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00:00 | starting to record this lecture. So is ours. Third Neuroscience Biology 43 |
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00:08 | Biology 63 15 Lecture There are some items that we have to discuss from |
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00:15 | syllabus in particular that we are now the confirmation for all of the Casa |
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00:28 | exam Dave's. So those days that Conrad are no longer draft dates. |
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00:35 | first midterm will be on September Monday. Your second mid term will |
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00:43 | on October 28th Wednesday. And your exam, which is your final |
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00:53 | Uh, equivalent in mid term exam be in December 14th on Monday. |
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01:00 | falls to be the regular David for particular exam schedule when I know that |
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01:09 | is quite a bit of time between 7th Monday in December 14th. So |
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01:17 | December 7th, I will hold a session before the exam, where you |
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01:24 | ask me any questions that are related that section, that exam, and |
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01:30 | you will have a week. So have to time yourself and pace yourself |
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01:35 | you still have material fresh and you it, uh, so that you |
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01:42 | be essentially, um, well prepared the exam. Okay, now. |
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01:50 | the exam dates a set in Casa virtual. I have spoken with Casa |
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01:56 | they have, uh, said that will have a sample test for |
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02:05 | Teoh register with costed to log in take the sample test. I think |
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02:11 | the sample test aspires. Understand? along the lines of a very general |
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02:18 | of information that you will be asked you log in to make sure that |
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02:22 | are navigating the virtual space successfully. Once that virtual examines set up, |
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02:29 | just received the confirmations for the days the weekend on the news that they |
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02:34 | have the virtual test sample. for you set up. I will |
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02:41 | you know once that sample was set , the test sample set up so |
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02:45 | we can all go through it. the meantime, if you go Teoh |
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02:50 | cost A website. Ah, you be able to see information that, |
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02:57 | , basically explains to you everything about virtual examination. Now again, the |
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03:06 | EC stand is not cumulative. It over the last section. But as |
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03:11 | explained earlier, second exam will build the material that you learned on the |
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03:17 | section and third example build on the from the previous two sections as |
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03:25 | All right, so this is a a bust again on Wednesday after the |
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03:31 | will have a review, um, the material. And also later this |
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03:38 | , I will send a message to of the graduate students and 63 15 |
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03:44 | a time for us all together and on Zoom. I think maybe that |
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03:49 | be, if the course for everyone class next Monday. But we can |
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03:56 | the additional assignment for the graduate students this course. Okay, so please |
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04:05 | . Teoh cost a website. I establish a folder in black board over |
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04:11 | next day that will have the links cost a website. And if there |
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04:16 | any additional information, I will put post it there in that folder. |
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04:21 | once we have a sample that you log on and virtually taken and |
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04:27 | make sure all the systems are a , I will again notify everyone in |
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04:35 | . Okay, so I am recording lecture. Thank you for reminding |
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04:40 | Please continue reminding me, um, you, for some reason. See |
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04:44 | I don't I'm gonna pause the recording , just to switch the screen are |
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04:51 | . Third lecture material were sort of , um, going through some of |
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04:58 | slides that are listed in lecture, , lectured to. But in |
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05:03 | we have already started talking about neurons glia and is a reminder the three |
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05:10 | important cathedrals with their unique accomplishments communion with the Golgi stain, sir. |
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05:19 | Ramon Alcohol with the the drawings and descriptions of neural networks and brain |
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05:29 | uh, Sir Charles Sherington, who has spent time in coining the term |
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05:35 | and forecasting and describing some of the and some of the interesting, |
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05:43 | biological descriptions off this synaptic cleft in synapse. So if you're in cold |
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05:51 | , Goldie was, ah, proponent since the shell or a theory that |
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05:59 | called the ridiculous theory and particular theory for single side of plasma continuity between |
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06:07 | nuclei and Ramon. Alcohol was a off the during doctrine or the South |
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06:14 | , arguing that the South Dorantes, individual discreet units and this drawing in |
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06:20 | middle of the slide in yellow illustrates what Ramon alcohol do sows their |
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06:28 | The accents that carry the signal has and black, and they have arrows |
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06:33 | indicate that there is a flow of signal, and through these processes, |
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06:37 | particular, other cells will be The other synopsis so quite remarkable that |
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06:45 | had such a four side more than years ago. Another very important |
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06:52 | And it's different from the Golgi Golgi Stain isn't shown, and as |
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06:57 | adventure, that class picks up only 3 to 5% of all of the |
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07:02 | . But Durrance it pick up the silver, uh, Golgi. Stain |
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07:08 | stain extensively. So not just So most, but all of their |
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07:13 | that down drives these air, usually upwards and the shown on brown. |
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07:18 | these drawings here in the middle of page and ASEAN's Andi accents and all |
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07:25 | the processes of all of the ramifications these processes and contacts with other neurons |
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07:33 | that works on that is staying there very important was missile stained missile stain |
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07:39 | all of the neurons and glial cells essentially does not stain. The process |
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07:45 | so you cannot see the process is you can see here some of the |
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07:49 | coming of the cell body. It's used to describe the anatomy of the |
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07:54 | , but try that that architecture of neural networks, where these styles neuron |
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08:00 | are like building blocks and building a architecture. So what we're looking at |
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08:07 | , for example, is a and the brain is a cross section |
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08:14 | the brain and the top blue. ah, structure that we mentioned |
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08:21 | It's called the hippocampus of the hippocampus this very sharp blue lime and one |
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08:28 | the loot desire sharp blue line is all of the neuronal soma cell bodies |
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08:35 | concentrated. And so, if you at the Jason structure nearby, you |
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08:40 | see that this structure you can actually six layers In that structure, they |
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08:45 | like sort of, Ah, don't, uh, layers one over |
