| 00:02 | this is lecture ton of neuroscience and we finished the first section we finished |
|
| 00:09 | about the back propagating action potential. general, we talked about two types |
|
| 00:15 | the action potentials. The forward propagating potential, the one that gets generated |
|
| 00:21 | the axon initial segment and gets regenerated each note of Ron beer. You |
|
| 00:28 | . Each note of ranveer is loaded voltage gated sodium and potassium channels that |
|
| 00:34 | for that action potential to get And so this forward propagating action potential |
|
| 00:41 | de polarize external terminals and as it polarizes the external terminals here it will |
|
| 00:48 | the release of neurotransmitter chemicals into the . And that's what we will talk |
|
| 00:54 | in the next section. But we discussed the back propagating action potential. |
|
| 01:00 | we said that the back propagating action serves a different function. We discussed |
|
| 01:06 | types of voltage gated sodium channels, the low threshold and maybe 1.6 will |
|
| 01:12 | the forward propagating action potential and the threshold and maybe 1.2 which are in |
|
| 01:18 | located closer to the soma. Because the high threshold, they will produce |
|
| 01:23 | back propagating action potential and the purpose the function of the back propagating action |
|
| 01:30 | is different from the forward propagating action . It is really concerned more about |
|
| 01:36 | dendritic spine plasticity in general, the of the signals incoming de polarizing signals |
|
| 01:43 | are some mating with the external response the form of the back propagating action |
|
| 01:49 | . It is also very important for concept of spike timing dependent plasticity, |
|
| 01:55 | refers to the timing between the inputs the response of the south neurons operate |
|
| 02:02 | very fast millisecond scales. And so there is an input coming into the |
|
| 02:07 | and that cell responds within milliseconds and inputs. No when the cell responds |
|
| 02:13 | it produces an action potential and there a back propagating action potential. So |
|
| 02:19 | this relationship and time is very close time, within a few milliseconds 10 |
|
| 02:27 | the signals get strengthened their meaningful the and the output producing an action |
|
| 02:34 | They're getting linked up together, they're their activity inputs coming in and there's |
|
| 02:39 | synaptic response from the south and that synaptic response now informs the inputs coming |
|
| 02:45 | . We're in business if there's too time that passes and the neuronal timescales |
|
| 02:50 | can be tens of milliseconds and hundreds milliseconds, it's too much time passing |
|
| 02:56 | when there is this input coming in polarization and you're waiting for 10 |
|
| 03:02 | 20 100 milliseconds and then only some 100 milliseconds Later this neuron produces an |
|
| 03:09 | potential. Then the inputs, The inputs coming in, they're not really |
|
| 03:16 | this is did we cause that action ? Or is it something else in |
|
| 03:21 | cell or some other inputs of causing action potential. So the spike |
|
| 03:26 | so the timing between the inputs and the spike is produced. The spike |
|
| 03:31 | dependent plasticity, the shorter the time , The better uh plastic properties the |
|
| 03:39 | will have, the longer the time passes, the less meaningful those inputs |
|
| 03:44 | strengthening of those inputs will mean. there's a really very cool article that |
|
| 03:53 | already pointed out to you and uh talks about caged neurotransmitters. And as |
|
| 04:02 | imagine, if you have an electrode you want to for example, apply |
|
| 04:10 | from that electrode and you want to stimulate one dendritic spine. You're only |
|
| 04:18 | in a single dendritic spine that you're . You want to target this specific |
|
| 04:26 | then expand. The problem is the is is this glutamate is going to |
|
| 04:34 | ? Allies and it's going to So when you apply something through the |
|
| 04:40 | through the pipe pad and you want to be really small, about one |
|
| 04:47 | because this is about the size of synapse. And what you're getting is |
|
| 04:52 | getting this cloud for glutamate that most it will be concentrated around where the |
|
| 05:02 | is putting the glutamate on that But a lot of it is going |
|
| 05:07 | spread or dia lists through the extra space and start affecting other synopses |
|
| 05:15 | So it's it's it's still you still quite get to that single synapse level |
|
| 05:22 | the challenge of the day I had in which direction do dendrites like to |
|
| 05:28 | the electrical signal in this direction. is selma, are they going into |
|
| 05:37 | soma or they they preferring to conduct Selma there, preferring to conduct |
|
| 05:42 | So I said, how would you us? So, you will |
|
| 05:46 | okay, I'm gonna do multiple recordings the dendrite. Just like in the |
|
| 05:52 | days I will put and the electrode number one. And I'm gonna put |
|
| 05:58 | electrode here number two. I'm going put in the lecture in here number |
|
| 06:06 | . And I can pass the current number one and see how much of |
|
| 06:10 | current travels down to two and travels to three. So, it's a |
|
| 06:17 | difficult experiment. Think about it. have to have a den drive which |
|
| 06:21 | about one micrometer in diameter. You to have three electrodes. The tip |
|
| 06:26 | the electrode is my micro meter. actual electrode you're holding is millimeters and |
|
| 06:31 | in length. You have to place of these micro electrodes on a single |
|
