| 00:01 | This is neuroscience. Midterm one Spring , Mid Term one Review where we |
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| 00:13 | go over some of the key material we covered in the first section of |
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| 00:18 | course. This is the very first from the lecture materials that you saw |
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| 00:26 | we started building our understanding of what are, what their functions are, |
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| 00:34 | a glial cells, what a different self functions. Understanding that diverse set |
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| 00:42 | neurons and glial cells comprised neuronal networks these neuronal networks are interconnected within the |
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| 00:52 | nervous system in generating emotions, motor expressions and thoughts that all live |
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| 01:06 | the cerebral cortex. The book again the course is neuroscience exploring the brain |
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| 01:16 | we started discussing prehistoric times, mentioned nations for interpretations as the first neuro |
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| 01:26 | that were performed in different parts of world. We further discussed Imhotep as |
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| 01:33 | important figure that not only developed and this triage medical treatment system, but |
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| 01:44 | recognize the distant effects of central nervous injury on the periphery. From these |
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| 01:52 | injury cases that he studied in ancient , Hippocrates, different Egyptians considered bring |
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| 02:01 | major controlling organ center of the but Aristotle did not uh and dozen |
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| 02:12 | of you an understanding of the brain renaissance times questions the previous anatomical descriptions |
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| 02:21 | the brain that were mostly based on animal anatomy, concentrating very much during |
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| 02:28 | time on this ventricular view of the , ventricles are important. They're filled |
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| 02:35 | fluids and also distinguishing between the gray white matter. We then highlighted work |
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| 02:42 | rene the car guitar Go soon I therefore I am and his ability to |
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| 02:52 | distinguishing what is a reflex of behavior theory and his understanding of a higher |
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| 02:59 | and connection of the outside world with inside brain and higher consciousness through pineal |
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| 03:06 | and further his proposal of the brain the body operating in a fluid mechanical |
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| 03:13 | model again, where the fluids from ventricle also being pumped into the periphery |
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| 03:19 | order to perform certain actions and then Galvani shows that it is not the |
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| 03:24 | . It is the electricity by shocking nerve or by shocking frogs. |
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| 03:32 | dogs muscle contracts and so shocking the sends an electrical signal to the muscle |
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| 03:39 | nerves can generate electricity that a lot water pipes. The major parts of |
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| 03:44 | cns is the brain, which is cerebral cortex divided into the frontal |
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| 03:51 | parietal lobe, occipital lobe and temporal . Is the major lobes, frontal |
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| 03:56 | parietal is separated by the central Or this imagination exhibit a love is |
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| 04:02 | the back of the brain and that is this large sylvian fissure separating the |
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| 04:08 | lobe here from uh the rest of cerebral cortex and the doc. You |
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| 04:13 | the cerebellum or the little brain that's to the brain stem and the brain |
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| 04:19 | extends into the spinal cord. And have spinal nerves that radiate out in |
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| 04:24 | each vertebra, spinal cord proper goes to about lumber 23. And from |
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| 04:32 | you have caught in a queen a off the nerves and projecting into the |
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| 04:37 | extremities of the body. Mhm. discussed this uh arrangement of uh the |
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| 04:48 | information where all of this sensor information from the periphery from the skin muscles |
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| 04:55 | joints and it travels through the dorsal and enters into the dorsal part of |
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| 05:03 | spinal cord through the dorsal root ganglion . So these are accents that pick |
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| 05:09 | information in the periphery in red are different accents that carry that information to |
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| 05:15 | , so most of dorsal root ganglion located right outside the spy little court |
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| 05:22 | . And their projections going into the cord dorsal in and on the ventral |
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| 05:28 | which would be the front side and ventral side. You have the output |
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| 05:33 | the form of the motor nerves. the motor nerves from the spinal cord |
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| 05:38 | come out and they will innovate these fibers that will innovate the muscles and |
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| 05:44 | the contraction or relaxation of the So you have the sensory after current |
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| 05:52 | going through the dorsal regain mint. dorsal aspects of the spinal cord and |
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| 05:57 | neuron information coming out from the ventral . Innovating the muscles to output the |
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| 06:05 | command. And all of this information the neck below Comes from the Spinal |
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| 06:11 | , 31 pairs of spinal nerves that a different extent along the body from |
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| 06:19 | shoulders all the way to toes and we started understanding more and more brain |
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| 06:29 | , we started trying to locally specific functions. And so please review the |
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| 06:35 | and chronology where chronologies try to predict of specific brain function by looking at |
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| 06:41 | shape of the skull. Yeah. anatomy rather than inside the brain |
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| 06:49 | And of course there were quite wrong this led us to trying to understand |
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| 06:54 | parts of the brain are responsible for functions and where can we find |
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| 06:59 | And paul Broca was the first one definitive was showed through damage. Now |
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| 07:04 | can see that these localization of brain came through finding damage to specific areas |
