| 00:01 | Progress. This is lecture 10 of . We will start talking about neural |
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| 00:08 | today if you recall. We ended section of this course before your midterm |
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| 00:17 | discussing the forward and back propagating action . And we said that the function |
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| 00:25 | ultimate goal for the forward propagating action is to cause the release of a |
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| 00:33 | . Yes or not somehow Islamic And so we talked about two types |
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| 00:41 | channels that are located in excellent initial , the low threshold channels and the |
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| 00:47 | threshold channels and the low threshold channels a little bit further away from the |
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| 00:52 | , produced the forward propagating action And then we talked about the back |
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| 00:58 | action potential, traveling back into the and into so Mazz and playing an |
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| 01:04 | role in learning rules and synaptic I had this homework challenge of the |
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| 01:12 | question and this is really up to if you want to look into |
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| 01:16 | But if you're really interested in advanced single synapse stimulation, there is a |
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| 01:24 | that I've attached of how to excite synopsis in four dimensions using what we |
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| 01:30 | the cage neurotransmitters. There's chemicals that can put in the chemical cages but |
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| 01:36 | can also break these cages using And that shows us that there is |
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| 01:42 | propagation preference from these distal dendrites into soma is rather than from the dendrite |
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| 01:49 | out into the distal parts of the right. Just there is a certain |
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| 01:55 | . The receptors and channels in the dendrites that promotes the signals from distant |
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| 02:01 | rights to reach the soma to be affected here to still in both this |
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| 02:06 | response and the plasticity and the sinking the pre synaptic and post synaptic |
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| 02:14 | So today we will talk about neural . This used to be my old |
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| 02:22 | exam is not in two weeks exam coming up. It's an older slide |
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| 02:27 | just want to remind you it's not two weeks with the quiz. My |
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| 02:31 | be in about two weeks. Uh office is not an S. |
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| 02:35 | Two room 2 42 were advised not meet in person if you'd like to |
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| 02:39 | . Health one On the 4th One is the building behind the recreational |
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| 02:48 | . Uh So email is the same start to is this building that looks |
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| 02:58 | it's you know soviet union. And and now we have this uh building |
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| 03:09 | to be the satellite that looks like . It's a full mode of |
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| 03:16 | So anyways but health one is uh too. The building next to it |
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| 03:24 | where the medical school is, University Houston and where the pharmacy department is |
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| 03:30 | optometry. And so there's some clinical basically that is that is going on |
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| 03:34 | these buildings now from early days we about Monica hall, how he was |
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| 03:43 | golgi stain and he was drawing these sells the morphology is reconstructing them, |
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| 03:50 | just drawing reconstructing the morphology of the using camera lucida and then Charles. |
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| 03:58 | was coining and trying to explain this , what is happening in the |
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| 04:04 | A special place where the two neurons communicate with each other. And Otto |
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| 04:12 | was instrumental in demonstrating that there is neural transmission in the synopsis. We'll |
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| 04:20 | about his story in a minute. when you think about the brain it's |
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| 04:27 | of like thinking about the space. you look in the space, you |
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| 04:32 | all of these stars and now with of these powerful telescopes we're seeing |
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| 04:41 | we're seeing black holes and it's so and there's so many different elements and |
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| 04:48 | somehow interacting with each other. And if you think about the brain, |
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| 04:54 | contains billions of neurons and they They communicate by forming sometimes, like |
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| 05:03 | talked about tens or hundreds of thousands synapses. So there's trillions of |
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| 05:09 | So it's basically billions of cells that capable of interacting with each other in |
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| 05:14 | different ways and combinations. And that's of the equivalent of the complexity that |
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| 05:21 | see out in the space with the and everything. The systems you have |
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| 05:26 | with elements of part of different systems complex and we understand a lot of |
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| 05:32 | but we still are exploring and trying understand more of it and everything that |
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| 05:37 | understand is always limited by what science do, what we can see what |
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| 05:43 | can capture, how fast we can certain race and so on. If |
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| 05:50 | were to take the neuronal membranes from C. N. S. Then |
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| 05:56 | were to kind of a fold them . Each neuron would fold flat in |
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| 06:00 | a little rough napkin shape. You be able to lay four soccer fields |
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| 06:08 | four soccer fields with membranes of It's all compacted here inside this |
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| 06:17 | If you flatten it all out for fields, the book and some other |
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| 06:22 | refer to it that this is a of our minds. You can think |
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| 06:26 | it. If you laid a massive the size of four soccer fields, |
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| 06:32 | the fabric of our minds. That's vastness of it. And the number |
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| 06:37 | communications that we can have and the these communications are happening are happening through |
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| 06:45 | and chemical synopsis. But there's also synopsis and this neural transmission. Remember |
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| 06:54 | discovered electricity photo uh low. We neural transmission. But electricity was discovered |
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| 07:03 | Luigi and Neural transmission. Chemical synaptic was discovered only 100 years ago in |
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| 07:16 | and this is the story of Otto . In the night of easter, |
