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00:00 | Mhm. This is neuroscience midterm one session And we'll actually start talking about |
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00:11 | because it hasn't gone away although it reduced the infection And the threat of |
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00:20 | has reduced significantly with this are micron going away slowly and hopefully there will |
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00:28 | be another wave. But from day we talked about how this virus And |
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00:36 | other viruses. So COVID-19 is just of the viruses that is out |
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00:42 | Oh this particular virus though enters into brain. And so we discussed a |
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00:50 | topics such as fire amia infection in blood. We discussed entry through nasal |
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00:58 | through these um through these very specialized in the skull here, through which |
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01:09 | olfactory nerves enter into the nasal And so these will be physical openings |
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01:17 | these what is called crib reform quibbles form plate or creek reform formation |
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01:24 | that will have these administrations. So virus can enter directly into the olfactory |
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01:32 | and caused the infection here. Cause the infection of the nerve endings which |
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01:38 | result in the loss of smell. so the virus can just be inhaled |
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01:46 | if you may into the brain. some instances Baier EMEA is one blood |
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01:53 | the virus enters into the blood either ventilation through the lungs that carries that |
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02:00 | and infection of the lungs that carries virus into the blood or through hands |
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02:07 | mouth going into your system into the system, staying there and being absorbed |
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02:12 | the blood. Once you have infection COVID-19, there's a significant hypoxia lack |
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02:21 | oxygenation. So if you have a infection, you're not delivering enough oxygen |
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02:26 | and lack of oxygen can compromise the brain barrier. And now you know |
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02:31 | lot more about blood brain barrier than did the first lecture. Remember that |
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02:36 | Cov two which is a studio separates neuronal tissue. This is where the |
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02:42 | protium hangs onto this engine tents and enzyme to receptors and they are present |
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02:50 | neurons. So that's how it's capable entering into the brain tissue is capable |
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02:56 | infecting there are so this epithelial circuit haven't discussed in great detail and we'll |
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03:06 | back to it later and of but what we have learned in the |
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03:11 | is the fact that this blood brain is controlled very titling, having the |
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03:17 | yourselves that make it up. And also have Astra asides that are part |
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03:21 | the checkpoint for the substances that would exiting out of the blood and entering |
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03:29 | the brain. And you have Ace receptors in the cns and you have |
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03:36 | in the in the glial cells. cells and neurons allowing for multiple sides |
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03:43 | invasion and infection. And if there a compromised blood brain barrier then you |
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03:48 | that the barrier will be leaky, for more viruses and other compromising molecules |
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03:55 | leak into the brain promoting this So now when you look at this |
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04:01 | , you also understand the ostracized, role of blood brain barrier as well |
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04:07 | that agree ourselves, which we will back to in a second. Now |
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04:14 | last slide we discussed as overview of major type of physiology ease viral entry |
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04:24 | the brain, adverse immune response respiratory as well as major symptoms. Main |
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04:30 | such as headache and vertigo or the . N. S. Major symptoms |
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04:37 | somebody suffered from major symptoms of COVID-19 brain, they may suffer stroke, |
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04:45 | or infection of the brain and this accurate necrotizing encephalopathy, also known as |
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04:53 | of infection induced by accuracy falopa. it's basically a massive, accurate necrotizing |
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05:02 | , massive inflammation of the brain and or death of the cells hemorrhaging means |
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05:09 | of blood in the brain tissue. are the major major ones that can |
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05:16 | in the CNS and the peripheral nervous . The major things that we talked |
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05:22 | are a Nars mia and a Er These are the main symptoms and |
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05:29 | major symptoms we didn't really discuss but really in a bar syndrome, the |
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05:34 | fisher syndrome, a lot of it to do with very good loss of |
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05:38 | and such. So these are the that virus does lost me and his |
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05:44 | of sense of snuff, loss of is also because you would have infection |
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05:51 | the nerve endings in your mouth that and deliver the perception of taste of |
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05:58 | taste. So manifestations as if you hospitalization with Covid 19 and 2020 45% |
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06:12 | those with respiratory illness, 85% of with acute respiratory disease syndrome. They |
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06:19 | neurological abnormalities from encephalopathy encephalitis. We talked about encephalitis when we talked about |
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06:26 | Myelin nation. Ischemic stroke, close complications and intensive care, neurological manifestations |
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06:35 | your in intensive care and intubated. affects your whole body, your brain |
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06:42 | and also psychological list is a long to recovery After COVID 19. |
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06:54 | We talked about the history of neurosurgeons I specifically talked about COVID-19 because it's |
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07:00 | relevant to what is happening. And said as if the first lecture you're |
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07:05 | about the blood brain barrier, it's politis, infections, hemorrhaging. Those |
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07:10 | maybe the terms you heard the very time. And then throughout the first |
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07:15 | of the force, you already heard terms repeated several columns. So now |
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07:21 | like to tell you that. For , when I showed you the slide |
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07:26 | , I said, let's think about much you know about the slide. |