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| 07:11 | the brain and broker found this damage this in the frontal lobe. You're |
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| 07:15 | close to the motor cortex and damage brokers. Air causes expressive aphasia inability |
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| 07:22 | express yourself through speech or writing in with motor cortex that will be producing |
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| 07:29 | commands for you to speak or We also discussed vernon CAS area and |
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| 07:34 | to veronica's area will cause receptive And we also touched on the least |
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| 07:42 | form of aphasia, economic or Aphasia as well as the most severe |
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| 07:47 | or global aphasia. So please review terms. The story of finance gauge |
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| 07:53 | also very important for localization of brain . If you recall damage to his |
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| 07:59 | lobe did not render him completely incapacitated in a wheelchair but instead it impaired |
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| 08:08 | executive functions and impaired here control of emotions and aggressions and the fact that |
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| 08:15 | I. And it showed also this study that depends where you have a |
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| 08:20 | in the brain but that damage can quite specific. You may still write |
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| 08:25 | read and walk, you may not vision in one eye, but you |
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| 08:30 | a lot of functions and that's because parts of the brain are responsible for |
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| 08:35 | functions. In the light of this evolutionary concepts of neuroscience, we discuss |
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| 08:44 | Darwin and we brought up this very structure in the somatosensory cortex and we |
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| 08:51 | that there is a cortical map. you see in the periphery? And |
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| 08:55 | cortical map is the barrel cortex where one of these brown barrels and the |
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| 09:00 | represents a whisker on the whisker And so we discussed this within the |
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| 09:05 | that for rodents that whisk around and their environment will influence the development of |
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| 09:12 | peripheral structures as well as the reflection the networks that encode the peripheral structures |
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| 09:18 | the brain that we call cortical maps that anatomical and functional cortical maps. |
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| 09:24 | of course monkeys are very visual Therefore their environment in their uh cortical |
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| 09:33 | is advanced in in other areas. finally we came to this very important |
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| 09:45 | . So please review the difference between particular theory and neuron doctrine and these |
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| 09:51 | very important figures. Camelia gold, invented the Golgi stain and know that |
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| 09:57 | stain stays only a fraction of neurons all of their processes in great |
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| 10:02 | Ramona alcohol was Camelia Gold's student that these stains and describing the morphological |
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| 10:09 | the morphology, the structure of these and also the cell networks and |
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| 10:15 | I'll strengthen that in a huge way the synapse, this very specialist place |
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| 10:21 | the communication between neurons takes place. so ramon alcohol predicted that neurons will |
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| 10:26 | inputs in certain parts and will transmit outputs through accents in a certain |
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| 10:33 | And Camelia Golda was proponent of ridiculous . Ramona ca hollis, proponent of |
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| 10:41 | doctrine and even proposed a concept of that these connections are valuable and they |
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| 10:47 | change over time and activity between the together accepted a noble noble prize, |
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| 10:54 | on the particular theory, neuron other very important state. It is |
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| 11:00 | and you should know these differences with stain. Uh This is a missile |
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| 11:07 | . Missile stain by France, missile a great way to stay in all |
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| 11:13 | the cells and missile stain was used comedian bradman to describe the side architectural |
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| 11:19 | densities, population arrangements stacking off the in different parts of the brain for |
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| 11:27 | to understand how the brain works. have to go on a really small |
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| 11:32 | level And we need to have electron that have a resolution of 0.1 nm |
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| 11:39 | the synaptic space between this pre synaptic that is filled with vesicles filled with |
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| 11:47 | . And this pasta synaptic them drive is located year and the dendritic |
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| 11:52 | This past synaptic density that we can visualize the space and the synapse which |
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| 11:57 | 10 20 nanometers across. We can that. And this is very important |
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| 12:04 | we start understanding these micro cellular single , even single molecule level events and |
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| 12:13 | only anatomy but also functionality. You have to always stay in cells. |
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| 12:21 | so we discussed this infrared microscopy technique allows us to visualize neurons and allows |
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| 12:27 | to target neurons with micro electrodes and electrical activity. It's in the current |
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| 12:34 | of neuroscience. We have the ability study anatomy the changes in structure as |
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| 12:42 | as the functionality of the level of molecule single receptor protein, single dendritic |
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| 12:49 | and synapse single cell war as is here with pauses, drama emission |
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| 12:55 | which is a non invasive imaging. can study the larger brain maps and |
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| 13:01 | brain maps maps of activity of active as they get activated by performance of |
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| 13:09 | tasks such as looking at war versus words. So we have a lot |
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| 13:17 | processes. We know that each function absurd more by more than one neural |
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| 13:25 | that we know that we involve different of the brain and performing these different |
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| 13:32 | . And so we're gaining understanding and these brain maps. Uh I mean |
