| 00:02 | This is electric town of neuroscience. our election nine was natural wonder |
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| 00:09 | This is lecture 10. We will it on video points. And just |
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| 00:14 | a reminder at the end of the section, we talked about action |
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| 00:19 | We talked about two modes in which action potential gets generated and gets |
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| 00:27 | So as we know if neurons summits excited three. Excitatory post synaptic potentials |
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| 00:35 | excitatory inputs. Excitatory synopsis and inhibitor synaptic potentials from inhibitory synopsis. |
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| 00:41 | this neuron is d polarized enough. is built to produce an action |
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| 00:47 | That action potential gets generated in the initial segment and most of the |
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| 00:53 | And probably up until now you just about the forward propagating action potential. |
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| 00:59 | the action potential that will get regenerated each note of Around here each note |
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| 01:04 | ranveer will also have high densities of same or similar evolved educated sodium channels |
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| 01:10 | potassium channels that you will find an initial segment allowing for this action potential |
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| 01:16 | regenerate. And so that when it the external terminal the size of that |
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| 01:23 | potential is the same as it was . Excellent initial segment and the purpose |
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| 01:29 | this action potential that is forward propagating to release neurotransmitter at the synapse. |
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| 01:36 | we also looked into the anatomy of axon initial segment and discussed that there |
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| 01:41 | two types of channels, high threshold low threshold voltage gated sodium channels and |
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| 01:48 | low threshold. Both educated sodium channels the ones that will produce follower propagating |
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| 01:53 | potential responsible for neurotransmitter release the high n 81.2 channels. They will produce |
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| 02:05 | propagating action potential. And the purpose that back propagating action potential is |
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| 02:10 | It is a positive back propagating action back into the selma and enter the |
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| 02:16 | rights. And so we discussed what's purpose of this action potential And the |
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| 02:23 | of the matter is that inputs have into the cell. If there are |
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| 02:28 | inputs that are coming into the cell will generate an action potential, they |
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| 02:34 | generate a response. And the sooner cell reacts to the cell on the |
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| 02:41 | and produces an action potential in In the temporal sequence, the more |
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| 02:46 | it is for neurons, neurons make decisions and produce action potentials from the |
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| 02:52 | of milliseconds. The neuron will integrate sometimes thousands of synoptic infants excited during |
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| 03:00 | . See how they submit in space time and make that decision whether it's |
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| 03:05 | to produce an action potential or So if you stimulate the cell and |
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| 03:11 | milliseconds 10 milliseconds 20 milliseconds later this responds with an action potential. It |
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| 03:17 | informs the input cell that the cell reacting to the input and it allows |
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| 03:23 | the inputs to strengthen the dendritic inputs in to actually strengthen. Now if |
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| 03:28 | is too long of a time that between cell a on the left communicating |
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| 03:33 | Selby. And that contrary it becomes of milliseconds or maybe a second then |
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| 03:39 | L. A. Doesn't think that it's communicating is actually meaningful and that |
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| 03:44 | response because it's so delayed must becoming processing some other information and not the |
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| 03:50 | that I'm communicating. So the spike the timing between when this inputs coming |
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| 03:57 | the cell and excite the cell and the time period from the inputs coming |
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| 04:04 | and from when the spy gets the shorter that time period it is |
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| 04:09 | more plasticity and more strengthening of this happens in the synopsis. And the |
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| 04:15 | the time period elapses the less meaningful becomes for this synapse that is communicating |
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| 04:22 | each other. So this is what refer to as spike timing dependent |
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| 04:28 | It's very important that this backwash, comes in here participates in a very |
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| 04:33 | manner informing the activated synopsis that yes cell is responsive, the cell is |
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| 04:40 | and we're tuned in a very fast to the infants. It's very important |
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| 04:45 | the nordic spine plasticity. And again backwash of the signal can reinforce and |
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| 04:51 | for the signal of the summit. then I actually asked you a question |
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| 04:58 | I said do you think the dem prefer to d polarized in one direction |
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| 05:04 | the other one. And the reason I asked that question is because Denver |
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| 05:08 | are actually non myelin ated. So inputs and the electrical flux that comes |
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| 05:13 | Denver rides. You can not You do not propagate? There's no |
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| 05:18 | of around here and then drive some . So if you wanted to report |
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| 05:25 | and you wanted to know in which this signal likes to propagate, you |
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| 05:32 | have it then right? Would have critics. Science each one of these |
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| 05:38 | , there is a separate syntax. we have different shapes, experience certain |
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| 05:45 | . And if you wanted to ask experiment, let's say this is the |
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| 05:49 | , the top of the democrats, . And this is the best. |
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| 06:00 | he said, hold on the dog the summer is near the bottom here |
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| 06:05 | to know does like to propagate from to the apex of the soma or |
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| 06:12 | the infection to the salman to the . So how would you address a |
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| 06:17 | like this? So in the old , what you would do is you |
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| 06:22 | stimulate ideally want synapse, how would stimulate on synopsis? So you would |
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| 06:30 | Pipat, okay. And then that that there's a fluid. So let's |
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| 06:35 | you're applying glue the minute and each of these dots is a glutamate molecule |
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| 06:41 | coming from the pipette because you want activate this is a good example here |
