| 00:01 | So this is Lecture five of Neuroscience 15 63 15. Biology. Now |
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| 00:10 | telling the classroom that I have actually the videos, Thio video points, |
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| 00:18 | points is essentially a platform. I'm to get out of it for just |
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| 00:26 | second. Oh, if you're not with video points, what you do |
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| 00:38 | you go to World Wide Web video dot u h dot e d |
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| 00:47 | I'm also gonna insert the link to points on your syllabus because I have |
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| 00:55 | your lectures, your videos off the into the video points. Now, |
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| 01:03 | you come to video points, it's something that you have tow access with |
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| 01:09 | Cougar net again. So you will the same U H cougar and that |
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| 01:15 | in that you use for other things you use for the library research on |
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| 01:20 | Med, right? You're gonna log and you're going to see a list |
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| 01:26 | the courses that are available for viewing the video points, and you will |
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| 01:32 | as you're seeing on my screen Two courses Neuroscience 43 63 15 and |
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| 01:41 | are signs 43 63 15. So two different, actually, four different |
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| 01:47 | . And what you will do with section is when you click on your |
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| 01:54 | your section. Actually, it just neuro 2020 Lecture 01 lecture zero to |
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| 02:02 | threes. Electra 04 and so So once you click on the |
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| 02:09 | let's say this is the latest Takes a second toe world up, |
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| 02:27 | ? And so this is your viewing . You can make it full |
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| 02:33 | and you can school scroll through Um, you can advance basically through |
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| 02:42 | lecture is your wish. And so can remind ourselves that last lecture we |
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| 02:50 | talking about the diversity off Interneuron and they're diverse. And then we moved |
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| 03:01 | talking about glial cells, and we about neurological dysfunctions that are related to |
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| 03:09 | nation and dysfunction of violent nation. we discussed essentially that impairment. |
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| 03:18 | uh, Milen, whether, it iss, uh, genetic, |
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| 03:27 | at least can be modeled genetically. it has an onset later and live |
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| 03:35 | a multiple sclerosis we distinguish some symptoms multiple sclerosis is well as the fact |
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| 03:41 | it's auto immune disorder. And I've you to keep track off neurological disorders |
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| 03:47 | this is one of them. And we also discussed Charcot Marie Tooth |
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| 03:52 | which has peripheral myelin protein PMP to expression of that program. So this |
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| 04:00 | a good way Thio remind ourselves what talked about in the last lecture and |
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| 04:06 | last slide that we ended reviewing Waas of the beautiful and diverse substance off |
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| 04:15 | cells. So the video points should able. Thio show you all of |
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| 04:22 | lectures. I may still experience an with one lecture. I'm not sure |
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| 04:31 | it is in your class or another , so we'll try to solve all |
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| 04:36 | them to make sure that all of are completely functional. Okay, Last |
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| 04:44 | . We emphasize that there are very subsets of neurons in the brain. |
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| 04:51 | talked about the fact that when you in the hippocampus, there is 21 |
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| 04:56 | subtypes of the inhibitory cells that are inhibitory cells that inhibit activity of these |
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| 05:03 | Torrey cells and these air excited or cells which project out of the hippocampus |
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| 05:10 | the distal regions off the hippocampus or of the hippocampus altogether. and we |
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| 05:16 | that Teoh definitively determine what sub type cell it is, for example, |
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| 05:23 | some type of cell you're studying in this case performing electro physiological recordings |
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| 05:30 | or other types off experiments. What have to know is you have to |
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| 05:36 | the location of these cells. You identify them using infrared differential contrast |
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| 05:43 | You can use electric physiological electrodes and physiological recordings. Thio detect the action |
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| 05:52 | and the patterns of action potentials that cells produce as you stimulate them. |
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| 05:59 | these electrical electrodes, these glass electrodes passed the currents into the south. |
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| 06:05 | also have to reconstruct the morphology or anatomy of the South Soma location and |
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| 06:12 | pretty projections in this diagram of cartoon showed that done brides and black and |
