treating Alzheimer's |
|
| 39:37 | and the fact that they're quite there's no cure for Alzheimer's disease. |
|
| 39:42 | we can only slow down with progression the existing uh pharmaceutical drugs. So |
|
| 39:55 | features that we already discussed is do have axon axon initial segment will produce |
|
| 40:00 | action potential. This axon typically has terminal and like the further stand is |
|
| 40:06 | the terminal. And and then in are buttons of Bhutan's and present buttons |
|
| 40:13 | passing could be collaterals killing off these and contacting more local cells in the |
|
| 40:21 | . And you can see that axon will happen by the congress will have |
|
| 40:25 | vesicles that are loaded with neurotransmitter juxtaposed the post synaptic densities that will contain |
|
| 40:32 | collections of receptors that will bind to neurotransmitters. You have two types of |
|
| 40:41 | of plasmid transport. You have slow fast transport. The slow transport was |
|
| 40:47 | in the early days it would be injection of a die until larger axon |
|
| 40:50 | they would tie it off with a and they would watch how fast this |
|
| 40:55 | travels over distance. And so that a slow the fast was later |
|
| 41:00 | And radioactivity plate acids can be used trace this fast transport. You have |
|
| 41:09 | that are so horrible like little motor or carrier molecules that will be involved |
|
| 41:15 | this transport and it will be associated the Migra tubules. And Ineson is |
|
| 41:21 | to transport. Things enter greatly from soma into the periphery and dynamic is |
|
| 41:28 | to be a mother uh equivalent kind a motor protein that will transport the |
|
| 41:34 | back. Retrograde lee from the preference the cell. Right so again, |
|
| 41:41 | need this transport. You need the structure without any entanglements. Without any |
|
| 41:48 | . In order to have that Sir transport, which is important for both |
|
| 41:53 | necessities of the sound. Also slow that the cell needs to survive and |
|
| 41:59 | on. Okay, so we talked the stains and the stains will reveal |
|
| 42:09 | south and the axonal transport. We take advantage of this axonal transport in |
|
| 42:16 | to reveal the connectivity ease between different of the brain or skin to neurons |
|
| 42:22 | neurons to neurons. And some of popular dies or tracer. Our horseradish |
|
| 42:30 | dates and also viruses like herpes virus rabies virus that are capable of retrograde |
|
| 42:37 | and retrograde transport is really cool because can take advantage of it. Inject |
|
| 42:43 | in the periphery or ask a question neurons innovating this part of the |
|
| 42:49 | And so you inject a little The dye gets taken on by axons |
|
| 42:54 | gets transported retrograde into the selma. you can answer that question. It's |
|
| 43:00 | these neurons, this network that is to this piece of the brain and |
|
| 43:06 | in. There are some diets that capable and viruses. And we'll talk |
|
| 43:11 | herpes simplex virus when we talk about matter sensor systems and shingles. Some |
|
| 43:18 | are capable of bidirectional movement. They go retrograde lee and then they can |
|
| 43:25 | and terror greatly. There are certain that are trans synaptic. So that |
|
| 43:31 | that if you inject something here it travel to these neurons and then it |
|
| 43:37 | cross the synapse that die from this into another neuron. So you could |
|
| 43:43 | the secondary or the tertiary basically you have two or three junctions that you |
|
| 43:48 | synaptic connectivity and interconnected networks that you follow with these traces. Some dies |
|
| 43:54 | viruses but they will take advantage of axonal transport that we were discussing a |
|
| 44:00 | ago. This is a familiar slide that we discussed but every time you |
|
| 44:08 | at these you probably think about it little differently. We just talked about |
|
| 44:13 | fluid this is the plasma membrane and also talked about how you can change |
|
| 44:19 | side of skeletal elements, their their number, their position and as |
|
| 44:23 | change the underlying side of skeletal numb brain shape is going to |
|
| 44:28 | And we said that these dendritic spines the most plastic and the most dynamic |
|
| 44:34 | plastic means that they actually can change shape. They can change their size |
|