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| 13:37 | we're performing different functions, how may be altered by altering the reality around |
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| 13:43 | or as a consequence of neurological This part we discussed that there are |
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| 13:50 | uh specialists in nervous system with their as well as other careers that are |
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| 14:00 | associated him could benefit from having this perspective, the general learning. We |
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| 14:09 | moved to discuss functions of neurons and . We reviewed some of the basic |
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| 14:15 | anatomy and organize that we find the as well as other cells. The |
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| 14:22 | principles of transcription, splicing and translation the proteins. We looked at how |
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| 14:31 | organelles such as rough and the plasma and others contribute to buy a synthesis |
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| 14:36 | different audience uh in the cells and the micro race where we can track |
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| 14:45 | in thousands of genes as a consequence let's say, a neurological disorder where |
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| 14:51 | can compare tissue from normal brains and brains and tracking hundreds or thousands of |
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| 14:58 | that you know because it's supposed genomic that you synthesize DNA to match the |
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| 15:03 | genes to track the changes in these race. Review these organelles which are |
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| 15:10 | basic smooth er Golgi apparatus and their mitochondria which produces 80 P. And |
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| 15:16 | brain uses a lot of a. . P. Http in the brain |
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| 15:20 | not only the energy molecule is also neurotransmitter. The concept of dynamic or |
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| 15:27 | mosaic model of the fossil olympic, the plasma membrane of neurons that have |
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| 15:33 | proteins and cholesterol and lipoproteins associated with and receptor and channel proteins of transport |
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| 15:42 | . And this movement of proteins through membrane is constant. Then it can |
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| 15:48 | very fast and the overall shape of plasma membrane and the shape of those |
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| 15:54 | The synapses has supported by the underlying . A skeletal uh elements such as |
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| 16:02 | tubules are filaments of micro filaments. filaments are the smallest ones. These |
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| 16:06 | the micro tubular highways that are very and transport external transport. You can |
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| 16:12 | the myelin sheath surrounding the axon to external transport and finally that you have |
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| 16:19 | expression of these active molecules shown here blue is the smallest elements that can |
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| 16:26 | longer change. Prelim arise or d arise and shorter chains and stack themselves |
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| 16:31 | at the outer edges, providing for outer shape of the plasma membrane. |
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| 16:38 | you can see the turbulence which belongs micro tubules. The turbulent molecules are |
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| 16:45 | closer with the nucleus of the After we discussed the state of skeletal |
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| 16:54 | amounts to introduce the fact that during course, we will be discussing several |
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| 17:01 | disorders and we talked about Alzheimer's So this is a reminder of the |
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| 17:08 | plaques nor particularly tangles that form inside these neural february tangles form that actually |
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| 17:14 | wrap up neurofibromatosis, tangle them up off the side of skeletal elements, |
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| 17:21 | up the micro tubular highways and preventing transport within the south. This is |
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| 17:26 | pathology and pathological law marks of Alzheimer's . Extra cellular beta amyloid or senile |
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| 17:33 | , intracellular early Euro formula early And if you look at the growth |
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| 17:38 | changes in severe Alzheimer's disease, you an atrophy and neuro degeneration of large |
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| 17:45 | of the brain and strength image of brain compared to the healthy brains. |
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| 17:50 | is the pathology of the disease. we also discussed the symptomology of this |
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| 17:56 | . So please remind yourself some of things that we mentioned in relation to |
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| 18:01 | disease. In addition to the pathological shown here. Okay, so make |
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| 18:07 | you keep track off the nose for neurological disorders and you review them and |
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| 18:15 | then started discussing some other elements of the acts on the mitochondria, lot |
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| 18:21 | energy needed for synaptic vesicles release into synaptic cleft and the post synaptic densities |
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| 18:27 | will contain austin optic receptors and ectoplasmic . Again, it's very important that |
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| 18:35 | only the neural transmission and the action travel down the accidents, but there's |
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| 18:39 | the supply of nutrients and goods and . Great transport bike in essen, |
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| 18:45 | transport, buying, dining and delivering elements from this moment through the accents |
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| 18:49 | other distal parts off the cell. also can use uh injections and tracers |
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| 18:57 | order to trace where certain axons project also trace the transport through these axons |
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| 19:04 | so retrograde transport, tracers, horseradish is and if you injected it will |
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| 19:11 | picked up. Retro gravely transported into some of the South. Retrograde transport |
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| 19:16 | also viruses are capable of retrograde travel as herpes and rabies viruses. And |
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| 19:23 | we entered into this very interesting anatomical . Were reviewing neurons and dendrites and |
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| 19:29 | good explains the good experience containing polarized complexes in ADP making them biochemically somewhat |
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| 19:37 | but in good experiences where the synapses formed and that could explain anatomy changes |
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| 19:44 | that could explain anatomy can cause a retardation. And we discussed another |