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08:51 | one over another. And this is sixth layer lateral Jinich alert nucleus of |
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08:57 | follows. So as I mentioned to , that is no signs of Senator |
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09:02 | . We high certain landmarks that indicate us the location of specific brain not |
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09:08 | infrastructures, the layers or maybe even subtypes of cells. And this sort |
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09:15 | description is called site Architecture and Corbyn Brockman, Doctor Brockman used this missile |
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09:24 | in order to very carefully, describe different functional areas. So he |
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09:31 | there different functional areas as he determined by different system structure, positioning and |
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09:41 | connectivity between the cells. So these still Rodman areas that are being referred |
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09:48 | and used to. And, I have ah, homework question for |
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09:54 | that I'm really road right, right and maybe even almost answered immediately because |
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10:00 | have all of the digital tools in of you. But the question |
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10:05 | what is Bronfman's area for Broca's What is the number one number of |
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10:13 | areas for brokers Area What number is learning guests area. Okay, so |
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10:21 | remember when we looked at that Soon we looked at the damage to |
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10:25 | area, which is in the frontal . But we said that it is |
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10:30 | Teoh expressive aphasia. So find out broad months area number corresponds to Broca's |
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10:39 | and which one corresponds to Vernon kiss if you call recall Vernick, it's |
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10:43 | , which is located on the border sort of Ah, temporal parietal and |
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10:48 | loves was related. Teoh. Receptive . Okay, so this is your |
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10:54 | task, Thio Thio Investigate now is important is a modern understanding of neurons |
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11:02 | line Eurostar different. We're gonna go some of the basics, lies and |
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11:08 | blunt, uh, and you will that mirrors and many instances are just |
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11:13 | other cells. Blood neurons have very specific features to themselves, and |
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11:20 | could really distinguish these features in Once we had the electron microscopes. |
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11:27 | we could visualize the synapses between the and started a standard line microscope results |
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11:33 | 0.1 micro meter. So we said the diameter of the neuron is about |
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11:39 | micro meters, so standard, like will show a self but synapse. |
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11:46 | spaces between neurons is only 20 nana , which is very, very small |
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11:53 | . And it would not be resolved 200.1 micro Vera resolution. This 0.1 |
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11:59 | meter resolution is 100 nanometers, so wouldn't be able to resolve a single |
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12:09 | electron microscopes they resolve after 0.1 nana spaces. So that means that you |
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12:17 | have in this 29 a meter you could have 29 m divided by |
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12:24 | one. You could have essentially 200 resolving images in the space that is |
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12:37 | the two neurons. So with this shows is the image off dead |
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12:46 | And that's why in euros a different they have these down drives and these |
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12:52 | rise have these tiny protrusions that come of them and these air dendritic spines |
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12:57 | indeed expires. The terminal I, the end of these dendritic spines will |
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13:02 | contacting other accents on the agenda, said. That's almost informing the |
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13:08 | and there is a different varieties of shapes of the 100 expire. Some |
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13:13 | them are described as a study. is shown in green, where it |
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13:20 | P S. D stands for the topic density than the some very interesting |
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13:25 | There. There's new transmitter, receptors that are found here on the |
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13:31 | nonstick density, and you can see read on the opposite side. You |
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13:35 | see these small little, uh, red vesicles, red little balloons and |
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13:45 | will contain neurotransmitters. So on the , you see the pre synaptic neuron |
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13:52 | has neurotransmitters and the vesicles. On last, you see the pasta traffic |
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13:57 | and used to the pasta ethic Neuron the Boston Athletic. Noon contains the |
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14:02 | , but these neurotransmitter chemicals also the space in between and lose almost fused |
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14:08 | is the actual soon after to And so the shape of the dendritic |
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14:14 | changes. The number of the dendritic changes with Is that mean that needs |
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14:20 | the grid expires? Or the most segment anatomical segment off the neuron, |
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14:27 | by forming new gendered experience, you be forming new memories. New experiences |
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14:35 | be registered. If you persistently experiencing , you will form new synapses when |
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14:42 | learning you're registering certain pathways in your , and then you can recall the |
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14:48 | places because you're reactivating certain synapses that active when you were learning. A |
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14:55 | synapses informed is a part of that process equally so you can also lose |
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15:00 | some of these dendritic spines and lose synapse. This is the normal process |
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15:05 | plasticity, and some gaining synopsis and its called, uh, Clinton she |
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15:13 | of the synapses, strengthening the efficacy the synapses is potentially aiding the synapses |
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15:19 | weakening or eliminating. These include ex and abscesses, repurchase depression or depressing |
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15:27 | in these synapses. That these dendritic and potentially driving the synapses away altogether |
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15:34 | that happens is a part of normal and forgetting. Process is a part |
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15:39 | normal experiences and emotional development process, and also abnormal loss of the synapses |
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15:49 | with neurological disorders, imbalances in the . So most of our brains are |
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15:57 | . They don't have neurological disorders in in the sense of normalcy. And |
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16:01 | have very dynamic struck cious Lee synapse system. One neuron could have up |
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16:08 | 100,000 off these dendritic spines and so the amount of the computation the |
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16:17 | on does is by gathering information from of the active. And all of |
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16:21 | have been it's an absence. Some these different experience will be contacted by |
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16:27 | turn their transmitters and other these spines be, ah, uh, targeted |
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16:33 | the inhibitory neurotransmitters. So by balancing and inhibition but balancing activity and having |
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16:41 | plasticity, the ability to reshape the , this is very key to normal |
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16:47 | function a very key dysfunction that can in the case of neurological disorders. |
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16:57 | . So this is some of the from my laboratory and the microscope that |
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17:05 | use here is light microscope. But we have is we have ah, |
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17:13 | infrared contrast microscope built in here, infrared camera that, speaking of the |
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17:21 | So the eyepieces in the front is you would see the specimens yourself. |