| 06:38 | shaft past the current from one direction one measured in to measure it in |
|
| 06:44 | . Past the current from three and it. What happens to current into |
|
| 06:48 | what happens in one. So, can play around with it. And |
|
| 06:51 | say like whenever I pass the current one, it has large response in |
|
| 06:56 | . But whenever I pass the current three, it doesn't have a very |
|
| 06:59 | response in one. So then you say, well, it's preferring to |
|
| 07:03 | that direction into Selma. All this is a good way to test |
|
| 07:08 | like this. And I'm not even that there is a definitive answer to |
|
| 07:11 | question. But what I'm saying is these techniques with the electrodes recording electrodes |
|
| 07:18 | we learned about, you can also chemicals on the synapses and think about |
|
| 07:25 | these chemicals affect synapses. But you to get very specific. You want |
|
| 07:30 | get down to that very one single lava. And by using injections of |
|
| 07:39 | through this kind of a setup and the dialysis, you will not accomplish |
|
| 07:44 | . You will activate inevitably the surrounding . And what is going to be |
|
| 07:50 | water of this activation? This is and then this is second or this |
|
| 07:53 | second. You don't know. So has been developed is a very interesting |
|
| 08:02 | that is called neurotransmitter caging and So in this case glutamate is actually |
|
| 08:12 | inside the cage. It's a chemical and these eliminate molecules are actually |
|
| 08:20 | So everywhere you're seeing a square, going to be glutamate molecules. Those |
|
| 08:36 | molecules, they're caged. They're actually in a chemical cage. So they're |
|
| 08:42 | available to activate any of these So how would you engage it? |
|
| 08:49 | have to break the cage and the that you break the cage is through |
|
| 08:55 | license with a laser. You shine very precise small laser beam in just |
|
| 09:03 | one area of interest right here, around one synapse And you on cage |
|
| 09:11 | of the glued innate molecules. You them from their cages. Chemical cages |
|
| 09:20 | now does within eight molecules Can affect that one single synapse. And the |
|
| 09:29 | these days are very fast. You how fast they are. The fastest |
|
| 09:36 | . Does anybody know the fastest 20 seconds? I don't know what |
|
| 09:42 | . It's really, really fast. , really, really, really |
|
| 09:48 | So what what what means is The lasers are much faster than the |
|
| 09:54 | , right laser so much faster than . So what can you do? |
|
| 10:00 | can produce several laser beams but On three synapses of interest. And the |
|
| 10:10 | of this is that you're releasing glutamate the laser beam, just over one |
|
| 10:18 | , there's no license of course that can can leak out but its so |
|
| 10:23 | compared to an electrode. Just just screwing glutamate out onto the sent |
|
| 10:29 | So you have a laser activation of single synapse. You can have that |
|
| 10:34 | moved very fast across tissue and have lasers. So within, within a |
|
| 10:43 | of a millisecond, you can go boom boom and release glutamate, 123321232323 |
|
| 10:51 | record electrical activity and record what's happening this den drive. And you can |
|
| 10:57 | electrical activity without the electrodes. You actually record electrical activity using dyes, |
|
| 11:04 | dyes that show you flux is of ions or electrical potential changes. And |
|
| 11:10 | talk about some of those imaging experimental imaging techniques that allow you to |
|
| 11:16 | functional imaging. So this is functional of the synopsis and functional imaging, |
|
| 11:23 | your imaging the activity in these neurons and single synapses. So there is |
|
| 11:29 | supporting article of how you do this in four dimensions ah including time three |
|
| 11:38 | in space. And then over time three dimensions in space. Is that |
|
| 11:44 | laser, you can direct the laser penetrate deeper into the tissue or keep |
|
| 11:49 | on the surface of the tissue. the beam actually can penetrate deeper or |
|
| 11:56 | more on the surface. So you three dimensions in space and you have |
|
| 12:00 | time dimension in doing these very fast beams onto individual synopsis. Very very |
|
| 12:10 | . So this is uh the diversity the channels that we talked about and |
|
| 12:17 | ivy plus that the channels will produce different frequencies of action potentials and each |
|
| 12:24 | potential means a release of neurotransmitter. when you look at the frequency of |
|
| 12:29 | action potentials on the other end in chemical synapse, neural transmission, have |
|
| 12:36 | certain frequency of the chemical release. this electrical activity equates to a pattern |
|
| 12:42 | chemical release at the level of the synaptic transmission exam, tune in two |
|
| 12:50 | . It's not exactly right. This an older slide and this used to |
|
| 12:54 | my old office in the soviet looking and start to room 2 42 but |
|
| 13:00 | no longer there and then the new Hb SB So thank God he got |
|
| 13:06 | of the soviet union and time. it looks like putting once we're all |
|
| 13:11 | now anyways, I'm from Lithuania So this this subject matter is quite |
|
| 13:18 | to me of what's happening now. neurons you have billions of neurons in |
|
| 13:24 | brain and those neurons will communicate, communicate with us very complex patterns of |
|
| 13:30 | which is action potential. This very patterns, electrical patterns will turn into |
|
| 13:35 | complex chemical and synaptic transmission patterns and response patterns. You have trillions of |
|