| 44:40 | dendritic spines that are going to be and establish themselves and form 123 pop |
|
| 44:50 | density. So three points of contact the symbols. And did X. |
|
| 44:55 | it expands that are not active. can be driven away completely and |
|
| 45:03 | And that for that to take place for the expanse to either become larger |
|
| 45:08 | disappear. You need energy, its dependent process. So the synapses that |
|
| 45:15 | active in the firing are likely to and strengthen. The ones that are |
|
| 45:19 | receiving any activity. The cell will what are you doing here? I |
|
| 45:23 | need you. I'm gonna reshuffle my my side of skeletal elements and I'm |
|
| 45:28 | go to this guy because he's getting of the inputs information. I'm gonna |
|
| 45:32 | him stronger and bigger. And that's you'll have to have rearrangement of |
|
| 45:37 | scalable elements. You will have the of the receptors potentially that uh translated |
|
| 45:46 | at least process post translation only at level of the spines where you'll have |
|
| 45:51 | . You'll have this polaroid como Um These are the most dynamic |
|
| 45:59 | We have more synapses and more spines born with and we end up in |
|
| 46:05 | . The ones that we don't use pruned as a part of natural |
|
| 46:10 | Just developmental process. The ones that strengthened and how they get strengthened and |
|
| 46:18 | ones and which neuronal networks that's actually individual human experience what we spend time |
|
| 46:25 | , you spend time on fantasy football for hours a day, you're gonna |
|
| 46:31 | really great circuits for you know, to do with team building things like |
|
| 46:37 | , you know. Um so we're these things when you're here sitting in |
|
| 46:43 | course and you learn something and you that means you strengthened or you may |
|
| 46:48 | built a new connection, you have a new spine or you have strengthened |
|
| 46:55 | communication a lot of it and you . So repetitive repetition, associative |
|
| 47:02 | associating things will help you learn. what you have. Bio one, |
|
| 47:06 | two and then other things because bio will repeat a lot of what bio |
|
| 47:09 | did. So this is all about shaping these spines and the connectivity. |
|
| 47:18 | one of the major issues with abnormal and one of the major conditions that |
|
| 47:29 | associated with abnormal formation of dendritic a lack of dendritic spines or abnormal |
|
| 47:37 | of index pines is associated with mental . So these are developmental mental |
|
| 47:46 | Most of the mental renovations are You read in your textbook, there |
|
| 47:51 | two boxes on the great expanse and representations. One of them talks about |
|
| 47:59 | Kiddo Nuria. Another one discusses a called fragile X syndrome and that's something |
|
| 48:05 | I will mention to you. It's genetic disorder and when fragile X syndrome |
|
| 48:17 | it happens because of this united it falls under the umbrella of autism |
|
| 48:24 | disorders. Because kids, it's X length more. So the Children will |
|
| 48:36 | certain features that artistic white Children have well. So the other thing is |
|
| 48:44 | you're learning about symptoms of the disease you will notice that there is an |
|
| 48:51 | between symptoms and many diseases. You Parkinson ian tremors and you can confuse |
|
| 49:01 | Iain Chalmers with life tonic clonic seizures epilepsy. You have anxiety and that |
|
| 49:10 | can be a part of the depression be a part of the alzheimer's |
|
| 49:16 | headaches can be a symptom of infection the brain. Apple upsy tumor traumatic |
|
| 49:26 | injury, the symptoms are can be . So, these these Children with |
|
| 49:33 | X syndrome, they are also likely have epilepsy and see years. The |
|
| 49:39 | point I'm trying to make here is at the normal spine arrangement and dendritic |
|
| 49:49 | versus one from the mentally retarded in or animal model. But it's found |
|
| 49:56 | infants like that, it's very clear if you look at the dendritic |
|
| 50:01 | he said, well, I don't much difference between the shaft, but |
|
| 50:04 | you look at it didn't really expand protrusions that are coming out and |
|
| 50:08 | well, this doesn't look like a spine anatomy. They are very much |
|
| 50:16 | , their protruding, that there's parts there's no dendritic spines and there's parts |
|