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| 06:18 | and white as well as external Finally, you have to cross stain |
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| 06:23 | with self specific markers, which could different types of molecules that are expressed |
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| 06:32 | by these different subsets off cells to diversity in the brain way Discuss. |
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| 06:41 | is sort of like a dialect. language is the language of action potential |
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| 06:47 | deep polarization, where each action It's sort of like a digital code |
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| 06:53 | of course it's Ah, it's a that gets created not by, |
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| 06:58 | by different dialects, but in the , for the networks to be active |
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| 07:02 | the networks to the meaningful. A of these cells inhibitory cells and excited |
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| 07:08 | cells that have thio produce not just , but they have to sing songs |
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| 07:14 | have to harmonize. They have to . They have to speak at the |
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| 07:22 | time, to be heard effectively or excited Torrey cells effectively and thereby creating |
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| 07:30 | we already discussed from the very beginning these excited, touring, inhibitory network |
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| 07:37 | and these oscillations that result in what call brain rhythms of brain with the |
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| 07:43 | that is essentially representation of different behavior different emotions in different paradigms off our |
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| 07:50 | activity, such as learning memory and encoding. So when we moved on |
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| 07:58 | glia, we talked about the the two disorders. But then we |
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| 08:03 | to the to the slide and we reviewing the glial cells. So I'd |
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| 08:07 | Thio also, um, share that now, for example, if if |
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| 08:14 | go thio so if you go to , uh, blackboard supporting class lecture |
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| 08:26 | folder. You will see some activated there and some of the key important |
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| 08:36 | that we've discussed. Last lecture, example, This is, ah, |
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| 08:42 | off radial glial cell on what it is that neuron is this little egg |
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| 08:51 | like looking structure that is slowly migrating this glial lattice. It's almost like |
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| 08:59 | little ladder. Now the neuron Continuity Side applies with continuity with this |
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| 09:06 | glial cells. So this line, the slightest, is the radio glial |
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| 09:13 | that provides the latter on a pathway the road to the final destination. |
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| 09:17 | this neuron, there's only two special in the brain for more than |
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| 09:24 | but mostly to special places in the . Zones where neurons new neurons are |
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| 09:30 | are born, and from there they to migrate to populate different parts of |
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| 09:35 | brain. Like we discussed that, neuron has to find that it's, |
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| 09:40 | , city. It's neighborhood, it's , it's mailbox, and it's correct |
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| 09:47 | or apartment within the house where it this particular function. So this is |
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| 09:54 | , um, illustration of how neuron use radio glial cells to migrate |
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| 10:04 | There is another neuron all chain migration illustrates many neurons migrating at the same |
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| 10:15 | . Yes, you can see again form cytoplasmic continuity and use the glial |
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| 10:23 | almost like branches. Thio traverse across brain, the developing brain tissues into |
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| 10:33 | final destinations. So you will find lengths now available, uh, than |
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| 10:41 | folder We talked about how micro glial are very dynamic on DWI. Talked |
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| 10:50 | the fact that micro glial cells if I could just get a confirmation |
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| 11:00 | you're seeing the movie, says, showing them. I would appreciate that |
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| 11:05 | the chat. When you're looking at this video is the following is this |
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| 11:24 | this bright wide spot that gets forum there's a time lapse video on this |
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| 11:31 | bright spot is an actual injury onto brain tissue and illuminated or glowing are |
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| 11:40 | glial cells and their processes. And you will see is that as the |
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| 11:46 | gets injured, statistic gets injured. have micro glial processes, extend an |
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| 11:54 | soma start moving in within hours, meters within hours toward decided the injury |
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| 12:04 | they're taking care of the debris off cleaning up a swell as mediating inflammatory |
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| 12:11 | through side of time release and mediation side of kind release. Alright, |
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| 12:20 | again you will. You will find movies on that same folder or the |
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| 12:26 | to these movies is there are some According So we talked about it. |
