| 00:01 | This is lecture town of neuroscience and we spend most of our time in |
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| 00:07 | last few lectures we're discussing the membrane and action potential and ionic currents and |
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| 00:17 | different rising and problem phases of action as well as the resting membrane |
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| 00:23 | We talked about both educated sodium channels quite a great depth and we talked |
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| 00:32 | how there are really two action So there is a forward propagating action |
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| 00:38 | and that forward propagating action potential will deep polarization of the external terminal in |
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| 00:45 | release. And this is where we study for the next three lectures and |
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| 00:49 | there's also in addition to the forward action potential, there is back propagating |
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| 00:54 | potential and that back propagating action potential a function and synaptic plasticity in particular |
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| 01:03 | spike timing dependent plasticity and it's very in binding the pre synaptic inputs with |
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| 01:12 | post synaptic response of the post synaptic produces. So have your challenge of |
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| 01:17 | day do you think done drives prefer propagate deep polarization and forward and backward |
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| 01:26 | . So let's think about this First of all dendrite. So dendrites |
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| 01:31 | not accidents, signal is not being , it is propagating, it's probably |
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| 01:41 | lost over distance right now the other is deep polarization and forward is towards |
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| 01:52 | backward is away from selma because we're talking about inputs coming in to selma |
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| 01:59 | hundreds. How would you test the of how dumb drivers prefer to conduct |
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| 02:09 | which direction, what is the cage and what is in Cajun. So |
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| 02:19 | you're talking about done drive here right it goes into selma. And I'm |
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| 02:32 | this this signal, the polarizing signal to go and to soma away from |
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| 02:39 | much. Why would it have any here? We saw this is done |
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| 02:46 | at the level of the axon. saw that the is a preference for |
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| 02:52 | over propagating spike in this direction Back despite a small one in this |
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| 03:00 | So there's definitely a preference to conduct current major action potential into this external |
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| 03:07 | direction. But gun rights are not same. Axons are my eliminated and |
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| 03:16 | potentials will regenerate each note around Okay. Hundreds. Don't have |
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| 03:26 | There are no nos of ranveer. if you don't have Myelin, you |
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| 03:31 | have proper insulation of the membrane. means your membrane, given that the |
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| 03:38 | are open. Can do what with current can actually cause a lot of |
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| 03:43 | current to leak out over the And you are trying to figure out |
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| 03:50 | direction does this number. I prefer conduct which what you've learned already. |
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| 03:56 | will say. Well I have all these electrophysiology tools at my disposal. |
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| 04:03 | I'm gonna use duel. No, actually gonna use triple dendritic recordings |
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| 04:14 | 1, 2, 3. What you do in this experimental setup? |
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| 04:21 | can generate current and one recorded in quarter in three. You can generate |
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| 04:32 | into recorded in three. Recorded in . We generated in two. Recorded |
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| 04:37 | one and it preferred to conduct away the soma. Then you would record |
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| 04:42 | larger current than one away from But if you'd prefer to conduct over |
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| 04:48 | soma you would record a larger current three if this was the source of |
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| 04:53 | challenge. Mhm. So Not But that's 1990s And we're in |
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| 05:06 | And so the second part of that this challenge of the day is for |
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| 05:11 | to think about. There's gonna be question on the quiz. Maybe maybe |
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| 05:15 | exam about this. Well what are other tools that we have at hand |
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| 05:24 | what we're really good at is, , first of all, apart from |
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| 05:33 | electrical stimulations, we can bring an and we're interested in stimulating this dendritic |
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| 05:43 | here we can bring an electorate with and let's say it will have glutamate |
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| 05:51 | the electrode and we can apply it this spine here. What? So |
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| 06:01 | will say, instead of electrical I can do chemical stimulation of the |
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| 06:08 | that we call this? Uh synoptic , we'll get to that in a |
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| 06:11 | slides. Affirm that. But what the problem here is how specific if |
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| 06:20 | applying from the electrode, how specific is to just this one synapse rather |
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| 06:27 | too many synopses in the area. do you know that most of the |
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| 06:35 | is flowing in this direction versus in direction. So this kind of a |
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| 06:41 | stimulation with application of a chemical, lends itself to dialysis, to the |
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| 06:49 | of that signal, to the dilution that signal whereby the tip of the |
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| 06:54 | will have the most concentration. You'll the most concentration maybe by this dendritic |
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| 06:58 | , but you'll surely be affecting the spines as well. So it's not |
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| 07:05 | precise and you still need to measure signal because this is just stimulation. |
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| 07:11 | you still need to measure electrical signal it's not precise because you're spreading this |
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| 07:20 | around a larger area than you would to. So I wanted for |
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| 07:27 | have something that allows me to stimulate dendritic spines on the dendrite, it's |
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| 07:37 | something is additional reading material in your supporting lecture holder. Well, basically |
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| 07:48 | another technique we're neurotransmitters can get caged this case the neurotransmitters will be placed |
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| 08:05 | a chemical cage and they will be throughout the solution. But these neurotransmitters |
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| 08:14 | caged and they're not available to bind glutamate is not available to bind to |