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17:26 | will, we have year is we a microscope. And where you see |
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17:32 | green line is where you have a it In this case, the specimens |
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17:36 | a piece of the brain. And you zoom in even Mawr, you |
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17:40 | see that there is a number off electrodes that are targeting and are actually |
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17:48 | of the electricity placed underneath this lancer the neural Titian or inside the 1000 |
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17:56 | tissue. So why this is important because using this technique and this, |
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18:05 | , microscope, we no longer need stain cells. These the slices that |
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18:10 | made from Brad brains and we can visualize neurons and visualize the processes on |
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18:19 | you're seeing here is to cells that two different cells, and they're being |
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18:25 | by the micro electrodes. Sir Michael cell diameters 10 micro meters The diameter |
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18:33 | the micro electrode is about one micro , and this is the way in |
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18:39 | we can perform whole cell patch clamp or interest cellular recordings. This is |
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18:46 | way in which we can visualize individual . Some target individual near us with |
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18:51 | tiny micro electrodes. It's a quite difficult feat to accomplish, especially if |
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18:58 | recording from multiple sauce at the same . At some point in my |
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19:03 | I think I was mad enough to able to record from three and four |
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19:07 | at the same time. Um, do need sliced brain slice preparations in |
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19:13 | to do that, because you would be able to visualize individual neurons using |
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19:19 | veal imaging techniques that you have in to recordings that happen in hospitals that |
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19:25 | from the brain tissue. Most of are extra SABMiller recordings. That means |
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19:30 | the electrodes air located outside of this versus these recordings that I'm showing you |
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19:36 | , where individual south and electrons are the inside of the cell, forming |
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19:42 | pash clown or interest Saleh type recordings will discuss us actually later in and |
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19:49 | the course as well. Now some the important ideas and concepts that led |
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19:57 | to this understanding off neurons and we'll about glee um, with Leo cells |
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20:03 | is really a multidisciplinary historical development of size, with some of the key |
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20:10 | along the way that we have mentioned you can review in the recorded |
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20:17 | Um and, uh, now we that there's functional specificity. We know |
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20:24 | certain parts of the brain and certain are responsible for specific functions. We |
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20:32 | know is that simple tasks and some the basic mental functions associated with simple |
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20:38 | within their simple motor control task is . Mental. Uh, performance tasks |
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20:45 | localized to small areas of the cortex could be singular areas of the |
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20:51 | But the more complex a task the more modalities that involves the more |
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20:57 | of tries. Teoh blends together such smell, taste and vision, the |
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21:03 | off the brain becomes involved in more between different several functional size, unnecessary |
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21:13 | what we have in the brain. have both times of processing. We |
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21:17 | serial and parallel distributed processing. So have cereal processors in the brain, |
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21:23 | that means that we have redundant tactless certain information processing. For example, |
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21:29 | the unusual on system in the we have three types of color |
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21:36 | We can have one, but we three times, and there's three times |
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21:39 | one is dysfunctional. That means you lose all of the colors. You |
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21:43 | some of the colors, but you need tame. That's serial processing in |
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21:49 | way they're also pathways, visual pathways other auditory, exactly. Said have |
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21:55 | processing. And most of the systems will discuss ha streams. Neural streams |
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22:01 | neural never wear extremes that are in and in parallel. So when they're |
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22:09 | cereal, it's increasing in complexity. I say parallel, that means it |
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22:17 | redundancy just like it with the example I used with the right now, |
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22:24 | I meant is you have in parallel uh, color cones that are processing |
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22:31 | , but that visual information, redundant that's processed in parallel by three cones |
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22:37 | the level of the writing lists quite . You don't have the image off |
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22:42 | visual information of the visual gestalt. visual image at the retina. That |
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22:48 | that the complexity of that processing happens serious than at the higher brain |
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22:54 | which is the thalamus. You will a more complex processing of the visual |
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22:59 | , and the whole full picture of usual image will be formed on Lee |
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23:04 | the occipital cortex is activated. And was the third major station along the |
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23:11 | of the visual information processing. So processing and parallel color information through three |
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23:18 | processors, while the serial processing is by increasingly having more complex interpretation |
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23:28 | uh, sensory processing and blending off modalities in in the brain. So |
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23:38 | put the sling tackle. Do you a dumpy? Do you feel like |
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23:43 | ? Look, there's some pretty cool that I but I sometimes look at |
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23:51 | . So the Clarins view is, know, we have imaging techniques that |
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23:57 | actually show us activity inside the brain having to open the skull. So |
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24:06 | have pad, uh, which is and emission tomography. We have Emma |
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24:12 | , which is magnetic resonance imaging and Marai, which actually shows the activity |
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24:22 | the brain. So these air the techniques, the patent and AM arrive |
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24:26 | in the course will discuss them in little greater detail, then will allow |
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24:31 | to visualize the activity of the brain intact brains. Um, and what |
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24:39 | have here is an image that was the museum here in Houston. That's |
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24:44 | interesting, and the study was based this image Where you can actually detect |
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24:49 | difference is what you see here in last in the black box are to |
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24:56 | and in one case, is the individual that is looking at the environment |
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25:02 | has no virtual reality. And on right is the same individual that's looking |
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25:07 | the environment that has virtual reality and these are those yellow and red dogs |
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25:14 | the brain, on the active neurons the active networks that light up and |
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25:19 | this experiment in the cases of the actually reacts differently, not just looking |
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25:26 | the same image. But if this is all of a sudden Marcin virtual |
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25:32 | or in additional dimensions, three or dimensions, then the map of the |