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| 07:21 | 1921 I awoke, turned on the and jotted down a few notes on |
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| 07:26 | tiny slip of paper. Then I asleep again. It occurred to me |
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| 07:31 | six o'clock in the morning that during night I had written down something most |
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| 07:37 | but I was unable to decipher the so that sunday was the most desperate |
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| 07:43 | in my whole scientific life. During next night, however, I awoke |
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| 07:49 | at 3:00 and I remembered what it . This time. I did not |
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| 07:54 | any risk. I got up, went to the lab, made the |
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| 08:00 | on frogs heart described below. And 5:00 the chemical neural transmission of nervous |
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| 08:10 | was conclusively proved. And that's the from his workshop discoveries, 1953. |
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| 08:21 | now when I was doing my second at George Mason University, my mentor |
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| 08:28 | to say that sleep is for the , that means that if you need |
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| 08:32 | dumb, sleep is just an And if you're worn down you just |
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| 08:37 | to take it and then you continue with what you have to |
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| 08:41 | Um In reality if you don't sleep , you don't function well. But |
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| 08:47 | happens if you have a great idea how many of you have experienced this |
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| 08:54 | laying at night in the evening falling or maybe dreaming and thinking, |
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| 09:02 | this is a great idea tomorrow And and then it disappears And that |
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| 09:08 | that you had, What was It was so awesome. And I |
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| 09:10 | like, you know, I was champion of bike racing and I had |
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| 09:14 | like idea for the gadget its I heard music falling asleep, it |
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| 09:20 | better than Mozart. But so that's thing, The other thing is how |
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| 09:26 | you get these things out of your , Right? And uh this is |
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| 09:31 | way to get up, take the . That's not even sufficient enough go |
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| 09:37 | the lab, you know? So if you're really burning question and it's |
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| 09:42 | a.m. Get up, you know and sold it, write it down. |
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| 09:48 | what he did, he did a simple experiment is he had two |
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| 09:52 | One of them is called the donor . Another one is called the recipient |
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| 09:57 | . And in the donor heart to the vagus nerve which is cranial |
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| 10:01 | 10. It comes out of the and will study the cranial nerves in |
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| 10:05 | course it comes out of the brainstem vagus nerve runs very extensively through the |
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| 10:12 | and into the organs into the But it also innovates the heart has |
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| 10:18 | very strong component that innovates the And so what he did is he |
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| 10:23 | to frog hearts, One of them the vagus nerve attached on it. |
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| 10:28 | he stimulated this name this number. as he stimulated the vagus nerve, |
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| 10:34 | heart rate slows down. So that's fact that the vagus nerve is active |
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| 10:40 | it has stimulated the heart rate slows and he had this heart sitting in |
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| 10:45 | dish and after the stimulation he collected removed this fluid from the stimulated |
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| 10:55 | And he applied that fluid on the that was recipient heart that had no |
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| 11:02 | nerve attached in it. And he this naive or recipient heart to the |
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| 11:10 | that he collected from the stimulated And as he applied this fluid on |
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| 11:17 | recipient heart, he saw the equivalent fact that the heart rate slowed |
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| 11:22 | So that was his experimental demonstration that you stimulate the nerve there is some |
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| 11:31 | that gets released in the fluid. if you apply that fluid onto a |
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| 11:37 | that has not been stimulated will have equivalent effect of the stimulated Vegas |
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| 11:45 | And that you're a transmitter is And the seed alkaline on the cardiac |
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| 11:56 | has a slowing effect that slows down heart rate. But we will also |
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| 12:02 | at the acetylcholine in the neuro muscular . This is also by the way |
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| 12:08 | muscular junction. This is a nerve heart is a cardiac muscle, there's |
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| 12:18 | a neuro muscular junction from a nerve the spinal cord to your skeletal |
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| 12:26 | Okay, so now the other form communication between south happens through the electrical |
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| 12:37 | and these are referred to as electrical or gap junctions. Gap junctions form |
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| 12:46 | junction a LCI channels. What happens that there are certain situations where two |
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| 12:54 | come very close to each other And the typical distance from pre synaptic to |
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| 13:02 | post synaptic cell that space between the membranes is about 20 nm. There's |
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| 13:09 | areas where the two members come very together. and they're barely separated by |
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| 13:15 | few nanometers, typically around 3 4 nanometers distance. So there's this |
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| 13:22 | like very come coming close together. two members from the two south. |
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| 13:28 | that happens, you have these channels are formed these channels connection to subunits |
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| 13:37 | form connects on channel on both pre side and posson attic side. And |
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| 13:47 | two channels extend from the number and this open route of communication. These |
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| 13:56 | junctions allow for the ions to pass without any delay without synaptic transmission between |
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| 14:05 | cells. So typically what we've been , what we'll be learning is how |
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| 14:10 | release neurotransmitter that neurotransmitter binds to the and if it is excitatory transmitter excited |
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| 14:17 | receptor, it will de polarize the that is inhibitory transmitter inhibitory receptor. |
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| 14:22 | will hyper polarize the cell. But you're not releasing anything. These gap |
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| 14:28 | allowed for the fast passage of it allows for the fast passage of |