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| 08:20 | glutamate receptors and to de polarize these as long as it is caged. |
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| 08:27 | now in addition to electrical stimulation and , we also have pretty powerful optical |
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| 08:36 | , optical stimulation, optical imaging and cages. Chemical cages can be broken |
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| 08:47 | photo license photo license is a little of laser that targets a very specific |
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| 09:00 | around just one synapse and in cages in much more specific area, it |
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| 09:09 | still diffuse a little bit but not much as from the electrode in just |
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| 09:15 | and succeeding to activate a single dendritic after this. Blue debate has been |
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| 09:22 | from the cage. So it gets by photo license. And the beauty |
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| 09:28 | this technique is that the lasers are fast, lasers are going into the |
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| 09:35 | second speeds these days for various applications scientific applications. So you can very |
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| 09:43 | with the laser activate very small area dendritic spine. You can do multiple |
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| 09:49 | activations, you can activate spines throughout three dimensions and connectivity that it has |
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| 10:01 | the slice if you're doing it in slice. So this is a much |
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| 10:06 | technique on caging neurotransmitters for activating single and imaging this in four dimensions. |
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| 10:20 | X. Y. Z. Three . Tea time in the fourth |
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| 10:26 | So one of the articles that I've for you and your course lecture |
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| 10:30 | talks about uh Cajun neurotransmitters in four to understand how den rights conduct the |
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| 10:40 | is. We were understanding how action are generated in the axons propagates. |
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| 10:46 | gonna talk about how it reaches external . It regenerates each note around here |
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| 10:53 | it has high densities of our favorite gated sodium and potassium channels. We've |
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| 10:58 | about this is a different situation We're talking about synaptic receptors. We're |
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| 11:05 | about receptor channels for neural transmission. receptor channels for glutamate or Gaba and |
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| 11:15 | chemicals that will cause deep polarization or polarization. And so we want to |
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| 11:23 | how these deep polarization in the dendrites distal dendrites will travel into selma's from |
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| 11:30 | dendrites will travel into selma's. A dendrites will travel into distal dendrites. |
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| 11:37 | why we want to apply all of techniques. Multiple dendritic recordings from selma |
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| 11:42 | the way to the apex imaging or these caged neurotransmitter photo license for engaging |
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| 11:52 | along very precise spatially and temporally areas the of the cell. Yeah, |
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| 12:05 | example. In terms of the like if you injected, if you |
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| 12:16 | current here, for example, And you will respond recording a response |
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| 12:22 | one and your response would be this this amplitude. Right? And then |
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| 12:28 | recorded the same response in in electorate . But that same response was only |
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| 12:35 | amplitude. You would now think that something about the signal that is much |
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| 12:41 | floods from this direction into the distal . That's what it would tell |
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| 12:47 | Yeah, where it is spatially traveling along the you're welcome along the |
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| 12:54 | You have these noses run beer, where the signals would regenerate. And |
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| 13:01 | you don't have that, then the over time that travels. If it |
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| 13:06 | not surrounded by this insulating sheets of part of that signals go to be |
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| 13:14 | over distance. We finished the course about different ion channels are distributed and |
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| 13:24 | expressed in different subtypes of cells. we said that different subtypes of |
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| 13:31 | The reason why they can produce various behaviors with the action potential patterns is |
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| 13:38 | of the certain expression of these voltage channels that we're talking about. Other |
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| 13:45 | channels. And this is an example a parameter will sell which we learned |
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| 13:51 | in hippocampus. They're also very predominant the neocortex side of theirselves. This |
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| 13:58 | another type of external tough itself and you see a red staying here and |
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| 14:06 | for this particular uh next time channel . C. N. One. |
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| 14:13 | it says that in tropical selves this receptor this channel is expressed in the |
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| 14:18 | very typical gun rights and theft This channel is expressed in optical |
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| 14:25 | basal dendrites and all over the selma these cells. If we Campbell basket |
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| 14:32 | , which is an inhibitor interneuron you expression of this channel only in the |
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| 14:41 | . The different cells will express these . First of all different cells will |
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| 14:47 | different subsets of different channels. And of all, if they express the |
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| 14:52 | channel, they may express it in cellular locations, then drive versus axons |
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| 14:59 | soma which will in the end influence output that they're capable of producing in |
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| 15:04 | processing they're capable of doing because of variety of the expression of these |
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| 15:12 | We discussed that there is a differences firing patterns that call these dialects of |
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| 15:19 | neurons and that the diversity of these patterns, cells primarily from the inhibitory |
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| 15:28 | cells in hippocampus and neocortex. Neocortex other areas that will be discussing, |
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| 15:37 | , exam is not in two my office used to be in this |
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| 15:41 | , I start to wear a long ago I left the slide because it's |
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| 15:45 | a reminder that I used to have office in that building. My |
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| 15:50 | email address is still the same. if you want to email me about |
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| 15:53 | exam or set up a meeting the best way is communicating with me |
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| 15:58 | that over email. So when we're about synaptic transmission now when this uh |