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| 06:47 | the Senate. And then he would an electrode, The recording electrode, |
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| 06:54 | , the recording elected to The recording three here. Mhm. And then |
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| 07:02 | said, okay, when I applied him in here, Does it respond |
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| 07:06 | in one. How does it respond what's the response through? Then you |
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| 07:11 | also play around and say you know ? I'm just gonna stimulate past the |
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| 07:15 | from one and recorded in two and . And then I'm gonna do the |
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| 07:19 | , I'm gonna pass the current In . And the record responses in two |
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| 07:24 | 3. So you can play around this. It's extremely complicated experiments because |
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| 07:32 | is one micro meter diameter done drives report from dendrites is very difficult. |
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| 07:38 | people didn't start reporting from dendrites until nineties and then to do multiple dendritic |
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| 07:46 | . That's very very technically difficult. a very difficult experiment that's very important |
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| 07:53 | to know. Now the other complication is that when you use application of |
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| 08:01 | through a pipe at what happens is these village, although they will be |
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| 08:07 | concentrated around the apex and around the that you're stimulating. A lot of |
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| 08:13 | have little will actually die allies And so you will have lower concentrations |
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| 08:19 | glutamate floating everywhere around. Just that spread with the fluid that's surrounding the |
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| 08:26 | . So it's not quite specific. ? And one that there was a |
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| 08:30 | of glutamate actually going this way more activating this and your electorate is |
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| 08:36 | And you're thinking you're activating here. you made yourself an experimental nasa |
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| 08:41 | You don't really know what you're So there's two important concepts here. |
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| 08:46 | of all you have this dialysis from pipe out of the fluids and it |
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| 08:52 | not really this kind of mountain although is spatially specific, spatially confined mostly |
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| 08:59 | area because of the spread of glutamate another chemical that you may have in |
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| 09:04 | bible but it's still not quite specific singles or not. So as opposed |
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| 09:11 | the spy path and the spread of that in your class supporting election |
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| 09:24 | I started talking about glutamate, Cajun molecule Cajun. So now what you |
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| 09:33 | is these glutamate molecules. They're not the but they're actually in the chemical |
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| 09:45 | . That means that this glutamate molecule another molecule of interest that you may |
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| 09:50 | . It's not it's applicable to to , it's applicable to other chemicals to |
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| 09:56 | glutamate molecule that you have is not . Canada actually then the synapses and |
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| 10:02 | only way you can make it available it you shine the laser beam and |
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| 10:10 | that laser beam you weiss you've opened the cage and these molecules escape the |
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| 10:21 | And very specifically with that laser beam you can have activation and release of |
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| 10:28 | on. So obviously imaging things is to greater advantage you can image an |
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| 10:39 | dendrite. You can potentially, instead recording from Three locations with the |
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| 10:43 | you can image over 2100 locations along entire done right? Maybe you can |
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| 10:49 | individual spines precisely individual sin taxes. that's the advantage of this laser photo |
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| 10:57 | . Use lasers that are very precise that you can release the laser beam |
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| 11:03 | three dimensions. You can target it the surface or deeper in the |
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| 11:07 | So three done nines. And structurally other thing is neuron so fast. |
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| 11:13 | second sub nanosecond computation, lasers are . The fastest lasers. Now our |
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| 11:21 | a second. I don't know what per second is, but it's very |
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| 11:24 | , very fast, but somewhat To the 12th Or to the 15th. |
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| 11:31 | we're talking about, you know, of magnitude faster than neurons and what |
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| 11:37 | can process. What does that That means that you can play around |
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| 11:41 | time and in space and have these flash here and flash here and flash |
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| 11:49 | and now. You can very precisely and release glutamate. Listen, |
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| 11:54 | this is an option. This you can still record that electrical activity |
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| 11:59 | now you're very precisely activating this Now you have the fourth dimension. |
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| 12:04 | have the time dimension as you can these laser beams. Imagine 200 laser |
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| 12:11 | activated centre. 2nd speed. It's a fraction of very small fraction of |
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| 12:16 | millisecond. Now you know exactly how information gets processed. And so I |
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| 12:21 | a paper especially for for interest to students in the class supporting materials that |
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| 12:28 | about engaging in four dimensions. And what I meant by this question is |
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| 12:33 | is engaging neurotransmitters. what is occasionally transmitter. So it's chemical cages. |
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| 12:41 | literally chemical cages like a little envelope holds that glutamate is not available and |
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| 12:47 | break the envelope if you shine a on it, that one that's when |
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| 12:52 | becomes available. The lasers are very precise and small, very fast and |
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| 12:58 | for this precise single synapse activation within style along with the shaft with one |
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| 13:05 | . And neurons actually prefer to conduct forward. The soma. That was |
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| 13:11 | answer to. So we also recall different cells will have different channels that |
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| 13:19 | express and that's why they produced these dialects, different frequency. Now when |
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| 13:25 | think about different frequencies of action what does an action potential do this |
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| 13:32 | forward propagating action potentials? They released chemicals. So that means that this |
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| 13:40 | pattern, one action potential is a of neurotransmitter from the vehicle. A |