| 50:21 | there's a lot of them seems to very dense, it's very disorganized. |
|
| 50:29 | what happens if you have this abnormal of dendritic spines. Dendritic spines from |
|
| 50:36 | early days of ramon, alcohol and were thought to be then tennis receiving |
|
| 50:41 | information or the sides where the synaptic are taking place. If you look |
|
| 50:47 | this cell here, the major excitatory in the brain is glutamate, it's |
|
| 50:54 | acid neurotransmitter, glutamate, wherever there glutamate release and wherever you see these |
|
| 51:01 | dots that means that they're excitatory glutamate and glutamate in the brain. Its |
|
| 51:08 | is to excite of the south is polarized to de polarize this neuron to |
|
| 51:13 | this neuro more excited to make this fire an action potential and communicate the |
|
| 51:20 | that the glue. Dramaturgical synopses excited her synopsis A lot of times they |
|
| 51:24 | it's a plus gloss positive charge, positive charge. Fire, fire fire |
|
| 51:33 | same neurons will also be receiving. synopsis which stands for gamma immuno butyric |
|
| 51:42 | . It's a major inhibitory neurotransmitter in brain. The function of Gaba is |
|
| 51:48 | hyper polarize themselves to add more negative into yourselves to make them silent and |
|
| 51:56 | dampen their activity preventing them from firing forming action productions. And you have |
|
| 52:05 | cells in the brain that can receive 250,000 synopses, the South neurons will |
|
| 52:15 | most of the synopsis along the dendritic . Normally functioning dendritic spines will process |
|
| 52:24 | information, will process, gather urging . This neuron potentially can receive hundreds |
|
| 52:30 | thousands of inputs within a few milliseconds within a few milliseconds this neuron is |
|
| 52:36 | to integrate all of that information. it pluses and minuses and say I'm |
|
| 52:43 | to fire an action potential is like I'm good. I've been I've been |
|
| 52:47 | down. If you have impairment of than dirt response there is no normal |
|
| 52:54 | communication. There's no normal inhibitory Have impaired communication. Synaptic transmission therefore |
|
| 53:03 | to the significant consequences of mental Neurons have four functional regions. You |
|
| 53:13 | an input region. Can come from neuron from the skin. Uh You |
|
| 53:20 | integrated region which is the selma's. have the conduct I'll regions which is |
|
| 53:25 | axons and there are insulated and you the output region and neurons can contact |
|
| 53:31 | neurons. The motor neuron can contact muscle cell and tell the muscle to |
|
| 53:37 | the motor neuron from the spinal There are local into neurons. The |
|
| 53:43 | neurons are the cells that don't project the other networks but rather stay confined |
|
| 53:50 | within a normal network. And most the local inter neurons are Gaba. |
|
| 53:54 | or inhibitory cells. That means they Gaba although there are exceptions to the |
|
| 54:01 | and there are some projection into neurons are not very typical. But most |
|
| 54:06 | the production cells will be excitatory cells most of the inter neurons and stay |
|
| 54:12 | local networks will be inhibitory and they be releasing Gaba. So what are |
|
| 54:21 | ways in which we discover that the actually has different neuronal subtypes? We |
|
| 54:29 | know that there's potentially over 140, different neuronal subtypes in the brain. |
|
| 54:40 | what we discovered through history of neuroscience we've got to decide architect tonic |
|
| 54:47 | We got to the ability to see cells and the processes. We |
|
| 54:51 | The ability with electron microscopes to look the synopsis and see all of the |
|
| 54:56 | elements now. But what it is one neuronal subtype from another is purely |
|
| 55:03 | on morphology. They look different. located in different parts of the |
|
| 55:07 | therefore they will have different functions. there's more to and to classify |
|
| 55:12 | There was a lot of techniques and that were applied and developed to definitively |
|
| 55:19 | these neurons in 200 plus different subtypes the brain. One of them is |
|
| 55:24 | on morphology. Just anatomy. The of the south, you have unit |
|
| 55:29 | south, you have just one north . This is an invertebrate neuron |
|
| 55:35 | south, such as bipolar, South neuron bipolar bipolar south, the retina |
