| 00:03 | This is Lecture 10 of neuroscience and spent the last three hours of talking |
|
| 00:12 | action potentials, how action potentials get whether the channels and the ions and |
|
| 00:18 | action potentials. We finished by talking the action potentials are generated and we |
|
| 00:25 | that there are these specialized areas action segments, that's where the action potentials |
|
| 00:31 | generated. We said that they get each note of wrong here. And |
|
| 00:38 | reason for it is action initial segments those around here contain some of our |
|
| 00:45 | multi educated sodium channels and potassium channels well and allow us to regenerate the |
|
| 00:53 | potentials. And we talked about how forward propagating action potential will cause the |
|
| 01:02 | of the neurotransmitter will cause the deep of the pre synaptic terminal and release |
|
| 01:08 | neurotransmitter into the synapse and therefore communicate information to the adjacent connected neurons. |
|
| 01:19 | apart from the forward propagating spike, also talked about back propagating spike. |
|
| 01:25 | talked about how it acts on initial here you have two types of voltage |
|
| 01:30 | sodium channels. So if you recall channels are gated by voltage. Today |
|
| 01:36 | start talking about channels that are gated Liggins or chemicals And the low threshold |
|
| 01:44 | maybe 1.6 produces forward propagating spike high in 81 42 produces back propagating actual |
|
| 01:52 | . The main purpose for the forward action potential is because neurotransmitter release external |
|
| 01:58 | . The main purpose for the back action potential is its significance in playing |
|
| 02:06 | role in synaptic plasticity. And in what we call spike timing dependent plasticity |
|
| 02:14 | the timing in two cells communicating with another from pre synaptic cell. Post |
|
| 02:20 | cells. That timing has to be short And depending on that timing, |
|
| 02:26 | cell is going to be able to to communicate better with one another, |
|
| 02:32 | stronger through this process of plasticity and bind the activity from the pre synaptic |
|
| 02:41 | with the post synaptic activity that the synaptic neuron. So when we talk |
|
| 02:48 | axons, we talk about my eliminated that are coming off itself that have |
|
| 02:55 | of Ron dear and action potentials get at the axons. But when we |
|
| 03:04 | about down rights, we're not talking nodes of Rome beer, we're not |
|
| 03:14 | about insulation. This is all specific axon and this is where the action |
|
| 03:23 | gets produced, regenerated reaches the final and causes neurotransmitter release. But gun |
|
| 03:33 | don't have insulation. They don't have and they don't have the same types |
|
| 03:42 | channels? Gun rights have a lot receptor channels. And then when you |
|
| 03:49 | about well done rights are also not like axons. So what happens if |
|
| 03:56 | no insulation on the wires and on equipment that you're using since the charge |
|
| 04:03 | be partly leaking out of this wire of the axon in this case, |
|
| 04:09 | of the dendrite that is non violin . Mhm. And I have this |
|
| 04:15 | of the day. And I have article for you in your folder class |
|
| 04:21 | election Reading documents that you can look challenge of the days. Do you |
|
| 04:25 | dendrites referred to propagate deep polarization forward direction. So let's ask this |
|
| 04:32 | You got Dendrites propagates deep polarization. that means that there is a an |
|
| 04:40 | input like glutamate input. Right? excitatory and it's going to cause some |
|
| 04:48 | of a in this dendritic spine It's going to cause some sort of |
|
| 04:55 | deep polarization in the sound. We a good experience in the other |
|
| 05:00 | Also something. So there's going to deep polarization here in distal dendrites. |
|
| 05:14 | what if the deep polarization happens here the middle of this done dried? |
|
| 05:20 | that signal once you have this signal which you can record in the middle |
|
| 05:26 | the dendrite with electrodes at the optical dry with an electrode and the basal |
|
| 05:34 | from an electrodes? This electrode This is elected to and this is |
|
| 05:38 | three. So if there was a polarization here in the middle of the |
|
| 05:42 | right. Is it more likely that deep polarization is gonna spread to the |
|
| 05:47 | regions away from the someone or is more likely that it's going to travel |
|
| 05:53 | the summer. Remember. Soma is integrated unit like this neurons is going |
|
| 05:59 | decide whether producing action potential or So how would you test this |
|
| 06:06 | I'm already giving it away that. you could stimulate electrode to and record |
|
| 06:12 | electrode one. So if you produce stimulation in electrode to and you recorded |
|
| 06:18 | E. P. S. An electrode one. And you could |
|
| 06:21 | the size of this E. S. P. Which is excited |
|
| 06:25 | post synaptic potential. And you can measure it an electrode one and you |
|
| 06:32 | Compare the size of these two. in this case you injected this current |
|
| 06:38 | you can see more of that current recorded an electorate three. So it |
|
| 06:43 | has a preference to move forward to . There's something about the anatomy and |
|
| 06:48 | receptor channel and ion channel expressions along . It does that. Now you |
|
| 06:55 | stimulating in an experimental setup. You have much control of what fibers you're |
|
| 07:02 | to where they're projecting. And you to get very precise on stimulating a |
|
| 07:08 | synapse or a very small area on down. Right? So another way |
|
| 07:15 | to replace this neuron that releases glutamate you're stimulating with an electrode that contains |
|
| 07:27 | . And you could apply this glutamate you can apply this Ludin made right |
|
| 07:34 | targeting this middle area of the done ? Where electorate to is that would |