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25:37 | perceiving the same imagery changes. It like it becomes more specific when it |
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25:43 | experiencing war for real environment. But point is to say that there is |
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25:50 | changes that were killed, recognize, these is pretty subtle changes, special |
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25:56 | and versus no virtual reality, as Teoh epilepsy and no apple, |
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26:01 | So some of the severe neurological conditions activities can also be picked out by |
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26:07 | a Marai. But if you really to record electrical activity of the brain |
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26:12 | the clinical setting, you're still on surface of the brainier reduced Teoh E |
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26:17 | G, which is electroencephalogram. And severe cases, if you're undergoing a |
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26:23 | surgery after trauma or um is related Cem oncological problems, then you will |
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26:31 | intracranial recordings and actual placed in the the actual skull. And so, |
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26:38 | off that, uh, I would Teoh mention something pretty pretty interesting, |
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26:47 | me see if I can, pause the recording. But it's a |
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26:57 | interesting device that he is, commercializing and this really an implanted electrode |
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27:08 | . And it's really interesting because it's chip that gets implanted that is recording |
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27:16 | brain activity, and there is some say ethical backlash that he is |
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27:26 | But I would also suggest that in cases where you have complete loss of |
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27:33 | Oster their paralysis Yeah, but you have brain activity. I'm looking at |
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27:39 | from or of ah, neuro degenerative healing perspective to actually see if, |
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27:47 | , this device it's not billings to is not going to be used something |
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27:53 | enhances, um, our performance. try that maybe helps people that have |
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28:00 | severe brain injuries. But the, , the startup is already testing distin |
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28:10 | humans. So I just wanted to that out that every day we're advancing |
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28:17 | we as humans are not only recording Nick Kennedy in this case with |
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28:23 | but also how are we going to that information that we record for what |
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28:28 | ? And in my view, we help neurological patients that are severe near |
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28:35 | generation that can reactivate awakened retrain brain to improve their function is really a |
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28:45 | tool. Okay, with me imported your gown Now we know that each |
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28:52 | is subsumed by more than one neural . That's why I said that there's |
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28:56 | processing when one thought ways damaged. have others that may compensate, you |
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29:01 | , other parts of the brain that take over the damaged part of the |
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29:07 | . Emotions, things like emotions, also localized memories, the localize and |
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29:12 | distributed through the brakes. While there structures that are responsible for encoding the |
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29:17 | or recall of the memory storage of memory and is widely distributed emotional tac |
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29:24 | and emotional stark, it's also pretty distributed within the limbic system. We |
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29:30 | balls very key structures such as frontal , hippocampus and make the loans |
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29:37 | So once we have the cell elementary and things that we dio that even |
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29:45 | , you know, we're had writing down as we're talking and we're looking |
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29:51 | the wash at the same time. pretty seamless for us, but if |
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29:55 | can imagine with those brain maps, inside the brain as we change our |
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30:00 | functions in our thinking tyrants that these mass also changing because these brain maps |
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30:07 | really representation of the activity. A of these into the EC, spines |
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30:11 | critics in absence. We know that spines and synapses change therefore These maps |
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30:19 | change these maps Learn to become something you using them a lot to learn |
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30:25 | become something else. If you're using parts of the off their off your |
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30:29 | , different parts of the body. , if you look at some of |
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30:34 | image ing like positron uh, emission image ing, which is really what |
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30:41 | have to realize when your image ing of the brain year image ing the |
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30:46 | , consumption of oxygen consumption of Lucas these techniques are really just, |
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30:52 | telling you how much, uh, activity is happening in these particular |
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30:58 | But it's very clear that when you're at the words, your occipital lobe |
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31:02 | the left top is eliminated in A B when you're listening towards, you |
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31:08 | see the on auditory area, and temporal lobe is illuminated. When, |
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31:15 | Steve's speaking words, guess what it's motor cortex and very close to the |
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31:20 | area or it assistant get illuminated. what happens in D when you're thinking |
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31:26 | large these different areas, So it's a different area from when you were |
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31:32 | to words, or that when you looking at horses get activated because the |
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31:39 | involves other parts of the brain that not primarily concerned with sensor information |
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31:44 | But as much as with Com Uh, intellectual information processing? |
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31:53 | these spines. You know, these are now being described This mushroom shaped |
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32:00 | Stan or shortened stubby. And there's about this anatomy, different types of |
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32:06 | and the length of the spice. is very important. So in cases |
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32:10 | neurological disorders, you may have and Spicer will review conditions and which |
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32:17 | have, uh, dysfunctional dendritic We can also this age visualize even |
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32:25 | molecule so we can trace single molecules just single synapse activity in a single |
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32:32 | as but activity of a single How that molecule it's traversing through through |
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32:38 | south. Okay, so with I'm gonna, uh, switch into |
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32:50 | following lecture on, uh, can see now the screen of neurons and |
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32:59 | ? Can somebody confirm that they're seeing nerds Ingredients came? Yes. Thank |
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33:05 | . Great. So, again, stain and unearned doctrine were very important |
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33:10 | order for us toe. Understand that have these cells called neurons, |
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33:17 | uh, now we understand we have and we understand a lot about neurons |
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33:23 | we understand a lot about genetics and genetics and things like that and some |
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33:30 | the basic things that happened. Endurance . All of the styles you have |
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33:34 | transcription, uh, into the are a you have already and processing. |
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33:41 | , you have slicing that happens between and I are in a and so |
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33:48 | you refer to splice variants during the variance one pieces off, the genetic |
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33:54 | in transfer being thrown out and the are being kept from us a journey |