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07:29 | let's think about how much you will about the slide later in the |
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07:35 | And so we'll look at the slide at the end of the course and |
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07:38 | see how much you remember and understand you can conjure up in your |
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07:42 | As you're looking up at the slide first uh neurosurgeons. As we discussed |
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07:50 | these prehistoric neurosurgeons that we're performing brain relations that were done often multiple times |
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07:59 | to treat hemorrhaging of normal fluid formations the brain. In Egypt mambo tap |
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08:08 | the brain and the brain functions, Egyptians considered the heart is the most |
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08:13 | for him ingredients. It was Hippocrates already realized the importance off the brain |
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08:22 | the most important organ. And so , this is a major shift from |
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08:29 | in ancient Greece, but at the time even at that time there's still |
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08:34 | in the points of view. The is viewed as our conditioner and some |
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08:41 | like Aristotle in ancient Greece still think the heart is the most important but |
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08:45 | is already shifting. And then before times was not really possible to do |
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08:53 | of the brains and look inside the body for dissections. So until then |
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09:01 | lot of anatomy was derived based on paige anatomy and then part of the |
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09:06 | anatomy glimpses of it that could be following the injuries. But in renaissance |
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09:14 | . Andrews, Scalia's starts describing the localization of brain function. He finds |
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09:21 | large ventricles in the brain and distinguishing white and gray matter Grenada. Card |
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09:28 | this um understanding of reflexive behavior but in the Western our culture describes the |
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09:40 | body relationship but treats the body and brain is the fluid mechanical mechanism |
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09:51 | And so the postulating that nerves are some sort of gas or water and |
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09:58 | Lonnie discovers that nerves actually generate electricity can contract the muscles. But we |
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10:06 | know the major divisions of the the brain and the spinal cord. |
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10:11 | nervous system. Brain divided cerebellum, brain stem spinal cord going down when |
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10:18 | have pairs of spinal nerves rating a in between each vertebra all the way |
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10:25 | to the bottom of your feet and brain itself. The cerebrum is divided |
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10:32 | lobes, frontal, parietal, temporal lobe, cerebellum in the back |
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10:39 | the brain this is brain stem, and parietal lobes are separated by central |
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10:44 | focus and the sylvian fissure separates the lobe from the parietal and frontal |
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10:51 | All of the sensor information. We'll in through the dorsal ganglia themselves and |
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10:57 | enter into the dorsal part of the cord will be processed there and the |
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11:02 | neurons from the ventral part of the cord will be executing the motor commands |
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11:06 | the contraction and relaxation of the And then we talked about in the |
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11:13 | century and 19th century and up until the liberalization of the brain function was |
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11:19 | important and criminologist approach that by looking the surface of the scholar and measuring |
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11:24 | of the skull. subdividing the brain many different parts responsible for different |
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11:30 | So they were not completely right in early recognition of specific brain functions came |
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11:39 | injury experiments, loss of function experiments broken, discovering Broca's area responsible for |
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11:46 | aphasia veronica discovering veronica's area responsible for aphasia. We also discussed the |
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11:54 | amnesia, aphasia and global aphasia as . And finally we have this most |
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12:00 | patient in neuroscience genetics gauge that suffered massive trauma to the brain last as |
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12:06 | and suffered from personality and aggression issues did not lose some of the major |
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12:13 | and abilities. And uh example of . Darwin was used that animals when |
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12:20 | are in different environments, they change outside appearances but their outside appearance system |
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12:27 | on the outside is also reflected, in the brains. And so we |
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12:31 | out that animals like rodents and sniff will have very large factory involved in |
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12:37 | matter sensory sensing Oregon is gonna have barrel cortex where each barrel actually represents |
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12:45 | whisker the whisker pad, more sophisticated also like non human primates and humans |
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12:52 | use vision will have very sophisticated visual in the back of the bread. |
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12:58 | so in the 19th and going into 20th century, there's a raging debate |
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13:03 | the brain, the neuron doctrine versus articular theory. Familia ecology and then |
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13:09 | Ramona alcohol draws these cells and Charles coins the term synapse and describes it |
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13:19 | if you recall harmonica, How do beautiful circuits describing the dendrites, the |
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13:24 | coming into the cinemas and then the these black arrows that indicated the flux |
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13:29 | what we call the principle of dynamic through the accents that are interconnected to |
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13:33 | adjacent neurons in the circuit. There's stain in addition to Golgi stain. |
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13:42 | Gold Standard stands only a fraction of and reveals all of their processes in |
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13:47 | detail. And this will stain will in all of the neurons and glial |
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13:51 | . And it's really a great way use our site architecture of the cells |
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13:57 | the densities stacking the layering of the and the brain, comedian Broadmoor described |
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14:04 | video and broadband areas based on the , implying that this anatomy will also |
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14:09 | a different functionality for different parts of brain, neurons are very small. |
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14:15 | if we want to visualize them individual we can use live microscope. But |
