| 00:04 | This is Cellular Neuro Science lecture And we will talk a little bit |
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| 00:11 | the origins, I would say of neuroscience uh for the rest of the |
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| 00:16 | 20 minutes or so in neuroscience. if you haven't taken my course |
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| 00:23 | if you have taken, do you what I asked you to do? |
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| 00:26 | said, look at the slide at very first lecture. I'm gonna look |
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| 00:28 | the slide at the end of the . So the same way with those |
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| 00:32 | haven't taken this course, just meditate this for a few seconds and see |
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| 00:36 | you understand. But it's an activity billions of neurons surrounded by glial cells |
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| 00:44 | form neuronal networks that communicate with each through specific connections or synopsis. And |
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| 00:52 | trillions of these synopsis that are formed neurons informing the high central nervous |
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| 00:59 | which is the brain with uh with , with the lobes, uh frontal |
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| 01:07 | , parietal lobe, temporal lobe, lobes, and of course, the |
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| 01:13 | stem and the spinal cord that goes the vertebrae. Of course textbook. |
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| 01:19 | the same textbook that I use for section 4315. But it's a different |
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| 01:28 | in particular. It's interesting that we through the beginning of this book and |
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| 01:34 | we go to the end of this , we kind of uh leave some |
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| 01:37 | in the middle and that's simply we cover a lot of information. And |
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| 01:42 | a while I didn't even rely on book for the cellular neuroscience course, |
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| 01:46 | they have improved it, updated it I found it pretty suitable for what |
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| 01:51 | want to cover this semester. Neuroscience comes in many different levels of |
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| 01:57 | We're going to focus on cellular At the very beginning, our understanding |
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| 02:07 | different functions of the brain came from loss of function studies. So this |
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| 02:14 | Doctor Paul Broca, the uh for , so we speak with the left |
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| 02:23 | . Now, the reason why he that is because he had a patient |
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| 02:30 | that patient had damage to this which is now called the Brocas area |
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| 02:40 | the left hemisphere. And patients that damage to that specific area, which |
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| 02:46 | called brokers area had expressive aphasia, aphasia is an ability to convey thoughts |
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| 02:54 | speech or writing. So it affects motor ability because Broca area here shown |
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| 03:02 | in blue is very closely located to primary motor cortex. So it affects |
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| 03:11 | ability to speak or write. And several brains by Doctor Broer were studied |
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| 03:20 | had damage to the same area and had expressive aphasia. There was also |
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| 03:27 | discovery of localization of specific brain Uh Shortly after Doctor Vernet discovered that |
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| 03:35 | damage to an area that is located in the temporal lobe and temporal lobe |
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| 03:43 | into the parietal lobes area. damage to Vernis area results in receptive |
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| 03:52 | which is a difficulty to understand uh or written language. So expressive is |
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| 04:01 | to express yourself or subject is difficulty receive that language. And it was |
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| 04:08 | clear that there are now two areas the brain Broca area responsible for expression |
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| 04:17 | Vernik area responsible for receptive and reception this speech. But it came from |
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| 04:24 | of function studies and it still is a gross anatomical level, not like |
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| 04:31 | , gross but gross anatomy and gross level. So big holes in the |
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| 04:39 | . Uh There's also another form of called anomic amnesia, aphasia, which |
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| 04:47 | the least severe form of aphasia. I think that I definitely suffer from |
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| 04:53 | after long weekends especially and having too fun and global aphasia, which can |
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| 04:59 | from severe and extensive damage to the and typically damaging large areas of the |
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| 05:08 | involving many many areas that process the and produce the language. And that |
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| 05:17 | another lesson from the slide is there one area responsible for language. There |
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| 05:24 | two areas, there are many areas are interconnected with their own specific functions |
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| 05:32 | language such as understanding it or expressing um and such now, one of |
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| 05:43 | most famous patients in Neurosciences concerns the of function as P GAUGE. He |
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| 05:51 | a massive accident in 1848 where this strip that he's holding that is shown |
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| 05:59 | the picture, this metal strip penetrated the bottom of the skull, through |
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| 06:05 | eye and exited out at the top the skull just like it was shown |
