| 00:01 | Aziz, you can see your final is comprised off the three midterm exams |
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| 00:08 | final exam. Being one of those , final exam is not cumulative. |
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| 00:14 | I have received a couple of questions the folks asking Thio, drop one |
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| 00:22 | on and keep the best two I will think about this. I |
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| 00:28 | see how, uh potentially the second exam goes. And I will also |
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| 00:34 | that in the past what I have is I have given one or two |
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| 00:42 | . There were pop up quizzes in case. Obviously we cannot do a |
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| 00:47 | up quiz, but I have given the past one or two pop up |
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| 00:52 | in person. And as I have them, I have added those quiz |
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| 00:59 | onto one midterm exam points. And I have taken the average of all |
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| 01:06 | . So this is in the past this is now again if it is |
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| 01:13 | one or two, uh, folks didn't feel they did well because they |
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| 01:18 | study enough and they want to keep better to grades. I'm not sure |
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| 01:23 | is really justifiable for me. Thio changes, but I will discuss with |
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| 01:29 | the possibility of scheduling potentially scheduling requests along during this course. Okay, |
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| 01:42 | and that quiz will contain about 5 7 questions. If that happens, |
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| 01:48 | CASS allows me to do that, essentially is, uh, another event |
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| 01:54 | I have the schedule for two sections this course to do that. But |
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| 02:00 | any case, let me explore that . And let's now talk for a |
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| 02:07 | how everyone did on this, exams and recording. Do you have |
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| 02:14 | questions about this midterm? One on questions that you have missed? I |
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| 02:20 | . I will release the exam so you can see at the end of |
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| 02:24 | week or early next week. And you review the questions, please address |
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| 02:30 | you have any concerns about specific question once in a while there's one or |
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| 02:37 | errors. And within my, question, the answer marking for Casa |
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| 02:45 | just a technical error. And I repair that so that the score for |
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| 02:50 | question would change if that actually indeed to be changed. So but this |
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| 02:56 | what is exam one. Just to you an idea that typically exam to |
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| 03:02 | exam. Three scores are a little by anywhere between in the past 25 |
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| 03:12 | lower on average. Uh, there's always somebody that that's course, |
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| 03:22 | , 100. Um, so there's perfect scores in the mix here in |
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| 03:30 | sections. So congratulations to those folks really, really well. And, |
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| 03:36 | , I'm gonna look at the chat see if there's any questions that I |
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| 03:40 | toe address Now about this. Will test baby curved or the A possibly |
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| 03:50 | lowered from a 95 e? Don't that they will be lowered from |
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| 03:59 | I have considered a curve. And I explained, I'm also considering having |
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| 04:07 | safe. Aiken, have it scheduled Casa because of these unprecedented schedule. |
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| 04:14 | we can. There might be an quiz that will essentially serve as a |
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| 04:20 | curve for yourself. And so we . We will. We're discussing these |
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| 04:25 | possibilities. Is it possible for you give us any notes? Absolutely. |
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| 04:33 | of my election outs are on All of the videos around video |
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| 04:41 | This is the best notes you can , and you can watch it back |
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| 04:45 | forth and skip it forward. Is else having this audio clip Ellen |
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| 04:52 | I explained that I'm having bad Internet Oto and I think that maybe this |
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| 05:00 | what's happening. See what time it ? It may be happening now. |
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| 05:07 | you know how quiz will be? If it happens, it will be |
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| 05:15 | Qassem. But I have to discuss with them first. How the quiz |
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| 05:21 | do you the same question. Good . Thank you for the questions. |
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| 05:27 | think that if there is no more about exam, I would recommend that |
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| 05:35 | you're not sure about your grave, for a couple of days when the |
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| 05:39 | are released so that you can review and as you review them on, |
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| 05:45 | should be able Thio, ask any . And also I heard you to |
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| 05:52 | the material because as you review the , you will find the sections. |
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| 06:01 | of all, you will find the that you missed and you will understand |
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| 06:06 | maybe a certain section that you want was not as clear for you was |
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| 06:13 | one of the strong points. And is important because some of these topics |
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| 06:19 | be getting more complex will be building some of the basic concepts we've learned |
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| 06:24 | this first section. But today we're on to a very, very cool |
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| 06:34 | off neuroscience, a synaptic transmission. communication between the cells that is happening |
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| 06:42 | the synapse. This is where I spent years of my life poking |
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| 06:48 | stimulating the fibers and recording from self and cell bodies and, uh, |
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| 06:56 | cells and stimulating them all. Addressing and excited Terry synaptic transmission and interactions |
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| 07:04 | neuronal species. So now this says in two weeks in office, that's |
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| 07:10 | two. This is my old office an S r two room to 42 |
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| 07:15 | if you are that building on the floor, you will still see my |
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| 07:20 | plaque there. It has taken the a few years. They probably missed |
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| 07:26 | in that building and kept the plaque . But I'm in the biomedical |
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| 07:31 | HBs be, um, won which is where the school of the |
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| 07:40 | surgery is. So I am really the office these days because Off Cove |