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| 14:33 | molecules including secondary messengers like cyclic M. P. For example, |
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| 14:39 | can freely travel between the cells when gap junctions are fully open and most |
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| 14:44 | the time these gap junctions are open have to seem to have a little |
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| 14:49 | of a torch where they like twist little bit and are less open and |
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| 14:54 | a little bit and are more But gap junctions typically the way we |
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| 14:59 | at them and understand them is that never close. They're always they're always |
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| 15:04 | . And that's one way by which talk that for example Astra sides can |
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| 15:12 | off potassium locally and send it into cell bodies and processes and then spread |
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| 15:20 | in between themselves. So Astra sites just neurons but ble ourselves will also |
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| 15:26 | these gap junctions. And that's the in which you can slurp up high |
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| 15:32 | of potassium and send it through the astra site network where you stabilize it |
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| 15:38 | larger areas in the brain. So you can see if you for example |
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| 15:49 | current into one neuron. Some of current will leak out. But some |
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| 15:56 | it you will record down this drive down the selma and you will |
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| 16:03 | a cellular response. Remember it has resistance capacitive component to discuss. So |
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| 16:09 | is a cellular response. This is stimulation by instrumentation and immediately you can |
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| 16:16 | that there's no delay delay. Almost this adjacent south that's interconnected gap junctions |
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| 16:24 | also see a small response? That the fraction of that deep polarization from |
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| 16:30 | a has immediately transferred the charge fraction that deep polarization onto the Selby. |
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| 16:41 | is the purpose? Why would you to activate networks of neurons? Because |
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| 16:47 | you activate one cell and neurons that is connected to other neurons through gap |
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| 16:55 | . That means you can activate many without synaptic transmission through this electrical |
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| 17:02 | What is the function of that electrical passage between glial cells. So obviously |
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| 17:14 | already discussed the function for glial cells be regulating neurotransmitters for neurons. It |
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| 17:23 | actually synchronize and engage larger neuronal networks gap junctions. So they can do |
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| 17:30 | without the delay. With the synaptic . There is 5-20 millisecond delay neurotransmitter |
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| 17:39 | defused the vesicles, has to fuse neurotransmitter has to travel. 20 nanometers |
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| 17:46 | to bind to the receptor. That has to have an effect. So |
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| 17:51 | takes 5 to 20 milliseconds. This instantaneous. So it's sometimes it's for |
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| 17:57 | advantage of one stimulus that wants to a larger neuronal network for that network |
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| 18:04 | be synchronized is through the gap junctions and fast synchronization. And that's important |
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| 18:12 | you want to synchronize the networks of . That means you want large numbers |
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| 18:17 | neurons doing the same thing. And is because it takes a large number |
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| 18:23 | neurons to accomplish tasks. But you want to engage larger number of neurons |
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| 18:28 | a specific task And that's a good of doing it is by synchronizing activity |
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| 18:33 | doing it instantaneously through the gap The pre synaptic lee. As you |
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| 18:41 | see there's also mitochondria and you have differentiations on both sides. Pre synaptic |
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| 18:48 | you have these vesicles that are typically on the areas that are called active |
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| 18:55 | ready to be released into the synopsis posson optically. You have these dense |
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| 19:01 | of post synaptic receptors. So this the chemical synopsis, that's why I |
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| 19:06 | saying that the chemical synopsis you have have the fusion of the mystical neurotransmitter |
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| 19:11 | neurotransmitter environment, posson optic effect. takes time. Five milliseconds. |
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| 19:17 | 1520 depends on the synapse, depends the strength of the activation of all |
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| 19:21 | these other components. But as you see pre synaptic Lee will require energy |
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| 19:28 | the form of a teepee. Uh some synapses are formed on the selma's |
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| 19:39 | whenever they are formed from axle on selma were called axis. Somatic Simpson |
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| 19:46 | are formed from axon on the down . Those are called. In some |
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| 19:54 | instances there are synapses that are formed other axles and those are called accent |
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| 20:03 | . What else did you listen? ato somatic dendritic and they all |
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| 20:10 | But these are kind of the most . Most of the synapses will take |
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| 20:14 | on the dem drives among the selma's some of them on the accents. |
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| 20:22 | if you are and excited to a or if you're an inhibitory neurons and |
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| 20:29 | project them to downriver the selma you're be able to affect the integrative properties |
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| 20:35 | the soma. In other words you're influence whether the selma produces an action |
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| 20:41 | or not. If you're excited, strong input, you will influence the |
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| 20:46 | to integrate and produce an action However, if you're a neuron that |
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| 20:53 | targets another axon over here, the potential has already been produced here. |
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| 21:00 | action potential is traveling down the Saxon you can no longer influence whether the |
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| 21:07 | will produce an action potential. You longer influence of the integrative properties of |
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| 21:13 | writes in the silver than the axon segments. Too late the action potential |
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| 21:18 | produced. The only thing you can here is maybe you can disrupt and |
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| 21:23 | type of disruption of this type of we call modulation. You can modulate |