| 13:45 | that are formed between these billions of . The complexity think about the |
|
| 13:52 | billions of something. So the whole has population of seven plus billion And |
|
| 14:00 | of the people on Earth, seven people on Earth. They communicate with |
|
| 14:05 | other in different ways and different means text messages and Facebook and phone calls |
|
| 14:10 | and their relatives and their friends and enemies and they're going to war. |
|
| 14:15 | this is this is like if you about it, this is one brain |
|
| 14:20 | that's how many units it has seven units that are interacting or billions of |
|
| 14:25 | that are interacting and interacting through trillions different connections and means of interacting with |
|
| 14:31 | other. If you were to take um membrane area, the neurons in |
|
| 14:38 | brain and you just laid out, flattened out all of the neurons, |
|
| 14:41 | of their dendritic spines, all of processes. You flattened it out completely |
|
| 14:45 | one cell next to another cell, place to another. The total membrane |
|
| 14:52 | area would cover four soccer fields from human brain. So if you were |
|
| 14:58 | basically unroll the plasma membrane, you cover for soccer peels or for football |
|
| 15:06 | with the plasma number. So it's lot a lot of surface area, |
|
| 15:10 | lot of information. And I like description as the fabric of our |
|
| 15:17 | It's sort of like the kilt. lay out this massive kilt, that's |
|
| 15:22 | brain and different parts of the kill colors or different networks and cells and |
|
| 15:29 | different functions. So these three men lead to modern understanding of the chemical |
|
| 15:39 | transmission. If you recall. Ramona um is the most famous spanish |
|
| 15:47 | So if you're in spain, there's harmonica hall neuroscience institute um Charles Sherington |
|
| 15:57 | claimed this term of the synapse and about synapse and Otto Loewy that discovered |
|
| 16:04 | chemical neural transmission. And this is great story that I like In the |
|
| 16:12 | of Easter Saturday 1921, I awoke turned on the light and jotted down |
|
| 16:20 | few notes on a tiny slip of . Then I fall asleep again. |
|
| 16:25 | occurred to me at 6:00 AM that the night I had written down something |
|
| 16:31 | important. But I was not able decipher the scroll that sunday was the |
|
| 16:38 | desperate day in my whole scientific During the next night, however, |
|
| 16:43 | awoke again at three o'clock and I what it was this time I didn't |
|
| 16:49 | it didn't take any risk. I up immediately, went to the |
|
| 16:53 | made the experiment on the frog's heart below. And at five o'clock the |
|
| 17:01 | transmission of nervous impulse was conclusively It's quoted from Auto Louis's Workshop of |
|
| 17:08 | in 1953. So 101 years author Louis discovered that neurons released |
|
| 17:18 | Not only discovered he proved it If you recall Luigi Galvani me hundreds |
|
| 17:27 | years. Hundreds of years before we understood that neurons produce electricity. But |
|
| 17:35 | suspect that there is chemical transmission communication them. But you have to prove |
|
| 17:41 | . And this is how he proved . So there were two hearts. |
|
| 17:46 | was a donor heart on the left the recipient heart. The donor heart |
|
| 17:53 | the left has vagus nerve coming into and blue here. And if you |
|
| 18:02 | the vagus nerve, it slows down heart rate, Vagus Nerve, as |
|
| 18:09 | will learn is cranial nerve 10 that in the brain stem and has extensive |
|
| 18:16 | into the heart and also throughout different in the body. It's it's the |
|
| 18:23 | largest projections of any of the cranial is the vagus nerve. But it |
|
| 18:28 | a very important function in the heart down when vagus nerve is stimulated, |
|
| 18:35 | hard grade slows down so he placed donor heart into a jar and after |
|
| 18:42 | stimulated the nerve he removed the fluid surrounded the stimulated heart. And on |
|
| 18:49 | right he had a recipient heart and recipient heart does not have the vagus |
|
| 18:55 | coming onto it and he's not stimulating like in the donor heart. But |
|
| 19:01 | on this recipient heart that is sitting a jar this is a frog |
|
| 19:06 | He applied the fluid that he removed the donor heart sample and as he |
|
| 19:14 | the fluid that he collected around the heart. The instant related or the |
|
| 19:19 | heart should the equivalent the fact of rate slowing down. So he's isolated |
|
| 19:26 | chemical after stimulating the nerve and applied chemical and too naive or in stimulated |
|
| 19:33 | and accomplished the same results. So proved and the neurotransmitter chemical that he |
|
| 19:41 | is a single cone. So when study acetylcholine and neuromuscular junctions. Acetylcholine |
|
| 19:54 | excitatory neuromuscular junctions with acetylcholine activity depends the post synaptic receptors that are |
|
| 20:04 | And the skeletal muscles where it's excitatory is also a neuro muscular junction. |
|
| 20:11 | a junction between nerve, the vagus and muscle. The heart muscle. |
|
| 20:17 | it's a cardiac muscle cardiac muscle will different acetylcholine receptors And because of the |
|
| 20:24 | acetylcholine receptors. The fact of a colon on the cardiac muscle is to |
|
| 20:29 | down the heart rate and slow down contraction on the skeletal muscles. Acetylcholine |
|
| 20:37 | through a different type of civil choline that are called nicotine acetylcholine receptors. |
|
| 20:42 | in the skeletal muscle it's only excited it. And this is the only |
|
| 20:48 | civil Kogan and the skeletal muscles is acetylcholine in the brains, in the |