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| 13:46 | frequency of action potentials. A certain frequency of the membrane results in a |
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| 13:54 | frequency of chemical release and pasta. subsequent stimulation of the results. So |
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| 14:01 | are very fast electrochemical communications and some slower electrochemical communications. But most of |
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| 14:10 | diversity that we see and we discussed the and the brain comes from the |
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| 14:16 | cells. So it's the inhibitory cells have these very diverse subsets of channels |
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| 14:21 | I. V. Curves and diverse properties that will sculpt the activity of |
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| 14:28 | parameter cells of the excited for Yeah. So when this spike arrives |
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| 14:35 | the external terminal, it reaches a that we now know as synapse exam |
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| 14:42 | two weeks. That's not true. in S. R. Two room |
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| 14:46 | 42. That's not true. That old news and haven't changed that slide |
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| 14:50 | to remind myself that I was had office in an old building when I |
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| 14:55 | came here In 2006. And my is the same And I believe I |
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| 15:01 | still find emails from 2600 ch Can you find the most in 2006 |
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| 15:07 | any other you know? Probably You know, so this is this |
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| 15:11 | really cool anyways so you can find in my other office. But if |
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| 15:16 | want to meet with me and if have questions about the exam, my |
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| 15:20 | is the following. Later this week will release the exam. There's two |
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| 15:24 | that are taking the exam because of medical and other reasons and I don't |
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| 15:29 | the release for them to see that want to write a separate exam for |
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| 15:33 | . So sometimes this friday or this I will release the exam please look |
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| 15:39 | anything. I know there's one mistake my part wrong answer and one |
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| 15:43 | If you guys can find it, email me come back on monday we |
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| 15:48 | address that question and any other questions you have missed. Now I also |
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| 15:53 | to some students that if you want talk to me discuss the exam. |
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| 15:57 | think the best thing is to schedule off to the class. I saved |
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| 16:01 | the lecture and upload and it's kind getting late when I do that. |
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| 16:07 | if you want a different times, can schedule it on zoom to go |
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| 16:12 | your questions that the people that didn't well and did on the lower |
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| 16:17 | We can see if there is a in what you're missing. If maybe |
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| 16:20 | missed the subject matter or if you're everything across and typically if you're missing |
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| 16:25 | across, you're probably not putting enough into studying the material. If you |
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| 16:32 | a chunk of questions. And I that person missed everything on reversal potentials |
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| 16:37 | resting membrane potential, then they know that person is having difficult farmers biophysics |
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| 16:43 | these concepts. But if it's then it tells me that probably not |
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| 16:48 | effort being placed in the whole study overall. So we'll discuss that next |
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| 16:54 | . Okay, now, when we about synaptic transmission and communication, we're |
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| 17:00 | about 100 billion neurons in the How many people live on this |
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| 17:08 | seven billion. How many ways of we have with each other. |
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| 17:15 | letters, emails, phone calls, , screaming. Um, it's very |
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| 17:26 | , right? We can't even get . Right. We tried, there's |
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| 17:32 | , there's no like coherent understanding sometimes nations. Like right now we have |
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| 17:37 | taking over Ukraine because they just decided do so and to rewrite the whole |
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| 17:43 | . But this is very complex. the brain, if it had seven |
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| 17:48 | people in it, it has 100 people in it. So each neuron |
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| 17:52 | like a person has a different way communicating with another neuron. Electrical, |
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| 17:57 | ways of communication, different chemical And you form trillions of synapses. |
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| 18:05 | the scale and the complexity is uh much unmatched. Mhm. If you |
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| 18:18 | the membrane of your brain cells and laid it out flat, follow the |
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| 18:25 | membrane, just kind of unroll the dendrite and Selma and laid it out |
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| 18:31 | . It would cover about four soccer . So you take this brand and |
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| 18:36 | basically subscribe all membrane over four soccer for football fields about the same |
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| 18:45 | Ah And you have a variety of in there and it's sort of like |
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| 18:49 | sort of like a fabric of our just laid out like that. And |
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| 18:58 | three people contributed the most modern understanding the synapse or Monica hall who use |
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| 19:05 | stain two to argue for neuron He argued that neurons are discreet, |
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| 19:14 | argued that there is a directionality and . So principle dynamic polarization. He |
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| 19:19 | know about the back propagating action He thought it was only communicating in |
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| 19:23 | direction, which he's right with synaptic transmission. And he also suggested |
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| 19:30 | points of contact and these communication points plastic. That means that they can |
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| 19:37 | . They can rearrange themselves. So was thinking over 100 years ago about |
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| 19:43 | plasticity and rearrangement of synoptic efforts and done rights. And of course dendritic |
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| 19:49 | which he actually saw using the oldest Some of the spice show up quite |
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| 19:57 | with technology state. Yeah, Sherington coined the storm of the |
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| 20:03 | It really started discussing what is going in this case, how it is |
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| 20:07 | about. And you can see that is a man that made synopsis |
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| 20:12 | But the Lowy actually discovered chemical synaptic . So that happened, That happened |
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| 20:22 | 19 21 101 years ago. We celebrated 100 years of chemical neural |
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| 20:34 | , discovered once the end when we about this. So this is from |