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| 07:47 | and your exam is not in two , my email JSA burgers at U |
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| 07:52 | u has not changed, and you all of that information in your syllabus |
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| 07:57 | well. Now what? ISS synaptic ? Well, it's not. The |
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| 08:04 | is imagined. Us. The brain billions of neurons, billions of |
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| 08:19 | billions of neurons. That means that can have hundreds of thousands of |
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| 08:27 | Millions of cells, hundreds of millions cells active them talking to each |
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| 08:38 | A trillion Selves, which might be pathological condition off massive seizure, massive |
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| 08:47 | infarct going on in the brain, of synapses, trillions of synapses. |
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| 08:58 | the computation. That's the complexity of computation billions and individual units communicating through |
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| 09:08 | of synapses in the brain. If were thio, take the cerebral cortex |
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| 09:17 | you were thio. Lay flat, of the membrane area from all of |
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| 09:23 | neurons from CNN's you would laid All of the membrane area from all |
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| 09:30 | the neurons would cover four soccer If if you laid out the whole |
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| 09:41 | flat, all of the neurons flattened and connected them in this imaginary hypothetical |
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| 09:50 | . In this blanket, it would four soccer fields. That's what comprises |
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| 09:57 | fabric of our minds. When we about synaptic transmission, we have to |
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| 10:06 | ourselves of some of the key individuals . And this process ra Monica |
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| 10:16 | Sir Charles Sherington. Today we're gonna about Otto Louis and what we have |
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| 10:25 | in the past few lectures. We at how the ax on initial segment |
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| 10:32 | an action potential, and we talked forward propagating action potential. We talked |
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| 10:37 | that propagating action potential, and so understood the dynamics behind how this action |
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| 10:45 | is generated by voltage gated sodium two types of voltage, gated sodium |
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| 10:50 | and both educated potassium channels. We it. We discuss the salvatori conductive |
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| 10:57 | off the action potential regenerating in each of around here. As you can |
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| 11:03 | it, external terminals ram if I they split into several different external |
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| 11:11 | Each terminal becomes an individual synapse that synapse can target. A seller can |
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| 11:18 | and critic spine. And so when action potential, the nerve impulse arrives |
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| 11:24 | the synapse the size, the amplitude that action potential is the same as |
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| 11:30 | was when it was generated at the . Initial segments that strong, deep |
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| 11:37 | , that strong action potential, the , the synaptic terminals, what allows |
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| 11:44 | the vesicles to fuse to the remembering released neurotransmitters and for the pasta |
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| 11:50 | , pick receptors to respond to the of these neurotransmitter chemical molecules. |
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| 11:58 | auto Lowy again is one of the that is really inspirational in many |
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| 12:07 | And this is a story by auto the night of Easter Saturday in 1921 |
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| 12:14 | almost 100 years ago I awoke, on the light and jotted down a |
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| 12:21 | notes on a tiny slip of Then I fell asleep again. It |
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| 12:27 | to me at six o'clock in the , but during the night I had |
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| 12:31 | down something most important. But I unable to decipher the scroll that Sunday |
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| 12:38 | the most desperate day in my whole life. During the next night, |
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| 12:45 | , I awoke again at 30 and I remembered what it waas this |
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| 12:52 | . I did not take any I got up immediately, went to |
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| 12:57 | laboratory, made the experiment on the heart described above, below, and |
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| 13:03 | five o'clock in the chemical at five , the chemical transmission of nervous impulse |
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| 13:09 | conclusively proved. It is quoted from of discoveries. Um, auto Lowi |
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| 13:16 | University of Kansas, pressed from 1953 account. And so what? What |
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| 13:24 | oughta Lowy to Uncle Louie isolated to heart. And he's saying here he |
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| 13:36 | and he did an experiment on the heart. So this is the lowest |
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| 13:41 | . That bottle. Oh, we . Frogs Heart has a very large |
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| 13:48 | . Cranial nerve. We will learn cranial nerves toward the end of the |
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| 13:53 | section Cranial nerve 10 or vagus which has very strong innovation and controls |
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| 14:03 | off the heart. So what utter did is that he had this heart |
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| 14:11 | the donor heart. My Internet is , so I will pause for a |
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| 14:19 | . What Otto Low we did is took this heart and placed it in |
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| 14:25 | vessel, the heart on the left the donor heart. He placed it |
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| 14:30 | a actual jar in the vessel and that heart he had this blue vagus |
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| 14:37 | that was attached. And so he vagus nerve number one. As he |
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| 14:44 | my vagus nerve, he recorded the rate and he was observing the beating |
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| 14:49 | the heart. So as he stimulated vagus nerve, the heart laid rate |
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| 14:55 | , slowed down. Stimulation of vagus causes the slowing off the hard |
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| 15:03 | And what we What he did is this jar in which this donor heart |
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| 15:08 | sitting. He collected to remove the that its surrounding he had fluid in |
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| 15:15 | jar and he stimulated the vagus And then he removed the fluid, |
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| 15:21 | that there is some chemical in the nerve on the right, he had |
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| 15:27 | naive heart or recipient heart. It's because it doesn't have like the one |
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| 15:33 | the left. It doesn't have vagus attached to it. And Davis nerve |
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| 15:39 | not bean stimulated. So the frog is sitting in its beating. In |