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14:23 | we want to visualize individual dendritic spines then the individual synapses, we have |
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14:29 | go too much higher resolutions, such an electron microscope. However, in |
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14:33 | days you don't always have to use stains to visualize neurons in the tissue |
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14:39 | the brain slices. At least you visualize them using the furniture, infrared |
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14:44 | . Without a stain. You can these neurons and then bring up the |
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14:48 | electrodes and perform military physiological recordings that talked about, such as the whole |
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14:54 | patch clamp voltage clamp recordings and these of setups that you see here. |
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15:01 | current view of understanding of the brain quite complex and we understand it from |
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15:06 | level of a single molecule and even single single molecule and a single |
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15:12 | And it expires to understand the brain plastic and these finds rearrange themselves and |
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15:19 | it on the cellular level, but on a macro level and on the |
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15:23 | level. This is an example of human brain energy using positron emission |
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15:30 | pet scans when we understand the different of the brain now we can actually |
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15:35 | it functionally with alka loss of can visualize what parts of the brain |
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15:40 | active during specific tasks. And so have functions that are happening in parallel |
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15:49 | also in series and parallel. We two eyes processing visual information in parallel |
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15:55 | they have overlapping field of view in . That visual information will get more |
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16:01 | from the retina into the following list into the visual cortex where the visual |
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16:07 | of view will get formed. So serious it's hierarchical, being more |
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16:10 | Apply. We talked about the professionals neuroscience such as neurologists, psychiatrists, |
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16:17 | . You're a pharmacologist uh neuropathologist. you can review these. This is |
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16:22 | for your my method to know what be done with this type of science |
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16:27 | this type of mt through the following covered neurons and glia neurons comprising in |
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16:36 | by self population, about 10 Of of the brain cells. And we |
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16:42 | are a lot more numerous, 90 of the science of his knowledge of |
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16:47 | murals as we discussed and europe's have similar anatomy and organized structure. Too |
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16:58 | songs that you have already studied in body but it also has very distinct |
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17:03 | . It has these axons and thereby . They have those of frontier, |
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17:07 | these damn rights and you have been spine formation and the applicable and basil |
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17:13 | rights. And this is the side the synopsis that takes place and Selma |
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17:18 | integrate all of this electrochemical activity and Kellogg axel initial segment. This is |
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17:25 | we will produce the forward and the propagating action potential. Some of the |
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17:31 | things on transcription and translation um formation the proteins inside the south. We |
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17:40 | these micro raises a great method basically or having a bird's eye view on |
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17:50 | gene expression has changed and brainwashing versus to a tissue along versus tissue to |
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17:56 | conditional on versus condition too. So discussed this technique and it is a |
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18:01 | way to is the synthetic DNA with specific sequences to track the over expression |
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18:09 | expression of genes in this type of smooth and the plasma critical er Perata's |
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18:20 | in neurons demand a lot of energy that's where a TPS produced the main |
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18:25 | of energy. Uh neurons demand a of blue coast to oxygen. So |
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18:32 | there is an increased firing or activity neurons, increased consumption rates of the |
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18:39 | of oxygen increase. Also consumption of and http the mitochondria gets very much |
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18:47 | . We talked about possible lipid bi and if you recall we watched movie |
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18:53 | fluid mosaic model and how dynamic these components. Cell cell membrane attached components |
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19:01 | trans membrane components actually moved through the through this lateral diffusion through the membrane |
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19:08 | a way. And if you rearrange mosaic of the member and you also |
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19:17 | the activity on the member in properties underlying these membrane structures, you have |
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19:24 | of skeletal elements. Three types of migratory peoples in europe elements and um |
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19:30 | filaments. Micro filaments comprised of active are the smallest micro tubules. As |
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19:37 | can see here the myelin surrounding axon these micro tubular highways that are very |
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19:44 | for acts of plasma transport from Soma into Soma. And this example illustrates |
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19:51 | you will see larger two billion molecules the yellow located at the core of |
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19:56 | south, closer to the nucleus and smallest elements that can prelim arise And |
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20:01 | problem arise for longer and shorter chains reshape the outer boundaries of the plasma |
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20:08 | . The active molecules will be located the most difficult boundaries of the |
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20:14 | closest to the to the plasma We next talked about Alzheimer's disease and |
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20:25 | asked you to make a patient Alzheimer's and to write down all of the |
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20:31 | because all of these are gonna be questions. So I'm not gonna go |
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20:34 | great detail what we talked about. we talked about the prevalence of the |
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20:40 | when it starts occurring some of the symptomology, some of the advanced symptomology |
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20:47 | the disease. And in particular then focused on the pathology of the disease |
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20:52 | we didn't cover the pharmacology or neuro pharmacological treatments of the disease which will |
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20:58 | in the future. But for the homeworks of pathologies to cellular there is |