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| 12:33 | go down the sides their role in elimination and de Milo nation and the |
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| 12:41 | . N s multiple sclerosis would be loss off good undersides essentially and we |
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| 12:51 | talked about we all cells. We about Astra sites that we said that |
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| 12:59 | are responsible for mediating synaptic transmission from and modulating the cleanup. Where there |
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| 13:09 | increases local increases in ionic concentrations in synapses such as potassium or calcium, |
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| 13:17 | could be detrimental. Thio the living to neuronal tissues and Astra sites have |
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| 13:24 | complex, far reaching processes and interconnected where they can siphon off thes large |
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| 13:34 | concentrations of ions through their network through interconnected network. By essentially eliminating the |
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| 13:43 | spots of these concentrations of ions or chemicals, elements in the synapses now |
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| 13:51 | . Um, all cells we discuss also be potentially cells that are stem |
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| 14:00 | stem like cells is, uh, enough that we know about it, |
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| 14:06 | we're also, as I mentioned, finding out that adult issue does have |
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| 14:11 | cells. It's a question whether we're the ability for stem cells to be |
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| 14:17 | polluted, potent going dormant, or we're actually losing the number of stem |
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| 14:23 | that we have as the brain is . So it z partly up to |
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| 14:32 | debate, I would say, and blood brain barrier and what you're seeing |
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| 14:38 | a blood brain barrier is essentially if you can think of it as |
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| 14:42 | very complex filter. There's a filter decide what passes between the brain tissue |
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| 14:50 | the blood and the blood and the tissue. But blood brain barrier blood |
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| 14:55 | a lot of different elements and supplies brain with nutrients and supplies the brain |
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| 15:00 | oxygen neuron, especially a very, sensitive to oxygen law. So when |
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| 15:07 | talk about hypoxia again, which is , Thio Cove it 19 we basically |
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| 15:14 | to remind ourselves that loss of oxygenation the brain for 2 to 5 |
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| 15:20 | I'm not talking about decreased of oxygenation you cannot inhale through the lungs properly |
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| 15:27 | you don't have the enough oxygen saturated in the bloodstream. But you cannot |
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| 15:35 | . You get cut off completely from for two minutes or longer. That |
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| 15:41 | actually have a reversible damage to parts certain sensitive parts off the brain. |
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| 15:46 | the longer the time period. Lots two minutes. Let's say if |
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| 15:51 | um has an unfortunate event of a or so in their heart stops. |
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| 15:58 | that oxygenation on circulation in the brain not rebuild within minutes, then the |
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| 16:07 | could be hugely hugely detrimental. So brain varia is comprised of under Ferial |
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| 16:15 | You know, vessels essentially, that tight junctions that already don't let stuff |
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| 16:21 | through very easily there surrounded by And they have Astra glial processes, |
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| 16:27 | Astra side processes that are wrapped around would be like basement membrane as the |
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| 16:35 | policing station for the substances to pass the prey. What we talked about |
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| 16:41 | that it's a good thing, but also a challenge, a challenge because |
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| 16:47 | if you especially a designing neuro logical nure owed drugs for neurological dysfunction such |
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| 16:58 | epilepsy, such as Alzheimer's disease, as depression, post traumatic stress |
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| 17:06 | If you designing neuro drugs. If targeting the brain, most of the |
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| 17:12 | that are on the market come in form of a pill, and you |
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| 17:17 | that pill in that pill. Get . It gets started, digest being |
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| 17:23 | by the gastric juices in your stomach then once part of it gets broken |
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| 17:31 | and enters into the intestines and gets into the blood stream. It's only |
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| 17:38 | fraction off the active elements that you into that pill, and it really |
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| 17:43 | depends on the quality and the preparation they it's micro encapsulated whether it's not |
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| 17:49 | particularized pill, whether it's, envelope for Thio to prevent the degradation |
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| 17:55 | assets, all of these centric intricacies into the product development for the |
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| 18:01 | But from our perspective, once you the pill on Lee, a fraction |
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| 18:05 | that active ingredient gets into the Now it is in the bloodstream, |