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| 21:30 | external output of the other cell versus you're you're affecting the integrative properties and |
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| 21:40 | you're hoping that you're going to somehow the output of the cell that is |
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| 21:44 | communicating to another cell. So these exist. Now. If we look |
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| 21:50 | the at the electron microscope image, very clearly you can see these mitochondria |
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| 21:58 | round bubbles. They're vesicles their organelles have their own plasma membrane. Inside |
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| 22:06 | vesicles you have neurotransmitters and you can that a lot of these vesicles, |
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| 22:12 | sitting very close to the pre synaptic zones. They're what we call primed |
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| 22:18 | they're ready to be released on the and that triggers action potential. And |
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| 22:23 | can see that these pre synaptic objects supposed to the post synaptic receptors |
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| 22:29 | are passed synaptic densities again, this not the electrical synapses. Chemical synapse |
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| 22:36 | , electrical synapses look almost like the cells that fused together. When we |
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| 22:41 | on the electron microscope and we look the symmetry of the synopsis. It |
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| 22:48 | out that most of the excitatory synapses have these asymmetrical member in differentiations. |
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| 22:56 | means these are glutamate releasing pre synaptic and glutamate receiving receptors. Person optically |
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| 23:05 | will be biased and they will have larger differentiation on the post synaptic |
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| 23:12 | And that is one way in which can observe these synapses on electron microscopy |
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| 23:19 | staining for neurotransmitters like Gaba or And you can say oh these are |
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| 23:26 | , they're most likely excitatory and inhibitory . They're symmetrical the pre synaptic and |
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| 23:34 | synaptic differentiation. The other interesting thing that inhibitory synopsis that release Gaba. |
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| 23:41 | vesicles are somewhat flattened. They have somewhat different shape and they're excited to |
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| 23:47 | vesicles are quite round. So there's visual differentiations on the anatomy of the |
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| 23:56 | synapses and the morphology or the look the actual the rough there's morphology of |
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| 24:04 | neurotransmitter vesicles. Okay. And so we go and look at the neural |
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| 24:14 | in the brain and study the neurotransmitters their receptors. It is always good |
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| 24:21 | review very basic synapse and the synapse we already know and now kind of |
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| 24:27 | to understand what we know and also we can learn more from this. |
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| 24:35 | We talked during the first section of course about the reflex arch, we |
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| 24:40 | about the dorsal root ganglion cells in neurons that release glutamate and they can |
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| 24:46 | into neurons in the spinal cord and motor neurons in the spinal cord. |
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| 24:50 | then we said that when motor neurons they will contact onto the muscles they |
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| 24:57 | release acetylcholine. And this is a cold will cause contraction of the |
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| 25:03 | And this Is neuro muscular junction. this case it's a neuro muscular |
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| 25:12 | Well, two Biceps muscle, not cardiac muscle. And you should ask |
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| 25:18 | question. Didn't you just tell us this little polling slows down the heart |
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| 25:24 | which means it slows down the contraction that muscle. That means that it's |
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| 25:31 | it's having a negative effect on the of the muscle. But aren't you |
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| 25:35 | us that for these biceps and how if you release the seat of coal |
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| 25:42 | it's going to cause the contraction? why does it cause an inhibition of |
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| 25:49 | cardiac muscle? And why does it an excitation and contraction in these muscles |
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| 25:59 | and answer for it, is that response the post synaptic response in this |
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| 26:04 | the post synaptic element is a The post synaptic response will depend on |
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| 26:10 | type of a civil cooling receptor that has. And in the heart we |
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| 26:16 | acetylcholine receptor that will cause a slowing of the heart rate and slowing down |
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| 26:23 | the muscular contractions. And in these junctions, the classical ones that we're |
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| 26:30 | about with the skeletal muscles with the here there is only one subtype of |
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| 26:39 | receptor that acetylcholine receptor is nicotine nick . Why is it called nicotine? |
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| 26:54 | nicotine is also nicotine because would be agonist to these receptors. So in |
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| 27:08 | neuro muscular junction you have nicotine acetylcholine and they're abbreviated as um N A |
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| 27:21 | A. Right. Sure. It's much life, something like that. |
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| 27:36 | and what happens is you see these optical we have this large number uh |
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| 27:44 | vesicles. The other thing that you're here is that these synapses are very |
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| 27:49 | from one axon you have these what we call axonal ramifications or axons |
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| 27:56 | split and each one of these, one of these axonal terminals is a |
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| 28:03 | powerful synapse. Okay, and this a zoom in onto just one synapse |
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| 28:12 | the terminal year and post synaptic alie you have post synaptic alie you have |
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| 28:20 | junction all falls that are going in , well illustrated and very close you |
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| 28:30 | a single Colin nicotine IHC receptor. when there is a release of acetylcholine |
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| 28:37 | these vesicles. Right sis the secular the massive locally molecules to acetylcholine molecules |
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| 28:49 | to bind 21 receptor in order to that receptor. Okay. And then |
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| 29:00 | other interesting thing is that further down in these junction all falls deeper in |
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| 29:07 | junction all falls. You have both sodium channels. So for the muscle |
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| 29:17 | contract, the muscle has to produce cardiac action potential it's different from their |
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| 29:23 | election potential. We won't spend time cardiac action potential. But we want |