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| 06:10 | this diagram. And this is his skull in the FG skull. The |
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| 06:16 | and it's such a severe trauma. lot of people observing what happened, |
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| 06:22 | was a a fault explosive device that off, that set off this uh |
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| 06:29 | metal bar into his brain. Many that he was probably going to die |
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| 06:36 | that he's not going to recover. he recovers that he's probably gonna not |
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| 06:42 | able to walk or talk or be vegetable. And in fact, he |
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| 06:46 | not, he came back and he his job back. He could |
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| 06:51 | he could walk, he could you couldn't see with one eye, |
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| 06:54 | his behavior was awful and uh he aggressive, he couldn't control himself specifically |
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| 07:04 | aggression. And we now understood that large areas of the brain, it |
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| 07:10 | matter if you lose a large area the brain is what those parts or |
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| 07:14 | of the brain are responsible for. can lose much smaller area of the |
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| 07:19 | and not being able to see At all very small area of the |
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| 07:23 | or you can have sustained this damage that to large area of the frontal |
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| 07:30 | . But seemingly almost have all of functions except for behavioral cognitive aggression, |
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| 07:41 | functions that get compromised as a consequence the damage to the frontal lobe. |
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| 07:47 | still is a loss of function. still is on the gross anatomical |
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| 07:53 | And cellular neuroscience starts when it starts we can see the cells. So |
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| 08:01 | comes the cell theory and Neuroscience is neuron doctrine. In order to see |
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| 08:09 | , you need tools to see these and these tools are microscopes and only |
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| 08:15 | the 19th century and really talk about . Uh end of the 19th century |
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| 08:23 | when you have microscopes that have enough to see individual cells. But the |
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| 08:35 | presents a problem because if you just the brain out or if you cut |
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| 08:40 | brain into slices, you really don't anything, it's translucent. And therefore |
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| 08:48 | debate enrages in the field. The of reticular theory argue that all of |
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| 08:56 | brain, all of the neurons are of one humongous structure envelope by the |
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| 09:04 | cytoplasmic membrane. Therefore, they have continuity and they're all this massive multi |
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| 09:12 | structure that's all together CSI. And the opposing side, you have the |
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| 09:21 | doctrine. So Camello Golgi is a of the reticular theory, his student |
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| 09:27 | Cajal, which is probably one of most famous neuroscientists in the world |
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| 09:33 | undoubtedly in Spain Ramona Cajal is a of the neuron doctrine. And so |
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| 09:39 | Sir Charles Sherrington that comes into picture on, uh neuron doctrine argued that |
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| 09:47 | , this is not big clump surrounded one membrane. In fact that these |
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| 09:52 | individual discrete unit cells or later called that have their own membrane surrounding each |
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| 10:02 | individual discrete cells. And in order really understand the cells and to visualize |
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| 10:11 | cells in the brain, we needed . So Camelio Golgi invented the Golgi |
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| 10:18 | . Ramona Cajal was a student and Cajal used the Gogi stain under microscope |
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| 10:26 | perform these beautiful reconstructions. This is two eyes and the nerves. And |
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| 10:33 | can see that he drew the projections the eyes, some that remain on |
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| 10:39 | same side of so lateral others coming the nasal part of the retina here |
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| 10:45 | those would be in the middle are crossing over through the optics. |
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| 10:52 | he depicted these cells that are called cells in the cerebellum that to this |
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| 10:59 | are known to contain hundreds of thousands synopsis or points of contact onto |
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| 11:08 | Uh This is a reconstruction of the of the brain that will study in |
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| 11:14 | detail called the hippocampus. And he the cell or reconstructed the cell. |
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| 11:21 | these are not drawings that are called . So Golgi stain gets picked up |
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| 11:27 | a fraction of neurons And when you the Golgi stain, those neurons will |
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| 11:34 | all of their processes. So we'll the dendrites the dendritic projections. This |
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| 11:41 | the dendritic tree, the camus and the axons axons is where you will |
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| 11:47 | the synaptic transmission, take place of between the neurons. And even so |
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| 11:55 | this stain, uh you can see lot of details, you can even |
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| 11:59 | dendritic spines using Golgi stain and Golgi is still actually used to study some |
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| 12:05 | the dendritic spine anatomy, static But you cannot uh visualize those |