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| 18:11 | it is in Europe. Intestinal digestive tracks, so for it to get |
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| 18:19 | the blood from there into the only a fraction of it is gonna |
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| 18:23 | up and pass into the relevant parts the brain and only a fraction of |
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| 18:29 | if it is not very easily blood barrier soluble. So anything that passes |
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| 18:38 | blood brain barrier, anything that is soluble that would penetrate through the blood |
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| 18:43 | barrier anything that would attached to one the existing known transporters that could be |
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| 18:51 | up easily is gonna have an Otherwise, you have to take high |
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| 18:57 | off some of the drugs and the are that you experience side effects. |
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| 19:04 | lot of times these side effects have to do with the central nervous system |
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| 19:10 | with a disorder. So let's say taking an O. P. |
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| 19:14 | It's very common. We have an epidemic, not just coded 19 |
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| 19:20 | We also have opiate epidemic where we thousands of people dying from overdoses and |
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| 19:27 | , and the reason for it is opiate receptors affect the vital centers in |
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| 19:34 | brain of control. The vital functions such as breathing and heart trade and |
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| 19:39 | effective does is very small. For like this, few milligrams mortal does |
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| 19:46 | deadly does is just three or four sometimes five or 10 times, sometimes |
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| 19:52 | few times of the effective those so . Then, by controlling this breathing |
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| 19:57 | heart rate, centers are really are control off your faith There. Now |
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| 20:04 | opiates, what happens is that you often get constipation constipated. And |
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| 20:13 | if you look, there's actual There's another drug that is the basically |
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| 20:21 | constipation that is specifically produced by So now we have another drug that |
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| 20:27 | treating a peripheral problem. That is side effect that is created by the |
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| 20:33 | drug that is supposed to be treating your your your your your pain and |
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| 20:41 | perception, which a lot of pain comes from, you know, activating |
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| 20:46 | nerves, activating the opiate receptors in nervous system. So this is just |
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| 20:52 | Zen example where it's a. It's very fine line between designing drugs that |
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| 20:59 | the brain that are penetrable through through brain barrier that don't require high concentrations |
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| 21:06 | have low side effect on but maybe thio specific cell. This is really |
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| 21:15 | future of the drugs that we want target. Specific cells were already |
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| 21:19 | Specific cancer cells want to target specific subtypes. Now that would be |
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| 21:25 | very interesting little cells and specific subtypes inhibitory cells. Somehow with drugs that |
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| 21:31 | effective would be terrific. And I that learning from from nature is always |
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| 21:37 | . Because plant based medicines existed for long time and thinking that food is |
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| 21:45 | , what your intake goes into, God goes into your blood, some |
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| 21:48 | the classes into your brain. It sense that there is a very tight |
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| 21:54 | , actually, between our gut and brain is called the gut brain axis |
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| 22:00 | a system that we're not studying This car, of course, is |
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| 22:03 | Mess and Eric System. And that's system in the periphery that lines with |
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| 22:10 | the whole digestive system. And it's that has almost brain on its |
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| 22:16 | Um, complex city is as complex the central nervous system, and so |
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| 22:22 | Terek or Mesen Terek nervous system interacts the central nervous system. That's a |
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| 22:28 | brain axis, and in the you also have a lot of things |
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| 22:33 | live in there. It's called the , so you carry um, billions |
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| 22:41 | different microorganisms inside the whole digestive system now interacts with your enteric system that |
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| 22:49 | also has a connection to your And this is something that your scientists |
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| 22:55 | mawr interested in and looking into the between the gut in the brain, |
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| 23:00 | intake of the foods, the intake supplements and medicines and the fact that |
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| 23:05 | on the body and the brain is whole. All right, we're gonna |
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| 23:11 | a little pause here. Resume neuronal addressed or a lot of times the |
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| 23:18 | membrane potential is going to be the today, essentially, what you |