|
| 07:40 | mimicking the stimulation. Right? This positive card. You're injecting here your |
|
| 07:47 | glutamate which is gonna cause E. . S. P. Two. |
|
| 07:50 | . Equalization. You can again recorded electoral one electrode to an electric |
|
| 07:57 | Uh There are some issues with this of an experimental satellite because your electro |
|
| 08:02 | may be small and you may be targeting this one then didn't spine here |
|
| 08:07 | this one very small area on the drive. However the fluids that surround |
|
| 08:14 | cell will die allies and spread and many different synopsis in the area. |
|
| 08:22 | then this this experimental setup, this of a dialysis and the spread of |
|
| 08:27 | signal that will be most concentrated in area will also be spreading in the |
|
| 08:33 | areas. It's not very good. don't control the time by which this |
|
| 08:39 | spreads very well around the neuron. again you don't know exactly how much |
|
| 08:44 | it spreads to the pop distantly or the soma. So you can't answer |
|
| 08:49 | question very well with these injections of neurotransmitter. And so we come to |
|
| 08:57 | other very interesting technique in which glutamate are present everywhere in your solution except |
|
| 09:10 | of them are contained within cages. you have glue made molecules everywhere in |
|
| 09:23 | solution but they're contained in the cage one of the cages. The cages |
|
| 09:31 | actual chemical cages that do not allow these glutamate to be freely floating and |
|
| 09:40 | any of the dendrites here at the spines. And the only way that |
|
| 09:47 | can be released from these cages is you break that chemical cage. One |
|
| 09:52 | the ways in which you can break chemical cages with lasers, it's called |
|
| 09:57 | license of photo light Photons of light something breaking something in this case it's |
|
| 10:03 | izing the cage. As you lasers are very precise in space can |
|
| 10:10 | very small, lasers are very Commercial lasers and medical lasers are moving |
|
| 10:16 | the tent of second uh timescales for . You can activate lasers very precisely |
|
| 10:26 | just once in apps and release glutamate just this one cage, which would |
|
| 10:32 | it a lot more specific to this . Also with this UNQ aging of |
|
| 10:39 | neurotransmitters with total ISIS imaging, you do it in four dimensions. So |
|
| 10:45 | . Y. Z. X. . The third dimension is Z. |
|
| 10:51 | can go through the tissue. That's third dimension. The fourth dimension is |
|
| 10:55 | T. So X. Y. . T. Into a four dimensional |
|
| 11:00 | around these dendrites. Around these dendritic , you can use very small lasers |
|
| 11:06 | release glutamate. And there's other neurotransmitters and chemicals. If you can |
|
| 11:11 | as well to study kind of the of what do these dendrites conduct now |
|
| 11:17 | we understand that once the action potential the inaction initial segment, it gets |
|
| 11:24 | that direction, majority of that signal of the back flows. But what's |
|
| 11:29 | here. And so if you're there's an article that discusses the Cajun |
|
| 11:33 | engaging and this kind of techniques that modern day analysis that allows us to |
|
| 11:41 | activation on a single dendritic spine in singular Cinemax essentially. So again you |
|
| 11:51 | regeneration. You have the nose of gear which are loaded with our favorite |
|
| 11:57 | within the cells to have gun They not only have axons and nose |
|
| 12:02 | here and axon initial segments, each can express up to 12 different types |
|
| 12:08 | iron channels. This is an example one channel called HCM channel and wherever |
|
| 12:15 | see red, that's where within that that channel is expressed. So in |
|
| 12:21 | Haram it'll cells which we started in hippocampus or excitatory cells are also probably |
|
| 12:26 | the cortex will study even more in phenomenal cells. It's mostly the optical |
|
| 12:35 | the tufted external tufted cells. This channel is expressed everywhere in the soma |
|
| 12:45 | all throughout the day in this basket which is a pecan, apple basket |
|
| 12:51 | inhibit to internet in this basket These channels are only expressed in the |
|
| 12:59 | here in the terminals. So there's sub cellular ion channel distribution that varies |
|
| 13:08 | different cell subtypes for the same And there's also diverse subset of of |
|
| 13:18 | that each subtype of cells can And then once they express these channels |
|
| 13:25 | will express themselves cellular early within certain . Because of that we are capable |
|
| 13:34 | having many different neurons that will have diverse action potential output patterns. And |
|
| 13:41 | because of the diversity of the ion express where those ion channels are |
|
| 13:46 | how the conductance is the travel along dendrite how they're integrated in the |
|
| 13:53 | How fast they're produced in action initial . How long is the relatively factor |
|
| 13:59 | in all of these things are gonna into play in producing these different |
|
| 14:05 | So we also stress that the diversity what are called dialects in neuronal subtypes |
|
| 14:13 | from the inhibitor intermune. It's excitatory speak kind of the same or very |
|
| 14:20 | to three dialects and inhibitory cell c very different, diverse types of |
|
| 14:31 | Mhm. Alright so we're gonna move synaptic transmission for the next three |
|
| 14:40 | Exam is not in two weeks. office used to be an S. |
|
| 14:45 | . two. It's a reminder where used to be. So I love |
|
| 14:48 | slide and my email is the So if anybody wants to schedule a |
|
| 14:54 | with me to review their exams it's to do by email. Uh and |
|
| 14:59 | better to do exam. Reviews over rather than in person because I can |
|
| 15:05 | the screen better your screen to You can share it away looking the |
|