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21:04 | of amyloid beta plaques outside of the and once they start forming outside of |
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21:10 | south they cause inflammatory processes. There's of marco glial cells and they physically |
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21:17 | killing neurons and affecting the signaling and in these neurons. Intracellular early you |
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21:24 | your attribute early tangles and those neurotic tangles can now tangle up beside his |
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21:30 | elements and compete with the transport inside south. On the outside the gross |
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21:37 | anatomical features of Alzheimer's disease severe. disease will be significant loss of neurons |
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21:45 | degeneration. Deputy neurons shrinkage of the shrinkage of the brain matter as well |
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21:52 | the white matter is that these are of Alzheimer's disease that we've discussed. |
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22:08 | instead of that slide, that is slide that we've discussed now these are |
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22:13 | of the features of neurons with their and external terminals that will already be |
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22:20 | seeing loaded with mitochondria energy that is for synaptic vesicles refused to release the |
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22:28 | in the synaptic collapse. Transposon there will be receptors that will cause |
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22:34 | potentials in the synopsis, excitatory inhibitory town shops. There's two types of |
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22:41 | and territory transport by knesset and retrograde by dynamic is also slow ectoplasmic transport |
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22:48 | fast and supplies and transport. Some the dyes like horseradish, peroxide AIDS |
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22:53 | herpes virus or rabies virus retrograde lee from the periphery. For example, |
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23:01 | the injection into the stillness of the can reveal the exact area that is |
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23:05 | processed from that area of the skin neurons. The soma. Is that |
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23:11 | that specific information from that area. retrograde transport. Hundreds and dendritic spines |
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23:17 | incredibly important for normal development. Dendritic will contain synaptic polarized bizonal complexes and |
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23:26 | will contain mitochondria, making the dendritic somewhat of a biochemical independent units that |
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23:34 | spines, densities, shapes and their of communication will depend on activity and |
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23:40 | and is very much involved in the processes. And so we discussed another |
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23:46 | here and I will not talk in detail remind you to go through your |
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23:50 | , autism spectrum disorders under that umbrella X syndrome. And it's a mental |
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23:59 | retardation that is associated with the loss dendritic spines and proper shape and density |
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24:06 | of the dendritic spines and it's very that you have the exact anatomy and |
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24:12 | of these finds because exactly turn inhibitory decided to glutamate inputs inhibitory Gavin inputs |
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24:18 | be processed by these neurons, neurons integrate and information and producing action potential |
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24:24 | not. So please remind yourself of fragile X syndrome. Some of the |
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24:28 | that we discussed in particular with that and how that disease is very different |
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24:34 | the Alzheimer's disease that we discussed. are the four functional regions the input |
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24:40 | from lockdown output region targeting different muscles, capillaries from the brain. |
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24:47 | then we talked about classification of neuron we talked about you know polar bipolar |
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24:53 | uni polar cells here the studio unit cell is the dorsal root ganglion |
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24:58 | We talked about most of the neurons the brain of multipolar and we have |
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25:02 | lot of details from motor neuron and in the criminal south. And this |
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25:06 | a beautiful park in the cellar sarah . So we can classify neurons using |
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25:12 | . We can classify neurons using their with their production cells or local inter |
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25:18 | whether they're excited to inhibitory and finally they express specific cell markets and what |
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25:24 | potential frequencies they produce. This is hippocampal circuit. And in Hippocampus we |
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25:29 | about these 21 different subtypes of they their into neurons that are local into |
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25:35 | and those local inter neurons will be excitatory cell activity and this excitatory cells |
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25:41 | projection cells and will project that activity of the hippocampus into the other adjacent |
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25:47 | . And so they inhibit their into . And the classification of these subtypes |
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25:51 | based on their morphology. The right done rights whether they have horizontal or |
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25:58 | down rights. The axonal projections on barometer, sauce Ocloo cops their specific |
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26:06 | markets uh that are necessary that they in order for us to subtype and |
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26:13 | that. We're doing an experiment for from a specific sub type of |
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26:18 | These cells will also have this thing frequencies and these firing frequencies is like |
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26:24 | dialect and this dialect is created by different subtypes of channels and different cells |
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26:31 | and there are different I. Curves that you learned about recently. |
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26:35 | this is an example if you plug an electrode into these different neurons and |
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26:41 | patch of the cortex. Most of fire and diversity will come from the |
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26:46 | into neurons and they will be responsible creating the diverse rhythms and complex computational |
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26:53 | in the brain. We then moved to talk about leah. We talked |
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26:58 | my elimination of the PNS by Schwann and the CMS by illegal down her |
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27:05 | . Loss of Myelin nation can resolve two disorders that we talked about multiple |
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27:12 | Which is linked to chromosome 18 mutation it's also an auto immune disorder. |
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27:19 | sclerosis and we took some notes and sclerosis and I urge you to go |
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27:23 | and review it. We talked about experiment here of the shiver mouse and |