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| 15:45 | first case, you stimulate the night vagus nerve and you collect the |
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| 15:49 | In the second case, the heart beating and you apply the fluid on |
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| 15:55 | beating heart that you collected from the heart. So when you apply this |
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| 16:03 | from the donor heart onto naive or heart, the same thing happens. |
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| 16:10 | rate slows down. The difference is in the left to slow down the |
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| 16:16 | rate, you stimulated the vagus nerve the right. You did not simulate |
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| 16:22 | vagus nerve to slow down the heart , but instead you apply the fluid |
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| 16:27 | was collected from the vessel in which stimulated donor heart was placed and that |
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| 16:35 | approved, that there was something in liquid. There was something in that |
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| 16:44 | that was causing the heart rate to down. And so that's something turned |
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| 16:51 | to be Siddle, Coleene and the home message and inspirational sort of a |
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| 16:59 | of. The story about Otto Lowy if you are on a quest and |
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| 17:07 | you are driven by discovery, if haven't ah ha moment, you don't |
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| 17:15 | any time. If it's three o'clock your mentor allows you go in the |
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| 17:22 | and write down experiment, prepare Um, some. In case of |
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| 17:30 | . We have these moments off clairvoyance moments off Ah ha, moments at |
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| 17:39 | during a sleep during the sleep, brains replay information. A lot of |
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| 17:45 | that we experienced during the day, actually strengthen certain synapses. There's plasticity |
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| 17:53 | happens at night during that plasticity. lot off information is being coded in |
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| 18:00 | brain that happened during the day and patterns they activated. Our brain. |
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| 18:08 | and brain networks during the day are in different frequencies, air now active |
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| 18:15 | night as well. So this is interesting way of thinking not only about |
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| 18:21 | Lowy, about the discoveries about how doesn't wait and some good ideas, |
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| 18:28 | you can apply them quickly, do but also, in general, about |
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| 18:33 | and the role of sleep and synaptic . The fact that sleep and |
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| 18:39 | some interesting information that sometimes leads Thio says the one by Buffalo. We |
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| 18:50 | believe there was a couple of Yes, again, I'm having trouble |
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| 19:04 | computer with Internet speed. It's going in and out today, and usually |
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| 19:11 | I apologize if my voice is fading and out. Okay, sure, |
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| 19:33 | . So this is a story of . Let's let's move on. I |
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| 19:36 | that Internet will we'll stabilize, and we may think about that. The |
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| 19:43 | hopefully will be stable so some of parts of this get muffled, then |
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| 19:49 | they will not be, uh, on the actual video recording. Now |
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| 19:55 | know that apart from chemical synapses, are also second type off synapses that |
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| 20:01 | call electrical synapses. Electrical synapses would refer to as gap junctions, and |
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| 20:10 | essentially gap junctions of pictured here. they're different from the chemical synopsis that |
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| 20:18 | the synaptic cleft. So in chemical in general, the distance between the |
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| 20:25 | Selves is about 20 nanometers, and is the synaptic space in the chemical |
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| 20:32 | but and electrical synopsis of gap There is a special indentation that |
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| 20:41 | and the plasma membranes that brings the Junction channels on the pre synaptic side |
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| 20:48 | a trans membrane channels to connect with counterparts on the pasta, not pick |
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| 20:54 | sell one to sell to. In case, the indentations and plasma membrane |
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| 21:01 | closer to each other physically in space are only about 3.5 nanometers apart, |
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| 21:07 | opposed to 20 nanometers in the synapses the formation off these gap junctions, |
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| 21:16 | are essentially complementary proteins that formed between synaptic and Boston optic side that are |
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| 21:25 | from connections. Connections form a connects and to connects on some pre synaptic |
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| 21:31 | Boston optic side form of gap And what gap junctions allowed thio happen |
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| 21:38 | gap. Junctions allow for the free of ions and small molecules. They |
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| 21:47 | , to some degree gated by However, once there is an opening |
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| 21:56 | , there is an increase off the , or small molecules ions such a |
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| 22:02 | potassium, such as calcium. Then will be a free flow down, |
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| 22:07 | concentration radiant across these gap junctions and bi directional so it can go from |
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| 22:15 | . Want to sell tune from cell from to sell Juan. So the |
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| 22:19 | junctions of bi directional. Where is synaptic transmission? Is unit direction? |
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| 22:26 | if you may think, uh, that we will learn about retrograde synaptic |
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| 22:34 | , which would also essentially signaled that bi directional but differently here. That |
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| 22:40 | directionality is that ions and small including cycling and be can cross in |
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| 22:47 | directions, depending on the concentration. if you recall when we talked about |
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| 22:53 | concentration increases locally and Astra sites keeping and slurping up the potassium and siphoning |
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| 23:02 | off through its interconnected network, it so through the gap junctions, so |
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| 23:08 | can pass, uh, potassium and waves through the interconnected Astra City Gap |
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| 23:16 | between Astra sites. So a lot glia will contain gap junctions. But |
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| 23:21 | some neurons will contain gap gap junctions electrical junctions as well. So you |
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| 23:28 | think of neuron scan can actually have types of the synapses. They can |
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| 23:33 | an electrical synapse that requires action potential requires opening of the voltage gated |