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| 29:29 | understand is how powerful the synapses. what happens when the civil Colin binds |
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| 29:36 | nicotine acetylcholine receptors. sodium flux is sodium flux is in and causes deep |
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| 29:52 | and this deep polarization opens voltage gated channels activates flux of calcium in the |
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| 30:01 | . Okay. And produces this massive prolonged action potential in the muscle. |
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| 30:09 | much longer in duration. The point is this is the receptor potentials and |
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| 30:16 | receptor potentials are coming from the casino coding receptors. The receptor potentials there |
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| 30:23 | deep polarization because they're allowing facility in come in. That initial deep polarization |
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| 30:29 | what open sodium channel opens downstream casting and produces the potential. But what |
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| 30:35 | receptors produce these receptors produce an end potential. The single synapse From -65 |
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| 30:45 | balls a single synapse produces and and potential. This E. P. |
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| 30:57 | . That is about 70 million -45 volts. So this is really |
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| 31:22 | So these synapses are very simple. only have excitatory receptor. There's no |
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| 31:30 | no gaba there's no glycerine, they're released only excitatory synapse. So if |
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| 31:35 | synapses excited, the muscle contracts if synapses not excited, the muscle is |
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| 31:42 | and the opposing muscle can contract. , when you release this neurotransmitter and |
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| 31:49 | neurotransmitter binds to acetylcholine receptors. It this massive and plate potential. We |
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| 31:56 | it E. P. P. empty plate. Okay. And plate |
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| 32:02 | and plate region and plate potential. it's 70 million balls in size. |
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| 32:10 | the resting membrane potential is -65 levels always guarantees excitation and production of action |
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| 32:19 | . So if there is activation of synapse here is a twitch of the |
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| 32:26 | . If there is activation release of a twitch of the muscle fiber, |
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| 32:31 | activate all of these. There's twitch least all of these muscle fibers. |
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| 32:35 | can control muscles from adjustment. That's we're capable of. These fine uh |
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| 32:41 | movements now. So these are ligand channels. That's something new for |
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| 32:48 | gated by ligand acetylcholine two molecules have bind to open this channel. The |
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| 32:55 | thing is that if this sodium influx responsible for the deep polarization during employed |
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| 33:07 | , what is responsible for re polarization them play potential the return here and |
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| 33:17 | is potassium and where's potassium potassium is to be leaving through the same acetylcholine |
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| 33:31 | . So acetylcholine. I'm trying to it here so that people on zoom |
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| 33:38 | so they can serve these meals essentially receptors. One to settle. codeine |
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| 33:52 | violent. This is calling receptors as to serve you to build inside and |
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| 34:02 | potassium to leave. This is different what we started when we studied the |
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| 34:11 | gated sodium channels, voltage gated potassium . They said they're selected for one |
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| 34:17 | . They're regulated by voltage change. charge has to build up here in |
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| 34:23 | for this voltage gated sodium channels to and to allow for the formation of |
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| 34:28 | action potential. It's a simple It's only excitatory. If neurotransmitter is |
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| 34:37 | it will get a massive potential and is very different from the C. |
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| 34:43 | . S. The sienna synopsis are reliable. The single synapse in the |
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| 34:50 | . N. S. Will cause deep polarization of half a no adult |
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| 34:55 | 70 millimeter lens. So you have have 40, 50, 60 excitatory |
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| 35:05 | a lot of times. Fighting synapses and neurons which are non existent |
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| 35:12 | . It's either positive charge on and or there's no positive charge in real |
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| 35:18 | . Only inhibition exists is at the of the spinal cord. Okay, |
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| 35:26 | on the neuro muscular junction and later the course you will learn that apart |
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| 35:34 | nicotine acetylcholine receptor syrup, what are mascara nick. So hang on to |
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| 35:39 | . We'll study that with greater There are Mascarenas. Acetylcholine receptors and |
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| 35:45 | silk road in binding to masculinity receptions turn the cardiac muscle will cause a |
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| 35:53 | effect. So the post synaptic A response in the muscle depends on |
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| 35:58 | subtype of the receptor on this neuro junction with great potentials and This 70 |
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| 36:06 | volt response. You have nicotine holding so only and it's only excited to |
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| 36:13 | to us. So it's easy to because neurons will be receiving excitatory synapses |
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| 36:20 | inhibitory synapses and you have to activate excitatory synapses. Not just one for |
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| 36:28 | post synaptic neuron to respond. And what's different from what we call this |
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| 36:35 | fidelity system. 1-1. So action which of a muscle action potential twitch |
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| 36:41 | a muscle. Put it here, and employ a potential. Um But |
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| 36:50 | is the drawing that goes along with in the class and it's also in |
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| 37:01 | image in the previous slide it's a systems and we're gonna study acetylcholine, |
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| 37:11 | neurotransmitter system in the C. S. A great detail. You'll |
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| 37:16 | how silicone into synthesized how it's broken and you'll understand how alzheimer's medications interact |
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| 37:24 | little Colin metabolism and turnover in the . So you'll have to add more |
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| 37:29 | and the alzheimer's page that you started the first section of the course. |
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| 37:35 | neurotransmitter system. First of all you this pre synaptic plus synaptic components and |
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| 37:42 | you have different neurotransmitters. So you a glutamate system. Excitatory pre synaptic |