|
| 20:55 | . We'll have a combination of acetylcholine that you find in the skeletal muscle |
|
| 21:01 | you find the cardiac muscle. Of you'll find it in neurons. So |
|
| 21:04 | response to that chemical depends on the per synaptic or past membrane receptors on |
|
| 21:12 | other side that are expressed. And important lesson is sleep is for the |
|
| 21:20 | . That's what people say, meaning if you want to get something |
|
| 21:24 | you may need to pull off that nighter. I always say sometimes you |
|
| 21:29 | your best fish at night but you to be prepared to do that. |
|
| 21:37 | you sleep, you will not discover neural transmission. But if you get |
|
| 21:45 | and you go to the lab you discover chemical neural transmission or at least |
|
| 21:51 | the notes and I've actually had these happen to me where the ah ha |
|
| 21:57 | happens in the sleep, human, know like you're trying to get something |
|
| 22:02 | you're studying you know that aha moment you can be in math, it |
|
| 22:06 | be in science or something, it's , oh my God, finally, |
|
| 22:09 | know, I've been standing at this two years and I finally just got |
|
| 22:12 | , you know, so, and happens sometimes that that, that aha |
|
| 22:16 | that whatever, sometimes I have music my head at night and I wish |
|
| 22:21 | was like a, you know, that could just take out a piece |
|
| 22:26 | paper and just write it down and know, it's there. But so |
|
| 22:31 | was just telling my colleagues sometimes it's difficult to get stuff out of your |
|
| 22:35 | actually it is. And so sometimes have to just make yourself, get |
|
| 22:41 | , spring up, you know, the notes, go to the lab |
|
| 22:44 | uh Mhm discover new things. great example. So now we have |
|
| 22:50 | neural transmission and uh some years we also discovered that neurons have electrical |
|
| 22:59 | , there's electrical synopsis we call gap . And the way it was discovered |
|
| 23:06 | discovered in in crayfish. The One cell, as you can |
|
| 23:13 | it has a stimulating electrode here on . And this stimulating electrode passes the |
|
| 23:20 | and the cell on top also has recording electron. And when you pass |
|
| 23:25 | current, remember the cell membrane has capacitive properties. So you will get |
|
| 23:30 | slow build up within a few milliseconds the maximal car and you'll have this |
|
| 23:36 | deep polarization and the cell into which injecting the current but adjacent to that |
|
| 23:43 | , there was another axle or another . And the scientists then for the |
|
| 23:50 | lecture in the second cell and what saw is that immediately without any delay |
|
| 23:58 | recorded activity in cell one where the was passed And they also recorded activity |
|
| 24:06 | cell two. There was no delay there's a gap junctions or electrical synopsis |
|
| 24:13 | allow for very fast flux of ions between physically interconnected selves. So only |
|
| 24:24 | fraction of this current fluxus through the junctions because other parts of the current |
|
| 24:30 | escape Through cell number one. But showed that because there is no delay |
|
| 24:38 | activity in cell one and activity in two. This is not a chemical |
|
| 24:44 | . When the action potential arrives at terminal it causes deep polarization, it |
|
| 24:51 | release of chemical neurotransmitter and then that neurotransmitter houses travel through the synoptic |
|
| 25:00 | Synaptic cleft and bind receptors sponsor fanatical that is synaptic delay of typically a |
|
| 25:06 | milliseconds, five milliseconds it can be as long as 10 millisecond delay from |
|
| 25:12 | the action potential happens to when there's haptic response. And when they saw |
|
| 25:18 | delay they then postulated that there is junctions between the cells because there was |
|
| 25:28 | that 5 to 10 millisecond delay between activation of silwan the response and so |
|
| 25:34 | . And the response and sell to gap junctions are formed by neuronal plasma |
|
| 25:41 | actually coming in space very close And where the regular synaptic cleft, |
|
| 25:49 | synaptic cleft is about 20 nanometers of between the two adjacent neurons. The |
|
| 25:57 | junctions, the areas where there are junction channels and proteins. This distance |
|
| 26:03 | only about three, 3.5 nanometers in and one cell cell one side of |
|
| 26:13 | . And this is sell one plasma , This is cell to plasma |
|
| 26:18 | They will contain portions of this gap . So it will have a connection |
|
| 26:27 | the connections of the sub units. connections come together and form a connects |
|
| 26:33 | on one plasma membrane cell too. so and former connects on on plasma |
|
| 26:40 | cell one and the two literally joined in this 3.5 nanometer space. So |
|
| 26:48 | is a continuity. The two gap essentially are joined together from the two |
|
| 26:55 | and the gap junctions are different because almost always open. But they actually |
|
| 27:02 | twist a little bit and have some change and they can actually be more |
|
| 27:09 | but they cannot be closed so We don't know how they closed physiologically |
|
| 27:13 | we use blockers or closing those Um so this is the gap junction |
|
| 27:27 | on both cells and this is why would have no delay and in the |
|
| 27:33 | between the two selves, ions with freely flux in between the two |
|
| 27:41 | Chemical synopsis, as you can see the pre synaptic side, you will |
|
| 27:47 | mitochondria. So you need a lot energy, a lot of energy |
|
| 27:51 | You have synaptic vesicles gathered here pre aly that are called active zones preseason |