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| 20:40 | local Lowes workshop of discoveries in 1953 the 9th of Easter Saturday Before the |
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| 20:49 | , I guess 1921 I was turned on the light and jotted down |
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| 20:53 | few notes from a tiny slip of . Then I fell asleep again. |
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| 20:57 | occurred to me at 6:00 AM that the matter had written down something most |
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| 21:03 | , but I was unable to decipher scroll that sunday was the most desperate |
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| 21:08 | of my whole simplistic life During the night. However, I awoke again |
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| 21:14 | 3:00 and I remembered what it was time I did not take any |
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| 21:18 | I got up immediately went to the made the experiment on the frog's heart |
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| 21:24 | the law. And at 5:00 the transmission of nervous samples was conclusively |
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| 21:33 | two nights 2 dreams. One The experiment was that he had to |
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| 21:39 | hearts. The one on the left called the donor heart. The one |
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| 21:43 | the left has a vagus nerve and vagus nerve has a very strong impact |
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| 21:48 | the heart when Vegas nervous stimulated it down the heart rate. And so |
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| 21:53 | stimulated the vagus nerve and observed this , heart slowed down its heart |
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| 21:58 | And we've collected the fluid around his . He sampled this fluid after the |
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| 22:06 | and he applied this fluid onto the or naive heart that does not have |
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| 22:13 | nerve attached to it and this when isolated from the stimulated heart and |
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| 22:19 | it onto the IV heart cause the effect as if vagus nerve was stimulated |
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| 22:25 | heart rate slow down. And so definitively prove that there's something in the |
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| 22:31 | . There's a chemical here that want stimulate vagus nerve. That chemical is |
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| 22:36 | . And if I collect that chemical apply onto another heart, that chemical |
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| 22:41 | an equivalent the fact that slowing down heart rate. So the chemical that |
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| 22:46 | we discovered it was a secret code disjunction is a nerve to muscle |
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| 22:55 | a single Colin in the cardiac muscle an inhibitory effect. And the super |
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| 23:03 | and the skeletal muscle. Since we at the patella tendon reflex and talked |
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| 23:08 | the circuit of the styles involved. talked about how modern neurons would release |
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| 23:14 | and acetylcholine is only excitatory on the muscle. That's because of the certain |
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| 23:20 | receptors called nicotine acetylcholine receptors that are of the skeletal muscles and a different |
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| 23:27 | of acetylcholine receptors present in the cardiac . So the response of the cell |
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| 23:33 | the response of the muscle depends on type of the systematic receptivity contains amount |
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| 23:38 | the molecule which is being released. is also a lesson uh with my |
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| 23:45 | when I did my postdoc at penn University used to say that sleep is |
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| 23:51 | the weak And what he meant by is that if you need, if |
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| 23:56 | need something dumb it doesn't really matter it's easter weekend or 3:00 AM, |
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| 24:02 | have to get it done. If just going to go to sleep and |
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| 24:06 | about your schedule. You know, you may not have the discovery of |
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| 24:12 | transmission. So if you go and and don't wake up and don't drop |
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| 24:18 | down even or take notes. Sometimes very difficult to get stuff out of |
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| 24:23 | head. I still suffer with that the time. It's all beautiful in |
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| 24:27 | head. It's wonderful. But how you get it out explaining to other |
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| 24:32 | , write it down, measure prove it. That's very difficult. |
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| 24:37 | you have to make yourself get you know, I hear music in |
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| 24:42 | head sometimes and I wish I was composer. I was like Mozart that |
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| 24:46 | visualize the notes and write them down type them up on the computer, |
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| 24:51 | know, in the morning, I have a simple composed but it's |
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| 24:55 | it's difficult to get it up, know, So it's an inspiring story |
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| 25:01 | just going forward in the middle of night and by 5:00 really showing the |
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| 25:06 | that diamond has changed the world. now, apart from the chemical |
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| 25:15 | we also have electrical synopsis. And were discovered in this type of experiment |
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| 25:21 | was done in crayfish all the profits , but you have one stimulating electorate |
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| 25:28 | sol wong and you have a recording didn't. So we want to. |
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| 25:33 | you can see that if you pass nice stimulating current here, which is |
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| 25:36 | square wave falls the cell as you , has the resistance and capacity properties |
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| 25:42 | going to respond in this rounded like potential response and you can see a |
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| 25:48 | strong response and sell a that you're . And then in this experiment they |
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| 25:54 | an electrode into an adjacent cell. what they saw is that immediately as |
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| 26:01 | stimulated cell a and recorded the current so a immediately without almost any |
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| 26:09 | There was also current and sell And this thing that I'm saying without |
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| 26:14 | delay is important because when you release In the synoptic class, that neurotransmitter |
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| 26:21 | to travel 2019 m of space as bind to the receptor and then it |
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| 26:28 | post synaptic response to this. This what we call the synaptic delay In |
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| 26:33 | no transmission that synaptic delays on the of the few milliseconds, 10 |
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| 26:40 | But in chemical transmission you have these channels that are formed between the two |
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| 26:47 | . They're called gap junctions. And gap junctions allowed for the flux of |
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| 26:52 | and also for the flux of small . And even secondary messengers like slightly |
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| 26:57 | which is one of the secondary messengers the cells. So these gap junctions |
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| 27:03 | because typically the distance between the plasma of two neurons is about 20 |