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34:00 | code into pro dance according to channel put into, uh, something else |
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34:07 | Jewel. So what you have is have different Spice Arians, and it's |
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34:14 | in a way. We're sort of splice variants off of our own of |
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34:20 | own genetic material, and it's a thing, but you can also have |
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34:26 | pathological spice parents of during this transcription process, you missing part of the |
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34:35 | , slice it in the wrong kind way. You can have a pathological |
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34:40 | from these gene genetics plaice variations. Russell half regular organ. Now I'll |
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34:47 | the plasmid particular rival Sum's and Paul sums, uh, driver sums covering |
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34:54 | roof of the plasma. Critical, uh, messenger name will exit out |
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34:59 | the nuclear pores, and some of will be destined to become a freely |
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35:05 | protean, and others will be destined become a membrane associated protein from this |
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35:13 | code. Um, so what's important is we're reviewing some of the basic |
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35:21 | . I think that will be interesting your own to review how viruses, |
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35:27 | , work also. Now the debate we raised at the beginning of this |
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35:33 | is that we're still not certain if 19 of Corona virus enters into the |
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35:42 | . Right? We discussed a A study by the Boston grew that |
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35:51 | that they did not find much of viral load or inflammation in the |
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35:57 | but they found degeneration. So their is that the virus is not entering |
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36:03 | the brain. That's probably not crossing blood brain barrier cold in 19. |
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36:10 | other studies that were done previously, were indications that the virus actually interest |
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36:17 | the brain and causes what we described as a full athletic lesions or encephalitis |
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36:23 | condition where you have very prominent inflammatory and inflammation of the brain as well |
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36:31 | nearly generation. So if virus does into the cells, remind yourselves how |
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36:40 | work. So this is your second . What is oneness? Virus do |
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36:45 | restricts the cells and to generating zone . It's takes over the host genetic |
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36:56 | and in fact, a portion about . We keep talking about evolutionary |
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37:02 | We we have a lot of genes . A portion of our genetic code |
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37:08 | to be changed influence. And they together with the nation. Together with |
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37:14 | viruses, um, viral infections have down production of certain chemicals and plans |
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37:24 | potentially turned on evolution of certain systems immune responses that to date we have |
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37:31 | our bodies and our still evolving. talked about my current race, and |
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37:38 | month's try showed you Brain Atlas, is really Ah Alan brain half. |
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37:44 | , there is a Lincoln, our materials toe, Alan brain outlets that |
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37:48 | can review, and one of the . There was my crew race and |
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37:54 | studies of the brain, and this very simple terms trying Teoh explain what |
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38:00 | micro arrays are. What if you're familiar with these techniques Where you really |
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38:05 | simple terms? What do you really starving? We have a micro |
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38:10 | Where you tracking Here. So what have in the last years, you |
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38:13 | a plate to call micro plates, plates, and they will have these |
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38:18 | well, something have can have, 80,000 of these mind. It's called |
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38:24 | car a Jean Marc Cory and inside walls because we know two genetic A |
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38:29 | genomic Aris. So we know one of the delay is coding for for |
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38:35 | watts. And we have synthetic DNAs represent genes of interest or than each |
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38:41 | of these. Well, now we take two brains. Brain Juan. |
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38:45 | say that is normal Brain to that even in fact, that are maybe |
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38:50 | to that is a pill epic, ? And we essentially have ah, |
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38:55 | , are in a that we extract brain long and brain, too. |
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38:59 | we implying onto the DNA on my right, and so jeans that have |
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39:06 | expression and bring to will have a signal genes that have reduced expression. |
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39:15 | Bray Juan, we'll have a green . Genes that high equivalent expression or |
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39:23 | changes in an expression of that gene glow has yellow. So you have |
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39:31 | microscopic slide you have. These style are starting the day with specific gene |
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39:37 | in these little whiles and the way you can visualize that this is a |
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39:43 | specific and very sophisticated piece of dull , where a specific sequence has to |
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39:52 | to your synthetic DNA sequence of Emory, in a sequence isolated from |
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39:57 | brain, has to stick to your sequence in the more of it |
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40:01 | Or in this case, the lesson , the more gradual how half the |
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40:08 | of the brain one jean sticking the of the green you'll have lower. |
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40:16 | you have on the left is a map, and this heat map will |
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40:20 | , if you have 30,000 gene wells there, this heat mom, or |
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40:26 | you a bird's eye view what is in this brain. Let's see brain |
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40:31 | and pull out there, and this a brilliant technique to have an overall |
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40:38 | and try to understand what genes and expression Misch a changing as a consequence |
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40:44 | disease. Now, when you are likely based with this Migra ray, |
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40:52 | out split is you may have 200 and reduced on brain Teoh 500 different |
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41:00 | reduced on brain one. Uh, , so then you look for the |
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41:08 | and have the biggest differences. You're that the genes that have the biggest |
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41:14 | in expression or some of the most to this disease probably that is the |
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41:21 | , right? But we know that nations, sometimes little things not the |
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41:26 | expression changes actual addicting. The bigger changes very likely than you use other |
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41:34 | . You use that, uh, library searches and trying to understand what |
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41:41 | you're looking at. If you're looking Apple s TV and your song Jian |
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41:45 | on 400 genes. But you know only 20 of them are really, |
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41:50 | highly relevant to ample of senior. you can narrow down two twenties Now |
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41:56 | can maybe narrow down from this 25 then maybe your boss will tell you |
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42:03 | I'm studying this gene in the so make sure you pick this one |
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42:06 | of five that we study because, know, this is something the person |
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42:11 | passionate about. Um, but like said, it's not always the big |
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42:18 | addicted other things changes sometimes minor The a story changes and can can also |
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42:26 | in pretty significant changes. So let's through some of the organelles, the |