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| 19:49 | fragile X syndrome and this is the hallmark of fragile X syndrome that we |
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| 19:56 | is abnormal dendritic spine shape densities uh distribution along the dendrite. And that's |
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| 20:04 | important because if you have this impaired , the neuron has to make a |
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| 20:10 | to fire not to fire. And does so by integrating and calculating all |
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| 20:15 | positive excited to imports all of the inhibitor inputs and deciding whether it's going |
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| 20:20 | produce an action potential. So if have impairment and the synapses of course |
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| 20:26 | cell integration and the functioning of the is going to be impaired as |
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| 20:31 | Structure means function and impaired structure means function. These are the four functional |
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| 20:38 | of the south. We discuss how can classify neurons based on their |
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| 20:44 | uni polar bipolar, pseudo uni polar is our dorsal root ganglion cell. |
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| 20:50 | . And this is a multipolar The motor neurons in the spinal cord |
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| 20:54 | multipolar and most of the cells and cerebral cortex in other parts of the |
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| 21:00 | a multipolar as well. But we distinguish cells based on connectivity. Excitability |
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| 21:07 | with specific markers that finally the firing of the actual potentials. We discussed |
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| 21:14 | diversity and this exemplary circuit, the circuit. The diversity in the south |
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| 21:21 | comes from the diversity of the inhibitory and these inhibitory cells they live in |
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| 21:26 | layers. They have their dendritic anatomy specific. And these yellow cops is |
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| 21:31 | these inhibitory cells will target the excitatory which are pretty much one subtype of |
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| 21:36 | cell except the one that called into positive and the other one is |
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| 21:40 | These excited ourselves are the projection cells they'll communicate information out of the |
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| 21:46 | And these inhibitory cells will then produce complex interactions with these excitatory cells. |
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| 21:52 | the cielo cops are the synapses will either on the soma or the optical |
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| 21:57 | writes of the excited to prominence, influencing what output what information excited tourists |
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| 22:03 | going to put into the adjacent So in order for us to define |
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| 22:07 | various specific cells. Sometimes we have use electrophysiology. We have to patch |
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| 22:11 | cells and record the signatures. The signatures of the action potentials are called |
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| 22:18 | and we have to fill and we the morphology of the cells completely with |
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| 22:23 | diet and further we have to look specific markers they stain for. Some |
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| 22:29 | the cells that look identical like two four look identical in identical regions they |
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| 22:36 | . There is similarly but one of will be provided with positive and another |
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| 22:39 | will be CCK positive. And so definition distinction between the cellular sometimes comes |
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| 22:47 | you doing another step which is you use the chemistry and defining these cellular |
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| 22:52 | . We call the dialect and the of the different neurons. And that |
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| 22:59 | means different way of processing information. that diversity also is because you have |
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| 23:06 | diverse set of inhibitory into neurons that this dialect and influence activity on the |
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| 23:12 | circuit level and excitatory cells influence excited to any activity that will get |
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| 23:20 | out of these serpents into the other circus. This is a fun setup |
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| 23:25 | I showed you for electrophysiology and we moved into glia understanding glial functions recall |
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| 23:38 | you have a folder supporting materials folder you can find a lot of links |
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| 23:43 | it will lead you to microbe leo and radio glial cells. And we |
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| 23:49 | their functions. We talked about my PMS by Schwann cell C. |
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| 23:54 | S. Buy legal dangerous sites and difference and the properties and differences in |
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| 24:01 | Violin Nation and violent segment properties in PNS versus cns. Um We also |
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| 24:11 | that if you have impaired Myelin Nation you will have a myelin dysfunctions and |
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| 24:18 | these mile and dysfunctions stem from myelin proteins a lot of times and compaction |
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| 24:26 | these uh properties of the myelin. we discussed Charcot Marie tooth and multiple |
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| 24:34 | . So remember the features of multiple . Okay. The tremors, |
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| 24:41 | mrs symptomology and then the pathology is elimination. It's an autoimmune disorder. |
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| 24:48 | sclerosis. So the body starts attacking own violence. It expresses itself as |
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| 24:57 | , convulsions, pain but also affecting state, dim illumination and CNN's chocolate |
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| 25:06 | . The symptomology is this impaired gait deformity is swaying while walking. The |
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| 25:13 | again. Is that dim illumination. in this case is the PMS of |
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| 25:17 | peripheral in the periphery. And it's to the duplication of too much of |
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| 25:23 | peripheral protein. p. m. . And so review these two |
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| 25:30 | The great summary of the ostracized is for synapse maintenance synaptic transmission as well |
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| 25:37 | blood brain barrier. Micro glial This scavenger cleanup south. Really good |
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| 25:42 | is myelin formation, violent segment formation a pen dermal cells separating the interstitial |
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| 25:49 | from cerebrospinal fluid and potential acting as cells the blood brain barrier that we |
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| 25:58 | that has uh interesting anatomy. And come back to this in just one |