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| 16:05 | potential arrives at the terminal terminal we that causes the polarization that causes neurotransmitter |
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| 16:12 | and this neurotransmitter will go into the collapse. South Korea channels also allowed |
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| 16:19 | the conductance is polarized synaptic neuron The post synaptic neuron. Now, |
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| 16:26 | does this come about historically, while comes about from work off ramon |
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| 16:32 | Sir, Charles, carrington and most , Otto Loewy is concerns the chemical |
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| 16:38 | transmission. So Ramona alcohol postulated that is neurons are discrete and there's specialized |
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| 16:46 | where they connect to each other and these connections are not rigid that they're |
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| 16:53 | . Sir Charles Strengthen coined this whole of the synapse and communication between 2 |
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| 17:00 | neurons and not alone. We discovered neural transmission. What we know now |
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| 17:09 | the cns communication of 100 billion They make trillions of connections. So |
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| 17:24 | you think about that 100 billion, many people on this planet? Seven |
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| 17:30 | . So times that about 15 times of connections. So one brain is |
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| 17:44 | 15 Different individual units. 15 Hundreds of billion. I mean with |
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| 17:53 | . It's it's it's very, very system. If you were to take |
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| 17:58 | brain and flatten all of the membrane surrounds neurons and laid flat and would |
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| 18:05 | four soccer fields, laid all of one brain and laid flat all of |
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| 18:12 | membranes and roll everything through the spine everything. That's the fabric of our |
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| 18:17 | would cover about four soccer fields for fields. Story is fantastic In the |
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| 18:29 | of Easter Saturday 1921. So 102 ago I awoke, turned on the |
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| 18:36 | and jotted down a few notes on tiny slip of paper. Then I |
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| 18:39 | asleep again. It occurred to me six o'clock in the morning that during |
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| 18:43 | night I had written down something most , but I was not able to |
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| 18:48 | the scroll that sunday was the most day in my whole scientific life during |
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| 18:53 | next night. However, I awoke at three o'clock and I remembered what |
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| 18:59 | was this time. I did not any risk. I got up immediately |
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| 19:03 | to the laboratory made the experiment on frog's heart described below. And at |
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| 19:10 | o'clock, chemical transmission of nervous impulse conclusively proved great story. One of |
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| 19:21 | mentors used to say that sleep is the weak. Uh It's not |
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| 19:30 | I mean if you don't, if don't sleep well, you cannot |
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| 19:33 | However, if you are driven by by class and you need something you |
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| 19:40 | to get done. You may have not sleep for half a night or |
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| 19:48 | or something like that. You know you get older but your age, |
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| 19:51 | know, all night or sometimes it's a thing to do because you're capable |
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| 19:57 | doing that. But it's a lesson . Like what if you have some |
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| 20:02 | of like vision, How many of have things that come up in your |
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| 20:07 | as you're about to fall asleep while sleeping and you have a dream and |
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| 20:12 | wake up or you're about to And you know, sometimes I have |
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| 20:18 | in my head before I fall Not often, but there are |
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| 20:23 | Maybe it's related to concerts or I hear music and it's not the |
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| 20:28 | that I heard. But it's sort my own original music. I have |
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| 20:33 | uh no way of getting it I can't even reproduce it, recreate |
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| 20:39 | . You know, I can't even really. But it's all in my |
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| 20:43 | . They're kind of a locked up sometimes you have something and you can |
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| 20:50 | it out. You know you can it out and you put it on |
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| 20:54 | piece of paper like he did. when you put it on a piece |
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| 20:57 | paper you could get it out of head what it was and you didn't |
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| 21:01 | to put on a piece of He didn't want to risk it. |
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| 21:04 | went to the lab and did the . So the experiment that he did |
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| 21:09 | he had two hearts. One of was called the donor heart. And |
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| 21:14 | is from uh frog. So this a donor heart and this is recipient |
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| 21:23 | , donor heart has a vagus nerve blue nerve attached to the vagus nerve |
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| 21:28 | cranial nerve. 10 you will learn one of the nerves in this section |
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| 21:32 | nerve town, it innovates the And what you did is they stimulated |
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| 21:38 | vagus nerve. When you stimulate the nerve, the heart contractions or the |
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| 21:46 | rate, it slows down the muscle slow down. And he stimulated this |
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| 21:55 | and he collected the fluid around the point and this recipient heart has no |
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| 22:06 | nerve attached to it. So it have the vagus nerve attached to |
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| 22:12 | And he's not stimulating the vagus But instead he's applying the fluid that |
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| 22:19 | collected from the donor heart. He's onto this naive and stimulated heart and |
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| 22:31 | fact is the same. The heart also slows down. So there's something |
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| 22:41 | in the fluid. There is some in the fluid you don't need the |
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| 22:46 | nerve, you don't need the stimulation you need that chemical. That chemical |
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| 22:52 | acetylcholine. And in 1921 that was discovery of chemical neural transmission Biota Louis |
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| 23:04 | doing these experiments and the function of and the heart is the slowing of |
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| 23:13 | heart rate, slowing down of the in the brain. We have two |
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| 23:20 | of synopsis. We have chemical synopsis electrical synopsis. Chemical synopsis are the |
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| 23:26 | that will spend most of our time about pre synaptic neurotransmitter release and post |