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42:33 | particular more they have the protein You have Kallstrom regulations self. A |
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42:38 | of calcium is being stored on this your intracellular calcium stores in news suk |
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42:43 | lot of energy and they consume a off Ah, um uh, |
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42:54 | And they need a lot of calcium transportation in a lot of counseling for |
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43:00 | release. So this is a very organ. L energy, of |
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43:06 | is generated by modern Conry. In can remind yourself of the Krebs |
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43:12 | but essentially you have dietary and stored sources at the bottom, and a |
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43:19 | as protean should in fact, it on fire Olek Asset and goes through |
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43:25 | oxygenation process and conversion into the e . P on carbon dioxide. And |
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43:33 | have these crist a galley, this membranes on our remember and softer |
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43:41 | Bilal Khan DRI and in mitochondria and be located very much so around the |
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43:46 | , but also very much so within sin access and the genetic spines, |
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43:53 | look at the possible live it by uh, model. And it's |
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43:59 | It's also the fact that the plasma are the fossil lipid by Lares a |
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44:05 | dynamic structure that you have, channels with some trip Rodin's, |
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44:14 | channel Proteas. They're embedded inside this lipid by lair. It is actually |
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44:21 | just sitting there in space, but is constantly moving. It's constantly moving |
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44:29 | fluid. This environment underneath it is by side of skeletal elements inside of |
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44:36 | elements that are at the distal parts the synapses are also the most |
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44:42 | our man says So the composition of hospital it violated the plasma membrane gets |
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44:50 | , uh, and, uh, renewed by activity and by different environments |
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|
44:59 | the outside of the salad, the of the cell. So trying, |
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45:03 | , find this. Uh um, very cool movie. Give me one |
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45:12 | , please. Okay. This is very quick kind of a basic movie |
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|
45:18 | describes where I just talked about is fluid mosaic model off the off the |
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45:25 | membrane on the other cell at the the living machinery of beginner cell. |
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45:32 | the harsh conditions of the outside it stands the cells plasma membrane. |
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45:38 | crucial as this barrier is, it's flexible. It wasn't card enough, |
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45:46 | it might break and begin to Lipid molecules of the membrane, naturally |
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45:53 | in a double layer because their tails water, is their heads attractive, |
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45:59 | some cholesterol and a few couple and you have the basic structure of |
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46:05 | plasma membrane. Within these lipid we also find different proteins, which |
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46:12 | various things for the cell. For , they receive signals from the world |
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46:20 | or the transport nutrients it waste. denture composes the membrane with a combination |
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46:26 | mosaic of different lipids, carbohydrates and . And these molecules are not |
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46:35 | They constantly within the structure, fluidly their positions. The survival of our |
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46:44 | life rest on this veil of A simple membrane, just two molecules |
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46:54 | that's dictionary and when. When, it's when they're non station, where |
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47:01 | actually not stationary and when you think they're just bobbing around a little bit |
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47:06 | a very slow fashion. Some of receptor, uh, protean channels can |
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47:17 | the length of the entire cell within , the length of the entire synapse |
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47:24 | microseconds. So some of this movement insertion of the new Proteus into the |
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|
47:31 | because remember, the synapses ended very are possible. It that bile Aris's |
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|
47:37 | a very fast process. Okay, not according um, Now, if |
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|
47:47 | look at the side of skeletal elements narrows, you have micro tubules, |
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47:52 | filaments which are also Lomas intermediary fill and microfilm months. Um, |
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48:00 | the microfilm linens this has shown are smallest diameter side of skeletal elements are |
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48:06 | of the acting Bala kills. And you have a constant Poland memorization information |
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48:13 | these acting chains into microfilm nous and organization of break up a piece, |
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48:18 | filling this intra foreign chains that the chance or individual acting molecules altogether. |
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|
48:25 | new of elements are about 10 and meters in diameter, and they really |
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|
48:29 | ball like filaments of micro tubules are of like tubules that are organized from |
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|
48:37 | billion molecules arranging them in the tube spear like structures. If you look |
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|
48:43 | the right at the cross section, is a cross section through the axe |
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|
48:48 | The first thing to notice is that the outside of the axe onwards, |
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|
48:53 | Meilin axe on, you see these ? This is actual sheets of Meiling |
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|
48:59 | are raft up around axe on Honest cut in high. So you're |
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49:04 | through, sort of. Ah, , halfway through the accident, you |
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49:08 | the carrot in half care of this and you can see on the |
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|
49:13 | Here you see these sheets of my . Inside, you see these tubular |
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49:19 | highway, so you we would for as market tubular highways. And these |
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49:25 | micro tubules of micro tubular highways that be carrying the nutrients and the necessary |
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|
49:33 | molecules from the periphery and also from central locations in the soma into the |
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49:39 | peripheral parts of didn't rise and accents most of the biochemical machinery. The |
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49:47 | of the things that no, these still located around the soma. It |
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|
49:50 | to be transported a gust through the tubular dress board. But There is |
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|
49:56 | metabolic and independent metabolic and synthesizing machinery located at this and nationals as |
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|
50:04 | If we look at this stay in year, it's a three colors in |
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50:10 | . The yellow color, which is villain again, the yellow color as |
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|
50:14 | two billion, which stands for micro . The blue is active so |
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|
50:20 | Yes, for micro filaments. Acting of purple is this stain for the |
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|
50:27 | , and this is taken from a cell. But the reason why I'm |
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|
50:31 | you this is because it very clearly that the acting molecule, the smallest |
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|
50:38 | blocks of the side of skeletal are located in the most distal peripheral |
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50:44 | of the South, most closely associated a member Impossible it bit by layer |
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|
50:50 | the cell and the yellow tribulation, tubular, high oyster market tubules. |
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|
50:56 | very much concentrated around the SoMa unveiled certain processes, said radiate out of |
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|
51:02 | spinal blast sounds, whether in the of neurons would be gone. The |