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27:28 | demoralization can recreate some of the symptomology just travelers and convulsions that you'll see |
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27:34 | multiple sclerosis. And then we moved and talked about chromosome 17 gene duplication |
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27:40 | leads to fart like Marie Tooth disease symptomology. And the treatment with braces |
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27:48 | you can use for sharp but mer disease. The major subtypes of glial |
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27:53 | . We discussed our micro glial cells are the most mobile units involved in |
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27:59 | repair of the cell activity. And talked about astrology. Astrocytes astrocytes involved |
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28:06 | blood brain barrier. But astrocytes are involved in the regulation of the synoptic |
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28:11 | and of the genesis, birth of synopsis and also regulation of glutamate and |
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28:16 | of synaptic transmission. Legal dinner sides responsible for my elimination of fandom ourselves |
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28:22 | the cerebrospinal fluid from interstitial brain He also served as a precursor cells |
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28:30 | the last cell that is not shown here that we described as a radial |
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28:35 | cells which is also very important from own migration. Uh So these links |
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28:41 | movies are in your class supporting electoral . Please review them and also remember |
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28:47 | real cells do not produce action potentials rather they communicate in these calcium like |
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28:55 | . This is quick review of everything we just discussed the neurons, the |
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29:00 | of firing neurons, the glial the two disease models and the blood |
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29:07 | barrier. The structure of the blood barrier that astrocytes play a roll around |
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29:13 | the fact that not everything passes through blood brain barrier. So it's a |
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29:16 | thing but it is also a challenge you're a pharmacological drug treatments in |
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29:22 | Then we moved on and started talking neuronal control, wrestling member into |
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29:31 | Interesting number in potential is about The fluctuations you have a separation of |
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29:37 | . And then we talked about how charge has to flex very quickly. |
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29:41 | so we described three cell types subtypes . I asked you to know all |
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29:47 | the details from the sensory neuron and he turns and you're on r the |
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29:53 | cord and on the motor neurons. know what types of cells they |
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29:59 | Susan you know Polamalu bipolar, what of neurotransmitter release they released and whether |
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30:03 | excited or inhibitor. And review this simple reflex arch and this very simple |
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30:11 | tendon reflex uh circuit. So then talked about ions how there is unequal |
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30:19 | of charge, how there is a of sodium and chloride on the outside |
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30:24 | there's a lot of potassium on the and how there's a highest disparity actually |
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30:30 | a lot of calcium on the outside very little calcium on the inside and |
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30:34 | you have these ions that will be part driven by their concentrations, radiance |
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30:40 | gradients and the problems that will always and make a pump that will always |
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30:45 | against the concentration gradient. So I also passed through the ion channels |
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30:51 | are comprised for me, no assets are strung into these very complex |
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30:56 | extraordinary structures, making subunits subunits coming forming ion channel ion channels are |
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31:04 | they will be selected for sodium and ions and there are certain rules for |
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31:09 | selectivity alms law. We started talking all these lofty equals I. |
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31:17 | So remind us of of those And also the fact that if you |
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31:22 | had simple diffusion laws and the channels open and sodium chloride that is high |
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31:27 | the outside will flow inside the cell it reaches people in all the concentration |
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31:32 | both sides. But that is not the case because we have electrical forces |
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31:38 | we have a charge on piles and this case actually we're talking about the |
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31:47 | and uh where you have a lot potassium concentration on one side of the |
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31:53 | membrane and an a minus and negatively ion that doesn't have a channel that's |
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31:59 | and negatively charged podium that's accumulated on side, the potassium will start flowing |
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32:05 | its concentration gradient. But as soon potassium incomes as the positive charge build |
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32:09 | year due to its own flocks that positive charge will start repelling potassium. |
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32:15 | is where you have the equilibrium equilibrium potential is where diffusion a little |
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32:21 | gradient forces and electrical forces are equal each other. And there's no net |
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32:26 | movement, there's no net flux going . So we talked about this concept |
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32:32 | potassium to sodium and we said that is a way if you know the |
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32:38 | of these islands on the outside versus inside, you can calculate the equilibrium |
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32:44 | for these islands. So we used first equation 2.383 Rtz f log of |
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32:49 | on the outside versus inside. In these different values for reversal, controls |
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32:56 | calcium fluoride and sodium. Okay, review this and learns the equation is |
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33:03 | involvement equation because learns the equation calculates potential involvement equation, calculates membrane potential |
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33:11 | takes into consideration the same formula as equation the same abbreviation right here of |
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33:22 | R. T. Z. But now you're taking a log of |
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33:26 | than one ion concentration of potassium and and you're also taking into account their |
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33:31 | p here stands for permeability. So we talk about these two formulas, |
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33:41 | different. This is the equilibrium just one ionic species and this is |
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33:48 | potential which is can be 2344 It depends really on their permeability. |