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| 23:41 | And you have electrical synapses that are both educated and they're really concentration. |
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| 23:47 | Independent. So originally, chemical synopsis discovered by Auto Lowy and um first |
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| 23:58 | and Potter discovered the electrical synapses in . But what they did thio determine |
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| 24:07 | there is something different from chemical neural as they passed the current and the |
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| 24:14 | cell here with one Electra and then sells Axiron, or process and had |
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| 24:20 | recording election. And it recorded a that was very strong current based on |
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| 24:27 | stimulation in the top south, top produced very strong currents, but the |
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| 24:32 | also placed the second electorate in the south. Here can also they picked |
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| 24:38 | smaller current, so voltage change of vaulted change. Smaller current change was |
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| 24:45 | and self too, but it was immediate There was no delay then. |
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| 24:50 | is important because in chemical synaptic when the cell releases neurotransmitters and the |
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| 24:58 | crossed the space of 20 nanometers and to the pasta topic receptors that can |
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| 25:04 | few milliseconds off time. It's called delay, so for actual signal toe |
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| 25:12 | bind to the receptor synaptic delay before is a possum haptic response in Gap |
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| 25:17 | . Only a fraction of that signal transferred to the second self. But |
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| 25:22 | is no delay. There's no synoptic . It's just ah, smaller amplitude |
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| 25:29 | off the signal because of the resistance crosses into this salad of this cell |
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| 25:35 | connected to another neuron, it would him to that Norma's well so gap |
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| 25:41 | are important for for several reasons on important for synchronizing the cells for allowing |
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| 25:51 | large populations of cells to synchronize. , synchronization is activation of south on |
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| 25:58 | same frequency at the same time. if you imagine with synaptic transmission and |
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| 26:05 | thousands of synapses coming into the it doesn't necessarily synchronize the network because |
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| 26:13 | are synaptic delays. There's millisecond delays I built in, so you'll have |
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| 26:20 | waves, multiple signals that may look like this that are really not |
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| 26:31 | Okay, we signals can represent three networks. And if these three different |
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| 26:38 | or these three different groups of cells addition to the synaptic connectivity had electrical |
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| 26:46 | , then the some activity of them would translate into something that is quite |
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| 26:56 | and may differ in amplitude. But now synchronized, so the top is |
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| 27:04 | or population of cells. You can of it as a voltage. Fluctuations |
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| 27:08 | current fluctuations from three different cells and three different networks is synchronized and in |
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| 27:16 | bottom drawing that activity is not You have three different traces, three |
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| 27:22 | voltage fluctuations that are doing their own in their own time. But if |
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| 27:28 | have gap junctions, gap junctions, important for creating the synchrony, so |
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| 27:34 | is another important feature of gap The first one that we just talked |
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| 27:39 | was the inability to facilitate the transfer small molecules and ions. The ability |
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| 27:49 | transfer the current without any delay. fraction of that card in the third |
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| 27:55 | is the ability to synchronize so And that's synchronized activities quite often |
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| 28:05 | For efficient encoding of the sensor memory encoding or memory recall, our |
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| 28:14 | will actually operate the different frequencies during day. Different parts of the brain |
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| 28:20 | operate different frequencies during the day. parts will synchronize, others will be |
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| 28:25 | synchronize. The ones that I engaged communicating will have a certain degree of |
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| 28:31 | . And that is a way in the South's can effectively code the |
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| 28:37 | And so now next slide is we're back after this discussing this electrical synaptic |
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| 28:47 | , which is which is very where coming back and talking about chemical |
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| 28:53 | again. So we'll spend most of time trying to understand this chemical synaptic |
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| 28:59 | . So when the action potential arrives the pre synaptic external terminal, you |
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| 29:05 | see that this terminal will have a of mitochondria. So you need |
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| 29:09 | You need energy from exercise. It the release of neurotransmitters who we need |
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| 29:15 | for recycling and end of psychosis and of the vesicles. And in the |
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| 29:21 | you will have the synaptic vesicles that optically are located at what we call |
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| 29:27 | active zones where they gathered close to plasma membrane, ready and primed to |
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| 29:35 | with the plasma membrane is they're encased the membrane themselves to fuse with the |
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| 29:42 | terminal plasma membrane to release the neurotransmitters the synaptic, cleft and posson optically |
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| 29:51 | have pasta, synaptic density. So airpods synaptic densities that will express, |
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| 29:57 | , pasta synaptic receptors. This is electron microscope picture that you see on |
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| 30:05 | right off of a synapse, and can see pre synaptic side here at |
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| 30:14 | top. It has a mitochondria and double membrane. Krista galleon, |
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| 30:21 | If we sign optical, you can that there is a lot of synaptic |
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| 30:25 | . There's around little circles, prison , and you can see that they |
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| 30:31 | denser and congregate more so around what call that active zones. We synaptic |
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| 30:37 | that are matched in space but separated 20 nanometer synaptic cleft from these |
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| 30:45 | Nah, pick densities so you can again Boston optic densities Here on the |