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|
51:07 | , so when that tells you, the most dynamic element acting microfilm, |
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|
51:13 | looking at the very distant parts off membrane. Therefore, you will find |
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|
51:20 | polarization. Deep organization of these active , which would influence the shape of |
|
|
51:25 | plasma membrane, which would influence the of its UNIX science, which would |
|
|
51:31 | that function or efficacy of the doing or may breakdown of these active molecules |
|
|
51:40 | something good experience may be contributing to process of depression. And, |
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|
51:46 | the driving away off the necessary to it explains. I have the slide |
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|
51:54 | year, but I actually should have , much better sliced to share with |
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|
52:01 | recording. Uh, no. We about Alzheimer's disease, and when we |
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|
52:12 | about loss of memory, for and we talked about certain symptoms of |
|
|
52:18 | disease in our case, we're gonna talking more about neuropathology or false |
|
|
52:25 | And, uh ah, now the most important, um, features of |
|
|
52:35 | disease. No, psychologically of the off plaques they're referred to see now |
|
|
52:43 | . They're also referred to as bait plaques. Um, and you have |
|
|
52:49 | normal tangle formation and entanglement off, , information of these plaques, typically |
|
|
52:59 | of the cells and the closer toward so most of the south. They |
|
|
53:05 | the more been impact that will have the city of the South of depending |
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|
53:10 | where the plaques are located in what of the brain is gonna have the |
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|
53:14 | serious affect and damage in that part the brain. And the second your |
|
|
53:22 | feature is tangles. And, it says, dying neurons with tangles |
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|
53:29 | tall Prodi entangles performed so data amyloid and towel, Prodi and tangles, |
|
|
53:38 | Prodi and tangos. The reason why talking about that, uh, going |
|
|
53:43 | tangle op in the tangle lob the tubules, the tangle of the side |
|
|
53:49 | skeletal elements. And when the micro gets tangled micro tubules like you |
|
|
53:56 | they're like micro tubular highway, so tubular highways traversing through the processes. |
|
|
54:01 | so most of the euros are providing nutrients of transporting goods through the |
|
|
54:07 | Now what do you do with these ? Prodi? Entangles is you tangle |
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|
54:12 | the highways and what happens if you one over Passover that its major accidents |
|
|
54:18 | good scandal be delivered. And so start impairing the transportation off the goods |
|
|
54:27 | the sauce is well, eventually leading neuro degeneration leading to death off |
|
|
54:34 | dying murals with tangles and shrunken So what has shown here is the |
|
|
54:40 | of the healthy brain and then the divine stages of Alzheimer's disease. That |
|
|
54:46 | matter, especially the gray matter, known to be shrunken because of the |
|
|
54:51 | neurodegenerative processes. So these are pretty , dangerous of Alzheimer's disease and symptomatically |
|
|
54:59 | in early initial stages off Alzheimer's This is pathology fail, and we're |
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|
55:06 | about symptoms is what is happening to person. Short term memory loss, |
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|
55:11 | remembering, asking things the same Several cons a day. So start |
|
|
55:19 | that an elderly individual you just had conversation with them about Suzanne. And |
|
|
55:26 | minutes later or 10 minutes later, person will ask. So do you |
|
|
55:31 | Suzanne and you'll say, Well, just had a conversation about Suzanne and |
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|
55:37 | person, Uh, there's experiencing Well, look a little bit |
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|
55:43 | Uh, so confusion, which now on anxiety. Not not being able |
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|
55:51 | here everything correctly, maybe understand everything they and remember not remembering the |
|
|
55:59 | not remembering what you just discussed on short term, um, makes people |
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|
56:07 | , make people depressed and makes them withdrawing themselves from social interactions. |
|
|
56:18 | there is, um, also often confusion about the time of the |
|
|
56:25 | to when looking at the clock, could be seven o'clock and personal |
|
|
56:34 | They may forget that they just woke , and they may think that they |
|
|
56:40 | to go to that because it's in evening time some of the clocks or |
|
|
56:44 | of our time. So these are of the symptoms, and there some |
|
|
56:48 | that can be done to detect on symptoms of Offerman's this season. This |
|
|
56:54 | advanced stages. Now, when you in the brain and you see the |
|
|
56:59 | in the brain and see, maybe some questions, but this will go |
|
|
57:04 | your all time was Disease section, we will actually expand on. The |
|
|
57:09 | will look at some interesting things through course of the semester, so save |
|
|
57:14 | space under this, uh ah, , uh, disease section. Question |
|
|
57:21 | on the tangles between the same neurons different ones, so the tangles are |
|
|
57:26 | within neurons. The tangles are actually the neurons, but what they do |
|
|
57:31 | they wrap around and tangle of the . Tubular highways. The plaques that |
|
|
57:37 | data amyloid plaques are on the outside extra cellular. The protean aggregates that |
|
|
57:45 | together let me become calcified to sort like calcified lesions on the outside of |
|
|
57:51 | cell. But if those calcified lesions near Axiron, accidental function and accidental |
|
|
57:58 | and signalling is impaired. If it impinge ing and is located on the |
|
|
58:03 | and maybe some of the bias synthesis metabolic machinery is impaired. So the |
|
|
58:09 | of these blacks and I actually have very interesting article. I will post |
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|
58:12 | I publish with colleagues for Baylor College Medicine, where few years ago I |
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|
58:19 | a theory that the closer the plaques two neurons, the more impaired |
|
|
58:27 | uh, external firing going to And it wasn't sentient, unusual |
|
|
58:32 | except that I came up with a . I came up with a song |
|
|
58:36 | how we can measure the proximity that no methodology by which we could measure |
|
|
58:41 | proximity of the flax to certain And my colleague Matthew Raz Bond and |
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|
58:47 | got together Baylor College of Medicine and talented student. It is. Laborde |
|
|
58:52 | took upon this project, and indeed used an old way off, sort |
|
|
58:58 | a circular distance measurement that was used anatomical descriptions that we applied to look |
|
|
59:05 | the proximity and the correlation between the of the plaques to the accents in |
|
|
59:11 | to the level of the impairment by south of these toxins. So very |
|
|
59:16 | question. Okay, Okay, So you can share. Resource is |
|
|
59:25 | neurons that south? Yes. And more details that will discuss, for |
|
|
59:30 | , where we talk about hippocampus will back and talk about the semantic |
|
|
59:36 | So some of these, uh, about Alzheimer's disease are going to be |
|
|
59:41 | going through the semester. And it's interesting for me, because go that |
|
|
59:47 | seems to be causing pretty significant recovery is, like into traumatic brain |
|
|
59:53 | Some of it is like in almost like dementia like syndrome that seems |
|
|
59:59 | be transient. But in some patients lasts up to six months, which |
|
|
60:05 | really, really ah, significant, that the virus may not enter the |
|
|
60:11 | based on the articles that we looked . Okay, so let's go. |
|
|
60:18 | gonna partners, um, recording and moving on to Den Dries and you |
|
|
60:23 | to do. It expires that we . We have accidents coming out so |
|
|
60:27 | of the Denver rise would be sort apex. At the apex of the |
|
|
60:32 | bodies, the cell body here is is an exciting story, their own |
|
|
60:37 | Perama Nall cells that serve a shaped a three dimensional pyramid, with the |
|
|
60:41 | extra live containing the done drives from air called optical done dries. Of |
|
|
60:45 | down drives that are coming at the of the spare men are called basil |
|
|
60:49 | drives at the very bottom of the pyramid. You have the axe on |
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|
60:54 | acts on ratifies into collateral, so presence outfit as distilled terminal parts. |
|
|
61:02 | it also get contact cells along the . If you look at the pre |
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|
61:08 | terminal where you had excellent terminal, I mentioned, you will see a |
|
|
61:12 | of mitochondria there, too. Not a Selma's, but in the external |
|
|
61:17 | . The reason for it is because need a lot of energy. Diffuse |
|
|
61:21 | bicycle for exercise doses and back for psychosis. So once the nutrients that |
|
|
61:29 | the actual potential rise in the sudden pre synaptic terminal. Yeah, influx |
|
|
61:34 | Councilman Deep polarisation on fusion off Best possible number and release of newer transmitters |
|
|
61:41 | the synaptic class. And then they through the synaptic last 29 a meter |
|
|
61:47 | and Boston an ethically and these pasta densities binding to the respective receptor. |
|
|
61:54 | the state that is excited to re to make neurotransmitter glutamate is a major |
|
|
61:59 | for a neurotransmitter. The brain, pasta not preclude, um, interests |
|
|
62:03 | . That limit will bind to the , and the receptors will initiate cost |
|
|
62:09 | to the response of the cell of posson optic nerve and really depends on |
|
|
62:13 | type of there stab Chris that it with it. He's very specialized area |
|
|
62:18 | of sin options. Now extra synaptic outside of the synapses. You can |
|
|