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33:55 | For for that given moment in time talked about how if you have rises |
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34:01 | localized potassium concentrations it can cause massive and deep polarization. So the astra |
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34:07 | in addition to controlling synaptic transmission and neurotransmitters will also control these locally increased |
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34:16 | of potassium and calcium will slurp without their network and distributed through the specific |
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34:22 | and that interconnected extra civic network. we talked about roderick Mackinnon, how |
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34:28 | is a wonderful individual that was driven the quest to determine the structure of |
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34:32 | potassium channel. So he used different . He used fruit flies and did |
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34:39 | mutations and fruit flies and he was for the sequences that are concerned the |
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34:44 | acid sequences that were important in regulating channel structure. So he was using |
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34:50 | and electrophysiology. Toxins would bind to parts of this channel and affect the |
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34:55 | of ions and in order to finally assets channel. He also used X |
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35:00 | crystallography techniques to visualize the channel structure X rays and all of these techniques |
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35:09 | necessary in order to derive the potassium structure these days, as I |
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35:14 | it is not using artificial intelligence and sophisticated algorithms that calculate the structure of |
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35:24 | . So when we talk about the potentials, please remember that there are |
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35:27 | , intracellular extra cellular recording methods of potentials that the frequency of that action |
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35:34 | and park will represent the strength of stimulus that's been coming into these cells |
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35:40 | this concept of the driving force which the difference between the VM and equilibrium |
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35:48 | forgiven ion during the rising phase, you recall from the sodium currents are |
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35:56 | but it doesn't mean that there's no current at all. There is some |
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36:00 | current but sodium is dominating and during following faces the potassium current that is |
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36:05 | the resting membrane potentials. The membranes leaky to potassium so it's dominated by |
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36:13 | and after it re polarizes again, dominated by potassium on So in order |
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36:20 | uh to to to to review real this uh information here. These are |
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36:29 | equilibrium or reversal potentials for all of ions that are important for us to |
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36:35 | potassium chloride, this is resting membrane . If the membrane potential VM gets |
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36:41 | polarized enough with glutamate inputs, it reach the threshold for action potential. |
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36:46 | will produce an all or non event sodium ion will be in flux ng |
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36:53 | this positive feedback move deep polarization, deep polarization sodium, it will try |
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36:58 | drive the overall number of potential into liberal potential for sodium but it will |
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37:03 | to do so because at this point potential is very close to the Librium |
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37:09 | . The sodium, therefore, the force, which is the difference between |
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37:13 | and ion is very small for sodium at this point here, the number |
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37:17 | potential is very far away from the . It will have been potential. |
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37:21 | the driving force for potassium island is here and also the second reason why |
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37:26 | the kinetics of the sodium channels that reviewed sodium channels transient lee opening and |
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37:33 | and fast opening and fast closing due inactivation, potassium is the late conductors |
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37:39 | gets activated late but it's also sustained prolonged and responsible for re polarizing the |
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37:46 | potassium trying to drive the equilibrium membrane value to equilibrium potential value and gets |
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37:53 | slowly with sodium potassium pumps. Also the absolute refractory period versus the relative |
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38:00 | period that we talked about. So currents, as I indicated sodium and |
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38:06 | currents are actually happening at the same . It doesn't say the G. |
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38:10 | . Is equal to zero, it's G N. A. Is dominating |
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38:13 | G kg being conductors for sodium G for potassium and in order to isolate |
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38:20 | currents. We discussed a technique called voltage plant technique and this voltage clamp |
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38:25 | was used by Hodgkin and Huxley to that if you d polarize and clamp |
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38:30 | member of potential positive potentials, you see an inward current that's early and |
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38:35 | , followed by an outward card. inward current will reverse that approximately reversal |
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38:41 | equilibrium potential for sodium is you don't inward current anymore and at the numbering |
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38:47 | that are more positive. You will that this inward sodium current actually becomes |
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38:51 | outward current that's overlapping. Now with outgoing potassium current. So Hodgkin and |
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38:57 | described this inward transient sodium conductance is convention negative economic values. And these |
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39:07 | the outward potassium currents. Remember the of the sodium channel four. Sabina's |
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39:15 | trans membrane segments as force voltage That's five and six between the two |
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39:21 | four loop as six actually is going be a binding site to lidocaine. |
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39:26 | voltage sensor is an actual, you , acid positively charged residues. And |
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39:31 | deep polarization Voltage sensor will slide up open the activation gate. But the |
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39:37 | actually has two gates that has activation and inactivation gate. So with deep |
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39:43 | from -65, a resting membrane potential -40 past the threshold value for action |
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39:49 | . These individual civilian channel traces and . You will see that immediately following |
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39:55 | deep polarization sodium channels will open voltage will slide up as it gets repelled |
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40:01 | a build up of positive charge on inside of the cell. Both of |