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| 26:05 | with a different slide. I will with the slide. Would do recall |
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| 26:09 | you have a certain anatomy, die that are formed between endothelial cells or |
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| 26:14 | vessel cells here? The blood and parasites and the astra site astra cleo |
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| 26:21 | feed processes that surround this and controlling passes into the brain. And so |
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| 26:25 | discussed this within uh context off. neuro drugs should pass the blood brain |
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| 26:31 | easily that you can have impairment of brain barrier and it can either become |
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| 26:37 | loose or Impenetrable to medications and the effects that you may have in the |
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| 26:44 | because you're eating a lot of medications to treat a neurological condition could affect |
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| 26:51 | the periphery. Other side effects or parts of the brain that you're not |
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| 26:55 | because of the limited amount of drugs may be getting through the blood brain |
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| 26:59 | . And this is something very Very important. And also an obstacle |
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| 27:04 | developing Euro pharmacological drugs. All And then we moved into the neuronal |
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| 27:17 | at rust or resting membrane potential separation charge minus 65 million molds. Please |
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| 27:27 | the circuit. You have the dorsal dorsal root ganglion cells that pick up |
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| 27:33 | . This is our knee jerk reflex we said that you have to have |
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| 27:37 | on dorsal root ganglion cell. What of salad in studio unit polar? |
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| 27:42 | kind of a neurotransmitter release is excited glue domain? Well then it will |
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| 27:47 | motor neurons. Motor neuron. What of solid is anatomically multipolar? Excitatory |
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| 27:53 | , what kind of neurotransmitter it will on the muscle. Acetylcholine. Acetylcholine |
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| 27:57 | only excited turn the muscles but it also contact these door solder ganglion cells |
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| 28:03 | can contact inhibitory into neurons. These internals with kind of south side a |
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| 28:09 | anatomically neurotransmitter that releases glazing as an neurotransmitter which will inhibit their motor |
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| 28:16 | And so ideally in this reflex a unique uh unique mono synaptic response |
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| 28:25 | cause a contraction of the quadriceps. through this into your injunction, you're |
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| 28:30 | assuring that the opposing action muscle and hamstring the flexor muscle gets relaxed. |
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| 28:36 | review these cells. Review these The most important elements are sodium potassium |
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| 28:43 | calcium. These are individual channels for one of these ions are selective ion |
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| 28:50 | that there is a differential expression of ions. There is an equal distribution |
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| 28:57 | ions across plasma membrane that in order this uh ions to pass through the |
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| 29:07 | member. And they have to pass the protein channels that these protein channels |
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| 29:13 | built as from building blocks they built amino acids are strung together, sheeted |
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| 29:25 | beta sheet or twisted into alpha Is the secondary tertiary structures of multiple |
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| 29:34 | helix is forming a subunit ordinary structure subunits coming together? Multiple subunits forming |
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| 29:42 | or a protein channel in the plasma . And so these protein channels are |
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| 29:49 | to ions and there's an ionic selectivity an interaction with amino acid residues here |
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| 29:58 | then we moved onto the arms log they are. And the relevant scales |
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| 30:03 | us as millet balls, million pairs PICO amperes, megaphones and resistance and |
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| 30:11 | simmons and nano simmons for conductive. are all relevant scales for the |
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| 30:16 | On us. We discussed the fusion the concentration gradient. We also discussed |
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| 30:29 | electrical potential and the movement of positive violence in the direction of the |
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| 30:37 | the current movement. And the equilibrium , which if you recall, the |
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| 30:45 | potential is where the chemical driving force is trying to drive the concentration of |
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| 30:51 | across this channel to the other And the build up of positive charge |
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| 30:56 | on the other side before potassium equalizes concentration, the positive charge starts repelling |
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| 31:05 | and at this 0.2 forces the chemical and the repellant force. Electrical force |
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| 31:11 | equal and opposite to each other. is no net flow of ions which |
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| 31:15 | referred to as equilibrium potential for this ion or any other ion. There's |
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| 31:21 | equilibrium potential or reversal potential. It's them to change the same goes for |
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| 31:27 | sodium. So to calculate equilibrium we use nursed equation and we plug |
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| 31:35 | the either the million dollar values. that there's a lot of sodium chloride |
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| 31:40 | the outside of the cell. There's lot of potassium on the inside of |
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| 31:44 | cell and the highest disparity and concentration exists for calcium. There's 10,000 times |
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| 31:51 | calcium on the outside of the cell the inside of the cell. And |
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| 31:55 | each one of these ions has an potential. And that equilibrium potential is |
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| 32:01 | using nursed equation. E. Ion potential for island 2.303. Our gas |
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| 32:09 | T. Absolute temperature. Z. of the I. M. |
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| 32:12 | Faraday constant log base 10 of ion on the outside versus iron concentration |
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| 32:20 | And these individual calculations you're responsible for the values for these individual reversals that |
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| 32:29 | from the action potential. Drawing that will talk in a second but you |