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| 37:50 | neurotransmitter system, an inhibitory gaba system the C. M. S. |
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| 37:56 | then you have other neurotransmitters. You acetylcholine in the cns not just in |
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| 38:02 | muscles it just acts differently in the but you have to have a neurotransmitter |
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| 38:09 | enzymes inside neurons so they make that transmitter, they should be packaging it |
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| 38:17 | vesicles with the transporter so they should releasing it. And then these vesicles |
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| 38:25 | re up taken back and these neurotransmitters are released, they're not gonna stay |
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| 38:32 | just floating the synapse. They're also or re up taken back into this |
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| 38:39 | synaptic terminals and re packaged into vesicles also in the synopsis. Once neurotransmitters |
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| 38:48 | released their degradation enzymes and they will up those active neurotransmitters in many |
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| 38:55 | So once neurotransmitter is released it binds the receptors. It doesn't linger forever |
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| 39:00 | the synapse. It gets re uptake prison optical, it gets degraded through |
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| 39:06 | mechanisms but synaptic aly we have trans or ligand gated ion channels and those |
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| 39:15 | actual channels that allow the flux of boston optical t. We also have |
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| 39:21 | protein coupled receptors. These are receptors are not channels they will also be |
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| 39:30 | by chemicals and by logins but they open. They don't have a |
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| 39:35 | Rather they're linked to G. Protium is located intracellular early and through this |
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| 39:40 | protein activation. They can activate secondary and member and associated proteins and even |
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| 39:51 | transcription factors. So you have this dedicated iron channels and that is because |
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| 39:59 | ju protein can affect other channels on membrane that are ion channels and can |
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| 40:05 | the flux that way as well. you have secondary messenger cascades that get |
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| 40:12 | through both live in gated and channels do protein um a couple of |
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| 40:21 | So it's a pretty complex system. neurotransmitter criteria they have to be produced |
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| 40:29 | synthesized when the neuron has stimulated. neurons should release that chemical when a |
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| 40:36 | is released it must act on the synaptic receptor and cause a biological effect |
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| 40:42 | chemical is released it must be inactivated it cannot stay there. This is |
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| 40:49 | of the rules of neurotransmitter. It to be re uptake in so it |
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| 40:52 | to have other components in the If the chemical is applied on the |
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| 40:57 | synaptic member and should have the same when it is released by a neuron |
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| 41:02 | call it neurotransmitter mimicry. This is experiment that we did. So basically |
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| 41:09 | you take the stimulated heart fluids and stimulated heart it should do the same |
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| 41:16 | as if you stimulated the vagus. that's what it stated. So it |
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| 41:20 | to have a synaptic response. It to be an equivalent of a pre |
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| 41:24 | neuron stimulating a pre post synaptic Huh. Okay. The major neurotransmitters |
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| 41:44 | we already know about and we will in great detail some of them the |
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| 41:53 | neurotransmitters in the brain amino acids that discussed. Our Gaba glutamate and |
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| 42:05 | Gaba is a major inhibitor in neurotransmitter the C. M. S. |
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| 42:10 | is a major inhibitor neurotransmitter in the cord. Now glycerine is also present |
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| 42:22 | C. N. S. And serves a different function. We'll come |
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| 42:26 | to that in a little bit when delve more into the glue dramaturgical neural |
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| 42:34 | . So if it's gaba gaba if it's glutamate it's glue dramaturgical, |
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| 42:39 | glycerin, glycerin ergic neural transmission of ergic synopsis, if it's a acetylcholine |
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| 42:47 | Colin argent. So in addition to major major amino acid neurotransmitters, neurons |
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| 42:57 | synthesize and release acetylcholine dopamine epinephrine in norepinephrine, serotonin and all of these |
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| 43:13 | . They are like separate functions. what's interesting is amino acids, neurotransmitters |
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| 43:22 | be expressed by neurons throughout the You'll have excitatory parameter projection styles in |
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| 43:29 | cortex and the thalamus will have many locations inhibitory gaba will be also expressed |
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| 43:38 | the cNS and you know that the of neuronal function comes from this inhibitory |
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| 43:44 | containing into neurons in particular. But mean there are transmitters are going to |
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| 43:52 | expressed only in certain parts of the and they're gonna be sprinkled throughout the |
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| 43:59 | and the sprinkler like system very much to almost like a para crime like |
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| 44:11 | peptides, you also have peptides, token and diane, north and in |
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| 44:16 | and neuropeptide y semana staten and yes can color express I mean acid neurotransmitters |
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| 44:26 | as gaba and a peptide such as peptide. Why, for example. |
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| 44:34 | then for a mean neurotransmitters you have groups of cells that are gonna be |
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| 44:40 | locally in dopamine and all the other neurotransmitters. Okay so I left this |
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| 44:50 | here and I guess the box you add some your transmitters. Aren't you |
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| 45:22 | glad you didn't have to wait for an hour for your exams to sign |
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| 45:27 | sheets get them released. So there other neurotransmitters. There are other molecules |
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| 45:36 | are very important to break and there's way I would call like nonconventional |
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| 45:43 | So first of all we have gasses as nitrous oxide, carbon monoxide and |
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| 45:51 | can actually serve as neurotransmitters. Then also have a T. P. |
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| 46:02 | a second you said 80 P. the major energy molecule in the south |