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| 30:53 | of the neurotransmitter vesicles, you can some of the vesicles fusing to the |
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| 30:58 | membrane. Obviously very close and others attached but not fused yet. You |
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| 31:04 | actually zoom in and see all of . So I have a home or |
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| 31:09 | for you, which will probably get than this or next lecture work. |
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| 31:13 | a dance for vesicles and how are different from neurotransmitter? Vesicles can. |
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| 31:23 | a whole more question, Um, is unstable. Hopefully, Internet is |
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| 31:32 | stable again, and we're talking about , and we're talking about location of |
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| 31:42 | we can. These accents project accents project onto so much of other |
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| 31:48 | Accidents can project onto damned rights of nerves. Exxon's can actually project onto |
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| 31:57 | Axiron a swell. Finally, there's exception to every rule. There's also |
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| 32:05 | dendritic synopsis. How does that Well, for the purposes of our |
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| 32:11 | , you have to know that they . I myself don't understand much about |
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| 32:16 | dendritic synapses, but they are such phenomenon has done the dendritic synapses. |
|
| 32:22 | let's focus in MAWR and discuss what the difference between the accents that project |
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| 32:29 | Dan drives or accents that project into Selma's cells? If you're projecting onto |
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| 32:35 | dried and uran excited her synapse you to. Joel, that damn right |
|
| 32:40 | have to be a very powerful, tourists enough, or you have to |
|
| 32:56 | . I think the zoom crash for second. Could you hear me until |
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| 33:03 | crashed? Could you hear me When was the last time you heard |
|
| 33:13 | talking? So the home or question what are done? Score of vesicles |
|
| 33:20 | how they different from, uh, neurotransmitter of bicycles. And then we |
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| 33:29 | about the fact that we have this of the pre synaptic cell that has |
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| 33:41 | . We talked about the fact that have the synaptic vesicles and the synaptic |
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| 33:48 | that the active zones are located very to the plasma membrane and the pasta |
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| 33:53 | thickly. You have these pasta? . Pick densities of receptors that air |
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| 33:58 | across the synaptic cleft of 20 nanometers the pre synaptic side. And we |
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| 34:05 | on to discuss access somatic accident, , actual sonic and gender dendritic |
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| 34:11 | And I said that most of the are actual somatic and accident riddick. |
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| 34:16 | are actual external synapses and there are Denver dendritic synapses. For the purpose |
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| 34:23 | this course, we will focus on access Somatic Accident Critic and accidents Sonic |
|
| 34:29 | it is really interesting how the gender synopsis, uh, work, and |
|
| 34:35 | honestly don't know much about it But if you look at the acts |
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| 34:40 | somatic, if you are projecting onto Soma, then you have really strong |
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| 34:47 | to affect the integrative properties if you you're closer to sell more closer tax |
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| 34:52 | initial segment. So if you're an story style, you have a better |
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| 34:56 | on that cell to be excited by . If you have an inventory |
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| 34:59 | you have a better chance to inhibit self from producing the action potential. |
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| 35:05 | you are in a on the you have to produce a very |
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| 35:10 | either excited or inhibitory signal in order that Soma, or for the hacks |
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| 35:15 | initial segment to be either excited by excited, very strong input on the |
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| 35:21 | or inhibited. If that is a input on the Denver Finally, the |
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| 35:27 | Exxon IQ Synapses air different because in cases here, with the accident somatic |
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| 35:33 | accident critic synopsis, you are affecting integrative properties of the South. You |
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| 35:40 | controlling or you're controlling your affecting how cell is gonna integrate the snapping information |
|
| 35:48 | controlling, whether the cell is going produce an action potential or not from |
|
| 35:52 | damned writer from the Selma. If talking about access external synapses, in |
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| 35:57 | case you have Axiron that cannot contacts another Axiron. This acts on that |
|
| 36:05 | actually on the right, maybe producing potentials already. So when you have |
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| 36:11 | zonal synapses, you don't get you the fact that integrative property self the |
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| 36:18 | But instead you modulate the external You modulate the action potential frequency at |
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| 36:27 | level of the axon so you cannot the cell whether to produce an action |
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| 36:33 | , excited or inhibited. But you influence this Axiron from being too excited |
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| 36:41 | too inhibited. So this effect of external synopsis is a module, a |
|
| 36:48 | effect that modulates the output. It the other cells output in the sense |
|
| 36:54 | modulating the output and acts on the being the action potential mhm and, |
|
| 37:03 | , these student A and B, are affecting the integrative properties. They |
|
| 37:09 | affect whether the Selma can produce an potential now on the right. You |
|
| 37:14 | have anatomical features for the excited terror inhibitory synapses that are quite interesting. |
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| 37:22 | excited tourists analysis will have asymmetrical remembering in the sense that they're active pre |
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| 37:32 | zone area in the membrane thickening that in the synapse. A small thickening |
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| 37:40 | be narrower prison optically as compared to cost synaptic densities and in the inhibitory |
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| 37:51 | and the exciting Terry synapses will also very clear round vesicles. And the |
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| 37:57 | synapses are more likely to have these like shaped vesicles and have symmetrical numbering |
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| 38:05 | . So the thickness of the area the pre synaptic active zone is proportional |
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| 38:13 | symmetric to the pasta napping density All right. And so what we |
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| 38:21 | a lot about the CNS synapses comes our understanding off neuro muscular junction. |
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| 38:30 | historically you can see Luigi Kalani was the nerve onto frog muscle you can |
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| 38:38 | on Tele. We've was stimulating it on Thio Frog's heart Davison are projecting |
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| 38:46 | frog's heart On that is because these coming from spinal cord or cranial nerves |
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| 38:59 | from the brainstem, they're pretty And so you can you can stimulate |