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| 32:33 | be able to recognize an artist equation is the correct um reversal potential value |
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| 32:43 | potassium for sodium um Chloride and these four main islands. And this |
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| 32:54 | the potassium reversal potential value. If calculate plug in the values years -80 |
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| 33:00 | balls. And we talked about the between learns the equation of Goldman equation |
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| 33:05 | learns the equation based on the constant concentrations and the formula TCF will allow |
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| 33:14 | to calculate equilibrium potential forgiven iron. want to know where the number of |
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| 33:19 | is number of potential and Goldman equation premier ability variable here And incorporates more |
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| 33:29 | just one eye on so we can overall member and potential of VM by |
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| 33:35 | our TCF but now incorporating not only potassium but also sodium and their relative |
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| 33:43 | ratios. And so this shows that the trust is 40 times more permeable |
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| 33:47 | sodium 40 P. K. Process . N. A. Which stands |
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| 33:52 | permeability one this is a resting membrane . So VM addressed is a combination |
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| 34:00 | have nursed equation and that permeability ratios concentrations for sodium and potassium. So |
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| 34:09 | is comparing again uh equilibrium for each or reversal potential in D. |
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| 34:16 | Which is the overall member and potential by Goldman equation. The changes in |
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| 34:24 | permeability or concentrations of ions on the and the inside. If you change |
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| 34:30 | concentrations or permeability you will see that can change the number of potential |
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| 34:35 | So we discuss that if you raise concentration of potassium which is typically between |
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| 34:42 | million moller in this range. If raise it, if you just double |
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| 34:46 | to about seven or 10 you can polarize the cell and change the overall |
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| 34:52 | in potential to minus 60 minus And so it's very important that when |
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| 34:57 | local concentrations of these ions increase that astrocytes in this case are capable of |
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| 35:08 | up uh these uh increases in local of islands and redistributing it through its |
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| 35:17 | processes and through the interconnected astro acidic it's called potassium spatial buffering. So |
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| 35:24 | is another function of astra site in the abnormally increased concentrations and ions locally |
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| 35:34 | as you can see increase in this concentration can de polarize the south of |
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| 35:40 | threshold of action potential and generate firing that self. We wanted to know |
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| 35:48 | the potassium channel function and I referred you a story about roderick Mackinnon. |
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| 35:56 | talked about it and several techniques that used side directed me to genesis and |
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| 36:02 | potassium channel uh in order to solve structure of this channel and it's very |
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| 36:10 | . We saw the structure of this . You can do experiments and flies |
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| 36:13 | there is conserved amino acid sequences and important parts of the channel of the |
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| 36:18 | dimensional structure that was eventually solved by Mackinnon visualize. Not just solved if |
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| 36:26 | know the immune acid sequences, if know they're concerned immuno acid sequences that |
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| 36:31 | could postulate a lot of information you from simple, simple organisms like flies |
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| 36:37 | studies that you do with flies two it to the human brains and roderick |
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| 36:45 | stories, inspiration also. Please recall or review it or look him |
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| 36:50 | A very interesting, fascinating person, potential occupied pretty much the rest of |
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| 37:00 | time. And but before we moved an action potential, we actually reviewed |
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| 37:09 | membrane equivalent circuits. So know what a resistant conductor. What's the |
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| 37:16 | No, it's a capacitor. The symbols but you need to know resistors |
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| 37:21 | referred to as conduct a lot of for channels that open and close or |
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| 37:26 | open and close it's a variable conductor resistor. And this concept of the |
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| 37:33 | force which we've reviewed later and I'll back to now recall that the membrane |
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| 37:41 | R. C. Properties which is capacity resistant and capacity of properties. |
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| 37:47 | the smaller the cell to hire the and the larger the south area is |
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| 37:55 | larger the capacities because remember the good is the one that has a lot |
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| 37:59 | surface there and can store a lot charge. The two plates are located |
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| 38:03 | to each other, it can charge and discharge of the fast fashion. |
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| 38:06 | we've discussed these curves here R. . So it takes time to charge |
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| 38:12 | the plasma membrane several milliseconds. And is electronics that produces the current injection |
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| 38:19 | the south. So this is how member in response by having these resistance |
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| 38:23 | of properties. This is ivy plots I'll post another thing about ivy plots |
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| 38:30 | you can review. There's an exam in the ivy plots we already |
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| 38:34 | So you can watch a previous lecture on how to answer that exam |
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| 38:40 | This is number of equivalent surface now incorporating the capacitor, a symbol for |
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| 38:46 | capacity incorporating the active and it gave as well as active flow of current |
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| 38:52 | the plasma membrane and the rules for ability change. So if a interesting |
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| 39:01 | and potential you can see that potassium the most permissible. The permeability of |