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| 23:25 | an illustration is on the left that you take a micro electrode and that |
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| 23:30 | electrode is connected to a volt meter an amplifier that is grounded and assumes |
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| 23:38 | the ground is equal to zero there's no charge in the ground. |
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| 23:44 | if you stick an electrode across or the plasma member and off the |
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| 23:50 | what you have immediately on the Volt is a change to minus 65 minus |
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| 23:57 | minus 75 mil levels, depending on neuron that you're recording Thio and this |
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| 24:04 | is referred thio as resting membrane This is when you're on is resting |
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| 24:11 | this mind of 65 million volts is by uneven distribution of charge and the |
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| 24:17 | charge accumulated on the side. The Mick inside side off the neuron and |
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| 24:22 | positive side Positive charge accumulating on the cellular side of the membrane. |
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| 24:30 | I don't see this lecture on the board. See, this should be |
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| 24:40 | let me thought so. Action potential different from resting member and potential act |
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| 24:50 | potential. Is this very quick blip very, very quick change Vertical change |
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| 24:58 | amplitude and they're quick change off charge plasma membrane from resting membrane potential minus |
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| 25:07 | months 72 about positive 20 positive, million volts and returned back to the |
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| 25:14 | member and potential over sometimes. And the whole action as we talk about |
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| 25:20 | potential Later, after we discussed the member of potential, the whole action |
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| 25:26 | the action potential occurs in the cell on. We do need thes very |
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| 25:33 | blips. These very quick changes in member and potential thio react very quickly |
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| 25:40 | the environment. And some of these are reflexive. So let's discuss the |
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| 25:49 | . And let's now try Thio remind what we know about what we've already |
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| 25:56 | about the circuit within the contact A re flag, Sarge. So |
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| 26:04 | the reflex arch, which is, , it's the simplest kind of reflex |
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| 26:10 | . Actually, that goes between you me and the spinal cord and back |
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| 26:15 | the muscles in your leg. And lot of times the stock gets activated |
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| 26:22 | gets tested in the doctor's office. when you do your annual exam, |
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| 26:30 | up or if you're having some issues some pain or some numbness in your |
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| 26:36 | or foot or otherwise, a doctor sit you down and we'll take a |
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| 26:43 | knowledge. And with that, now it will stimulate, or it will |
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| 26:51 | . Tap onto your attendant onto your tendon. So the response and normal |
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| 27:00 | under tap is that reflexively without you or with you even trying to control |
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| 27:07 | , your leg will move forward. we'll jump forward so once. Once |
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| 27:13 | gets a hit, it will move like that. Okay, now what |
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| 27:19 | that mean? Well, it Actually, it's a reflexive behavior that |
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| 27:26 | mediated by a circuit that once it stimulated and the muscle spindle and the |
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| 27:35 | or the extensive muscle picks up that stimulus and the sensory after Aaron, |
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| 27:45 | is a part of the dorsal root cell through its peripheral Axiron. Because |
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| 27:55 | you remember dorsal root ganglion cell is pseudo unit polar cell. It has |
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| 28:04 | uh, two polls, so it's pseudo unit polar. It has this |
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| 28:09 | accent that it will, from muscle will carry information into the so most |
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| 28:15 | the censoring neuron. So so much were located in the ganglion, which |
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| 28:20 | right outside of the spinal cord And that sensor information that's process partly |
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| 28:28 | the summer will then be carried by central acts on into the spinal cord |
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| 28:37 | in the spinal cord proper. You see that there is by for |
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| 28:42 | There is a split of this ax one of these accents. Will contact |
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| 28:48 | Red Cell, the cell illustrated and . And that's motor neuron. |
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| 28:55 | motor neuron Well produce activity that will back, and it will tell this |
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| 29:09 | extensive muscle to contract. When the extends her muscle contracts, it moves |
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| 29:19 | tendon and it moves the leg. leg below the knee upwards in the |
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| 29:29 | motion. Okay, So, if you wanted to contract this quadriceps |