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40:04 | gates will open, sodium will start in and immediately the inactivation gates ball |
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40:10 | chain mechanism will plug up the sodium in the state number three here where |
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40:15 | channel is inactivated. And the only you can go into ST four which |
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40:20 | removed in activation gate called Dean activation close the channel is if you hyper |
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40:26 | the salary polarized interesting number in potential four. The sensor will slide back |
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40:33 | to the channel, the ball will out and the gates will close. |
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40:39 | is the second reason why the number potential doesn't reach the equilibrium potential for |
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40:45 | because sodium channels transient, They will fast activating, fast and activating. |
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40:50 | we discussed different patch clamp techniques that allow you to report single channel |
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40:55 | So if you have in the plasma that you've targeted with your micro electoral |
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40:59 | channels for sodium you can study a trace here. Single channel trades for |
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41:05 | different channel traces. And these are techniques that we discussed attached. So |
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41:10 | which you attach yourself to the cell use it sort of was a large |
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41:15 | also recording when you break into the and you have a continuous cytoplasmic environment |
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41:20 | the internal electorate solution and the side plasmid solution of the neuron. You |
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41:27 | all of the currents traversing through the membrane if you withdraw piece of the |
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41:32 | and you expose that inside of the protein to the outside world. It's |
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41:37 | Inside Out recording. And if you and exposed outside of this member and |
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41:43 | to the outside world is referred to Outside Out recording. Then we talked |
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41:47 | the story of Toshio Narahashi and Tetrodotoxin we talked about uh puffer fish and |
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42:00 | watched Simpsons. So remember some of things about tetrodotoxin that tetrodotoxin is a |
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42:08 | channel blocker and blocks this inward That's where the toxin is final with |
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42:14 | fish but it is not produced by produced by bacteria. And we also |
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42:20 | about other substances that I found in sacks a toxin that is found in |
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42:27 | clams and shellfish during warm temperatures that can affect sodium channels, uh cocaine |
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42:35 | instance sodium channels and Tetra kill So you have different nature blockers, |
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42:41 | in nature of toxins in nature. also you have chemical blockers. So |
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42:46 | example, ta or Tetra tell ammonium potassium awkward current block. So this |
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42:53 | what Toshio Narahashi did is he used used the voltage clown and showed the |
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42:59 | specifically blocks vault educated sodium channels and blocking voltage gated sodium channels that blocks |
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43:05 | action potential. And so that was big contribution to to neuroscience, a |
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43:13 | blocker. Remember the membrane we also as membrane equivalent circuits. So please |
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43:20 | the properties of the membrane capacitance I'm not gonna have time to review |
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43:26 | . But these are all going to great identification questions. The current's flocks |
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43:33 | action potential sodium will be coming This is a variable conductor. A |
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43:38 | resistance is a battery for sodium. have the active pump um bringing potassium |
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43:45 | sodium against the concentration gradient. This a symbol for capacitor with plasma number |
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43:50 | discussing great capacitors and they are small . So they have high resistance that |
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43:56 | have large uh surface areas and if have large surface areas they have great |
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44:03 | and conservative as great capacitors and that ratios remember in potential will change for |
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44:11 | items. Permeability ratios. So during resting number and potential islands will be |
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44:16 | permissible to potassium. During the action rising face that will be most permeable |
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44:20 | sodium. But you can also use equation fluoride. And if people are |
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44:25 | fluoride as you can see during either or action potential, chloride permeability doesn't |
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44:32 | much. Therefore it's not going to into the value of the action potential |
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44:36 | much for the number of potential value much. So we've gone through all |
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44:44 | this. Remember that when we measure conductance is for sodium inward conduct |
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44:50 | A composite of multiple sodium channels opening same outward potassium conductance is composite of |
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44:57 | channels opening. Remember the structure and function the kinetics of the sodium |
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45:03 | How these kinetics are different from potassium different reporting methods. Again, ttx |
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45:09 | that we just discussed and then V. Curves a variety of |
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45:13 | Q. V. Curves that you have. And there's a sample exam |
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45:17 | of, ask you about I. . Curves and you will be likely |
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45:20 | to identify an I. D. for sodium potassium channel. This is |
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45:24 | I. V. Curve for an channel which will be conducting both. |
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45:29 | you know potassium showing your reversal equilibrium for acetylcholine receptor channel zero null |
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45:36 | This is also where there's no net flux happening. That's where equilibrium potential |
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45:42 | just coincides with the zero nominal But as I drew on the board |
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45:48 | are called N. F. S. For each cell, each |
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45:51 | will have its own curves. Some these will be rectifying. That means |
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45:56 | a channel will prefer to conduct ions in this case outward direction versus inward |
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46:05 | . So this will be awkwardly And these different types of curves. |
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46:11 | cell can have 2030 different types of . Each curve linear, nonlinear representing |