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| 39:07 | is the greatest that during the action the premier ability switches and it becomes |
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| 39:13 | greatest sodium. And just by changing premier ability there you will hear the |
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| 39:20 | value for either potassium or sodium. can see that there's going to be |
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| 39:24 | pretty great change in the overall number potential value. So with this we |
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| 39:31 | finished resting membrane potential in the equivalent and then we moved into the action |
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| 39:41 | and we talked about voltage clamp. voltage clamp is a technique that will |
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| 39:45 | us to clamp a potential at a holding or experimental value. And if |
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| 39:51 | recall voltage clamp was very important for and Huxley that used it. Voltage |
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| 39:56 | is very important. So you can the potential at different holding potential levels |
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| 40:02 | you will see an early inward current is followed by our board card to |
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| 40:08 | the properties of this inward current which sodium, It's transient versus outward current |
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| 40:13 | is potassium and it's sustained the reversal for sodium happens here and you can |
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| 40:19 | that the sodium current which is inward it's negative current value by definition by |
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| 40:27 | , you can see that at this when the membrane gets past the equilibrium |
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| 40:32 | for sodium that inward current is no there. It actually reverses of this |
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| 40:37 | bump as a sodium conducting awkwardly followed a potassium awkward card. So Hodgkin |
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| 40:44 | Huxley using voltage clamp were able to individual sodium and potassium currents and understand |
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| 40:50 | kinetics of these currents, sodium being early inward car and potassium influx of |
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| 40:57 | and potassium being the uh late Albert when you have the flux of potassium |
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| 41:02 | this uh either the sodium or potassium during the action potential is a reflection |
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| 41:10 | many different sodium channels opening quickly in and many different potassium channels opening slowly |
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| 41:19 | having this prolonged sustained opening during the polarization, sodium channel anatomy recall that |
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| 41:28 | has four sub units six trans membrane . S four has a voltage |
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| 41:33 | voltage sensor will slide will react to changes off the charge across plasma membrane |
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| 41:40 | the poor loop and a poor loop be the selectivity felt that it's located |
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| 41:45 | these channels. And so these So we discussed our specific so sodium |
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| 41:52 | specific to sodium and sodium channel has gates and that you need deep polarization |
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| 41:57 | the confirmation will change along this vaulted and the protean channel structure in order |
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| 42:03 | open the channel gates and the sodium us to gaze that has activation |
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| 42:11 | And so with initial deep polarization it be fast opening up this gate. |
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| 42:16 | with prolonged deep polarization. This gate immediately close because as the voltage sensor |
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| 42:22 | up the second gate which is the gate will close and now the neuron |
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| 42:29 | inactivated. I mean this channel isn't . And in order for you to |
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| 42:34 | activated or removing activation gate, you have to hyper polarized when you hyper |
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| 42:41 | that voltage, sorry, when you polarized voltage sensor is going to slide |
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| 42:46 | down into its position and caused the of the gates. So one |
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| 42:52 | open and activated, de inactivated and enclosed. Mhm. And then it's |
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| 43:01 | , it goes back to open. this is the reason why during the |
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| 43:06 | of the action potential the membrane doesn't reach the membrane potential value doesn't reach |
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| 43:15 | equilibrium potential for sodium. So we the action potential dynamics and because as |
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| 43:23 | time restraints, I cannot go and this entire thing all over again. |
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| 43:29 | would refer for you to go to previous lecture when I talk about action |
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| 43:35 | . Some to use this map and show you how the driving force changes |
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| 43:42 | potassium and how the driving force changes sodium. And so follow these diagrams |
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| 43:50 | your values for resting membrane potential action threshold. Now that it's all or |
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| 43:56 | event, remember that initial deep polarization cause influx of sodium and it goes |
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| 44:02 | the positive feedback loop because there's a driving force for sodium to reach its |
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| 44:07 | potential, it doesn't reach, it reach the equilibrium potential for sodium at |
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| 44:15 | peak of the actual potential sodium because driving force reduces And because you have |
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| 44:23 | of sodium channels that I've just But in the big at this speak |
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| 44:29 | the action potential as you can the driving force for potassium is now |
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| 44:35 | . The difference between member and potential value and equilibrium potential for potassium potassium |
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| 44:41 | happens. And as potassium is the in trying to reach the Colombian potential |
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| 44:47 | potassium and it doesn't quite get there you have now the pumps that are |
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| 44:53 | in to re polarize the plasma membrane to re polarize it back to resting |
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| 44:59 | potential. This is an all or event that has an absolute refractory period |
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| 45:04 | relative refractory period. So the driving and the kinetics of this channel is |
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| 45:10 | influences for this channel too close and reached equilibrium potential. We can record |
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| 45:16 | activity using patch clamp techniques and that are different whole cell patch clamp |