|
| 27:59 | . So these vesicles are not just all over the external terminal but they're |
|
| 28:04 | very closely to the plasma member and sort of like primed, they're |
|
| 28:10 | They're waiting to be released then if have the fusion that will be synaptic |
|
| 28:16 | and post synaptic lee you have post densities. These post synaptic densities are |
|
| 28:22 | receptors ligand gated receptors that are juxtaposed space directly from the pre synaptic external |
|
| 28:35 | . So this is a electron microscope , you can see the mitochondria present |
|
| 28:40 | , you can see these rounded vesicles have their own plasma membranes and then |
|
| 28:45 | can see these active zones where the are in higher densities and they're closer |
|
| 28:52 | the plasma membrane and post synaptic lee would see these densities. So if |
|
| 29:00 | look at that symmetry present topic versus synaptic symmetry, you could actually say |
|
| 29:09 | cell is excitatory versus inhibitory. If use the electron microscope excited to itself |
|
| 29:15 | have asymmetric or asymmetrical numbering differentiations. post synaptic zones are much larger and |
|
| 29:24 | the pre synaptic active zones and they rounded vesicles. So the shape of |
|
| 29:30 | vesicles is more rounded, the inhibitory will have symmetrical member in differentiation. |
|
| 29:38 | the pre synaptic active zone is about similar sizes. The pasta topic densities |
|
| 29:44 | they're vesicles are flattened. So if did this is not a definitive but |
|
| 29:49 | is a very good guess. When do electron microscope we're looking at the |
|
| 29:54 | and hit the third synapse. Ultimately still may want to do some immunized |
|
| 29:59 | chemistry as some second way of identifying cell that we talked about. But |
|
| 30:05 | are some of the differences are rounded for excitatory and symmetrical flatten |
|
| 30:12 | For inhibitors synopsis most of the synapses form between neurons are forming between axons |
|
| 30:20 | Sonoma's and axons and dendrites and as spoke throughout the course and riddick spy |
|
| 30:27 | is one of the most common sides the synoptic connectivity of synaptic communication between |
|
| 30:34 | two neurons. So if it's between and soma it's acts of somatic. |
|
| 30:39 | it's between axon and dendrite it's actually and there's also a third type of |
|
| 30:46 | synapse that is more rare that is here Axl axon Oh now if you |
|
| 30:52 | at this setup this is very different the synopsis that contact onto dendrites and |
|
| 30:58 | onto So Mazz on the last year will affect the integrative properties of that |
|
| 31:05 | . In other words if this is excitatory synapse. So this is an |
|
| 31:09 | synapse that will make this past synaptic more likely to fire if it's excitatory |
|
| 31:14 | less likely to fire If it's inhibitor however if you have an accent exceptional |
|
| 31:23 | this neuron has already initiated action potential this action potential is traveling down the |
|
| 31:32 | . So if you have an actual synapse and quite often they're inhibitory |
|
| 31:39 | external synapses. What it can do actually can inhibit, they inhibit and |
|
| 31:47 | the frequency of the action potentials in axle. So it doesn't affect the |
|
| 31:54 | properties of this neuron but rather affects output properties of that self in acts |
|
| 32:01 | examining and in in in most cases inhibitory grab, allergic synopses have this |
|
| 32:11 | question that I actually answered and a slides I think I'll probably get to |
|
| 32:16 | . If not. Um We can about the next lecture. Okay, |
|
| 32:23 | now let's go into greater detail here the neuro muscular junction. So we |
|
| 32:32 | going to look now in the skeletal again. Uncle Louie looked in the |
|
| 32:38 | heart and he found a single But let's look at the synapse because |
|
| 32:47 | synapse is different from the cns It's very well studied and we can |
|
| 32:54 | it how different this synopsis to the synopses. This is our famous motor |
|
| 33:03 | remember that lives in the ventral side the spinal cord is a multipolar |
|
| 33:09 | It's excited to resell and it releases as the neurotransmitter and it targets these |
|
| 33:18 | junctions the muscle cells and each one these external terminals in gorgeous and largest |
|
| 33:26 | when it makes contact with the muscle fiber as possible mathematically. And this |
|
| 33:31 | referred to as motor and fileted region . And if you zoom in the |
|
| 33:37 | and plate region, presuming onto the here, you will see the |
|
| 33:42 | you will see the vesicles and then optical, you will see the receptors |
|
| 33:48 | post synaptic cell inside the muscle. have this really interesting structure of junction |
|
| 33:53 | folds in these junction, along the increase the surface area and the possible |
|
| 33:59 | of the post synaptic receptors that are there. So what are some of |
|
| 34:03 | features of this synapse in the neuro junction? First of all, it |
|
| 34:12 | quanta of neurotransmitter for packets uh for bicycle. And that quanta is typically |
|
| 34:26 | 2004 1000 molecules. So it's pretty almost the same. 2000 to 4000 |
|
| 34:37 | . And this is acetylcholine molecules that packaged and then one neurotransmitter vesicles. |
|
| 34:44 | will have 2 to 4000 and one say, okay, one or less |
|
| 34:48 | to 4000, that's one or That's not the same. Okay, |
|
| 34:54 | it's not 2000 and 20,000. It's 2020. So there is this this |
|
| 35:01 | of molecules that gets released to settle molecules when you go in the in |
|