|
| 55:43 | the sensory organ here as the north the south Pole. This is our |
|
| 55:47 | unipolar south sudo, you know, cell has a peripheral axon that goes |
|
| 55:52 | the skin and muscle, it goes the dorsal root ganglion on the dorsal |
|
| 55:58 | and it has a central axon that into the spinal cord. So this |
|
| 56:03 | the dorsal root ganglion cell. You motor neurons and motor neurons are multipolar |
|
| 56:11 | most of the neurons in the brain multipolar. Motor neuron will send from |
|
| 56:16 | ventral side will send it's output onto muscle cells. Okay, parameter sells |
|
| 56:24 | most prevalent excitatory cells in the You will find them in different parts |
|
| 56:31 | the cortex, you'll find them in parts of the sub cortical structures such |
|
| 56:37 | hippocampus, which we already alluded Will hopefully start discussing that today, |
|
| 56:42 | on the time, by the as far as the time goes for |
|
| 56:46 | class Must stop at 12:45. Because when I stop, I'm gonna immediately |
|
| 56:55 | saving the lecture because I'm still running my time a little bit for professor |
|
| 57:02 | me. And you can see it be quite distract fel and if you |
|
| 57:07 | leave somebody five minutes. So this what I'll do. You don't have |
|
| 57:11 | questions. You can email me or me, just wait for me. |
|
| 57:17 | If I freed up. But if stopping, it's because I looked at |
|
| 57:21 | watches, I gotta stop. So for you guys, it will be |
|
| 57:30 | . Maybe you need to set on alarm. Actually, it's okay. |
|
| 57:38 | you have these parameter cells that will they're called parameter cells because there's so |
|
| 57:44 | look like pyramids and they have the . And that the apex. You |
|
| 57:48 | the optical dendrites and at the You have basil done rides coming out |
|
| 57:53 | here you have an accent coming So this parameter cell that hit the |
|
| 57:57 | but you'll find parameter cells in many parts of this room and none |
|
| 58:02 | But was the first one to draw cell. Imagine that kind of fun |
|
| 58:09 | a big, big, big bush work in the south that contained up |
|
| 58:16 | synopsis from a single cell. That's beautiful anatomy. I think it looks |
|
| 58:22 | much like a like a plant like shrub Bush. Uh Some neurons are |
|
| 58:30 | and some neurons will not have the . So the spines, if you |
|
| 58:35 | have the spines in certain subtypes of is not part of the mental recommendation |
|
| 58:40 | certain types of neurons are social excited . Subtypes that will not have |
|
| 58:47 | uh connectivity. So we know the , We know the morphology of the |
|
| 58:53 | . How are these cells connected to other? Are they projection cells which |
|
| 58:58 | they travel long distances. Their accents out of one area of the |
|
| 59:02 | Go to another area or the local neurons and they stay locally and influence |
|
| 59:06 | on the local level. Excitability. they release glutamate or do they release |
|
| 59:14 | ? All of the cells that release are excitatory cells. All of the |
|
| 59:19 | that release Gaba inhibitory cells. But definitively distinguish between different subtypes of |
|
| 59:27 | We need more than morphology. We need the self specific markers or genetic |
|
| 59:34 | that is unique to this particular subset South. But we also need to |
|
| 59:40 | its activity. In this case, the action potential. So the cell |
|
| 59:45 | produce and each neuron can produce a different pattern of action potentials they call |
|
| 59:54 | the dialect of neurons. They all the same language. It's the language |
|
| 59:58 | action potential to like a morse but different subtypes of these neurons will |
|
| 60:07 | a different dialects. Some of them be very fast and others will be |
|
| 60:11 | slow to signaling and communicating that information many different patterns. So for us |
|
| 60:19 | definitively understand what's that type of the we're looking at. We need to |
|
| 60:24 | all of that information. We need have the mythology. We need to |
|
| 60:27 | the excitability, we need to have projection or connectivity patterns on that |
|
| 60:32 | We need to have self specific markers are expressed by that cell and we |
|
| 60:39 | to know the member and properties of cell. Part of the membrane properties |
|