| 15:10 | you like it. So synaptic transmission communication between the announcement. This neuron |
|
| 15:16 | action potential. Action potential reaches external D polarizes external terminal causes bicycle, |
|
| 15:23 | neurotransmitter release neurotransmitter advises the post synaptic and produce the post synaptic response. |
|
| 15:31 | deep polarization. Excitatory post synaptic potentials the cns and inhibitory is hyper polarization |
|
| 15:37 | inhibitory post synaptic potentials. And what know now comes from work hundreds of |
|
| 15:48 | by many different people harmonica how he , he was using goldie stain and |
|
| 15:54 | was doing the reconstructions of neurons in parts of the brain and he believed |
|
| 16:02 | neurons are discrete units are connected with other in a certain way. That |
|
| 16:07 | of dynamic polarization. But you also that those connections are not necessarily |
|
| 16:14 | they're plastic, They can be they can be changed. Uh Sir |
|
| 16:19 | Farrington was the one that coined this of the synapse and started describing the |
|
| 16:23 | synaptic possibly be calling it the And we will read a story in |
|
| 16:28 | next slide, discovered the chemical synaptic . What we know now is in |
|
| 16:35 | brain. You have communication of 100 Neowons, billion neurons, trillions of |
|
| 16:44 | . It's a very complex organ, billion people on this earth with trillions |
|
| 16:51 | connections. It's a very complex systems . And this is even more |
|
| 16:57 | If you think about it on a level, a single brain, if |
|
| 17:02 | were to lay out the number and you were to unfold all of the |
|
| 17:06 | spies, all of the dendrites and lay out the possible numb brain from |
|
| 17:11 | brain would cover four soccer fields If you were to lay killed out |
|
| 17:19 | the brain fabric of our minds would about four soccer, four football |
|
| 17:26 | huge surface area, basically pulled it the space and we is again one |
|
| 17:38 | the inspirational scientists I'd like to talk . He wrote that in the night |
|
| 17:43 | easter saturday 1921 I woke, turned the light and jotted down a few |
|
| 17:49 | on a tiny slip of paper. I fell asleep again. It occurred |
|
| 17:53 | me at six o'clock in the morning during the night I had written down |
|
| 17:57 | most important, but I was unable decipher the scrawl that sunday was the |
|
| 18:02 | desperate day in my whole scientific During the next night, however, |
|
| 18:07 | woke again at three o'clock and I what it was this time. It |
|
| 18:12 | not take any risk. I got immediately went to the laboratory, made |
|
| 18:16 | experiment on the frog's heart described And at five o'clock the chemical transmission |
|
| 18:22 | nervous impulse was conclusively proved. That's his 1953 When I was doing a |
|
| 18:31 | doc, my second postdoc at George University, my mentor used to say |
|
| 18:36 | sleep is for the weak and what you meant by that is not |
|
| 18:41 | you don't need to sleep is you need to sleep. You know, |
|
| 18:45 | don't have proper sleep. You don't normally, physically and mentally. But |
|
| 18:50 | times of the, if you're there are certain times of the year |
|
| 18:56 | at your age, you know, still appropriate to pull off an all |
|
| 19:00 | . You have to you know I always say that a lot of us |
|
| 19:06 | things in our heads and it's awesome we can get them out of our |
|
| 19:11 | whether it's created, scientific or whatever . It's tortuous when you can't get |
|
| 19:17 | out of your head. And I students that sometimes they hear music and |
|
| 19:21 | not the music that I already It's like original music that it's being |
|
| 19:26 | in my head. But I have way to write it down or express |
|
| 19:31 | through an instrument and it's there but there. So he didn't go to |
|
| 19:37 | lab the president. But when he he discovered chemical neural transmission. An |
|
| 19:43 | that he did was he had to hearts. One of them had the |
|
| 19:48 | nerve attached to it, Its cranial tan that comes from the brain stem |
|
| 19:53 | innovates throughout the body and into the . And when he stimulates the vagus |
|
| 20:00 | , this heart slows down. The rate slows down. And what he |
|
| 20:05 | is he removed the fluid, his was sitting in the dish with the |
|
| 20:09 | and so he removed the fluid with Pipat and he applied this fluid onto |
|
| 20:15 | other heart. But this heart, recipient heart, it doesn't have vagus |
|
| 20:19 | attached to it. And he's not the vagus nerve like in the donor |
|
| 20:25 | . But s he is dripping the on the recipient heart. It has |
|
| 20:30 | equivalent effect stimulating the vagus nerve here this situation it's equivalent. The heart |
|
| 20:37 | slows down. And so he definitively that there's something in the fluid. |
|
| 20:45 | some chemical in the fluid which he is released by the vagus nerve. |
|
| 20:51 | if you stimulate a very good you have the heart rate slowed down. |
|
| 20:57 | if you have that fluid that the nerve releases or that chemical that neurotransmitter |
|
| 21:04 | you just apply the neurotransmitter, it's mimicry. You're mimicking the vagus nerve |
|
| 21:11 | a spy pat and the fluid he that would you get the equivalent effect |
|
| 21:17 | the slowing the heart rate and the that is discovered as acetylcholine. And |
|
| 21:25 | fact of acetylcholine on the cardiac muscle to reduce contractions to slow down the |
|
| 21:37 | rate. In general. The fact the chemical depends on the post synaptic |
|
| 21:47 | to which that chemical binds. So spoke about voltage gated sodium channels in |
|
| 21:51 | previous section we're talking about ligand gated and we're talking about the seed alkaline |
|
| 21:58 | we'll understand that certain muscles like cardiac expresses certain type of acetylcholine receptor that |
|