62:22 | have receptors located there not as active don't contribute that much to levels of |
|
|
62:29 | , although they do contributes and levels activity that can also be actively recruited |
|
|
62:34 | the extra synaptic spaces. Mosey on you're the foster live with Beyeler through |
|
|
62:40 | fluid, most A into the synaptic based on demand, is the receptors |
|
|
62:46 | can also be internalized or they could inserted in the membranes of that process |
|
|
62:51 | dynamic to not only the movement through plasma membrane, but insertion of the |
|
|
62:56 | membrane or removal from the plasma membrane recycle on in the south machinery. |
|
|
63:05 | transport. You have supplies like transport a slow 1 to 10 millimeters today |
|
|
63:11 | fast except Kliment Ectoplasmic transport. that is 1 m today. Then |
|
|
63:21 | a great transport. Is all of molecules that are being used in terror |
|
|
63:26 | . That means from Soma through a . Retrograde is from the periphery and |
|
|
63:33 | into the soma. So you have micro tubular highways and you actually have |
|
|
63:38 | engine like motor like Prodi Incirlik And they will pass this this molecule |
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63:45 | their own will pass it, pass from one arm to the next arm |
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63:49 | the next time to the next time the next time. Carry it through |
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63:53 | Marco tubular highways. So contestant is do it in the entire great transport |
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63:59 | and dining him is another molecule that's for transporting goods in the retrograde life |
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64:12 | we can use different guys for horseradish peroxide days. Also, viruses |
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64:18 | so much about viruses. But viruses also great tracers because a lot of |
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64:24 | that say they, in fact the they may gets taken up by that |
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64:30 | endings in the periphery, such as the skin or in certain parts of |
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64:35 | brain map work. And then they retrograde. Lee transported retro Greenlee transported |
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64:42 | the so so this retrograde transport is great way to use for staining to |
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64:51 | where are the distal hands of these that are embedded in this piece of |
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64:56 | network or in this piece of the ? Where are the endurance of process |
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65:03 | from this particular part? Off the the structure We will wish you injected |
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65:08 | die so horse riders peroxide days much herpes and Rabies virus is we'll travel |
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65:15 | the retrograde like fashion and some Herbie Simplex virus, which caused the |
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65:24 | , can actually first cause chicken pox the per free and then travel into |
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65:31 | Selma's and into the spinal cord and . Dorman's of travel Retrograde Lyn ST |
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65:38 | months until fifties or sixties, when can reappear in a single spinal nerve |
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65:48 | shingles, causing shingles and reappear and and er greatly from the spinal |
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65:57 | Wrong. The dorsal root ganglion. roots house If you remember the dorsal |
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66:02 | of the spinal cord of travel back the periphery in the case of |
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66:08 | causing rashes and causing really painful, rashes and certain bands across the body |
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66:16 | associated with just that one single spinal one side that thus the body. |
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66:22 | viruses can also be used a When I said that damn tries in |
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66:29 | spines are acting sort of like independent and synthesis by. So this is |
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66:37 | , but this illustrates on the ride that end? That it did expire |
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66:40 | your Paul arrival SOMO complexes. So have my to Congress, and you |
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66:45 | a Paul Arrival Sobel complex system does necessary or the local bio synthesis so |
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66:52 | can think of these units, although connected to the big body. The |
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66:56 | that the whole damn drive the whole , these individual spines a someone of |
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67:02 | biochemical bias synthetic units. That means decisions can be made by the spine |
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67:10 | tracking with the rest of the But once again, just keep in |
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67:15 | that this is a complex process. Intel's usually activation of thousands of decent |
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67:23 | both an excited or anything inhibitory And the plasticity processes we discussed is |
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67:29 | activity dependent process. That means, say, if you are memorizing |
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67:33 | if you're developing that pathway, the between those neurons of those pathways done |
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67:40 | , and it expires. May increase number may increase insides. This is |
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67:46 | kid independent process. If you don't that title anymore, you're not exercising |
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67:52 | anymore. Those synapses may weekend. synapses may go away. It always |
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67:58 | , even for motor tasks. Cognitive , some plastic longer with motor tasks |
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68:04 | but even motor taxes for you forgot to play tennis after hold the racket |
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68:08 | . It may take a few Once you learn, it's because your |
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68:12 | that learn how to hold the racket play the times are now weekend because |
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68:17 | haven't exercised for a while. talents you're coming back to Tennison. |
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68:21 | re build these pathways, you re the Salar sisters dendritic spines and |
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68:29 | and the dream expires. This is final slide of the day the dude |
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68:35 | here from the normal infant shown on left and from a mentally retarded infant |
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68:42 | on the way. So, it is suspected in an autism spectrum |
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68:49 | . And there is ah syndrome called X Syndrome, where one of the |
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68:55 | marks off these neurodevelopmental and neurodegenerative disorders then are abnormal shapes. Abnormal numbers |
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69:07 | structures of the different expired structure equals , function, equal structure. Both |
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69:15 | inseparable. And so you can see by changing the morphology and the number |
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69:20 | spines, the processing along this complex down dried and you're on is going |
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69:27 | be very different on their four, in conditions such as autism spectrum like |
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69:38 | . I think he think to keep mind is that the image on the |
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69:41 | you have redstone access that are GABA , and these inhibit there is an |
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69:49 | and green synapses on the same cell are glued a mattress actress and those |
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69:54 | excited tourists. An absolute so when see is that these dendritic spines that |
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69:59 | see on the last that are expressed the dendritic trees of endurance there, |
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70:07 | by thousands off gabber allergic. The of looting, lethargic, excited tourists |
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70:14 | absence. So the job of this is to compute very quickly to |
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70:20 | to pay intention to strong synapses, compute to way out that excitation once |
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70:27 | an invention or innovation wins over depending on the type of task for |
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70:33 | level of activity that is happening in brain. Okay, so when we |
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70:40 | back, we're gonna, uh, talking and finish talking about narrows, |
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70:46 | then we're gonna talk about glial So we still going to continue talking |
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70:53 | neurons and glia. And if we're a little bit behind in our schedule |
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70:57 | the syllabus and will get adjusted and we will catch up on the following |
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71:03 | couple of electricity. So for I am |
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