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| 39:04 | single spinal nerve that comes in between vertebra. You can identify these bundles |
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| 39:11 | nerves, and you can also study synapses by stimulating the nerves in the |
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| 39:18 | easier than in the actual Serie And so we already discussed the |
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| 39:26 | We already know that reflects our We know the South players involved. |
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| 39:31 | know the neurotransmitters that their release. so here is a review and now |
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| 39:41 | anatomy off what we refer to his muscular junction. It's, um, |
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| 39:46 | between nerve and muscle like nerve and muscle like nerve and cardiac muscle. |
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| 39:54 | case of Boca Lily, this axon comes onto the muscle and of |
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| 39:59 | it comes from the mental side of spinal cord, where you have the |
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| 40:04 | neurons and project their my eliminated access . Terminate onto the muscles, in |
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| 40:13 | case, on the biceps muscle. forming these very large pre synaptic terminals |
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| 40:24 | each one off these synapses. Each of these external terminals is referred to |
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| 40:32 | motor and played region, and so have this motor employed region, which |
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| 40:37 | enlarged here on the right and the and played region pre synaptic Aly |
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| 40:44 | You see mitochondria, you see rows synaptic vesicles you see, synaptic |
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| 40:51 | we discussed. And then you see very interesting anatomy here onto the |
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| 40:57 | The muscle fibers themselves form these PAAs junction a lfa walls. You can |
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| 41:04 | that there are these deep imaginations that onto the surface of the muscle that |
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| 41:11 | referred to its junction off holds. these junction all falls especially closer toe |
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| 41:17 | the synaptic cleft express high densities, high levels off receptors. They |
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| 41:26 | uh, two types off receptors in case. So now we're talking about |
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| 41:32 | channels we talked about, uh, gated channels remember sodium channels and potassium |
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| 41:41 | open because the voltage change now these channels are actually different. The neurotransmitter |
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| 41:50 | vesicles will release in this case a coleene Aziz Well, and so you |
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| 41:55 | have receptors. He's acetylcholine. Receptors be located very close to the pre |
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| 42:01 | side. That will cause the initial polarization. So initial deep polarization of |
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| 42:07 | neuromuscular junction is caused by That's a . Colin receptors in the muscle |
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| 42:17 | So it's about golden receptors will polarize the muscle and subsequently there is |
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| 42:25 | in these junction a lfa walls close the muscle fibers of south. There |
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| 42:29 | voltage gated sodium channels, so deep , initial deep polarization from the it's |
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| 42:37 | topical interceptors will produce what we call end plate potential. And this is |
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| 42:43 | very large synaptic potential. And that polarization and the flow of ions through |
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| 42:49 | societal Colin receptors will then in deep polarized sodium channels that are located |
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| 42:57 | in the directional faults. Initiating the potential in the muscle. That will |
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| 43:03 | study really much of the dynamics of muscle of the action action potential in |
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| 43:09 | muscles because it has a significant calcium also, so it's a little different |
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| 43:15 | CNS action potentials. But we have understand this Neuromuscular Junction have to understand |
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| 43:23 | the chemical transmission that's a towel Colin will cause the initial deep polarization and |
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| 43:30 | voltage gated channels will initiate the production the action potential. So that's sort |
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| 43:35 | the sequence of events that happens in to cause a contraction in the |
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| 43:41 | Neuromuscular junctions are very, very, , effective a an action potential at |
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| 43:52 | end plate Mara and played region means twitch of a muscle action potential in |
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| 43:59 | neuron means the twitch of a It's what we call very high fidelity |
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| 44:05 | action potential. Which of the muscle potential deep polarization strong enough to cost |
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| 44:11 | other muscle? So this is what when you have the reflexive behavior in |
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| 44:16 | circuit that we discussed. It would released of excited or its pal |
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| 44:21 | and there will be contraction off the muscle. So you should wonder at |
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| 44:28 | point, wait a second. You told us that up the Lowy caused |
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| 44:34 | slowing down of the heart trade. is slowing down on the heart |
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| 44:39 | Heart is a muscle. It's So in the heart you're saying vagus |
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| 44:48 | slows down the heart rate, the of the heart. It uses a |
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| 44:56 | Colin, but in the skeletal the same neurotransmitter seal Colin increases. |
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| 45:05 | contraction causes the contraction off the So what is the difference? Anybody |
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| 45:15 | the difference. Why is this a ? Colin or Siddle? Colin Inhibitory |
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| 45:22 | the cardiac muscle or in the And why is it excited? Torrey |
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| 45:27 | the skeletal muscle. Very good The response of the cell for synaptic |
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| 45:36 | depends on the type of the receptor is located Austin Optical, so we |
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| 45:41 | understand a lot about It's a Towel and what we call Colin Arctic Neural |
|
| 45:46 | . So this is a vocabulary. , Kolinahr. It's called an urgent |
|
| 45:51 | transmission You're talking about South releasing a Colin. We talk about cells releasing |
|
| 45:58 | . We'll talk about dopamine urging neuronal . That's a tall Colin transmission. |
|
| 46:06 | do we need to know about the ? Colin Transmission. Why is call |
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| 46:12 | urging neural transmission is important for It's not on Lee, because off |
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| 46:17 | motor on planes, it's not only of the motor planned play that this |
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| 46:28 | important. Okay, Colin Ergic neural also happens. Acetyl Colin also gets |