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| 12:13 | the space between neurons and how they to each other is very small. |
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| 12:17 | so Goji probably takes these drawings and says, so what they're still all |
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| 12:23 | , even if you're showing me these tree that does not agree with |
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| 12:28 | How now uh in addition to the stain, there is another stain that |
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| 12:35 | our understanding of the anatomy of the . And that is the Niel stain |
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| 12:41 | contrast to Golgi stain, Nel stain picked up by all of the |
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| 12:47 | all neurons and all gluon. So stain gets picked up only by a |
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| 12:52 | of neurons and it will expose their brilliantly, all of the processes. |
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| 12:59 | stain will get picked up by all the neurons and glia and where you |
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| 13:03 | darker bands, this indicates higher densities higher presence packing densities of certain |
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| 13:12 | But Nissel stain does not reveal all precise morphology of neurons, the dendritic |
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| 13:20 | axonal projections. Instead, it is great tool to describe the architecture. |
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| 13:27 | overall what we call cyto architecture of brain cyto architecture is if you think |
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| 13:35 | the Celsus bricks, how they how densely are they stacked? Which |
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| 13:41 | are they pointing in that stack? so there are these methods that architectonic |
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| 13:48 | um that with the help of this , you get picked up by RN |
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| 13:55 | or polar ribosomes uh mostly near the right Irish expression of those would be |
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| 14:02 | the SOMA exposing all of them. um not a great tool for morphology |
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| 14:08 | individual neurons, but a great tool cytoarchitecture of neurons uh and neuronal |
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| 14:15 | the brain as a whole. So and Brodman uses Nissel stain and comes |
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| 14:22 | with broad areas of the brain where basically describes the cyto architecture of different |
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| 14:29 | in different parts of the brain. standard light microscope, if we look |
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| 14:40 | the standard light microscope, even if can go to 0.1 microns micrometers. |
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| 14:50 | let's start with this one centimeter is . How many micro meters? One |
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| 15:05 | ? 10,000? How about one millimeter have my phone or maybe a |
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| 15:18 | So one it's like 1,000,000 micro uh . So then centimeter is 10,000. |
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| 15:32 | . Oh All right. So this is 0.1 micrometer. What is that |
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| 15:46 | ? This Yeah. So that's the microscope. Maybe you can push it |
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| 16:01 | but you cannot, you cannot see uh or greater resolution, higher resolution |
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| 16:10 | oops runaway mouse uh the space between two synapses. So the space where |
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| 16:23 | neuron is going to release the chemical and the next neuron that has receptors |
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| 16:32 | going to receive this neurotransmitter. This here is 20 nanometers in chemical |
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| 16:41 | So now you cannot visualize, you have enough of resolution. If you're |
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| 16:48 | this is 20 nanometers and the resolution 100 nano meters, then no, |
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| 16:54 | will just see uh one point. electron microscopes which come about in the |
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| 17:03 | century, middle of the 20th century down to 0.1 nano be dis |
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| 17:10 | So those are sufficient enough to to visualize the synopsis that space actually. |
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| 17:23 | to visualize neurons, we don't need these days, we can still use |
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| 17:30 | , we still use a lot of . There's a whole chapter of stains |
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| 17:36 | sigma which that you can order for or different molecular stains, different cytoplasmic |
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| 17:43 | skeletal elements, anything you want. in electrophysiology and we'll talk about |
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| 17:50 | of course, quite a bit in , we use infrared microscopy. |
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| 17:57 | Ir so if you place a slice the brain and you expose it to |
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| 18:03 | wavelength of light and in the you have the Ir Camera, infrared |
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| 18:10 | , you can visualize individual neurons to individual neurons. Again, you don't |
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| 18:16 | that resolution of a single synapse. if you're talking about the scales, |
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| 18:22 | synapse is 20 nanometer. This is C OK. The cell is typically |
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| 18:33 | 10 micrometers of the the neuron. can be smaller, can be large |
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| 18:40 | it can be very large, can very small in some instances. But |
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| 18:43 | the most part, it's about 10 in di so can visualize these neurons |
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| 18:50 | . We can target them with the tip of the microelectrode that reports |
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| 18:58 | this cell or another cell. So tip of the microelectrode is typically one |
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| 19:05 | to one micrometer. So we can this technique, infrared microscopy or infrared |