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| 27:09 | And that's a typical so not the space that you would see. But |
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| 27:13 | some instances to neurons and their plasma will come very close in space, |
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| 27:20 | this very small gap of only about nanometers and one neuron will have connects |
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| 27:28 | connections are subunits that will build a on protein channel on one side and |
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| 27:34 | connects on protein channel on the other membrane and the two will co drawn |
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| 27:40 | and have this open electrical synapses to electrical junctions. Gap junctions. Electrical |
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| 27:48 | , they're always open and in some and some high levels of activity. |
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| 27:54 | can do a conformational twist on changing their twists on the on |
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| 28:00 | on the actual structure and allowing for to be even more open. So |
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| 28:06 | are regulated differently from the chemical, ligand gated channels that open close. |
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| 28:13 | could be essentially almost always open or open but never never really closed unless |
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| 28:20 | use blockers or as chemicals in the that will block the gap junction with |
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| 28:27 | chemical, with the electrical. So chemical neural transmission you have a delay |
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| 28:33 | electrical neuron transmission. There's no direct advantage of having the electrical gap junctions |
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| 28:40 | can flow from one cell to the cell very fast. There are networks |
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| 28:44 | cells that are interconnected with gap So if you wanted to engage an |
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| 28:47 | network in a very fast fashion and that network synchronized or respond in the |
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| 28:53 | fashion to the same stimulus synchronized in . These gap junctions come in very |
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| 28:59 | and allow for these circuits and networks neurons to pass the information without any |
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| 29:06 | . To synchronize them to synchronize activity the same time together. So the |
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| 29:14 | why it's faster because they're closer because no synaptic cleft and there is no |
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| 29:23 | . So the aisles, They will flux between the two South Square. |
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| 29:34 | . Chemical synopsis, we have these there. You need energy of synaptic |
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| 29:39 | synaptic vesicles are gathered in higher densities what we call pre synaptic active |
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| 29:45 | On the post synaptic side directly juxtaposes pre synaptic terminals. You have high |
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| 29:51 | of receptors that are referred to as synaptic dance. It is so this |
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| 29:58 | an electron microscope image of mitochondria. see these nice rounded vesicles here and |
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| 30:05 | vesicles are gathered around the active zone they're getting ready to be released and |
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| 30:11 | mathematically then you would have the densities these post synaptic receptors that are located |
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| 30:17 | So if you look at an electron with one interesting thing is that with |
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| 30:22 | electron microscopy you can actually distinguish between to inhibit their synopsis. Most of |
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| 30:27 | excitatory synopsis e will have a symmetric in differentiations, meaning that they're active |
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| 30:35 | are smaller and thinner in size as to the systematic dancing shoes and also |
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| 30:43 | shape of the vesicles surrounded. And you looked in the electron microscope and |
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| 30:50 | saw these flattened vesicles, you can that there are more oblong here and |
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| 30:56 | saw the symmetrical prison optic and fast size. This would indicate that their |
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| 31:02 | self. It's not really the best to determine excited inhibitory cells. But |
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| 31:06 | you're looking at electron microscopy without any . This is a good way to |
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| 31:11 | to find whether these cells are excited inhibited. I have a whole more |
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| 31:17 | here with a dense core vesicles and I think I'm not going to get |
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| 31:20 | today. I'll get to it in next lecture. You can look it |
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| 31:23 | , it's coming up with a few . Most of the synopsis that will |
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| 31:28 | for these electrochemical communications will be on gun rights and the soma. So |
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| 31:32 | it's a it's axa soma the facts somatic and these types of inputs, |
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| 31:40 | and somatic inputs. They will influence this neuron can produce an action potential |
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| 31:46 | not. In other words it will the integrative properties of the neuron with |
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| 31:50 | synapses. But on the right here bother you see another type of the |
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| 31:55 | that's referred to and called as actual synapse. The one acts on contacts |
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| 32:00 | not an accent in this case. cell right here has already produced an |
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| 32:07 | potential train, let's say a certain of action potentials that is traveling down |
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| 32:11 | axon. So this neuron that is its accent can no longer influence the |
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| 32:17 | properties of this self. But rather output properties it can only modulate the |
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| 32:23 | of action potentials that was already So these are the three major different |
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| 32:30 | and there's rare but also Denver. synopsis with some exceptions that we're trying |
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| 32:38 | understand them. Obviously they're not going have the same synaptic classical structure with |
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| 32:43 | and stuff but they are there. and now we'll come back and talk |
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| 32:50 | more about neuro muscular junction because it's important that we understand this neuro muscular |
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| 32:58 | and then we're able to confirm or this neuro muscular junction on what is |
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| 33:04 | with this very simple synopsis to what happening in very complex analysis. So |
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| 33:33 | you see here is a neuron that already know the modern era. It's |
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| 33:39 | market dollar sell. It was in mental part of the spinal cord. |
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| 33:43 | releases a still colleague. It's excitatory it releases a statement calling on the |
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| 33:50 | , those muscles contract. We talked the tele tendon reflex, there's no |
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| 33:57 | at the level of the neuro muscular . The only inhibition that we saw |
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| 34:01 | these circuits is in the spinal The motor neuron cannot inhibit a |