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| 46:36 | in the CNN's, So I have home or question, which will get |
|
| 46:43 | again. I have to home more for you and making you work |
|
| 46:47 | Today it's Wednesday. So the home question is which neurological disorder that we |
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| 46:54 | has ah, impairment in the central system and the colon allergic signaling, |
|
| 47:03 | neurological disorder we discussed no any other Sido Colleen system is impaired in this |
|
| 47:23 | disorder in the central nervous system. , no, yes, the Alzheimer's |
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| 47:37 | on. That's why I said you to keep notes on these neurological disorders |
|
| 47:42 | Alzheimer's disease, the plaques and the system, or neurotransmitter signaling in the |
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| 47:53 | that is effective, mostly affected and early on is a CDO Colin signaling |
|
| 48:00 | the brain. So this is this another pathology that you're learning about now |
|
| 48:08 | learned about the anatomy of Alzheimer's the hallmarks on atomic oh, pathological |
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| 48:15 | of Alzheimer's disease. The plaques and tau tangles inside the cells. Now |
|
| 48:21 | also learning with the impairment would specifically this system, which is Colin Ergic |
|
| 48:28 | , but not in the muscles. , this, this may be deceiving |
|
| 48:33 | image I'm discussing. This is a reliable synapse in the muscle that we |
|
| 48:38 | really well this large and it's easy study. But I'm discussing here a |
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| 48:43 | that it the response well off acetyl will be different in the heart of |
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| 48:48 | muscle. That response it depends on receptors, and then I have correlated |
|
| 48:52 | we also know a neurological disorder that discussed it in the CNN s not |
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| 48:58 | here. You're a Moscow junction in CNS will have impaired serial Colin signaling |
|
| 49:03 | all of this is very important as put these different pieces of neuroscience together |
|
| 49:09 | the course. So what? A system system components, of course, |
|
| 49:14 | have tohave neurotransmitter present optically neurotransmitter synthesizing that they have synaptic vesicles, |
|
| 49:22 | You have to have re update You have to have degradation of |
|
| 49:27 | Austin Optical. You have transmitter, ion channels or chemical or chemical a |
|
| 49:33 | ion channels for chemical lee gated You also have receptors that are called |
|
| 49:39 | protein coupled receptors that actually do not channels. But they also buying the |
|
| 49:44 | neurotransmitters that are connected to G pro . You have G protein gated ion |
|
| 49:51 | . The channel said. Get opened lee after chemical binds to G protein |
|
| 49:56 | receptor. And there's an activation of protein and costin optically downstream. You |
|
| 50:01 | secondary messenger cascades that get activated by channel proteins by G coupled receptor, |
|
| 50:12 | , pro dance as well as, , iron channels. So voltage gated |
|
| 50:19 | channel so neurotransmitter criteria neurotransmitter has to produced and synthesize and found within the |
|
| 50:26 | , so GABA, ergic neurons, and neurons will express gabba excited terry |
|
| 50:32 | glue dramaturgical neurons will express glutamate. . So when a neuron is |
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| 50:41 | de polarized Oreck stimulated or do the neural must release that chemical. |
|
| 50:47 | a chemical is released, it must on a person optic receptor and cause |
|
| 50:51 | biological effect that chemical must have in . After chemical is released, it |
|
| 50:56 | be inactivated. Okay, so when neurotransmitters get released in the synaptic |
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| 51:03 | they don't stay there for a long . They bind to the receptors, |
|
| 51:07 | the rest of them get We have back. Or they get enzymatic Lee |
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| 51:13 | down within the synapse and turned into constituent of molecules that are transported back |
|
| 51:20 | the south. If the chemical. that chemical that you've isolated, let's |
|
| 51:25 | , as a towel Colin is applied the pasta synaptic membrane, it should |
|
| 51:29 | the same effect as when it was by the neuron. It's called Minute |
|
| 51:34 | . So many create is a perfect of ultra low. He isolated a |
|
| 51:40 | and when he applied that chemical on frog heart. It also showed the |
|
| 51:44 | effect that when he stimulated Thio acquire chemical to isolate that chemical. And |
|
| 51:51 | we have many different neurotransmitter systems, we're gonna really delve into quite a |
|
| 51:57 | of them. There will be And so for this I'm gonna actually |
|
| 52:04 | positive recording a little bit. But is the different neurotransmitter systems that we |
|
| 52:12 | be discussing. And we already know of them that we will understand some |
|
| 52:17 | them in much greater detail in And some of them will just mention |
|
| 52:21 | some of them will come back and in greater detail during the third section |
|
| 52:27 | this, of course. So let's with amino acids. You have amino |
|
| 52:32 | or transmitters. Those are our favorite immuno beauty, Eric acid, which |
|
| 52:40 | for Gabba. This is the major neurotransmitter in the CMS. You have |
|
| 52:47 | , which is amino acid, and a major excited during their transmitter in |
|
| 52:52 | CNN's, you have glide seem, is a major inhibitory amino acid neurotransmitter |
|
| 52:58 | the spinal cord. Glisan can also as a co factor to some glutamate |
|
| 53:07 | in the central nervous system. there is exception to every rule, |
|
| 53:12 | glisten is inhibitor and the spinal cord favorite multipolar little into neurons in the |
|
| 53:19 | cord release inhibitory glycerine. That same has a different effect in the |
|
| 53:25 | Again, the fact depends on where specific I mean acid neurotransmitter a different |
|
| 53:32 | of neurotransmitter binds to what type of binds. The response of the cell |
|
| 53:38 | depend on the receptor, not on actual molecule that is released prison |
|
| 53:44 | we have a mean neurotransmitters. So have a seal coleene. There are |
|
| 53:53 | at dopamine happiness offering. Does that norepinephrine? Renan, Serra, |
|
| 54:04 | Pretty much anything that ends an I e. Okay. And one and |
|
| 54:13 | am isn't I mean so it is to remember this class just by remembering |
|
| 54:23 | all means are i n e in ending. It's a cowl Colleen open |
|
| 54:30 | I Any epinephrine? I any histamine exceptional serotonin? All of these air |
|
| 54:38 | , very important neurotransmitters in the brain most of our fast signaling in the |
|
| 54:47 | excited to an inhibitory signaling in the is determined by glutamate and by Gabba |
|
| 54:55 | the CNN's. And then these mean transmitters. They exert some longer lasting |
|
| 55:03 | and typically get released when there is activity and they get released and they |
|
| 55:12 | of very different functions again, it's Colleen eyes in the mean and you'll |
|
| 55:18 | it in the neuromuscular junction. We discussed it, and it's responsible for |
|
| 55:22 | end play potential again. The features the employees potential is that it is |
|
| 55:27 | very, very large potential. We discuss it again, the next lecture |
|
| 55:34 | allows to produce the action potential Tom will also found in the CMS. |
|
| 55:40 | we relate at the Hotel Colin neural system dysfunction With Alzheimer's disease, there |
|
| 55:47 | dopamine, and what we're on to is that we have normal signaling in |
|
| 55:55 | systems. And if one of these systems is impaired, it correlates and |
|
| 56:02 | has association or is model for a disorder. So dopamine is impaired and |
|
| 56:14 | neurological disorder that's Parkinson's disease. so we're adding another disease. Parkinson's |
|
| 56:24 | , which is doping in signaling But dopamine on dopamine receptor hypothesis and |
|
| 56:33 | receptor ratio impairment is also associate ID neuropsychiatric disorder called schizophrenia. Epinephrine in |
|
| 56:48 | , up enough in the sort of the adrenaline off the brain. Histamine |
|
| 56:53 | anti histamines. Do you know what , anti histamines or when you, |
|
| 56:59 | you're taking allergy, says producing inflammatory is to needs. Sir Tony, |
|
| 57:07 | , widely expressed in the CNS and neurotransmitters or not like I'll keep |
|
| 57:13 | repeating myself that these neurotransmitters or not unique to the CNN s, especially |
|
| 57:23 | and the peptides you'll find them throughout bodies. Serotonin fight each day is |
|
| 57:28 | very important system involved in quite a , uh, functions in the body |