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| 19:15 | . Uh you're not looking into the objectives here. This infrared camera is |
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| 19:21 | to a monitor and it shows you picture we can't see an infrared |
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| 19:25 | But it it shows it on the , we can see it and we |
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| 19:30 | now perform electrophysiological recordings by targeting the of interest with the micro electrons. |
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| 19:38 | is important uh aspect of neurons, spines that cover dendrites. These are |
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| 19:49 | , those protrusions come in different You can see that these dendritic spines |
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| 19:56 | contain PSD stands for den for dendrite , for cross synaptic density. They |
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| 20:02 | contain a lot of receptors and they're to the presynaptic terminal. So this |
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| 20:09 | the presynaptic terminal that contains these round vesicles that will contain neurotrans livers. |
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| 20:17 | most of the points of contact that onto neurons happen. The synopsis are |
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| 20:23 | on to these dendritic spines from axons the dendritic spines. So, there |
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| 20:29 | different variations and exceptions of how the and where they're formed, it can |
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| 20:34 | even formed between two dendrites. But the most part, they are a |
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| 20:41 | somatic or axodendritic and dendritic spines can for a lot of points of contact |
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| 20:47 | that dendritic uh tree. All So I think we're almost out of |
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| 20:56 | , but I would like to draw attention to the fact that in modern |
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| 21:02 | neuroscience, we can visualize individual molecules visualize individual dendritic spines. We can |
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| 21:10 | activity in single cells and networks of . And also in the clinical |
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| 21:16 | we can visualize the brain network This is using positives on emission tomography |
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| 21:22 | looking at the words will engage certain of the brain. Speaking of the |
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| 21:27 | , another part of the brain listening the words, another distinct oh brain |
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| 21:32 | will be produced because it shows the of neurons in that area and then |
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| 21:38 | of the words good. There are is this slide, there's three more |
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| 21:46 | that I'm not going to cover I'm gonna leave it here. But |
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| 21:50 | will mention this because a big problem neuroscience and in cellular neuroscience has been |
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| 21:59 | deep can you observe things even in imaging? When we talk about positron |
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| 22:05 | tomography or even F MRI functional Magnetic Symmetry. It's like how deep can |
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| 22:12 | see how deep can you record real ? So you can see pretty deep |
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| 22:17 | these, with these techniques pet scan MRI with electrophysiology, you can record |
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| 22:24 | deep as you can penetrate inside the . So what typically is on the |
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| 22:31 | ? And a lot of these techniques we have non invasive techniques that can |
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| 22:35 | activity deep will not do it on cell level, we'll do it on |
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| 22:40 | network level. And so that's where experimental neuroscience comes comes into play again |
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| 22:47 | techniques like two photon imaging analysis, photon imaging. This is done in |
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| 22:54 | imaging of neurons imaging of their activity within this is cortex and you can |
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| 23:03 | from 0 to 1000 micrometers deep. is almost the entire depth of the |
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| 23:10 | cortex. So this is another thing we're after we're after spatial resolution. |
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| 23:17 | we image individual cell synopsis? How connect molecules where after after death, |
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| 23:24 | deep can we image these things? deep can we understand this normal |
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| 23:29 | not just on the surface of electrodes also using microscopy techniques like three photon |
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| 23:37 | . All right. So I'm gonna here when we come back, we'll |
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| 23:39 | a little bit about artificial intelligence and it uh it can be used potentially |
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| 23:47 | neurological disorders. This is another point interest for some of you that mentioned |
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| 23:52 | you're interested in what happens in And I didn't go over the third |
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| 23:59 | of the course in the syllabus. our third section of the course is |
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| 24:05 | heavily focused on several neurological disorders uh we will instead of spending 1015 |
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| 24:12 | we will spend a whole hour and minutes or in case of epilepsy, |
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| 24:17 | three hours talking about epilepsy and understanding mechanisms, cellular mechanisms and uh some |
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| 24:24 | the clinical aspects like symptomology as well therapy for, for these disorders. |
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| 24:30 | . Thank you very much. Have great weekend this weekend. All |
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| 24:34 | And I'll see everyone here on |
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