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| 29:37 | muscle, it's enough to just go one synapse. The censoring or |
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| 29:45 | What I would like for you to you already have a column for |
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| 29:51 | uh, neurological disorders or you have pages that you reserved for your neurological |
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| 29:58 | . What I would like for you dio is actually to make a table |
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| 30:06 | dorsal root ganglion on motor neuron Other cells that we talked about, |
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| 30:17 | example, parameter all cells. And talked about Interneuron. So if you |
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| 30:31 | something like this, then underneath each of these, okay, you sort |
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| 30:38 | like, make a column, underneath each one of these. And |
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| 30:45 | have to know the following information. is the dorsal root ganglion cell? |
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| 30:51 | type of cell is a morphological in , you put pseudo unit polar. |
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| 31:01 | is so much located in the in ganglion Outside support spinal cord DRG. |
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| 31:09 | what's so much are located. It's real Donald information. When dorsal root |
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| 31:17 | gets activated, what neurotransmitter does it to activate motor neuron. Does anybody |
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| 31:28 | that answer? Are you showing the on a different screen, or are |
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| 31:32 | just, um oh, you cynical? Um eso somebody who's not |
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| 31:47 | that I'm showing. I'm not sure showing the table on the little screen |
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| 31:52 | you're not seeing the little screen. , I'm not able. You're not |
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| 31:58 | me in a little screen at No, it shows. I think |
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| 32:02 | just not very easy to see. in his video. You can expand |
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| 32:07 | the picture of this thing if you . Yeah, you know. Thank |
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| 32:11 | . Yeah, I just did something this. Yeah. Thank you. |
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| 32:15 | problem. So so now. No, But the good guess that's |
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| 32:20 | Kohli no. So dorsal root ganglion will excite motor neurons, The exciting |
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| 32:27 | cells, but they'll actually release a . Eight. Okay. Now, |
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| 32:35 | they excite motor neurons, what kind a morphological li cel iss motor neuron |
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| 32:43 | It's pseudo unit. Polar cell? , it's multipolar cell. And when |
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| 32:52 | neuron contacts Ah, the muscle. a top coal and coal is the |
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| 33:03 | that it releases. Okay. And muscle will contract upon the release of |
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| 33:11 | Tal Colin. So just through this synapse, you can have the contraction |
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| 33:16 | quadriceps muscle. So sensory apparent information is the is the mallet on your |
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| 33:25 | , Sensory after neuron is the dorsal ganglion pseudo una polo neuron, which |
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| 33:31 | glutamate onto motor neuron that can then processing in the C. N s |
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| 33:39 | within the spinal cord information processing, C N s and then activation of |
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| 33:46 | motor neuron, which is e Farrant and carries information into the central nervous |
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| 33:52 | into the spinal cord proper. And Farrant is the information exiting from the |
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| 33:58 | neuron back into the periphery into the , telling the muscle to contract. |
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| 34:08 | , I think somebody raised their hand I may may have missed it. |
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| 34:13 | , I'm sorry. Um, did want to try it again? |
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| 34:19 | I have. Ah, I just a quick question. So, |
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| 34:22 | isn't glutamate typically in the CNS? why would the firing be with glutamate |
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| 34:29 | it's a peripheral movement? Oh, a very good question. This is |
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| 34:40 | This is the neurotransmitter that the cells and and release. So this is |
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| 34:50 | what they code for now. It's very good question because I think maybe |
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| 34:56 | you're getting at, because if you glued innate in the periphery, do |
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| 35:02 | also have Gabba as the inhibitory And this is where the things that |
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| 35:08 | you actually have glide seen as inhibitory . So this leads me. This |
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| 35:15 | leads me on to the fact that order for this reflex to be effective |
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| 35:20 | order for the quadriceps, extensive muscle effectively contract, what has to happen |
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| 35:27 | the opposing muscle, which is the muscle the hamstring muscle has to |
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| 35:34 | Now is during this pathway, when neuron by for Cade's it first activates |
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| 35:40 | motor neuron that tells extensive muscle to . But at the same time, |
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| 35:47 | also activates inhibitory Interneuron with thin the cord. So you see this black |