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| 23:32 | receptor channels and G protein coupled receptors are located posson optically electrical synopsis are |
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| 23:40 | also gap junctions that made from two proteins. Those two connection proteins actually |
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| 23:48 | and merge between two neurons, specialized where Regular space and the synapses, |
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| 23:56 | 20 nm of space. But there some areas where two neurons come bring |
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| 24:03 | membranes very close together and allow for any channels protein from this side that |
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| 24:11 | on a protein from the other side form an opening the physical opening which |
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| 24:18 | called electrical synapses or gap junctions. called electrical synopsis, they were first |
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| 24:27 | in crayfish. So when the simulation produced in cell number one here and |
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| 24:34 | recording was done in cell number There was an immediate, just a |
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| 24:39 | itself. Signal recorded in stall number , But also without any delay. |
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| 24:46 | was a small signal that was recorded Stall # two. The idea was |
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| 24:52 | if you release neurotransmitter vesicles binds, a release of neurotransmitter. The chemical |
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| 24:59 | across the synapse. It binds to receptor channels that takes a few |
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| 25:05 | It's called synoptic delay. So chemical when you release a neurotransmitter to when |
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| 25:11 | have a post synaptic response, there this few milliseconds of synoptic delay when |
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| 25:19 | recorded from two neurons and they saw delay between the signal and cell one |
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| 25:24 | cell to accept that the signal and through was smaller. They said this |
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| 25:29 | be a chemical synapse because there is few millisecond delay here in the response |
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| 25:37 | your second cell. And so they the electrical synopsis and the electrical synopsis |
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| 25:44 | allow for the flux of ions from side to the other will allow for |
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| 25:50 | passage of small molecules including cyclic So secondary messenger molecules can pass their |
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| 25:57 | junctions. They're not voltage gated. don't really have the gate there either |
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| 26:05 | always open or there are more open the way they are more or less |
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| 26:13 | is they seem to have the sideway on it, which makes the channel |
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| 26:18 | the two selves a little bit a little bit smaller, but essentially |
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| 26:23 | almost police open ions. Small molecules as cyclic GMP cyclic mps, a |
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| 26:34 | messenger and I answers the current. why there is no delay. That |
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| 26:42 | current conflicts between one salad to the south. There is no delay. |
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| 26:48 | this this is an important system. was a synaptic delay. We already |
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| 26:53 | about several temporal scales in the First of all, we said that |
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| 26:58 | can produce action potentials that are very , 1 to 2 milliseconds. These |
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| 27:02 | large deep realizations. And we talked how glia do not produce action potentials |
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| 27:08 | glia instead produced these slower calcium wage the order of 10s and hundreds of |
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| 27:18 | . This is synaptic transmission. When talk about chemical transmission, you have |
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| 27:23 | delay. The synaptic delay, a milliseconds, five, sometimes 10 |
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| 27:29 | Here you have no delay. So is a reason why these gap junctions |
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| 27:36 | be very valuable for neurons if they formed between neurons and they formed an |
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| 27:45 | network of neurons that has gap That means activity in one cell can |
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| 27:52 | felt by interconnected cells without synaptic transmission a very fast fashion without any |
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| 27:59 | which is a great way to synchronize . And that's what the brain does |
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| 28:06 | lot is. Brain synchronizes excitatory and neurons to perform different tasks. And |
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| 28:15 | synaptic transmission will come with certain It can also synchronize neurons but electrical |
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| 28:22 | transmission is perfectly positioned for synchronizing adjacent or adjacent cells that are not unique |
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| 28:31 | neurons. But this is their function neurons. Prison optical, the cells |
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| 28:37 | have active zones. These active zones they will sequester the vesicles filled with |
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| 28:45 | . Mr boston optical there that's going be boston optic densities filled with post |
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| 28:53 | receptors. Another homework question which we probably answer in a few slides, |
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| 29:01 | are dense core vesicles? Are they from neurotransmitter vesicles? So we're talking |
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| 29:05 | neurotransmitter vesicles and when you look at neurotransmitter vesicles there seems to be two |
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| 29:12 | of vesicles anatomically and two types of synapses that you can observe Most of |
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| 29:19 | excitatory synopsis which are glutamate releasing neurons have asymmetrical differentiations, meaning that their |
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| 29:27 | synaptic active zones are gonna be smaller to their post synaptic receptor densities and |
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| 29:36 | vesicles are going to be around in . And we can see this using |
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| 29:40 | microscopy and other techniques these days, inhibitory cells that release gaba inhibitory neurotransmitter |
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| 29:50 | have these flattened vesicles but they will symmetrical pre synaptic and fast synaptic |
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| 30:00 | So this is one way in which can visually look through electron microscope without |
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| 30:05 | any stains such as stain for glutamate stain for gaba knowing, you |
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| 30:10 | is the chemistry no histology and you still be able to predict if you're |
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| 30:16 | at excitatory synapses or inhibitory synapses based some morphological differences in these two different |
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| 30:22 | of cells. You will first go . Mhm. Okay. In the |
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| 30:33 | structure there's a good explanation for that Yeah. So, so even though |
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| 30:52 | schematics argues, it's not guaranteed their that are they are, they would |
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| 31:12 | . That's a great comment. You're actually right that a lot of interconnected |