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| 45:22 | There's a cell attached recording a wholesale which is cycle plasmas continues inside out |
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| 45:28 | which exposes the cytoplasmic domain of the for experimental studies or outside out recording |
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| 45:35 | exposes the extra cellular domain accessible to manipulation and recordings. Then we watch |
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| 45:43 | and discuss tetrodotoxin. So the function tetrodotoxin. This that Toshiba Narahashi discovered |
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| 45:50 | and then use the voltage clamp etcetera to definitely prove that it blocks volt |
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| 45:57 | sodium channel and blocks action potentials by sodium channels but it doesn't affect the |
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| 46:04 | artwork card and that there are different or antagonists, things that block substances |
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| 46:11 | block such as chemicals or toxins that discussed with roderick Mackinnon case that you |
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| 46:17 | these substances that will be specific to outward potassium cards here. Yeah. |
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| 46:25 | that you have these toxins that come different buffer fish. News, frogs |
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| 46:32 | . Shellfish are formed by microorganisms by . They're found in nature. And |
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| 46:40 | discussed I. V. Curves. said that there are linear I. |
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| 46:45 | . Curves in this case it's a D. Curve. And with that |
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| 46:49 | . And that lecture we reviewed the from the exam asking you what is |
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| 46:54 | the the curve here for potassium for . So go refer you to go |
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| 46:59 | to that specific point in the previous . Also know that certain curves are |
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| 47:06 | . That means that certain channels in case it's outward rectifying, which means |
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| 47:11 | it prefers to conduct current outwardly. that downward current is inward in this |
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| 47:20 | . M. Versus I. This ivy plot again. So anything down |
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| 47:25 | this direction here is an inward current car moving in and this is an |
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| 47:32 | car. This is a linear on curve I. D. Current and |
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| 47:36 | can see that this one is bent it's bent in favor of the outward |
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| 47:41 | in this direction which means it's outwardly it. It was bent in the |
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| 47:46 | direction. It would be inwardly This is actually one of the possible |
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| 47:51 | questions, we talked about how sodium also have a different binding site for |
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| 47:58 | , which is a local anesthetic. then in order to study channel dynamics |
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| 48:02 | lot of times you have to go bigger systems such as boots size and |
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| 48:06 | express these channels In order to know function. And then you can go |
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| 48:11 | more precise smaller systems in the brain neurons that are much much smaller, |
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| 48:16 | micrometers, not one millim in understanding precise function of these channels that you've |
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| 48:22 | over expressed on some other activity and systems. You can go back to |
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| 48:27 | , more sensitive systems. Finally finished talking about the fact that Ramona alcohol |
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| 48:33 | that axons will produce these signals and send them in one direction. And |
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| 48:39 | was our understanding inputs come into sell integrates information and sends that information |
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| 48:45 | down the axon where neural transmission But what we've discovered is that there's |
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| 48:49 | second back propagating action potential. So forward actual potential is produced by low |
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| 48:57 | sodium channels. Any of these stands voltage gated sodium channel 1.6 A small |
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| 49:04 | polarization is enough to allow the opening the sodium channel influx of sodium. |
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| 49:09 | generation of action potential which will forward down the axon in this direction and |
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| 49:17 | this action potential is produced and you an incoming deep polarization. You have |
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| 49:23 | summation of the positive incoming deep polarization positive charge build up here which is |
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| 49:28 | strong enough to open high threshold multi sodium channels and 81.2 and generate another |
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| 49:36 | smallest part of activity in the form back propagating action potential. That back |
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| 49:42 | actual potential is very important to reach the gun rights to inform the damn |
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| 49:47 | that they're active that the cell is to this input and that can influence |
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| 49:52 | plasticity and the communications strength between these . Right. This was the last |
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| 49:59 | and back propagation. And you have material in your review folders uh that |
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| 50:07 | can open to review the specific description back property back propagating action potential. |
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| 50:13 | back propagating action potential is very important it makes these inputs meaningful to the |
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| 50:20 | that are contacting these synapses. It strengthen the synapses, make them more |
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| 50:26 | , make them stronger because the cell be responding. And the closer in |
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| 50:30 | this input coming in and the output generating the actual potential. The more |
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| 50:36 | the connection and the stronger the connection become between these cells. So by |
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| 50:40 | virtue you have forward action potential going Exxon initial segments external terminal for neural |
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| 50:47 | for the next section of this course that that propaganda action potential which informs |
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| 50:52 | soma and the dendrites and natural plasticity rearrangement of the communication onto this cell |
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| 50:59 | it is receiving the incoming. Be than happy to take any questions, |
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| 51:05 | you for your |
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