| 22:06 | the muscle to slow down. And see that as you saw in the |
|
| 22:12 | arch you should say wait a you taught us. And reflex arch |
|
| 22:16 | motor neuron releases acetylcholine which causes the of the of the skeletal muscles. |
|
| 22:24 | you're saying here that it causes to down. And that's because of the |
|
| 22:28 | of type of receptor channels that are in the cardiac muscle versus the skeletal |
|
| 22:35 | that we discussed earlier and we'll come and talk about it some more. |
|
| 22:39 | addition to chemical synapses, we also electrical synapses in the brain and they |
|
| 22:44 | first discovered in crayfish. When the of the current right here it's the |
|
| 22:51 | injection in this pre synaptic neuron one made, there was current response recorded |
|
| 22:58 | that same neuron. And immediately without delay there was a small fraction of |
|
| 23:05 | current response recorded in Neuron # And what made them believe. And |
|
| 23:13 | fact that this is different from chemical is because once the chemical gets released |
|
| 23:22 | pre synaptic terminal it has to travel the post synaptic cell and it has |
|
| 23:30 | bind the receptors and then cause an open these receptor channels and cause the |
|
| 23:39 | and the flux of ions. So takes a little bit of time from |
|
| 23:45 | you stimulate the pre synaptic axon to you get a response in the post |
|
| 23:51 | cell. So when you get the and this is synaptic delay and this |
|
| 23:57 | be five milliseconds can be 10 milliseconds . But there is a significant delay |
|
| 24:03 | you can observe. And when the uh they did these experiments originally we |
|
| 24:10 | no delay. They saw that the is smaller himself too. But they |
|
| 24:15 | no delay. So they postulated that not because of the chemical release and |
|
| 24:22 | of the neurotransmitter and then generating pas response. But it is electrical synopsis |
|
| 24:32 | we called gap junctions and allow for flux of ions. So positive |
|
| 24:38 | And this all will easily cross influx the other cell here that's interconnected. |
|
| 24:45 | these are unique because they are always . The gap junctions, they're comprised |
|
| 24:51 | connects. Um Most of the synoptic are about 20 nanometers in space between |
|
| 24:59 | neurons. And then in some areas two members of neurons come very close |
|
| 25:05 | , only 34 nanometers apart. And when the hemi channels from one south |
|
| 25:13 | synaptic the other south boston applicants to neurons with their plasma membranes. They |
|
| 25:21 | the gap junction channels. The gap channels are always open or they're more |
|
| 25:28 | so there's no gates that close them there seems to be some sort of |
|
| 25:33 | torque that can open them a little more and close them a little bit |
|
| 25:38 | they're always open. Not closed, a little bit but always open. |
|
| 25:45 | small molecules can also in addition to small molecules can pass through the gap |
|
| 25:52 | . Those are examples of cyclic M. She for example cyclic |
|
| 25:58 | M. P. S. Secondary . So small molecules that are secondary |
|
| 26:03 | can pass in between gap junk gap are very important because in order for |
|
| 26:10 | to perform different tasks to speak, your hands to generate any motor outfit |
|
| 26:21 | mental calculation, we have to involve cells. There's billions of neurons and |
|
| 26:33 | going to be thousands of neurons processing specific cast and so when we want |
|
| 26:42 | perform a certain task and if we to perform a repetitive task for example |
|
| 26:48 | have to engage many cells at the time and it's called synchronizing selectivity and |
|
| 26:56 | is ideal through the gap junctions. one cell that has very high level |
|
| 27:02 | activity, the cells that are connected the south through gap junctions will also |
|
| 27:09 | feel a certain level of activity, engaging them synchronizing their activity at about |
|
| 27:16 | same time. Chemical neural transmission is important for synchronizing cells and for the |
|
| 27:24 | but this happens much faster so it's significant for fast activity. Synchronization through |
|
| 27:33 | gap junctions. Chemical synopsis have pre zones that are loaded with the vesicles |
|
| 27:47 | have neurotransmitters, post synaptic densities that have post synaptic receptors that are basically |
|
| 27:55 | created channels or g protein coupled Now there's a homework question, what |
|
| 28:04 | does score vesicles? How are they from neurotransmitter vesicles? It's like, |
|
| 28:08 | there's still challenges challenge of the day the homework question today, what's going |
|
| 28:13 | the second section of the semester and be homework now. Just kidding. |
|
| 28:20 | just so it happens, it's in same, it's in the same presentation |
|
| 28:25 | we'll actually talk about dense core vesicles lecture. So I'm you know, |
|
| 28:29 | on this today. This is an microscope image pre synaptic terminal. You |
|
| 28:35 | these round vesicles that will contain And if we look at some of |
|
| 28:41 | electron microscopy images, we actually can that there is morphological differences between excitatory |
|
| 28:49 | and inhibitory synapses excited to re glue synopsis will have round of vesicles and |
|
| 28:56 | symmetric member and differentiations meaning that the synaptic zone is much bigger in size |
|
| 29:01 | surface area and the pre synaptic zone the inhibitory neurons which are Gaba ergic |
|
| 29:09 | . They'll have these flattened vesicles but member and differentiations prison african personality. |
|
| 29:16 | so just by looking at the electron images without additional stains for gaba or |
|
| 29:24 | or anything else you can actually start between excitatory and inhibitory synapses based on |
|
| 29:31 | morphological futures. And from the early I have explained to you that most |
|