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| 31:19 | we would call nuclei a lot of are defined as performing the same with |
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| 31:26 | function. Collections of cells and nuclei cells that are responsible for the same |
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| 31:31 | similar functions. So, yes. you will have gap junctions and you |
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| 31:37 | synchronization. Now, the synchronization is because brain signals are pretty weak if |
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| 31:45 | not performing a certain task or you're being stimulated by a certain sensory or |
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| 31:52 | matter sensors, stimulus. Okay, in order to perform the task, |
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| 31:57 | know, move the hand, move hand. I have to synchronize |
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| 32:01 | myself, myself and myself and the ganglia in the motor cortex to produce |
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| 32:10 | output into the spine to do So it's not just one neuron, |
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| 32:16 | the collections of grounds. And so far as like as far as |
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| 32:27 | Well, if one cell is seeing very strong signal, there is there |
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| 32:32 | an there's not necessarily uniform amount of , it's only a fraction of that |
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| 32:38 | that spreads into the adjacent cells. not I'm not sure if that's what |
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| 32:42 | remember uniformity, but uh now how cells and it can be, for |
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| 32:49 | , different subtypes of inhibitory cells, cells will have gap junctions too. |
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| 32:56 | how they're doing the synchronization or what the response following a stimulus to one |
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| 33:02 | that will depend on the subtype of cell that is involved in a particular |
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| 33:09 | . And I mean and and and like to think about have cells in |
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| 33:19 | heart actually to the cardiac muscle that gap junctions but you know why it's |
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| 33:27 | important so that so that the muscle immediately. So once the signal gets |
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| 33:33 | it spreads immediately that there is no and the contraction is failing and it's |
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| 33:42 | and it's synchronized to ensure that it beating and that it is not failing |
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| 33:47 | contract. So that's sort of an with with the brain and gap junctions |
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| 33:52 | synchronization or two. The idea of and I also want or whether or |
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| 34:06 | and also just synchronize Yes, for . And there are different frequencies for |
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| 34:15 | and they're different tasks that will be by different frequencies. What we call |
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| 34:21 | brain waves in our hand. So will be some slower frequencies that will |
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| 34:27 | present when you're drowsy faster frequencies when learning something then then will be something |
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| 34:34 | between as well. We'll come and about that when we talk about brain |
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| 34:38 | in the very last section. So good questions if the chemicals analysis that |
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| 34:50 | more common, more prevalent. very good. So now we have |
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| 35:02 | . Sorry um signaling um usually like great question. Um it's mostly dominantly |
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| 35:20 | sauce. Uh And it is not in all of the networks. So |
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| 35:29 | is favoring the inhibitor ourselves to synchronize with ourselves but you'll find them on |
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| 35:35 | parameter sauce as well. And there also a couple of different subtypes of |
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| 35:44 | cells. Gap junctions and uh Okay you guys ask some you know when |
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| 35:50 | go to some tropical countries there's a with malaria. Uh Tropical countries. |
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| 36:00 | you go on sub Saharan africa if go to you know central south America |
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| 36:07 | you may get malaria from the There's a lot of mosquito bites. |
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| 36:13 | one of the drugs that is used chloroquine actually in part blocks gap |
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| 36:21 | It's one of the actions of that . So um and uh there is |
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| 36:30 | also a myth that if you drink water, okay uh tonic water can |
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| 36:40 | you. It also potentially can affect little bit of the gap junction |
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| 36:45 | To so typically people do it with as gin and tonic but tonic water |
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| 36:52 | where the good stuff is in this . Okay so neuro muscular junction, |
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| 36:58 | you're talking about the brain excited inhibitory before we go to neuromuscular junctions. |
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| 37:04 | where can you form the synopsis and of the synapses I some of them |
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| 37:14 | formed out to selma somatic. Huh of them are formed on axons |
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| 37:23 | X sonic. You're forming a synopsis the dead dr or selma. You |
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| 37:30 | affect the integrated properties of these Whether this neuron is going to fire |
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| 37:35 | not, how does your handle subsided input In the fact that the cell |
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| 37:41 | not going to fire the inside of input. You can affect that the |
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| 37:45 | is going to fire. How the integrates. You're targeting the axon. |
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| 37:53 | can no longer affect how this neuro for me. All of the emphasis |
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| 37:58 | came in the Soma already decided to an action potential. Section potential travels |
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| 38:06 | the action gets regenerated. And then been college is an inhibitory sent |
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| 38:11 | So what happens here? So it affect the integration abilities of this neuron |
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| 38:17 | it modulates the output. The output action control not the integration but it |
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| 38:25 | modulates controls the output of this. not the integrated process. This is |
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| 38:32 | for axa axonal selections. Alright so talk about uh neuro muscular junction. |
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| 38:43 | is a part of that circuit that started to understand. Remember the sensory |
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| 38:52 | root ganglion cell. Okay connect into neuron and motor neuron connects onto the |
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| 39:06 | cell and causes the contraction of the cell. So the motor neuron is |
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| 39:16 | outfit from the spinal cord and it into the muscle and when it gets |
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| 39:25 | the muscle that acts on ratifies the into several large synapses. Each one |
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| 39:36 | these referred to as murder and plate . Motor on play from motor |