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| 35:57 | . This is the inhibitory Interneuron within spinal cord. It's also a multipolar |
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| 36:05 | , and it releases glisten. Glisten inhibitory neurotransmitter, and what glisten dies |
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| 36:13 | inhibits this motor neuron, the targets flexor muscle and by inhibiting that modern |
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| 36:22 | , it allows for that flexor muscle relax properly and for that jerk reflex |
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| 36:28 | stretch or patella tendon interchangeably. It's for that hotel attendant reflects to show |
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| 36:35 | proper movement off the lower leg. , now you can imagine that when |
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| 36:43 | or general and these looking at this there is thinking several things. Let's |
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| 36:52 | I will ask you a question. if you have a situation where a |
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| 37:02 | takes a mallets and taps the knee there's no response? So he taps |
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| 37:10 | knee stronger and there's no response, then he has to tap. Then |
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| 37:17 | really, really strong. And then sees very little response. What could |
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| 37:24 | wrong in this situation he inherited. , you're saying Interneuron, So your |
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| 37:36 | would be that you're you're the sensor is is reacting, but the Interneuron |
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| 37:47 | somehow stopping it from moving. So saying that you have too much inhibition |
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| 37:52 | somehow stopping it so that that's a That's kind of a good, good |
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| 37:58 | , but one thing to know that now you added an additional synapse here |
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| 38:05 | Interneuron. So there's a slight little delay off probably 10 15 milliseconds for |
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| 38:17 | inhibitory signal that lags excited. Terry . In other words, when the |
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| 38:24 | Nuri is activated, the quadriceps muscle start contracting a few milliseconds before hamstring |
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| 38:32 | is fairly relaxed. Mhm In that , I'm not a neurologist, but |
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| 38:39 | would say that that that is a . But I would also say that |
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| 38:45 | is a possibility that censoring neuron, something wrong with censoring. Or maybe |
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| 38:51 | is, uh, lack of glutamate . So you have to really have |
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| 38:58 | very strong stimulus in order for the to get released. Eso You know |
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| 39:07 | this This is a very simple circuit really we're comparing the simple amount of |
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| 39:13 | circuits and still a simple there's even the simple circuit, even for the |
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| 39:21 | optic circuit that correct and proper contraction quadriceps extensive muscle. You need even |
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| 39:29 | synapses than that. You need activation inhibitory neurons and you need relaxation of |
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| 39:34 | flexor muscle so you can have activation a muscle through a single synapse sensory |
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| 39:41 | motor. But for it to be effective, you have to involve on |
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| 39:45 | synopsis. And then when you talk complex reflexes, this is a very |
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| 39:49 | circuit complex reflexes such as gag let's say, or vomiting reflex. |
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| 39:57 | , that involves very complex cells and and several different parts of the brain |
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| 40:05 | networks involved, as well as uh, potentially, uh, sympathetic |
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| 40:12 | apparent sympathetic. Both nervous systems, , much more complex and much more |
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| 40:19 | synaptic. But just by looking at circuit now, you should be able |
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| 40:22 | identify three types of cells what type morphology they have and what type of |
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| 40:29 | their release and then eso motor neurons neurons. Um, uh, end |
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| 40:40 | root ganglia themselves. And if you yourselves about the parameter Selves So we |
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| 40:45 | about the hippocampus, they also released excited or glutamate, and the inhibitor |
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| 40:51 | . So we talked about in hippocampus in the cortex as well. Inhibitor |
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| 40:57 | Norris released Gabba in the CNS, is gamma mu no material. Cassidy |
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| 41:03 | then the spinal cord. It is eso. How does this membrane potential |
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| 41:10 | created or address so that it can this action potential. So again, |
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| 41:17 | here is not only to remind you sows involved to start talking about the |
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| 41:22 | , but to tell you that you something that will be very fast and |
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| 41:27 | . Therefore, you need action So let's understand the resting number and |
|
| 41:31 | before we move into the action. addressed the cast of chemicals. It's |
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| 41:38 | water. Oxygen attracts extra electrons and negative charge Very basic stuff. Hydrogen |
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| 41:45 | the net positive charge held by Covalin . Other polar molecules dissolved in |