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| 46:06 | the brain cells to It is it's a neurotransmitter. It combined two A |
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| 46:14 | for denison TP is triphosphate combined to denizen receptors. Just like another molecule |
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| 46:25 | it's called. I've done myself And it's a it's a receptor that you |
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| 46:38 | know because I can guarantee that 95% you use the substance every morning that |
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| 46:48 | with the deficit in the sector, comes in the form of coffee, |
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| 46:53 | chai bobo t. Whatever your choice caffeine interact with the dentist and |
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| 47:04 | And so this will come up later we'll have another table. So so |
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| 47:09 | does caffeine come from the brand Now the corner Starbucks. It's the actually |
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| 47:18 | of the probably most addictive. It's accepted most addictive substances in the |
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| 47:25 | There's bigger and more addictive substances that not accepted. And stigmatized coffee is |
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| 47:32 | okay it's essentially caffeine dispensaries. That's what coffee houses are. Uh and |
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| 47:42 | caffeine is coming from from the So it's exogenous which means it comes |
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| 47:50 | nature that comes from outside. And neurotransmitters including the gasses the dentist and |
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| 47:57 | their endogenous. That means they're produced our own bodies. Is that the |
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| 48:03 | receptors denizen molecule will interact with the interceptor And then we have botanical natural |
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| 48:11 | items that will also have active ingredients them that will interact with the same |
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| 48:16 | . Exogenous substances. What else I'd to? I'd like to mention endocannabinoid |
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| 48:33 | we will talk about and the cannabinoids two most prevalent abbreviated as to |
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| 48:40 | G. And and I'm demining. we will talk about under cannabinoids later |
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| 48:52 | the course when we talk about the they can add a new IT system |
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| 48:57 | endocannabinoid molecules are endogenous cannabis or cannabinoids that we produce inside our brains and |
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| 49:09 | systems that we're talking about for example system you will find in the brain |
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| 49:15 | this is our focus on the N. S. But this serotonin |
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| 49:19 | the rest of the body too. a lot of serotonin in the gut |
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| 49:22 | example serotonin receptors. The and the in oil molecules are everywhere they're in |
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| 49:30 | brain, in every organ, virtually every cell in our bodies. Since |
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| 49:37 | cannabinoid like molecules that produced by our , this is very interesting to start |
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| 49:47 | these because we have the whole cannabinoid candidates and medical cannabinoids that are state |
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| 49:56 | alternatives to pharmaceutical. We have pharmaceutical that are FDA regulated that are medications |
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| 50:05 | are FDA approved and we have the system. And so the cannabis cannabinoids |
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| 50:17 | the plant cannabinoids from pharmaceutical medications, will interact with the endocannabinoid system, |
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| 50:26 | one of these in order to exert effect in the body or the brain |
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| 50:32 | to have a receptor. So you serotonin molecule have a serotonin receptor, |
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| 50:37 | molecule, a denizen receptor and their serotonin molecule is not going to bind |
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| 50:43 | glutamate receptor and glutamate is not going bind to gaba receptors. The specificity |
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| 50:50 | rather than in the vault educated sodium potassium channels controlling the selectivity for an |
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| 50:56 | here. The specificity is determined by ligand that binds to this particular channel |
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| 51:03 | glutamate channel and the cannabinoids. The channels in the brain and the other |
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| 51:10 | part of them, the cannabinoid system under cannabinoid science that's emerging is something |
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| 51:16 | you have always been hearing about is and the Runner's high is this concept |
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| 51:27 | really kind of a happy moments when work out hard, you run long |
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| 51:33 | , especially for long distance. Somehow repetitive continuous minus stress on the body |
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| 51:40 | the brain metabolism gives a feeling of . It's referred to as the Runner's |
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| 51:46 | . When people finish their five K feel great. Their mood is better |
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| 51:51 | it's not just because they feel they now you know get another greasy burger |
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| 51:58 | just because their mood is better So it was always assumed it's |
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| 52:03 | endorphins, it's endogenous like morphine molecules they don't exist really. So the |
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| 52:12 | of cannabinoids with an emerging in the science is that end of cannabinoids are |
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| 52:18 | responsible for giving that feeling of happiness and undermined in Sanskrit, an ancient |
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| 52:29 | language from Himalayas. Ananda means bliss that's why this molecule when it was |
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| 52:38 | in the 90s it was named Kind of a happy, blissful |
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| 52:45 | Okay so we have these major amino everywhere. We have the means that |
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| 52:53 | confined to specific regions of the brain they're expressed we have peptides that are |
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| 52:59 | widely expressed and can be co expressed amino acids. We have these gasses |
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| 53:05 | are floating around. So next time says oh I had a brain fart |
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| 53:09 | say too much, I know or much C. O. Gasses in |
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| 53:14 | grave will have a teepee and the sense of power energy molecule binding to |
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| 53:20 | receptors interacting with the deficit. We endo cannabinoids and then the very last |
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| 53:27 | that I will our economic acid that adhere and the reason why I will |
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| 53:36 | our economic acid together with these molecules is these molecules actually our membrane |
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| 53:59 | That means that carbon monoxide and nitrous can cross through plasma membranes and the |
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| 54:07 | can cross the plasma membranes. These are economic acid can cross through plasma |