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| 39:44 | More radical inclusion what you have and motor neurons. In fact it's a |
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| 39:52 | simple synapse because you have one neurotransmitter the synaptic vesicles and that's acetylcholine. |
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| 40:03 | acetylcholine is in Davis nerve that was cardiac muscle through vagus nerve and a |
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| 40:12 | Colin on a cardiac muscle had inhibitory that slow down the heart rate. |
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| 40:19 | Colleen there's what here Siegel cooling causes of the muscles. So it's excitatory |
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| 40:28 | why is that? It's two different cardiac muscle versus the skeletal muscle and |
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| 40:36 | two different subtypes of a pseudo Colin channels in neuro muscular junction. This |
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| 40:46 | along falls into the muscles are containing high densities of nicotine acetylcholine receptors. |
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| 41:04 | is a subtype of acetylcholine receptor and a channel. So these junction along |
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| 41:14 | will be loaded especially in the areas are close to the synapse are going |
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| 41:22 | be loaded with nicotine nick Colin And when this synopsis here releases neurotransmitter |
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| 41:38 | optically these acetylcholine molecules to acetylcholine molecules necessary to bind the one receptor and |
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| 41:52 | receptor there's a channel. So release acetylcholine in the synaptic aly will cause |
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| 42:01 | binding of the civil code into nicotine with south cursed and it will cause |
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| 42:08 | influx of sodium causing the deep But these receptor channels will also conduct |
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| 42:20 | . So sodium is going to be in and potassium is going to be |
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| 42:29 | out. Okay, so these are channels that are permissible to to ionic |
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| 42:44 | sodium and potassium which is different from we talked about when we talked about |
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| 42:50 | selective channels. Both educated sodium channels a specific sodium vault educated calcium channels |
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| 42:55 | calcium voltage gated potassium channel potassium. are receptor channels that are no longer |
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| 43:03 | by voltage. Their gated by neurotransmitters by Ligon. So the binding of |
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| 43:08 | acetylcholine molecules will open this receptor channel will cause the initial influx of sodium |
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| 43:17 | initial D. Polarization at the level the muscle. Following this initial deep |
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| 43:24 | deeper within the junction falls. You have a lot of educated calcium channels |
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| 43:30 | are going to be contributing to generation the action potential in the muscle. |
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| 43:38 | if the action potential in neurons is short on the order of one or |
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| 43:44 | milliseconds, the action potential that the muscle is typically much at the at |
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| 43:53 | muscle tissue. Cardiac including is much longer in duration. Okay so there's |
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| 44:04 | big differences. But why is this simple synapse? Because deep polarization happens |
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| 44:12 | through the clothing will suffer channels and is at the level of the |
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| 44:18 | Because if we look at the level the brain and the C. |
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| 44:21 | S. We would see that there two types of acetylcholine receptor channels. |
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| 44:29 | receptors. One is the channel to because it'll go in receptor and another |
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| 44:33 | is a muscular clinic G protein coupled . So in cardiac muscle it slows |
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| 44:42 | the heart rate because it is dominated masculine acetylcholine receptors. It has inhibitory |
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| 44:49 | and skeletal muscle year in the bicep have nicotine acetylcholine receptors and that's the |
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| 45:01 | receptor shadow that you have. And synopses only excited. So between the |
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| 45:09 | and the muscle there is no Where do we have inhibition? We |
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| 45:17 | inhibition inside the spinal cord. Remember root, ganglion south, contacting to |
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| 45:27 | neuron that comes out and also to inhibitory interneuron of the spinal cord. |
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| 45:35 | this is in the spinal cord. . And at the level of the |
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| 45:44 | we have no inhibition. And that's you want the signal from the spine |
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| 45:51 | the muscle. This is your final output right? Anything that you're |
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| 45:56 | you're walking, you're kicking, moving sports, picking something up. This |
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| 46:03 | you want synchronized activity coming from the and forming a certain center, certain |
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| 46:11 | of your spinal cord and that spinal once it's activated, you know and |
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| 46:17 | wanna do something you know like start car that it's reliable. If the |
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| 46:25 | problem is final according to the into muscle is not reliable. You will |
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| 46:31 | start the car, start the start the car, you can't do |
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| 46:38 | . That means there's something wrong with with the commands that are coming from |
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| 46:42 | brain into the spine and that doesn't it's a very very reliable we call |
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| 46:49 | high fidelity synapse And action potential in pre synaptic terminal equals a twitch of |
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| 46:57 | muscle. Action potential equals a twitch a muscle. It's a very powerful |
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| 47:04 | . And the deep polarization that is by an academic acetylcholine receptors is on |
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| 47:10 | order of about 70 million volts. is called inflate potential because this is |
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| 47:23 | . Plate E. P. Or template potential Is a very large |
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| 47:31 | 17 million volt change in the membrane . So the resting number and potential |
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| 47:40 | -65 and the action potential threshold is . That's why the synapses very high |
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| 47:50 | because it will always cause the deep to reach the threshold for generating the |
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| 47:56 | action potential. And when we talked that you need multiple synapses in the |
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| 48:02 | . N. S. This is potential in the neuro muscular junction in |
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| 48:06 | C. N. S. You multiple excitatory synapses in order to reach |
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| 48:12 | threshold for action potential to generate the potential in the neuro muscular junction. |