| 29:41 | the synapse since formed on the And so my song about the |
|
| 29:49 | But there are some synopsis that can formed on the axons. So this |
|
| 29:56 | to drive. It's actually been It's excellent too. So it's actually |
|
| 30:01 | semantics. Its axon axon axon sonic even in some instances there is done |
|
| 30:08 | and done right. So what kind a synapse is that? Whereas the |
|
| 30:13 | done. Right. So these exceptions all of the rules. It's a |
|
| 30:16 | bit different kind of communication but it exist. Another interesting one in this |
|
| 30:24 | is that If you are a cell is targeting 100 or the selma of |
|
| 30:32 | neuron you're gonna influence the integrative properties this. You're gonna influence whether this |
|
| 30:39 | is going to fire an action to or not if you're an excitatory cell |
|
| 30:44 | you're right next to accident initial segment signal that you have a strong influence |
|
| 30:49 | this cell is going to get d and it's going to fire an action |
|
| 30:54 | the integrated properties and inhibitory input. don't have a strong influence whether the |
|
| 31:00 | is going to produce an action potential but in this situation it's access sonics |
|
| 31:08 | this cell has already produced an action . Action potential is regenerating. So |
|
| 31:16 | cannot influence the integrative properties of this anymore. And the ax sonic sonic |
|
| 31:22 | , you can only influence the output with yourself. So this is here |
|
| 31:28 | still influencing the input in the integration the signal number one neuron will receive |
|
| 31:34 | to 150,000 synapses in some basis. you're not talking about just one but |
|
| 31:41 | , hundreds of thousands. Uh And you're already generated an action potential already |
|
| 31:48 | have an output, you can only the output of this movement. So |
|
| 31:56 | we go into the synopsis in the . N. S. Which were |
|
| 32:02 | complex and you'll understand a lot about or inhibitors synopsis glutamate gaba At the |
|
| 32:11 | of this three plus hours. But we're gonna understand first the neuro muscular |
|
| 32:18 | . We already talked about it. talked about it with respect the reflex |
|
| 32:38 | and then the reflex sarge. We dorsal root ganglion south. Yeah the |
|
| 32:49 | cord, I don't know but that we had the three subtypes of cells |
|
| 33:04 | we discussed. We had the dorsal ganglion south. We had inside the |
|
| 33:10 | cord to inhibit the interneuron. Right we talked about motor in there for |
|
| 33:16 | exam. You have to learn these different cell subtypes morphology with a pseudo |
|
| 33:22 | and multipolar and so on. And new york transmitters to release. So |
|
| 33:29 | neuron releases acetylcholine. And what we is that when acetylcholine gets released on |
|
| 33:38 | muscle, if the motor neuron is and it releases this eagle Kolia, |
|
| 33:44 | causes a contraction. So this is from otello. We stimulating cardiac muscle |
|
| 33:52 | talking about here biceps, it's a muscles and the seed of colon is |
|
| 33:59 | during these muscles. These motor neurons waterfall motor and plates. The motor |
|
| 34:12 | . You can have this very large that spreads and ram if eyes innovating |
|
| 34:20 | , titian pre synaptic alie you will a lot of vesicles that are loaded |
|
| 34:27 | acetylcholine molecules. Siegel Colin once it to acetylcholine receptors. Person optically binds |
|
| 34:41 | nicotine acetylcholine receptors so very close what called the junction all falls here. |
|
| 34:49 | close proximity to the pre synaptic On the pasta synaptic side of the |
|
| 34:54 | . On the muscular side you have single Colin receptors and they're called nicotine |
|
| 35:01 | receptors. And when acetylcholine vines to acetylcholine receptors, you have to have |
|
| 35:15 | molecules of acetylcholine that binds acetylcholine There's going to be influx of sodium |
|
| 35:26 | the flux of potassium starting with an of sodium. So these are ligand |
|
| 35:33 | channels. They're no longer selective to ion as we learned for voltage gated |
|
| 35:40 | voltage gated castle potassium channels that are with sodium potassium. This receptor channel |
|
| 35:47 | for the flux of sodium and potassium release of acetylcholine results by the nicotine |
|
| 35:57 | receptors. It's the only neurotransmitter It's a very simple synapses only excitation |
|
| 36:08 | . There's no inhibition at the level the muscle. Where's the inhibition in |
|
| 36:15 | spinal cord last seen. That's right the spinal cord properly but on the |
|
| 36:21 | of the muscle so many see locally nicotine acetylcholine receptors only excitation which we |
|
| 36:29 | the high fidelity synapse deep polarization and potential and motor neuron release of the |
|
| 36:37 | action potential twitch of the muscle action twitch of a muscle action potential |
|
| 36:44 | action potential contraction action potential contraction, reason why is the release of acetylcholine |
|
| 36:55 | a massive deep polarization of acetylcholine binds nicotine nick. It's abbreviated nicotine acetylcholine |
|
| 37:05 | nicotine acetylcholine receptors. It produces an plate potential or E. P. |
|
| 37:14 | . Of about 70 million volts and . Then what happens? So then |
|
| 37:28 | inside you have both educated sodium channels both educated calcium channels. And this |
|
| 37:36 | massive deep polarization of the inflated potential guarantees that if you recall, the |
|
| 37:46 | membrane potential is -65, The threshold action potential is -45. This deep |
|
| 37:59 | through nicotine acetylcholine receptors and this inflate always guarantees that you reach the threshold |
|
| 38:09 | you open down below. It is illustrated. You have both educated sodium |
|
| 38:14 | involved educated calcium channels and it's sufficient initiate this very long prolonged action potential |
|