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| 54:15 | . So all of these guys our member insoluble other elements that we're |
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| 54:25 | at amino acid and I mean they're they're not remembering soluble and that's another |
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| 54:34 | way of communication that these molecules provide in the brain will also learn that |
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| 54:40 | cannabinoids and gasses very much signal in fashion from post synaptic to pre synaptic |
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| 54:49 | . So it's almost like they talk to pre synaptic cells and you learn |
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| 54:54 | that in the next couple of So this is I think just showing |
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| 55:01 | , there's a homework question or challenge so here's your answer here you have |
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| 55:06 | difference between the neurotransmitter vesicles which we . They're all stored in external terminals |
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| 55:13 | they're recycled and they're refilled and external , neuro peptides. So there you |
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| 55:20 | have your traditional glutamate neurotransmitter vesicles and cells can co express neuro peptides and |
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| 55:27 | go through a different mechanism they have butt off the rough and the plasma |
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| 55:33 | um go through the golgi apparatus processing they're surrounded by secretary Granules and no |
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| 55:43 | Granules loaded with neuropathy, eyes are going to be traveling down the axon |
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| 55:51 | to cause the release of neurotransmitter You need normal activation, deep |
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| 55:59 | normal action potential firing to start releasing but in order to activate the release |
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| 56:08 | neuro peptides you have to have prolonged sustained activity. That means the cell |
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| 56:14 | be receiving a lot of positive input it's sustained and it's continuous. Then |
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| 56:21 | cell will say okay let me call the neuro peptides now. So you |
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| 56:25 | to have a lot more activity. what happens is these secretary Granules not |
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| 56:32 | of them reach the external terminal what secret? So and we started getting |
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| 56:52 | . Not specific to extent to. there's the differences, right one is |
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| 57:00 | in the terminals fast trigger action potential , recycling this still all slower |
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| 57:11 | It's a lot of activity, repetitive potentials start producing it and it's not |
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| 57:18 | specific and precise facially as neurotransmitter vesicles it will get released along with axons |
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| 57:26 | will excite like neurons and south in area, not necessarily within the |
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| 57:34 | Okay that this neuron is communicating to neurotransmitter Los Angeles you can see the |
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| 57:42 | molecules that have their transport porter proteins will load them up into the |
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| 57:52 | Okay I think this is gonna be last lot for the day and I |
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| 57:57 | to emphasize The thing that is shown is that you have to have a |
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| 58:03 | deep polarization into c. n. . to reach the threshold, says |
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| 58:08 | N -55. For some reason they their mind, it's -45. But |
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| 58:14 | have to have a significant activation a CMS synapses half a mil a |
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| 58:19 | You can do the math. How do you have to, how many |
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| 58:23 | you have to activate from minus 70 minus 55 or minus 45 that's 40 |
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| 58:29 | 60 excited to a synopsis reached the . The pre sign active active zones |
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| 58:36 | have these bicycle sitting here doc closely to be released and to produce an |
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| 58:45 | potential. We needed sodium and potassium educated sodium channels and we need that |
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| 58:50 | external terminal and one of the reasons is once the action potential arrives here |
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| 58:57 | the terminal, the deep polarization from action potential will open bolt educated calcium |
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| 59:05 | and these voltage gated calcium channels are , influx of calcium is necessary in |
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| 59:12 | for the neurotransmitter vesicles fuse with the membrane and cause the release of the |
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| 59:20 | . So pre synaptic lee you have densities of vocal educated calcium channels that |
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| 59:27 | located close to these pre synaptic active and once you have the equalization calcium |
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| 59:34 | is in it allows for the fusion the vesicles through these voltage gated calcium |
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| 59:40 | . Once vesicles gets released the neurotransmitter the vesicles gets released. That neurotransmitter |
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| 59:46 | by post synaptic early two receptor channel can cause an influx of a positive |
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| 59:53 | such as sodium. So this would an excitatory synapses. And if you |
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| 59:59 | have calcium you can have the secular . If you don't have deep polarization |
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| 60:04 | the action potential, you can't open gated calcium channels. So both and |
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| 60:11 | the deep polarization through the action potential activation of voltage gated calcium channels. |
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| 60:18 | are necessary for the successful vesicles fusion neurotransmitter release. If you just have |
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| 60:24 | potential without calcium it's not going to again. The vesicles will be recycled |
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| 60:33 | and you'll use a lot of energy here to mediate these processes of the |
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| 60:39 | transmission. And the reason why calcium important, calcium influx is important is |
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| 60:46 | will bind to the particular proteins here the secular membrane and will allow for |
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| 60:52 | particular proteins to interact with the membrane allowing for this fusion and neurotransmitter |
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| 61:01 | Okay, So this will end our 10. Today we'll review a little |
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| 61:08 | of this next Wednesday and as a you don't have a lecture on |
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| 61:16 | It's not on your syllabus. It be on zoom or in person. |
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| 61:20 | Monday you have off and then I see you a week from now on |
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| 61:25 | and expect your exams to be released the end of this week. Maybe |
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| 61:31 | or saturday this week, thank you for being here. And I'll see |
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| 61:35 | next |
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