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| 48:18 | always there deep polarization and play potential of a muscle deep polarization and play |
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| 48:27 | twitch of a muscle. Where does play potential come from? Where does |
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| 48:31 | large deep polarization come from? Nicotine receptor channels. Once the initial deep |
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| 48:39 | through these channels happens down below there's gated sodium channels and voltage gated calcium |
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| 48:46 | that will play into generating this very action potential. That's also very prolonged |
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| 48:52 | part because of the calcium conductance is the muscle. Okay. But this |
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| 48:58 | E. P. P. Polarization happens. The activation of the |
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| 49:03 | receptors very reliable. There's a release neurotransmitter and play potential. Put your |
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| 49:16 | here So the whole page where you draw and take notes and write down |
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| 49:24 | of the information. So again I'm big proponent of drawing things and learning |
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| 49:31 | by drawing things. People will say a visual learner for me seeing a |
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| 49:38 | is not enough. It helps but not enough. But if I can |
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| 49:44 | it down you know in whatever shape form that works for me you know |
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| 49:52 | really helps me remember things. So recommend it. It's like movement. |
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| 50:04 | I guess in the brain and the sympathize all the neurons. I guess |
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| 50:12 | it goes to the gonna be um perceptive and it would be a chemical |
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| 50:17 | these. It will be chemical everywhere be multiple synopses of being activated from |
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| 50:25 | motor cortex into your um cortical spinal that go down inform your cerebellum cerebellum |
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| 50:37 | tracts that go down and activate specific and areas of the body that you're |
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| 50:46 | . So uh so this is all movement. The reflexive movement. The |
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| 50:53 | thing that we addressed was the reflex . So it is still conscious because |
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| 50:58 | will perceive a reflex if you get , you draw with your hands, |
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| 51:01 | gonna know you get burned and you're adjust your further motor actions and |
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| 51:07 | putting a band aid, putting it ice or something like that. |
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| 51:12 | um but the fact of the matter that once that conscious command or even |
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| 51:20 | stimulus has reached the synopses highly So if that command went to |
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| 51:28 | motor neuron is d polarized, there's be that command that you're executing because |
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| 51:38 | very large deep polarization. Yes, it's only excitation. There's no inhibition |
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| 51:43 | to compete with this excitation. precisely because very good questions. We |
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| 51:50 | a little bit of time left. see where it leads us to this |
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| 51:54 | page. So neurotransmitter systems, it's whole system. Pre synaptic components. |
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| 52:02 | neural transmitters are synthesized. They synthesize enzymes that will synthesizing synaptic vesicles. |
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| 52:10 | synaptic vesicles will have transporters that will to transport the chemicals into the |
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| 52:16 | Little organelles have their own number in envelope, then re uptake transporters. |
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| 52:22 | once the neurotransmitter gets released, there's transmitter is not just going to get |
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| 52:28 | . It's going to get really taken to the pre synaptic terminal reloaded again |
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| 52:34 | the synaptic transporters. Once it is in the synoptic collapsed in addition to |
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| 52:40 | recycled back recent topically. A lot it is also gonna get degraded. |
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| 52:45 | you'll have degradation and sin in the collapse that will be chewing up essentially |
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| 52:51 | of these neurotransmitter chemicals, boston you have transmitter gated ion channels, |
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| 52:57 | in the neuro muscular junction you have you have CMS. A lot of |
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| 53:01 | in gated transmitter gated ion channels have protein coupled receptors that are not channels |
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| 53:08 | they'll exert their activity possum applicability by cellular cascades even transcription factors inside the |
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| 53:17 | acting through G podiums And these Ukrainians they activated they can influence activity of |
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| 53:24 | iron channels on the plasma membranes as as secondary messenger messenger cascades and the |
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| 53:31 | amount themselves. The neurotransmitters have to produced and found within the neurons. |
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| 53:38 | a neuron is stimulated to de the neuron must release that chemical. |
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| 53:45 | a chemical is released it must act the cross synaptic receptor cause of biological |
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| 53:50 | . So when on a low we the chemical and stimulated heart cause the |
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| 53:55 | effect and slow down the heart rate by applying to the neuro muscular |
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| 53:59 | it will cause an increase in the muscle contraction. It's a different receptor |
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| 54:05 | the silicone. After a chemical is it must be inactivated. We uptake |
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| 54:11 | or enzymatic breakdown has to be present the system for it to be a |
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| 54:16 | system If chemical is applied on the synaptic number and it should have the |
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| 54:21 | effect when it is released by a mimicry. So I stimulated using my |
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| 54:29 | nerve stimulation onto the heart and collected fluid and I think that there's a |
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| 54:34 | Colin and applied it to the heart expect that that heart will have the |
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| 54:39 | effect will slow down the heart rate if it was stimulated through the Vegas |
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| 54:45 | . So I'm mimicking now chemical synaptic . Major neurotransmitters. We're gonna introduce |
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| 54:57 | today and uh don't worry we're gonna about these things a lot Throughout the |
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| 55:05 | 23 lectures. But I'm gonna in you know shape your understanding of the |
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| 55:12 | and the scores. And uh the I think about the brain is uh |
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| 55:22 | interesting at least to me. Um why it's interesting is because I tell |
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| 55:29 | about different temporal scale. So tell about different dialects which neuron stock started |