| 38:24 | the muscle which is mediated by vault sodium channels. Both educated calcium |
|
| 38:30 | which is different from neuronal action will not study the dynamics of this |
|
| 38:36 | potential channel dynamics, but it's very to know that end plate potential. |
|
| 38:42 | potential that gets generated the potential change generative level of the muscle in order |
|
| 38:49 | millibars is always reaches the threshold for potential, always produces the twitch of |
|
| 38:57 | muscle which is an action potential in cardiac muscle which causes the contraction that |
|
| 39:02 | must be. So why is it a single colon causes contractions and increases |
|
| 39:13 | in the skeletal muscle. Why is causing slowing of the heart rate and |
|
| 39:21 | is because of the different set type acetylcholine receptor that is dominating the cardiac |
|
| 39:29 | which is most chronic acetylcholine receptor. the response of the muscle the same |
|
| 39:37 | depends on the half of the ligand and in that case it's not a |
|
| 39:45 | but a wagon regulated receptor must clinic is metabolic tropic. And you understand |
|
| 39:52 | difference between iron, a tropical metal signaling in another hour or so, |
|
| 39:58 | and enclave potential, wow, look this, you can copy all of |
|
| 40:03 | onto the empty page and take notes like I said, it's a great |
|
| 40:09 | . I'm a visual learner myself what call and I think I've been tested |
|
| 40:16 | properly. But I know one thing when I see I remember about her |
|
| 40:23 | if I write it down or copy and you know, scribble around it |
|
| 40:30 | something then I'm really gonna remember. there's some, you'll see that there's |
|
| 40:37 | strong correlation between your motor learning Language speaking, all of this is |
|
| 40:47 | and writing something down. Can help remember things better. So I love |
|
| 40:56 | page live to write on okay, systems. It's a whole system that |
|
| 41:05 | to have different components to the First of all, if it's a |
|
| 41:12 | sell Gaba releasing, sell it has have an enzyme that synthesizes Gabba. |
|
| 41:18 | it's a slicing that has to realizing if it's glutamate, it has |
|
| 41:23 | synthesize glutamine, those chemicals they have be uploaded into the vesicles using synaptic |
|
| 41:33 | and re update transporters so they have be transported. Okay, we'll talk |
|
| 41:41 | that now if you release the chemical the synapse their degradation enzymes. So |
|
| 41:49 | chemicals will buy to the post synaptic and other chemicals will be another portion |
|
| 41:57 | those chemicals will be degraded. A will be we up taken back into |
|
| 42:06 | pre synaptic terminals to re uptake re uptake the neurotransmitter back into the |
|
| 42:11 | synaptic terminal and load the bicycles with neurotransmitter. So there's a recycling going |
|
| 42:19 | . There's synthesis, degradation but also of these chemicals on the post synaptic |
|
| 42:26 | . You have transmitter gated ion So this is an example of nicotine |
|
| 42:31 | casino coding receptor which is transmitter golden transmitter gated ion channel. It |
|
| 42:39 | for the flux of ions. You have G protein coupled receptors that are |
|
| 42:45 | tropic that are not channels but instead are linked to G protein complexes and |
|
| 42:54 | of catalysis of these G protein conflicts can now influence activity of the nearby |
|
| 43:00 | channels. G protein gated ion channels created by Liggins. They're created from |
|
| 43:09 | inside of the south by g protein and mediate cellular secondary messenger cascades. |
|
| 43:20 | , so you're a transmitter criteria, have to have produced emphasized and founded |
|
| 43:25 | Missouri if you stimulate this neuron then neuron should have a machinery to release |
|
| 43:33 | . If it's not releasing it, not uh neurotransmitter doesn't have the vesicles |
|
| 43:39 | some other chemical doing something else inside south. So when the chemicals released |
|
| 43:43 | must act on the synaptic receptor then the biological effect. Just like solo |
|
| 43:49 | I stimulated the vagus nerve and I the heart rate to slow down, |
|
| 43:54 | better take that chemical apply on their that has not been stimulated and see |
|
| 44:00 | that heart also has slowed down is . So after a chemical is released |
|
| 44:09 | must be inactivated. You have to a re uptake mechanism from the synapse |
|
| 44:14 | mechanism. If a chemical is applied a post synaptic member and should have |
|
| 44:19 | same effect when it is released by neuron a little bit redundancy here between |
|
| 44:25 | the chemical is released it's supposed to an effect. But also when it's |
|
| 44:28 | and applied another neurons it should also an effect. And the many different |
|
| 44:38 | in the brain. And we're gonna discussing the Sloman the scores and you'll |
|
| 44:48 | to know some of them but you know some of them. And we |
|
| 44:56 | amino acid neurotransmitters. Look at the acid neurotransmitters such as glutamate, the |
|
| 45:07 | excited amino acid in the brain. ! I can finish this all |
|
| 45:16 | we do appreciate that. Thank It will help me explain this. |
|
| 45:26 | Here's Our Brian Who is a good . Alright brainstem and going into the |
|
| 45:33 | quote gaba inhibitor major inhibitor neurotransmitter in C. N. S. So |
|
| 45:45 | everywhere you see an ax here everywhere everywhere you see an X. |
|
| 45:57 | there's going to be expression of Yabba the cns is gaba. We're gonna |
|
| 46:06 | all this X. And then the cord is glycerine. It's also |
|
| 46:14 | And what does that mean? That that the cells neurons that express gamma |
|
| 46:22 | neurotransmitters, you'll find their selma's widely throughout the court except cortical tissues. |
|
| 46:30 | stem cerebellum very widely spatially distributed. and billions of excited for it sells |
|