| 35:06 | junction all fold here. What you find in the junction of all |
|
| 35:15 | Our nicotine nick, acetylcholine receptors and are located at these parts of the |
|
| 35:25 | all fold that are closed to the being released. Cristiana, broccoli |
|
| 35:34 | So silk holding molecules will bind to receptor, still cold in molecules will |
|
| 35:44 | into this receptor here and this is muscle Salvatierra and it will cause an |
|
| 35:57 | of sodium so it will conduct But acetylcholine receptors will also cause an |
|
| 36:06 | influx of potassium. Okay person, . So our single colon receptors, |
|
| 36:17 | of all, what is the feature acetylcholine receptor? It's a ligand gated |
|
| 36:23 | . It is gated by Ligon. to acetylcholine molecules actually yeah have to |
|
| 36:30 | to one receptor in order to open receptor. So if you're released 2000 |
|
| 36:37 | 4000 Molecules, How many receptors you buy and divided by two. And |
|
| 36:43 | will see how many receptors you can . So this is really cool |
|
| 36:48 | But this acetylcholine fluxus of sodium potassium what produces an action potential in the |
|
| 36:55 | and contraction of the muscle. Note below you have both educated sodium |
|
| 37:03 | MTV and when you have the deep here you have the opening um sodium |
|
| 37:13 | sodium channels and you have the flux sodium and also the flux of calcium |
|
| 37:19 | is responsible for producing the action potential the muscle. And we're not going |
|
| 37:24 | talk much about it. So what the civil choline receptors produce them. |
|
| 37:30 | produce what is called the end plate . So you have the point of |
|
| 37:38 | diagram as the civil coding receptors. will be located here very approximately to |
|
| 37:44 | the vesicles are being released And the within those junction all falls you'll have |
|
| 37:51 | educated sodium channels, potassium and calcium that will be responsible for producing the |
|
| 37:58 | potential. Okay, so what is ? What does this look like? |
|
| 38:05 | looks like a very reliable synapse. a very high fidelity synapse. |
|
| 38:13 | 21 action potential in the synaptic terminal means the twitch of a muscle. |
|
| 38:21 | a high fidelity sent out what is city alkaline produce. Acetylcholine produces this |
|
| 38:30 | polarization in the form of the employees http. That's approximately 70 million balls |
|
| 38:45 | size. What is the threshold for potential is -40 million holes. And |
|
| 38:52 | this inflate potential will always turn on much longer action potential in the muscle |
|
| 38:59 | that's mediated by the sodium and calcium potassium flux is. So this inflate |
|
| 39:07 | of this post synaptic potential is always Every time there's a release of neurotransmitter |
|
| 39:16 | coding 70 mil of also deep What does that mean? That |
|
| 39:19 | Muscle twitches, muscle gets deep polarized potential gets produced. This template potential |
|
| 39:27 | causes the twitch of a muscle. very highly reliable synapse and because it's |
|
| 39:34 | acting through nicotine acetylcholine receptors. It only excited tori So this neuro muscular |
|
| 39:47 | is very simple. It releases it targets only nicotine acetylcholine receptors that |
|
| 39:55 | only excited to her. It's a code fire contract, fire contract. |
|
| 40:03 | no inhibition in the neuro muscular inhibition lives where inhibition lives in the |
|
| 40:12 | cord. This is the muscle in periphery here. This is the neuronal |
|
| 40:19 | are motor neuron terminals on the skeletal . So that's why you will have |
|
| 40:27 | massive employee potential. Its massive Bentley always causing the production of this action |
|
| 40:41 | in the muscle cells and the action in the muscle cells. It's much |
|
| 40:46 | you can look up a cardiac action that you record with the E k |
|
| 40:51 | 20 milliseconds. 40 milliseconds. It's scales. Okay. The point we're |
|
| 40:57 | to make now is that this is highly reliable synopsis Packet of neurotransmitter. |
|
| 41:03 | always enough to bind to the It's always producing 70 million balls. |
|
| 41:07 | always causes contraction of the muscle and is not the case in the cns |
|
| 41:13 | synopsis that are very very weak And you require activation of at least 20-40 |
|
| 41:20 | . They're synopsis. This is one that's enough to cause the twitch of |
|
| 41:25 | muscle so it's inhibition it would stop the I should have really stopped |
|
| 41:36 | It's only it's only if there is inhibition, it's only controlled by the |
|
| 41:40 | inter neurons telling this motor neuron to releasing. If it's not releasing then |
|
| 41:45 | muscle is relaxed. Which would be that circuit that we looked at for |
|
| 41:50 | patella tendon reflex. It was the muscle that would be relaxed, allowing |
|
| 41:55 | the main muscle to contract. So is this is what's happening at the |
|
| 42:06 | muscular junction. And I left this uh slide here so that you can |
|
| 42:13 | the definitions what the unplayed potential Uh These are ligand gated acetyl calling |
|
| 42:20 | Nicholas. It'll Colin nicotine it because actually bonds to them. That's what |
|
| 42:25 | called nicotine nick. Mhm. And the C. N. S. |
|
| 42:34 | have neurotransmitter systems that have certain criteria we have several different neurotransmitter systems so |
|
| 42:44 | up until today we have really been about amino acids, neurotransmitters, |
|
| 42:50 | excitatory major excitatory neuron testament around the . Gaba major inhibitor neurotransmitter in the |
|
| 42:58 | . When you learn the three subtypes cells in the spinal cord, we |
|