| 60:43 | the frequencies and the patterns of action that neurons can produce. These different |
|
| 60:49 | of cells. So, uh here we're looking at Is I believe it's |
|
| 61:02 | , it's the first publication of the the action potential. So, Put |
|
| 61:10 | in 1939, What's going on in . Yeah, World War II starting |
|
| 61:20 | Europe. The United States doesn't get in 1943. I'll learn directly involved |
|
| 61:26 | much all the time. Um these advancements allow for the fast circuits, |
|
| 61:35 | circuits to be developed to be improved . And british Navy and U. |
|
| 61:42 | . Navy come up with fast fast radar detectors on the eve of |
|
| 61:50 | World War two. And to this , if you go into electrophysiology |
|
| 61:56 | you will find that our equipment is with B. And C. Cables |
|
| 62:01 | B. And C. Stands for naval cable, british Navy cable. |
|
| 62:08 | they're the same fittings that you have the U. S. Navy |
|
| 62:11 | So you don't want to have the ones uh in the same circuits because |
|
| 62:16 | were fighting well at that time with , you didn't want the nazis to |
|
| 62:21 | the same circuits, Somebody you don't to have the same circuits now. |
|
| 62:28 | so uh what this happened in 1939 fast equipment. These fastest telescopes are |
|
| 62:36 | in and through the lives, electrophysiology stab an axon. And they project |
|
| 62:45 | thing on the, what do you with that 1939? What do |
|
| 62:53 | what tools do you have to let world know? You saw an action |
|
| 62:57 | in the wild, you actually have Polaroid camera. So you put a |
|
| 63:02 | camera over the screen of the you just captured the first action |
|
| 63:08 | This very fast milliseconds. That's why circuits needed to be fast in |
|
| 63:13 | This action potential is 1 to 2 . That means you need to sample |
|
| 63:18 | . One millisecond is what is 1/1000 1/2. So in order to visualize |
|
| 63:25 | , you need to sample something that faster, one that 1000 times per |
|
| 63:32 | or faster than one kilohertz. And they do that have a Polaroid to |
|
| 63:38 | a picture of that. How do tell the world you did it? |
|
| 63:43 | no email, there's no uh telegraph , right? But you can't really |
|
| 63:52 | an image. Um So you take black and white copies of that picture |
|
| 64:00 | you send it to the reviewers to at it and then they will publish |
|
| 64:06 | in a magazine where you're happy now , black and white pictures being |
|
| 64:11 | Uh So you send these pictures out you also have to write the paper |
|
| 64:19 | your work experiments hypothesis the results. . There's no computers. So you |
|
| 64:29 | to a typewriter and you tie one will photocopy that page. What happens |
|
| 64:37 | you mess up? There's no control . Start over. If you if |
|
| 64:44 | messed up a little bit, you , maybe it's wide out. But |
|
| 64:48 | you and if you messed up in middle it over the end of the |
|
| 64:52 | and it's a big mess up. you know after we do the whole |
|
| 64:55 | after we read type on the they just think about the determination for |
|
| 65:02 | to prove to the world that I an action potential without having all of |
|
| 65:06 | tools that we have around ourselves now communicating that information really fast and convincing |
|
| 65:12 | and we are right or wrong or else, we can do stuff |
|
| 65:23 | So um This is the Hippocampus and only four minutes but I have to |
|
| 65:32 | it. This is the part of brain that will study throughout this course |
|
| 65:38 | we'll talk about it multiple times. a part of the brain. Today |
|
| 65:42 | going to introduce to you is is to as R. K. Cortex |
|
| 65:46 | arche cortex because it has three dominant of island stratum and stratum organs. |
|
| 65:54 | the campus in the brain as part the limbic system, it's involved in |
|
| 66:00 | formation, memory, recall, emotional and emotional memory and the memory of |
|
| 66:07 | processes is semantic memory which is facts, names, places and |
|
| 66:14 | There are other types of memories in is a procedural memory, physical memory |
|
| 66:19 | that's mediated by another structure, mostly cerebellum in the back of the brain |
|
| 66:24 | procedural memories. So if the campuses memories of semantic memory is really how |
|
| 66:31 | live our lives. Um the Bold brain effect. And it would have |
|
| 66:39 | of the holzmann brain affect anybody using , bozeman brain. The fact is |