| 46:41 | themselves. Men you have glutamate and we're gonna mark as a dot and |
|
| 46:51 | have a lot more glue. Dramaturgical than Gaba ergic caos especially in the |
|
| 47:00 | . But the story is the same glutamate neurons will be widely, widely |
|
| 47:11 | and expressed throughout different regions of the . And then we come to this |
|
| 47:18 | class of neurotransmitters, major neurotransmitters in brain we refer to as a means |
|
| 47:25 | we have several seats alkaline is in 19 so already started discussing acetylcholine and |
|
| 47:32 | this exam you will know how acetylcholine synthesized, degraded and transported. |
|
| 47:40 | norepinephrine, histamine norepinephrine serotonin there all means and in addition to that means |
|
| 47:50 | also have times, polycystic kind in Northern Amanda Staton number of you will |
|
| 48:01 | what do I need to know for exam it will become a Canada over |
|
| 48:05 | next hour or two. But you to know about these chemicals for the |
|
| 48:10 | obviously Gabba and realizing the major inhibitor , glutamate is the major excited and |
|
| 48:20 | you look at an analogy of excitation on light on in condition switch off |
|
| 48:31 | off then what do these other chemicals ? Well, wouldn't it be nice |
|
| 48:37 | have sort of look at DJ set for your lights that light goes on |
|
| 48:43 | , different color kicks in and get to different rhythms, activity on and |
|
| 48:51 | off and that's exactly what it These different chemical systems, you can |
|
| 48:55 | them as different systems that mediate different , especially immune systems. Some of |
|
| 49:01 | are Chemicals that get activated when you're 5 um flight response or fright and |
|
| 49:12 | whichever it is, flight and fight . Norepinephrine, adrenaline of the |
|
| 49:18 | the big bears coming at, you don't get sleepy, you are, |
|
| 49:24 | get engaged a lot of times, will be happening very fast. I |
|
| 49:30 | know if any of you have happened experience accidents or things happening in front |
|
| 49:35 | you sometimes it seems like things slow isn't happening because different chemicals actually expressed |
|
| 49:42 | that traumatic event or sudden event is around you that let you perceive things |
|
| 49:49 | and maybe perceive the temporal scale, is happening differently to not that they |
|
| 49:54 | slowing down in front of you, just perceiving them differently. So serotonin |
|
| 50:02 | a mood neurotransmitter that we have neurotransmitters regulate move uh these neurotransmitter systems, |
|
| 50:12 | regulate different behaviors. Now what's interesting the means is that in comparison to |
|
| 50:18 | widely distributed amino assets, amines will their specific nuclei in which these substances |
|
| 50:29 | expressed. So there's going to be specific nucleus for serotonin. There's going |
|
| 50:34 | be a specific nucleus for cdo Colin going to be a specific nucleus for |
|
| 50:41 | in the brain stem mostly. What that mean? That means that it's |
|
| 50:47 | a few 100,000 cells actually in this that will express norepinephrine. It's not |
|
| 50:55 | distributed. The selma's of these cells not widely distributed like amino acids. |
|
| 51:00 | they're confined to these nuclei nuclei by or collections of cells often interconnected cells |
|
| 51:08 | are responsible for processing the same or functions or producing the same neurotransmitter and |
|
| 51:17 | that neurotransmitter to the brain. So do we get serotonin into the rest |
|
| 51:24 | the brain? We get it because systems have projections that go into the |
|
| 51:32 | . M. S. And into periphery supplying the periphery and the |
|
| 51:38 | M. S. With the Seattle with serotonin with norepinephrine. So it's |
|
| 51:46 | of it's a very different arrangement You have amino acids widely distributed expressed |
|
| 51:53 | the C. N. S. it means the confines of this |
|
| 51:56 | So so does that mean that if took out a nucleus that produces serotonin |
|
| 52:02 | like if I physically dissected out or a surgery or traumatic brain injury that |
|
| 52:08 | this piece of the brain out this that produces serotonin to does that mean |
|
| 52:13 | won't be any more serotonin in the . And the answer is that there |
|
| 52:19 | be any more sick economy. But you took equivalent or even larger chunk |
|
| 52:25 | the brain here, lost is a brain injury, you'll still have glutamate |
|
| 52:30 | gaba being expressed everywhere you lost this , you could lose the civil code |
|
| 52:38 | the brain will not have the privacy . Isn't that interesting? So that |
|
| 52:43 | that these neurotransmitters are responsible for different , different behaviors, fight or |
|
| 52:49 | getting in the mood, getting sleepy , motor functions. Dopamine. That |
|
| 52:57 | means that dysfunctions in these neurotransmitters are with distinct neurological disorders. Dopamine disorders |
|
| 53:07 | typically motor disorders such as Parkinson's serotonin disorders are typically mood disorders such |
|
| 53:17 | anxiety and depression. Siegel calling disorders Alzheimer's disease. One of the cellular |
|
| 53:29 | that means that neurons in this area the brain are disproportionately being affected by |
|
| 53:37 | the process is not happening during Alzheimer's pathology that is killing these acetylcholine neurons |
|
| 53:43 | early pathology is actually loss of colon neurons and that is important for learning |
|
| 53:51 | cognitive functions. So it's an interplay all of these chemicals that are necessary |
|
| 53:59 | processing activity for behavior outputs, they during the day sometimes and they serve |
|
| 54:07 | functions an injury or dysfunctions to these neurotransmitters and these specific nuclei that produced |
|
| 54:17 | means can result in loss of that warm class of chemicals being completely gone |
|