| 43:01 | about glutamate sensory cells lie seen, their neurotransmitter in the spinal cord, |
|
| 43:09 | and the motor neurons and there are junctions and the C. N. |
|
| 43:14 | . You have more systems than just . You have many different chemicals uh |
|
| 43:22 | the criteria are that they're produced, and synthesized and found within the |
|
| 43:28 | So if this neuron synthesizing has synthesizing for Gaba it will produce gaba it |
|
| 43:36 | be inhibited in neuron. We'll have synoptic mystical transporters that will load up |
|
| 43:44 | chemicals into the vesicles. When this is stimulated, the vesicles should views |
|
| 43:50 | be released and when the chemical is it should act on the post synaptic |
|
| 43:57 | and causes biological effects after chemical is and the synaptic collapse here, it |
|
| 44:04 | be inactivated. So we don't have vesicles and the chemicals that come out |
|
| 44:10 | the vesicles just hanging out there in synapse forever. They're very clear. |
|
| 44:15 | get cleared, they get transported back the pre synaptic terminals so they get |
|
| 44:19 | down and they get transported into glia get re synthesized. So there's a |
|
| 44:25 | optic mechanism and there's an enzymatic breakdown these molecules that is happening in the |
|
| 44:32 | . If the chemical is applied on post synaptic membrane it should have the |
|
| 44:37 | effect as when it is released by . So if you stimulated excited neuron |
|
| 44:42 | has glutamate and it caused deep polarization the post synaptic neuron then you should |
|
| 44:48 | able to take chemical glutamate and apply onto this neuron and have this neuron |
|
| 44:55 | be polarized. So it has to an effect and you have to have |
|
| 44:58 | measurable effect. You have to record boston optical, you have these transmitter |
|
| 45:04 | ion channels and we will talk about a tropic and measurable tropic transmission. |
|
| 45:11 | memorable, Tropical g protein coupled receptors also found fascinating. Typically g protein |
|
| 45:19 | ion channels and also secondary messenger cascades can be turned on downstream following the |
|
| 45:27 | chemical release here in the synopsis. when we talk about neurotransmitters. We |
|
| 45:41 | to realize some very interesting things and have to start learning about the major |
|
| 45:48 | groups in the brain. When we about Yabba and glued innovate neural |
|
| 46:00 | you will soon realize that Mhm. neurons that produce glutamate in green are |
|
| 46:14 | everywhere, everywhere throughout the C. . S. That means to sell |
|
| 46:21 | synthesizing glutamate are located everywhere in the . Mhm. It's almost that are |
|
| 46:35 | gaba, the other major chemical They inhibit the amino acid neurotransmitter and |
|
| 46:44 | in the spinal cord it will be . But those molecules and the so |
|
| 46:51 | that we do synthesize those molecules will throughout with C. N. |
|
| 46:58 | That will be found throughout the But mm hmm. There are other |
|
| 47:17 | such as esposito cohen, such as been Africans that will contain the soma |
|
| 47:36 | that produce these chemicals only in very nuclei, mostly in the brain stem |
|
| 47:44 | will come to that slide in the and a few slides. So how |
|
| 47:50 | this is still combing get into the and get into the different parts of |
|
| 47:56 | brain. You have these non specific that go everywhere for acetylcholine and penetrate |
|
| 48:05 | centrally and peripherally and the same for and the same for other substances like |
|
| 48:14 | and serotonin. So you have a of these different molecules. And the |
|
| 48:19 | is that amine amino acid neurotransmitters will so much will be expressing them throughout |
|
| 48:27 | cns. And these other classes of . They'll be confined and synthesized by |
|
| 48:34 | so most in very specific nuclei in C. N. S. But |
|
| 48:38 | they will be sprinkled throughout these wide projections over different neurons in the |
|
| 48:46 | cortical E. And also in the . So the major amino acid |
|
| 48:53 | gaba inhibitory glutamate excitatory and the spinal glycerine is a major inhibitory neurotransmitter in |
|
| 49:00 | inter neurons. Advertising is an interesting as we study an M. |
|
| 49:05 | A. Glutamate receptor transmission. We learn that license is also a co |
|
| 49:11 | in the cns outside of the spinal . That means this little covid still |
|
| 49:18 | . We just learned about the civil and the neuro muscular junction. But |
|
| 49:21 | city alkaline is involved in cNS throughout cerebral functions. And these are means |
|
| 49:30 | . There's an amine epinephrine, norepinephrine serotonin doesn't. I mean there |
|
| 49:40 | also neurotransmitters. So but there are neurotransmitters. You also have a variety |
|
| 49:49 | peptides that are also responsible for neural because mm hmm. What else do |
|
| 50:10 | have in the brain that are neurotransmitter . I left it open box |
|
| 50:18 | Mhm Naturists oxide. Carbon monoxide but and they're also there are transmitters. |
|
| 50:32 | gasses, mm hmm. I know can across the plasma membrane really their |
|
| 50:41 | number in solvable. The cost of numbers. So when somebody says I |
|
| 50:50 | had a brain fart they have too of gas in their in their |
|
| 51:00 | What? Yes it's also neurotransmitter. we'll talk about it with a little |
|
| 51:07 | . So um so you have you have a teepee and you have |
|
| 51:14 | denizen. So eight ep dennison is core from the denizen triphosphate http is |
|
| 51:25 | only the energy molecule, it's also neurotransmitter. So it will have its |
|
| 51:34 | receptors that it binds to. And talk about that a little bit and |