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| 34:08 | It can only excite the muscle with single golden and cause a contraction of |
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| 34:13 | muscle or it can stop and not acetylcholine, which will not contract the |
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| 34:21 | to relax the muscles. So we about this muscle contracting and opposing muscle |
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| 34:27 | . So inhibition the relaxation of this is not at the level of the |
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| 34:32 | , the level of the spinal cord . So now when these motor neurons |
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| 34:38 | onto the muscle cells, they form what are called axonal ramifications they |
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| 34:44 | They form these very large synopsis referred as murder and plates. And if |
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| 34:50 | look at this very large synapse. is pre synaptic neuron you have the |
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| 34:55 | zones with the vesicles sitting there the Typically this is a muscle cell. |
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| 35:00 | have these very deep imaginations that are the junction all faults and these functional |
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| 35:07 | will have very high densities, densities acetylcholine receptors. But there are certain |
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| 35:13 | of this neuro muscular majority. In case we're looking at the skeleton. |
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| 35:18 | first of all the it's only excited to the muscles in the vesicles and |
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| 35:31 | bicycle gets released. There's quanta of and molecules from here and that Quanta |
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| 35:43 | between two And 4000 molecules. So time we disclosed 2 to 4000 models |
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| 35:55 | is 2 to 4000 and three different But it's not $2,020,000. So 20 |
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| 36:05 | students one time 20,000 all this between and $4000 it doesn't always load |
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| 36:14 | Release release to a single colleague We'll have to bind to be cecile |
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| 36:27 | coding molecules. We'll have to find be cecile global perspective. This is |
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| 36:34 | this is the functional channels in the in the boat. So a ch |
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| 36:49 | to molecules by and when they opened receptor. What's going to happen, |
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| 36:55 | is going to flex it alright and also going to allow for potassium to |
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| 37:03 | out of this channel two this is gated channel it takes to libraries and |
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| 37:09 | it's open the channel first thing. he goes in and then later catastrophe |
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| 37:14 | out. So how does this generation that you have a lot of positive |
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| 37:25 | in the form of soviet influx in the south here. Positive positive trust |
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| 37:32 | there's actually a voltage gated sodium Little allow of flux. Absolutely. |
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| 37:40 | there's also all the changes down through channels. And so what happens is |
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| 37:48 | the first instance and uh in the instance when you generate The response from |
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| 37:59 | seed of building receptors, the new in memory potential about 1965. That |
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| 38:06 | response and casino building receptors produced it's . And this athlete potential will always |
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| 38:16 | Box 7 to know. So if recall the threshold for action potential is |
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| 38:23 | more roles. So the deep polarization through a single building the suckers. |
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| 38:28 | then when it reaches this threshold then will activate sodium. And calcium conductance |
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| 38:36 | which will account for the muscle accurate . And I'm going to really study |
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| 38:43 | dynamics of muscle action potential of muscle potential is much longer than the actual |
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| 38:48 | in neurons. So in the order 10 2040 milliseconds, cardiac action potential |
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| 38:55 | also longer Now. Uh this is very reliable center, always gonna cause |
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| 39:07 | action potential in the muscle cells. the initial deep polarization of the muscle |
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| 39:12 | happens to single poling receptors and the of sodium menopausal. This DPP and |
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| 39:19 | TPP will always drive the member of to activate both educated sodium channels and |
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| 39:25 | channels that will contribute to the action of the mosque. Mm hmm. |
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| 39:37 | People are From -65 the resting membrane . So we call the synopsis high |
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| 39:48 | synopsis 1 to 1 which means an potential here will always cause the twitch |
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| 39:59 | a muscle one synapse classical release 2000 4000 molecules As of 17 syllables. |
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| 40:12 | causes of torture. And you will that in the central nervous synopsis, |
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| 40:21 | excited to post synaptic potentials as opposed employee potentials are only about half a |
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| 40:26 | stars. So you need many many nervous synopses in order to cause a |
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| 40:32 | synaptic response. And in this neuro junction it's only the receptors and a |
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| 40:41 | because nicotine actually binds to those acetylcholine . Student, that's what they're called |
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| 40:48 | and they're only excited for it. these are the important details and it's |
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| 40:55 | very simple high fidelity system. But also incorporates some of the things that |
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| 41:00 | talked about how ligand activated channels, applicability will turn on voltage gated sodium |
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| 41:07 | that can then generate action potentials. we'll look into this more into the |
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| 41:11 | to. So left the page black here for your notes. Um This |
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| 41:17 | potential. I will try to maybe up because some students asked me to |
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| 41:23 | pictures of this. But then I really have a good way to upload |
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| 41:28 | . Uh If anybody. Uh Welcome to take pictures and put it |
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| 41:35 | chat. If you guys are on other than that, maybe I'll try |
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| 41:39 | come up with a little diagram for end plate potentials. Like it did |
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| 41:42 | action potentials. So in order for to exist, it's really a part |
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| 41:50 | the system. This molecule chemical is part of the system and the system |
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| 41:56 | of enzymes that can synthesize these neurotransmitters these neurotransmitters are typically with the exception |
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| 42:06 | some other classes that we'll discuss today in the vesicles, the neuron is |
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| 42:12 | when there is deep polarization here that neurotransmitter is released. That there's a |