| 54:23 | the brain or affecting these particular And these particular neurotransmitters as I |
|
| 54:31 | are associated with specific neurological dysfunctions. in addition to these neurotransmitters are also |
|
| 54:42 | to talk about. A few other will later come up in the courts |
|
| 54:47 | well. A T. P. a denizen. So A T. |
|
| 54:55 | . Is a dinosaur bone triphosphate. an energy molecule right reducing our |
|
| 55:04 | It also serves as a neurotransmitter. has its own receptors to which it |
|
| 55:09 | grind neurons. Dennison is the core A. D. P. Is |
|
| 55:14 | a separate chemical. The dentist the set levels for example go up in |
|
| 55:19 | evening and it helps you fall asleep . Some of these chemicals will cycle |
|
| 55:26 | the day cycle diurnal cycle. Some these chemicals will cycle as they react |
|
| 55:33 | the external environmental input or whatever the or tasks that you're performing. So |
|
| 55:40 | dentist in levels go up at The dentist in levels go down in |
|
| 55:44 | morning. Most of you this morning consumed the substance that bound to genesis |
|
| 55:54 | . It's called caffeine, Tea, and and uh 90% probably more consume |
|
| 56:11 | in the morning. And it influences release. So these chemicals like the |
|
| 56:20 | and they can control glutamate that And other chemicals can control how much |
|
| 56:26 | the light switches on how much of is off. Right. Excitation on |
|
| 56:32 | is on So eight ep and the and we'll address that. They can |
|
| 56:40 | luda me. So when you consume and buys the denis's receptors it stimulates |
|
| 56:46 | release. And uh it's a pretty drug. It is sold sometimes and |
|
| 56:52 | corners of one intersection by one company Starbucks. And it's uh all of |
|
| 57:01 | have a very strong habit with Some of us are like I can't |
|
| 57:05 | to let out my coffee, you my tea. Whatever the preference for |
|
| 57:14 | you shouldn't colon or something that that . But let's talk about some other |
|
| 57:26 | we have uh Lady barbara love They love Me too. So this |
|
| 57:41 | a dennison. Let's talk about So we have gasses, nitrous oxide |
|
| 57:52 | carbon monoxide. They also can serve neurotransmitters. It's not interesting. I |
|
| 58:00 | say it gives saying a brain fart new meaning. So they have too |
|
| 58:06 | gas in my brain and the same . Too much problem but they act |
|
| 58:12 | neurotransmitters. Huh? And um okay class that I want to point out |
|
| 58:31 | endo kanab in the legs and bill and another molecule called ara que tonic |
|
| 58:43 | by the way. I partly love because of the names like our academic |
|
| 58:49 | . I wanted impossible to be my name but triphosphate had to come with |
|
| 58:53 | . And I wasn't sure about Triphosphate parts. But endocannabinoid endo are |
|
| 59:03 | indo and though it's endogenous molecules, means it's produced by your body. |
|
| 59:13 | of the molecules we're looking at amino 80 P. And then isn't it |
|
| 59:19 | peptides and peptides they're produced inside our . So our bodies produce candidates like |
|
| 59:28 | that can add a mod like molecules you also find cannabis plants and they're |
|
| 59:33 | endocrine. Optimism will study them because have very interesting mode of action. |
|
| 59:39 | look at them in the next couple lectures and we'll look at them within |
|
| 59:43 | larger scope at the very end of course within the endocannabinoid system which is |
|
| 59:50 | of the major homo static regulatory body that we have. And the cannabinoids |
|
| 59:56 | your happy molecules. So for a time it was thought that when people |
|
| 60:04 | long distance activities or repetitive athletic long distance runners there's just such a |
|
| 60:11 | that runner's high and when people finish workout intense workout long run, just |
|
| 60:19 | feeling of euphoria cannot be explained just you know. Yes, I worked |
|
| 60:25 | it's more than that and people call endorphins. Endorphins such as endogenous morphine |
|
| 60:34 | molecules but it turns out we don't do that. We release under cannabinoids |
|
| 60:42 | as increasing under cannabinoids with repetitive levels activity with sustained stress and long distance |
|
| 60:52 | is a little bit of a sustained on the whole body and metabolism. |
|
| 60:57 | this is the positive stimulation by the of endocannabinoid in the last few |
|
| 61:02 | it's emerging the descent of cannabinoids that responsible for what we call the runner's |
|
| 61:08 | feeling, feeling happy after exercising. our economic asset will get to the |
|
| 61:14 | of the second. Our economic asset one of the precursors of under phenomenal |
|
| 61:20 | and why these molecules are interesting gasses anonymous. Their lipid soluble. That |
|
| 61:30 | that they don't have vesicles in which are stored vesicles are fossil olympics. |
|
| 61:37 | right. And these olympics soluble. that means they get produced on demand |
|
| 61:44 | they cross through plasma membranes easily. not stored in vesicles like other |
|
| 61:52 | Like the assets and the means that stored and released in vesicles. So |
|
| 61:58 | have quite a distinct and interesting function the brain. An endocannabinoid, just |
|
| 62:07 | the denizen also regulation release of glutamate release of gabba, ignorance. So |
|
| 62:14 | cannabinoids and other molecules denizen means can the cycling and release of the excited |
|
| 62:23 | the inhibitor. So, on this note, I'm gonna end here today |
|
| 62:33 | when we come back we will continue about neuro peptides, neurotransmitters. A |
|
| 62:40 | of good stuff. We're actually gonna into the next lecture. Either |
|
| 62:48 | I'll decide if we go into this it has some of the same slides |
|
| 62:54 | we're gonna jump immediately into the next which is a neurotransmitter system. All |
|
| 63:01 | . I'll see everyone next |
|