|
| 57:34 | the brain in the periphery and the system. A swell is in the |
|
| 57:40 | s and then CNN s. It involved in many different functions, |
|
| 57:46 | uh, sleep, uh, relaxation sexual behavior that gets controlled by these |
|
| 57:54 | means So would you really have to thinking about is how these different neurotransmitter |
|
| 58:02 | how these neurotransmitters and these systems actually . They represent certain behaviors fast and |
|
| 58:11 | behaviors. They're associate ID, the or dysfunctions in these neurotransmitter assistance is |
|
| 58:17 | with certain neurological nor degenerative conditions, psychiatric conditions, and on the |
|
| 58:24 | We have a list of tap ties we will not really have time to |
|
| 58:29 | much in that school system. Kind dine, orphan and careful in. |
|
| 58:33 | this it s part till glutamate neuropeptide , which is important. Some at |
|
| 58:39 | Staten, very importantly, mentioned it the past. And, uh, |
|
| 58:44 | off the hippocampal Interneuron substance P mediates important Tyra Trough and releasing hormone |
|
| 58:52 | Active intestinal followed peptide. So there's lot of neurotransmitter systems and that's not |
|
| 58:58 | end. So I'm gonna ADM or gonna add N o CEO. What |
|
| 59:12 | these? No call. Let's I can't see the chat room for |
|
| 59:21 | reason. Okay, So, natural Mhm Obama on outside. Wow, |
|
| 59:43 | it is? Yes, gas is . So next time when somebody |
|
| 59:51 | Oh, I just had a brain You actually can make a joke and |
|
| 59:56 | , Did you know that your brain uses gas is for neural transmission such |
|
| 60:03 | naturist oxide and carbon monoxide, carbon , a teepee? Dennis um cried |
|
| 60:18 | . Fate mhm And the Dennis. So we have with Dennison and Dennison |
|
| 60:34 | , you're gonna wanna learn about the and Dennison triphosphate because you actually block |
|
| 60:45 | Dennison receptors in the CNN's. A overwhelming majority of you use caffeine. |
|
| 60:54 | so when we start understanding the function these receptors and the synapses, you'll |
|
| 61:00 | that caffeine acts through a Dennison It blocks it Dennis and receptors and |
|
| 61:08 | and receptors on Denison levels go up the sleep cycle and at night. |
|
| 61:19 | decrease in the morning and Denison receptor blocks glutamate, signaling. So there's |
|
| 61:29 | between these different receptors. These different systems and also these amino acids and |
|
| 61:35 | interact with amino acids. Dennison and interacts with amino acids and Denison receptors |
|
| 61:41 | control blue make release, so caffeine blocks the Dennison receptors and promotes caffeine |
|
| 61:50 | glutamate release. So a lot of are typically consuming caffeine in the morning |
|
| 61:58 | give the glutamate boost so it has properties, and this far a stimulating |
|
| 62:04 | releasing glutamate. And some people are highly dependent. And caffeine in general |
|
| 62:12 | , ah, fairly addictive substance, , and so you know that an |
|
| 62:19 | does for caffeine is about 123 cups coffee a day. That's what usually |
|
| 62:26 | consume Thio, get their brains get there stimulation and glutamate release going |
|
| 62:35 | the way. Teeth contains caffeine as . So it's not just coffee |
|
| 62:41 | So 1 to 5123 cups of one thio, five cups of |
|
| 62:46 | something that typically people would consume. it's okay. It's a normal |
|
| 62:52 | It's a, uh, effective Deadly does from caffeine is only 100 |
|
| 62:58 | of the affected. Technically, consumption 100 cups of coffee a day. |
|
| 63:04 | , cam be toxic cannot toe kill . So it Zaveri interesting things that |
|
| 63:12 | talking about here because you don't think every day consuming something that actually has |
|
| 63:17 | psychoactive effect. Releases glue to May it is pretty addictive substance. And |
|
| 63:26 | about it. Think about all of coffee shop spots in Starbucks believable |
|
| 63:35 | One across the street from another. have a new intersection or can have |
|
| 63:39 | Starbucks one on each corner. Except that the one that will have Dunkin |
|
| 63:45 | if you're in New York or somewhere this. So wow, it's a |
|
| 63:51 | right? It's feeding, feeding caffeine the masses, feeding our our |
|
| 63:57 | our vices, our addictions in some . Right then we have membranes |
|
| 64:06 | or we can say lipid soluble transmitter . It is very interesting for me |
|
| 64:15 | academic acid. Oh, yeah. hum, Duncan abdomen. Okay. |
|
| 64:24 | cannabinoids are Ananda Mydd and to a actually, ever economic acid is a |
|
| 64:40 | . And then the cannabinoids are also , their Olympics soluble. So unlike |
|
| 64:47 | neurotransmitters like goblin glutamate and a stored the neurotransmitter vesicles or peptides that historic |
|
| 64:55 | dense core vesicles, these gasses air really stored anywhere. They're not enclosed |
|
| 65:02 | this organ, Al of the vessel the TPM and Dennis. And the |
|
| 65:09 | is not also necessarily encased and lipid molecules. Social circle Danek acid under |
|
| 65:15 | cannot be in case in the last . Our economic acid can be a |
|
| 65:21 | and also a by degrade, product by the gradation product often joke |
|
| 65:31 | Lloyds. So the two are very intertwined and the cross plasma membranes freely |
|
| 65:36 | they're not stored in the vesicles. then that cannabinoids typically again, just |
|
| 65:42 | in amino peptide neural transmission, especially the peptide neural transmission of them that |
|
| 65:48 | the phenomenal neural transmission you have to high levels of activity in the system |
|
| 65:53 | order to release under cannabinoids, and bodies will generate these cannabinoid molecules inside |
|
| 65:59 | bodies. Under Canavan on molecules and and to a G based on demand |
|
| 66:05 | its activity dependent process. If there's lot of demand, if there's a |
|
| 66:08 | of activity, there's going to be response. Production off Endo cannabinoid molecules |
|
| 66:14 | particular on DSO and the CA nominal molecules says also what we know these |
|
| 66:25 | says, We used to talk about and we used to talk about if |
|
| 66:32 | may have heard the runner's high. when you run and you run the |
|
| 66:37 | we call in the middle miles if run, uh, you know, |
|
| 66:43 | thio, 10 miles, half marathon even marathon. So the middle |
|
| 66:48 | If you're on, let's say 10-K middle miles or 10 kilometers your middle |
|
| 66:53 | sort of be or four toe 7 8 kilometers where there is runners, |
|
| 67:00 | second when they get a feeling of is just a runner's high that makes |
|
| 67:06 | want to run and run and run , and for a long time We |
|
| 67:10 | it as endorphins, or endogenous morphine that make us feel good. And |
|
| 67:17 | fact, that is not endorphins. is endo cannabinoids. We do not |
|
| 67:22 | endogenous morphine like molecules, but we a vast endo cannabinoid system that is |
|
| 67:29 | the C. M s in the . And that end of cannabinoid system |
|
| 67:35 | the Ciena's is responsible for the feeling bliss. And and a mind or |
|
| 67:41 | in Sanskrit or ancient India language san mean it means a bliss. The |
|
| 67:50 | of bless or this than the cannabinoid causes. The stronger is high the |
|
| 67:58 | cannabinoids that expressed in in the brains particular. Okay, so let me |
|
| 68:07 | me shut quickly. If there is questions in the chat Alzheimer's time that |
|
| 68:20 | video well, it zafaraniyah actually can , it's a psychiatric disorder. |
|
| 68:39 | Parkinson's is a neurodegenerative disorder. That that there is loss of neuronal |
|
| 68:45 | loss off dopamine, ergic neurons. this case and schizophrenia. You do |
|
| 68:50 | alterations, but not necessarily loss our of neurons. But it is also |
|
| 69:01 | in severe cases of schizophrenia, because it's correlated with information on the |
|
| 69:06 | which turns on the whole process off cell death as well. Parkinson's a |
|
| 69:19 | contractions? Uh, great. Not only that, that's that's That's very |
|
| 69:25 | . You're thinking about interactions of neurons blood vessels. But also, I |
|
| 69:29 | say that to think about the fact we have, ah, nitrous oxide |
|
| 69:38 | on neurons to and so that those will learn activity downstream pathways through the |
|
| 69:44 | messengers in the Boston outfit cells. so so we'll learn more about all |
|
| 69:49 | these neurotransmitter systems. Like I we're going to zone in and hone |
|
| 69:53 | on a few of them and study in great details. It's really interesting |
|
| 69:58 | stand by for your task being released you can ask any questions. If |
|
| 70:01 | had technical difficulties during Casa, please them with me now. Other than |
|
| 70:08 | , I wish you to have great of the week, and I will |
|
| 70:11 | him following Monday. Take |
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