|
| 66:46 | everything we experience. And we'll see just things that are virtual reality around |
|
| 66:53 | in a box. And that's actually because sometimes two people will remember the |
|
| 66:58 | situation in a different way and have different feeling, emotional feeling about the |
|
| 67:03 | situation, but they were the same . Something happened, there was something |
|
| 67:08 | physically factually there and two people may away, but within minutes having a |
|
| 67:15 | different interpretation of what happened. so anyways, so what happened? |
|
| 67:23 | just make it up? Who is , who is wrong? So just |
|
| 67:27 | up into that, the ball Zeman effects. It's quite interesting because it |
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| 67:31 | about randomness and randomness and universe and , maybe potentially long period of |
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| 67:39 | the system's complex systems and prefer to random can become something organized like a |
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| 67:45 | bang of potentially. And so this is archaic cortex is archaic cortex, |
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| 67:51 | three layer structure, it's called our and not neocortex. Neocortex is a |
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| 67:57 | letter structure. So archaic cortex is to become something else. Everything in |
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| 68:02 | brains and bodies over time evolution, to technologies, environment is going |
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| 68:09 | it's trying to become something else, trying to develop into something more complex |
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| 68:14 | adapt to the environment we live So hippocampus having these three different players |
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| 68:22 | a very interesting structure. It has excitatory cells that are glued in itself |
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| 68:27 | a projection cells that are going to out of the hippocampus and connect into |
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| 68:32 | areas of the brain. And 90% these projection excitatory cells live in the |
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| 68:38 | layer. That's why it's called strategy a dollar of parameters Selway. But |
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| 68:43 | only two subtypes of these excitatory cells their distinguished not by their location, |
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| 68:48 | by their morphology, not by their and action potentials by the specific marker |
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| 68:55 | IV expressed in the north. And is how we distinguish them. Silent |
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| 68:59 | . Pretty boring, pretty standard. excitement and the circuit comes from the |
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| 69:05 | of the inhibitory cells. And so 21 numbers that you're seeing here up |
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| 69:09 | here at different subtypes inhibitory cells. are local inter neurons that release Gaba |
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| 69:17 | inhibitory local interventions. So when we back on thursday I will explain to |
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| 69:23 | how this circuit inhibit the engineers control activity of this excited, very self |
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| 69:29 | will be projecting and communicating that information the adjacent networks. And we'll get |
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| 69:36 | to the functionality and the dialects of south where I'm gonna indicate how some |
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| 69:43 | these neurons stock. And I'm gonna you some real talking neurons that we |
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| 69:47 | in the lab to see you all thursday. Thank you everybody on |
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| 69:52 | Uh I'm about to start taking the |
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