|
| 51:40 | dentist and receptors that bind student the of the dentist and receptors to what |
|
| 51:47 | we have. Our economic acid orthodontic is also a neurotransmitter and we have |
|
| 52:03 | major major group of neurotransmitters that is listed here. Although your textbook talks |
|
| 52:09 | this. Thank you. Under cannabinoids A and undermine. And to |
|
| 52:28 | G. Which stands for two Oh the whistle endo cannabinoid molecules and |
|
| 52:35 | economic asset. They are lipid Yeah. Which means that they are |
|
| 52:47 | stored in vesicles because vesicles are membranes they are produced in the Selma's and |
|
| 52:57 | are not stored in the vesicles. gasses are not stored in the vesicles |
|
| 53:01 | carbonic acid and endocannabinoid levels are not in vesicles silence and the cannabinoids or |
|
| 53:08 | molecules like in the plant. But plan but cannabinoid molecules if we synthesize |
|
| 53:15 | endogenous. Everything we're talking about here endogenous which means it's produced by our |
|
| 53:20 | bodies. So we produce our own . Cannabinoid production goes up with stress |
|
| 53:27 | with repeated exercise. So you may have heard this uh expression, oh |
|
| 53:38 | having uh the runner's high and the high for the long distance runners. |
|
| 53:47 | something that they look forward to is really overwhelming feeling of happiness. And |
|
| 53:53 | long distance runners walkers, it seems be with this prolonged exerted repeated, |
|
| 54:00 | know, physical activity. But what is the interpretation was is endorphins in |
|
| 54:06 | brain, morphine like molecules in the . We all have endorphins when we |
|
| 54:10 | have endorphins, there's no morphine like in the brain and and the cannabinoids |
|
| 54:17 | the ones that the latest researchers are for that feeling of happiness in the |
|
| 54:22 | . For long distance runners, the high for the sportsman is high, |
|
| 54:27 | feeling of bliss. So it is production of endocannabinoid and molecules and that |
|
| 54:34 | you that these different molecules and these are actually have their own cycles during |
|
| 54:40 | day. There's not always the same of endocannabinoid, there's not always the |
|
| 54:46 | amount of a teepee. And the . The denison makes you sleepy so |
|
| 54:52 | goes up in the evening, goes at night and then the denison levels |
|
| 54:58 | in the morning. Under cannabinoid levels have some steady state of under cannabinoids |
|
| 55:05 | with the cannabinoid cannabinoid receptors in the . But if there's stress or physical |
|
| 55:11 | , Those levels go on nora ephron nothing. You have a fight or |
|
| 55:21 | response, adrenaline of the brain very response, it's also regulated. You |
|
| 55:32 | adrenaline kick in one when the big running at you, not when you're |
|
| 55:37 | know sitting and doing yoga and uh the river at some point. So |
|
| 55:44 | chemicals appetite, sexual activity, serotonin will increase. Will mediate that. |
|
| 55:52 | you'll have the fluxus of these chemicals the brain. You'll have different levels |
|
| 55:58 | those chemicals synthesized on demand depending on or depending on the dire eternal night |
|
| 56:06 | day cycle. I mean a means be confined to these nuclei. So |
|
| 56:18 | soul most so most of the neurons produced nothing. You will only find |
|
| 56:23 | here. If you apply to and up and stain on the entire |
|
| 56:28 | you'll only see the Soma is glowing . But if you're applying the stain |
|
| 56:32 | glutamate, you will see the selma's , everywhere, very widely distributed. |
|
| 56:41 | the question is, do we have know all of these neurotransmitters and all |
|
| 56:45 | their functions and what they do. answer is you definitely need to know |
|
| 56:49 | amino acids because we're talking about you have to know how different a |
|
| 56:57 | is because it's also an energy molecule it's also in their transmitter. You |
|
| 57:03 | definitely know that there are lipid soluble such as other cannabinoids, economic acid |
|
| 57:10 | gasses, that means that their But they're not stored in the vesicles |
|
| 57:14 | we talked about and from these acetylcholine norepinephrine, histamine norepinephrine and serotonin to |
|
| 57:22 | will touch upon them and some of in greater detail than others. So |
|
| 57:28 | we talk about synthesis of acetylcholine, will know a lot about acetylcholine and |
|
| 57:35 | will not ask you questions about the except for maybe a general question of |
|
| 57:42 | . There was a homework question there peptide comparison to the neurotransmitter vesicles but |
|
| 57:48 | not going to go into detail of statins substance steel though some of the |
|
| 57:53 | have appeared, you know our slides CCK remember colors sister qian or CCK |
|
| 58:00 | parameter cells in the hippocampus, some them were CCK positive, sum of |
|
| 58:05 | CCK negative. So what does that you releases what neurotransmitter glutamate synthesizes |
|
| 58:15 | So what is that other molecule doing CCK paralysis to kinda you can co |
|
| 58:24 | . So you can co express different . In other words, you can |
|
| 58:30 | express samina assets and you can co some of the means together the cells |
|
| 58:36 | produce the means they will not be expressed. Alright, so these are |
|
| 58:44 | different classes and this is the answer your question, homework question about the |
|
| 58:51 | and I will leave it at this come back and continue talking about neural |
|
| 58:56 | in the next two or three lectures so let me go ahead and stop |
|
| 59:01 | recording |
|