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46:18 | voltage gated channels as well as receptor gated channels. So the membrane properties |
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46:25 | complexity of neuronal firing will very much on the properties of the CV curves |
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46:31 | the south could create. Just light showing how light again binds the |
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46:37 | Six alpha helix right here and there's binding sites and light again on the |
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46:43 | channels are very a common anesthetic that use in these finding of these different |
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46:50 | that are the toxin can block the , lively, can can block the |
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46:55 | . Others can reduce the conductors so can actually prolong the conductors to. |
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47:00 | talked about how it's very difficult if have multiple of these curves I. |
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47:05 | . Curves, it's very difficult to which subtype of channel you may be |
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47:10 | at. So then you would go simpler systems like both sides that are |
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47:14 | large and would over express the channel would stimulate and voltage clamp you would |
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47:19 | up all of the properties and D. Cards of that channel. |
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47:23 | particular potassium current subtype channel if you're and then you would be able to |
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47:28 | it out from a more complex system is more noisy. A system more |
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47:34 | from neurons where its natural state. channel might not be expressed at such |
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47:39 | levels. And you would have to mathematics filtration of experimentation in order to |
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47:45 | that channel using voltage clamp and in . Then we talked about briefly back |
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47:53 | action potential and we said that Ramona have described this principle of dynamic polarization |
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47:59 | the action potential gets produced in the initial segment gets regenerated. Each note |
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48:04 | Ron beer, which is loaded with and potassium channels gets regenerated. Each |
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48:10 | of ranveer it reaches the external And this is the forward propagating spike |
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48:15 | is responsible for neurotransmitter release and chemicals transmission. And then we talked about |
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48:21 | back propagating spike. We said how back propagating spike is different from the |
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48:26 | propagating spike and that there are two of multi educated sodium channels in this |
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48:31 | initial segment. So when the incoming polarization, if it overcomes the inhibition |
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48:37 | this green arrow comes in and enters initial segment, it encounters two types |
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48:42 | voltage gated sodium channels and maybe 1.2 and maybe 1.6 m. Maybe 1.2 |
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48:50 | high threshold channels. That means they a lot of high voltage in order |
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48:54 | open up and this deep polarization is sufficient enough to open up the |
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48:59 | A. V. 1.2 channels which located closer to the summer and bypasses |
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49:03 | region and enters the region of N . V 1.6 channels which are low |
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49:08 | . That means they require low deep and low voltage in order to open |
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49:12 | 81.6 channels open, generate this explosion the form of forward propagating action potential |
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49:18 | will travel down the axon number three cause the neurotransmitter release 11. When |
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49:24 | deep polarization is produced by maybe the incoming deep polarization of the green |
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49:30 | and the deep polarization positive charge by activation of influx of sodium and then |
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49:35 | 1.6 is now enough. The summation the two signals positive input here and |
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49:42 | charge here. It's enough of a threshold to open N 81.2 and N |
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49:48 | will produce a smaller, much smaller amplitude, a few building walls and |
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49:53 | back propagating action potential which will enter into the cinemas and back into the |
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|
49:58 | . So the function of the back action potential is is very important in |
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|
50:08 | timing plasticity that we discussed from trying open the world. Look at your |
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|
50:17 | . So swell. It's very important despite having dependent plasticity, it's a |
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50:28 | of plasticity and communications of incoming inputs they're meaningful and if the cell reacts |
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50:36 | them and produces an action potential and closer in time they are, the |
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50:40 | capability, the synapses will have to plastic and to rearrange themselves and strengthen |
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50:48 | . So the timing between the inputs when the action potential is generated is |
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50:53 | important. When the action potential is . This back propagating spike will inform |
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50:58 | synapses in the cell that this action actually active and it's meaningful. It's |
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51:03 | important for the spine plasticity. This backwash. There were also the sort |
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51:11 | like the enforcement for active synopses and summation of the active inference of the |
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51:18 | that is coming from the axon initial in this back propagating way. And |
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51:23 | I left you with this challenge of day. And I said that especially |
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51:27 | you're interested in uh neurophysiology and microscopy biochemistry, then this is a very |
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51:36 | concept of engaging neurotransmitters that you can about the the hypothesis or the question |
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|
51:43 | I asked, do you think them prefer to propagate deposit ization and forward |
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51:48 | the soma. A backward away from directions. How would you test this |
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|
51:54 | ? And I said, what is neurotransmitter on what is what is |
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|
51:59 | What do you use to engage There's a great article, the supplementary |
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52:04 | that you can look up for I'm not saying this will be an |
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52:09 | question, but it may show up later in the course, there's a |
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52:14 | discussion, you never know. this is something that you can look |
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52:19 | on your own. This concludes pretty our midterm one review, and I |
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52:25 | be happy to take any |
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