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| 42:17 | receptor a lot of these transmitter gated channels but there are also metabolic |
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| 42:23 | These are ion a tropic channels and learn about medical tropic channels. So |
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| 42:28 | G protein coupled receptor uh receptors do that can affect other G protein ion |
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| 42:36 | . They're gated by g protium. of course downstream you have secondary messenger |
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| 42:43 | . So when you release that that chemical here should cause a post |
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| 42:48 | effect And chemicals neurotransmitters will not stick the synopsis and we'll get broken down |
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| 42:57 | they get re imported back into the at terminal so they get cleared in |
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| 43:03 | other ways. So there has to a mechanism to break it down and |
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| 43:08 | recycle that burgers but it's all part the system. And if you just |
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| 43:12 | that neurotransmitter and excitatory cell, we the glutamate and you apply that on |
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| 43:18 | . It should have the same responses you stimulated that excited yourself, connected |
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| 43:23 | the excited to another cell that it good to me. So you can |
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| 43:28 | with with the activity of just a , you should be able to mimic |
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| 43:33 | synoptic release of another by another neuron is often referred to as neurotransmitter |
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| 43:40 | And so there's applications within the lecture be a neurotransmitter mimicry with the occasion |
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| 43:47 | glutamate. This mimicry because you're mimicking that would be contacting that particular dendritic |
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| 43:57 | imitating. But we have a variety neurotransmitter systems and they're really quite diverse |
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| 44:06 | everything that we talked to date so really referred to glutamate and Gaba and |
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| 44:16 | of the rice in and this is important part of the understanding that I |
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| 44:22 | to start developing in this force. is our brain is not exactly like |
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| 44:30 | everywhere. You will see a green , there's glutamate synthesis going on. |
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| 44:40 | , you know, I need only few billion of these thoughts who's finishing |
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| 44:45 | for that? So this is Amazing everywhere you see billions of cells |
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| 44:56 | throughout the cortex support likely that synthesized one. Yes, Gabba everywhere you're |
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| 45:07 | a black dot here. You have , I can continue with glycerin here |
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| 45:17 | the spinal cord. Glycerin is the major amino acid neurotransmitter. Glycerin is |
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| 45:23 | a co factor for excitatory signaling in cns inside the spinal cord. So |
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| 45:27 | learn about that later out of these perform neural functions in different parts. |
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| 45:34 | they are very widely expressed. And you have this other really interesting classes |
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| 45:40 | the means, acetylcholine, dopamine up green. It's, to me it's |
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| 45:47 | enough green there Tony chemicals I any means and they're very different. So |
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| 45:59 | means for the most part we'll have for specific nuclear such as for |
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| 46:08 | serotonin and that serotonin or that is produced. So if you put a |
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| 46:18 | on the enzyme that synthesizes serotonin and that synthesizes the civil code instead of |
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| 46:25 | so much like you would find everywhere Gabrielle glutamate, you would find the |
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| 46:30 | nuclei stands for collections of cells responsible for doing the same with very similar |
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| 46:37 | in the brain. And those are only solves that will produce serotonin. |
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| 46:42 | how does that serotonin get throughout? that serotonin only here know that serotonin |
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| 46:48 | widely distributed for all supported cortical tissues has its outputs. So these nuclei |
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| 46:57 | produced serotonin can flood the cortex the and periphery with serotonin but it's produced |
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| 47:06 | here. The same with the civil . Some counseling may have one or |
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| 47:11 | nuclei that produced the atonement one or nuclei that produces Siegel cohen. but |
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| 47:17 | it. So these are very interesting because they are locally synthesized. But |
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| 47:28 | projections from these local chemicals and its chemicals get projected everywhere throughout the |
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| 47:38 | When we talk about these neurotransmitters. just gather such as glutamate or when |
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| 47:48 | saw just now we're talking about neurotransmitter that contain these molecules inside this neurotransmitter |
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| 48:00 | are sitting in those active zones. signed up and the means will also |
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| 48:07 | a little Colleen you start sitting in synaptic vesicles also and it's being released |
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| 48:14 | only a percent obsessed. So if serotonin is synthesized, the air projection |
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| 48:21 | certain um gets here certainly gets released with the axon terminal is let's say |
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| 48:26 | the cortex maybe in the hippocampus, in another part of the cortex. |
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| 48:34 | you have on the right here. have peptides or neural peptides and this |
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| 48:38 | your homework question actually. But they're different because they're stored in the secret |
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| 48:45 | and they're not as precise as the . They can sometimes get released along |
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| 48:50 | external extent and they are synthesized on . So when there's really high levels |
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| 48:57 | activity of these other molecules, especially acids then you will call upon the |
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| 49:05 | of neurotransmitter top tides and there are and the secretary Granules and because of |
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| 49:13 | heightened levels of activity. Those secret may not always reach the external |
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| 49:18 | So they're not spatially specific and can released along this external extent of the |
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| 49:26 | . That's how they're different peptides, ? But there's still packaged. It's |
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| 49:31 | packaged. So that's it's also about secretary manuals on this list. We |
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| 49:40 | have additional neurotransmitters that I want to . Start discussing. Some of them |
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| 49:47 | continue discussing some of them and not much about us. But in this |
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| 49:55 | here. But I have an empty that put mattress oxide and carbon |