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| 55:36 | talk about synchronization. We're looking to and brain maps and smell maps even |
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| 55:43 | the brain. All that. Look the brain here. So tell me |
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| 55:54 | for instance, going to spinal And I asked where are the glutamate |
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| 56:03 | were the selma's we're the neurons that glue to me the major excited to |
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| 56:08 | americans. And he would say it's in the hippocampus. No it's only |
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| 56:15 | neocortex. No it's everywhere. Yes everywhere. So if these were glutamate |
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| 56:24 | and you had hundreds of thousands and and hundreds of millions and billions of |
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| 56:31 | cells in the C. N. . You'll have the major amino acid |
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| 56:37 | glutamate neurons will be expressing glutamate Just seeing spinal cord about Gaba. |
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| 56:53 | man uh hippocampus. No it's Okay so I don't have a different |
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| 57:01 | pan. So let me just use . So X. Is Gabba, |
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| 57:06 | is glue made and this is But you get my point that everywhere |
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| 57:15 | and to a lesser extent because there less of the hindu very small cells |
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| 57:19 | excitatory cells with either Gaba or the cord is glycerine as a major inhibitor |
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| 57:29 | . Also in the nino asset also distributed. So expression of licensing and |
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| 57:37 | is widely distributed throughout the bread. then we have these other interesting |
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| 57:45 | Like for example we already started talking acetylcholine and you will say well where's |
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| 57:52 | ? So in the spinal cord you motor neurons that release acetylcholine. Okay |
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| 57:58 | everywhere there is acetylcholine. Okay a we have a civil coding motor neurons |
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| 58:08 | the spinal cord that it is released motor neurons right onto the muscle |
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| 58:17 | So motor neurons have a lot of and then it turns out in the |
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| 58:24 | there will only be two areas we're nuclei. This will have the cells |
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| 58:33 | expresses it locally. So they're very . And this is another definition of |
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| 58:39 | . Guys the collections of cells that responsible for the same or similar function |
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| 58:44 | quite often release or process the same of chemical neural transmission. Dopamine will |
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| 58:53 | have very specific nucleus D. That dopamine. Does that mean that there's |
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| 59:00 | two nuclei that have a single choline the C. N. S. |
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| 59:04 | one that has dopamine. No because projections from these nuclei they will go |
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| 59:12 | throughout the brain and to the So we call these amine systems that |
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| 59:19 | confined and expressed by specific nuclei sort like the sprinkler systems. There's only |
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| 59:25 | few 100,000 neurons that release norepinephrine in release their atonement and they're only producing |
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| 59:34 | nuclei in the brain. But the that I like to think about it |
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| 59:40 | if glutamate is the on switch gaba an off switch inhibition and all of |
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| 59:50 | different neurotransmitters and peptides they add all of control and color that you can |
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| 59:58 | . So different chemicals also can be as responsible for different behaviors. Some |
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| 60:03 | those chemicals are uppers norepinephrine dopamine. are molecules that engage you. The |
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| 60:13 | or flight norepinephrine, fight or flight . Big bears coming at you or |
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| 60:18 | in if you are in the it's serotonin okay acetylcholine will be responsible |
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| 60:31 | muscular functions moving the muscles but in C. N. S. It |
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| 60:35 | be responsible for a lot of cognitive cognitive information process. So this is |
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| 60:42 | big difference between major amino acid neurotransmitters major neurotransmitters. We also have to |
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| 60:49 | poses to kind and an orphan and and advice substance piece not attacking many |
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| 60:55 | ones. And then we have a box and inside the red box we |
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| 60:59 | start putting on a very interesting A. T. P. Is |
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| 61:05 | under our kind of sweater 80 The core of the D. |
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| 61:09 | is a denizen. It's a neurotransmitter goes up when you're sleeping and you |
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| 61:18 | to sleep. And then every morning of you from the 90-plus% uh interact |
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| 61:28 | your demos in receptors because caffeine interacts the devastating. So I understand the |
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| 61:36 | how cafe max. What is cappy mineral bodies. No it's Starbucks. |
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| 61:41 | a drug that's exogenous drug. It sold pretty much on every corner of |
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| 61:50 | major city intersection that interacts with the interceptors, E. T. |
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| 61:55 | A denizen, triphosphate, horrible. we have gasses as neurotransmitters, nitrous |
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| 62:07 | , carbon monoxide. So the neurotransmitters means and you will notice peptides they're |
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| 62:17 | in the vesicles or they're stored in done score vesicles. Gasses are not |
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| 62:24 | in the vesicles. Gas is a and formidable. So it gives a |
|
| 62:29 | meaning to brain farts. You can a lot of gas in the brain |
|
| 62:36 | they're signaling through natural oxide and carbon . And they'll have their receptor targets |
|
| 62:45 | that a class of neurotransmitters that will in the scores are endocannabinoid mm. |
|
| 63:05 | another neurotransmitter will not study that simulates economic or economic acid which is a |
|
| 63:12 | to the economic. So and economic are molecules that are made endogenous li |
|
| 63:20 | molecules that are similar to molecules that found in Canada's plan. Under cannabinoid |
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| 63:27 | , their precursors or Economic castle cannabinoids that's valuable, the lipid soluble. |
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| 63:36 | they're like gasses that are not stored the vestibule Thailand we can cross the |
|
| 63:41 | , some very interesting function in the by signaling retrograde lee just like the |
|
| 63:48 | neurotransmitters, nitric oxide and carbon Can. Okay, I'll end here |
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| 63:54 | . We'll review a little bit of when we come back on thursday, |
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| 63:58 | your patients today and we'll discuss the for us. Next lecture trying for |
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| 64:05 | |
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