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| 50:03 | So we have gasses and those gasses serve as neurotransmitter molecules in the |
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| 50:10 | And somebody tells you I'm having a fart. It's all there must have |
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| 50:14 | much nitrous oxide or carbon monoxide. so why are these different? These |
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| 50:21 | not stored in vesicles and their lipid . And so when nitrous oxide is |
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| 50:29 | the cell for carbon monoxide it can through that self and it can travel |
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| 50:37 | outside that self. It doesn't have scent of specificity to it. And |
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| 50:53 | economic models anandamide and to A And also another molecule that you make |
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| 51:12 | hear about which is not an endocannabinoid is our economic acid. Those are |
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| 51:21 | molecules that have certain levels that are inside our brains inside of our |
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| 51:28 | Everything we're talking here is endogenous you inside of you. So end of |
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| 51:35 | and cannabis molecules cannabinoid molecules that are inside your brain cells inside your body |
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| 51:43 | . Mm hmm He said the cannabinoid anandamide and two A. G. |
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| 51:48 | also lipid soluble. They're also not in the vesicles. And the phenomenon |
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| 51:54 | you may have heard this saying, the person who is a long distance |
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| 52:00 | or long distance walker and say oh still addicted to running. You heard |
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| 52:11 | saying, oh he's addicted, he to run, he's addicted to |
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| 52:14 | Have you heard of the saying runner's ? He's having a runner's high. |
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| 52:17 | the runner's high? Do you feel ? And you kind of your eyes |
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| 52:22 | crossed and you kind of recognize people into the table. What is it |
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| 52:28 | runners high? It's a feeling of , overwhelming happiness that people get from |
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| 52:35 | term exercise and repeated exercising. And lot of athletes would not exchange that |
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| 52:41 | of bliss. It will not exchange for the two hours of hard |
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| 52:47 | That may lead to that feeling of . And it's really this feeling that |
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| 52:52 | described as runners high. You may heard this concept of endorphins. So |
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| 52:59 | is no endorsements that's a made up , There's no endogenous morphine molecules. |
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| 53:06 | there are endogenous cannabinoid molecules. And latest research shows that in the |
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| 53:12 | one of their functions in the brain caused this happiness. Euphoria high bliss |
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| 53:18 | effect anandamide in Sanskrit. Ananda means . So it's a molecule of bliss |
|
| 53:27 | . Unhappiness. And the latest research that the runner's high. Another sort |
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| 53:32 | activities that lead to that similar feeling because of the build up of then |
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| 53:37 | phenomenon is and the activation of the system. There's no endorsement. Our |
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| 53:43 | acid is interesting because it's also uh neurotransmitter. It is also a precursor |
|
| 53:54 | also breakdown products of economical levels of is everything that you eat kind of |
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| 54:02 | what you have and the chemicals that have in your brain and how they |
|
| 54:07 | . So you may have heard of three, omega six omega nine fatty |
|
| 54:13 | . A lot of these fatty they could be precursors for some of |
|
| 54:18 | molecules that could be precursors to to the cannabinoids. And so dietary intake |
|
| 54:25 | lot of times can influence actually what bodies are producing. And when we |
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| 54:30 | about cannabinoids and you hear things like CBD, Now you're seeing Delta |
|
| 54:40 | these are cannabinoids that are plant derived referred to as phyto cannabinoids and they |
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| 54:46 | interact with the endocannabinoid system and other in the body including serotonin xyz correction |
|
| 54:53 | . So these are very interesting molecules certain steady level of them produced in |
|
| 54:58 | body, you go running 45 It's kind of like a continuous stress |
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| 55:04 | yourself, boost the production of some these molecules. These molecules will cycle |
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| 55:10 | the day and night. So for you have a teepee is a denizen |
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| 55:19 | and the core of the denizen triphosphate denizen are also neurotransmitter rations and how |
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| 55:28 | a dennison is there And how much . T. P. Is there |
|
| 55:31 | dennison is the core of a Is it always the same amount as |
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| 55:35 | denizen go up when you go Actually it's the opposite. A denizen |
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| 55:40 | up when you get sleepy at mount the denizen levels go up and then |
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| 55:45 | the morning and dennison levels go So there's the siren. All and |
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| 55:50 | cycles of the chemicals as a part the day cycle or activity dependent, |
|
| 55:57 | it depends what you're doing will be . The neurotransmitters are engaged that are |
|
| 56:04 | certain information. It's a big bear coming at you, your adrenaline and |
|
| 56:13 | at the national the brain systems Right. That's the fight or flight |
|
| 56:19 | . Serotonin appetite, sexual activity, levels fluctuate. So it's interesting. |
|
| 56:27 | and glutamate, these amino acids are plus and minus. And then all |
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| 56:33 | these amines and the cannabinoids acids they modulate and stop this plus and |
|
| 56:44 | . So it's almost like you have digital code. The digital code and |
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| 56:48 | is an action potential. zero or all or no. And you have |
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| 56:52 | analog code which is E. S. P. S excited for |
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| 56:57 | graded potentials. Some are larger. are smaller. The same way here |
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| 57:02 | can think of maybe the digital currencies and minus. And then how you |
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| 57:08 | the program with the code is for program is actually influence of all of |
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| 57:13 | other neurotransmitters and chemicals. And so you're learning about neural transmission, I |
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| 57:19 | you to start forming this view of spatial distribution of different chemicals and also |
|
| 57:27 | understanding that these chemicals and these different systems. They mean different behaviors. |
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| 57:34 | mean different times of day. They different receptors and the responsible very largely |
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| 57:43 | on the type of the past synaptic to which this chemical is being |
|
| 57:50 | So this actually answers your homework question the slide and this pretty much concludes |
|
| 57:58 | lecture today. So thank you very for being here and like I said |
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| 58:04 | on to your tax being released so you can see questions that you may |
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| 58:09 | missed or anything. Any questions you have for me and other than that |
|
| 58:16 | will see everyone next week on All |
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