|
| 41:51 | So essentially we have chloride and we sodium ions and we have calcium. |
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| 41:59 | we have all of these signs that surrounded by what we call water molecules |
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| 42:06 | sometimes clouds or waters of hydration, and molecules that have ah, you |
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| 42:12 | , net electrical charge, sodium plus chloride minus juan on you have ah |
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| 42:22 | C, which is a difference in and electrons. Uh, and a |
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| 42:28 | See a two plus calcium two plus Valin versus Dive Allen Cat ion positive |
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| 42:34 | an ion negative ion plasma membrane. you look at the plasma membrane, |
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| 42:40 | a false Philip it bile air and phosphor lipid Byler that allows for essentially |
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| 42:47 | distribution off charge across plasma membrane. what it shows here in this diagram |
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| 42:57 | on the left is a cartoon off off the plasma membrane on the |
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| 43:01 | You have, ah, measurement off off the electrical potential, and it |
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| 43:08 | that across plasma membrane, the resting potential ranges anywhere between 60 to minus |
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| 43:15 | million volts. Again, uh, cells may even have a slow of |
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| 43:20 | member of potential is minus 55 others low are as high as minus 65 |
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| 43:29 | is low or more polarized. A minus 80 and glial cells neurons is |
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| 43:36 | 70 minus 75 glial cells. They're . Membrane potential is of minus 90 |
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| 43:43 | levels in minus 90 million miles. is neuron, so we're talking about |
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| 43:50 | . It shows the four predominant Ionic Sodium Channel potassium channel, Claure Channel |
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| 43:57 | channel. It also shows an 80 ace and a k a T p |
|
| 44:04 | . Sodium potassium. 80 p pump channels act sort of our chemical diffusion |
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| 44:13 | the chemical diffusion model down the radiant the channels open. You have a |
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| 44:18 | of sodium on the outside of the . In parenthesis, 1 45 stands |
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| 44:24 | 1 45 million Moeller, so 1 million sodium On the outside of the |
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| 44:31 | , on inside of the cell, have 18 Miller Mahler sodium. Approximately |
|
| 44:38 | . These concentrations will also slightly vary different subtypes of different neurons. |
|
| 44:46 | then, if we look at potassium the outside and the parenthesis is about |
|
| 44:51 | million Mueller potassium On the inside side plastic intracellular side, there's 135 million |
|
| 44:58 | of potassium chloride. You have seven the inside, and on the outside |
|
| 45:04 | have 120 million bone calcium. You 0.1 Micro Mueller on the inside. |
|
| 45:14 | is not that much free floating side all. The calcium, most of |
|
| 45:19 | calcium, the stored in the intracellular stores, most of the calcium is |
|
| 45:24 | up by calcium buffering calcium binding It's about 0.1 micro Mueller inside the |
|
| 45:33 | of calcium, and on the outside 1.2 mil. E. More |
|
| 45:41 | with the exception of calcium on the of the cell, everything here in |
|
| 45:46 | . Miller, Mueller and Calcium with . Um, it's micro mauler on |
|
| 45:56 | inside and Mila mauler on the Okay, so why is this |
|
| 46:06 | Well, it's important for the following . First of all, the A |
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| 46:12 | solution on the outside of the cell mostly sodium chloride. A salty solution |
|
| 46:18 | the inside of the cell is dominated protection. The other thing is that |
|
| 46:24 | biggest discrepancy in the concentration the biggest in the Ionic concentration, actually exists |
|
| 46:31 | council because 0.1 micro Mahler is 10 the negative. Six versus Mila Mahler |
|
| 46:40 | 10 to the negative three. So have a big discrepancy of the concentration |
|
| 46:46 | calcium on the outside versus the There's a very strong chemical Grady in |
|
| 46:52 | Grady Int that would drive calcium to inside the South Janek council, utilize |
|
| 46:58 | teepee well, converting DP into di a. D P. And will |
|
| 47:06 | transport ions against their concentration. Radiant sodium will be transported from inside of |
|
| 47:14 | cytoplasm to the outside, despite the that there's a lot more of sodium |
|
| 47:19 | the outside of the cell and Despite the fact that there's a lot |
|
| 47:24 | potassium on the inside of the side Lasmo of the neuron, potassium with |
|
| 47:29 | pump and the energy from the TP be transported inside the Selves and re |
|
| 47:37 | and maintaining this concentration. Grady Int concentration, radiant and uneven distribution off |
|
| 47:45 | across plasma membrane. So these are of the basic reminders off. I |
|
| 47:53 | our assets, with the fact that ourselves that we have a central, |
|
| 48:01 | essential amino acids. Amino acids are building blocks that combine into change through |
|
| 48:11 | Thai bonds that then can fold themselves sheets that can twist themselves, |
|
| 48:20 | and form very complex structure. So individual amino assets, you can form |
|
| 48:29 | structures. Thes helical, thes amino lines can be laid in sheets that |
|
| 48:35 | be twisted into hell. Icis and helix of amino acids can start comprising |
|
| 48:43 | trans membrane segment, a single trans segment as a shown here on the |
|
| 48:52 | and this channel here, for has 123 for five sub units, |
|
| 49:02 | each one of these subunits is comprised four trans membrane segments, and each |
|
| 49:09 | of these segments is these Alfa helix that air made off these amino acid |
|
| 49:20 | being built through the through the left bonds polyta peptides. So you have |
|
| 49:27 | secondary tertiary structures and finally, Rick structure, which is a combination off |
|
| 49:34 | thats of units coming together and forming is illustrated in this case as a |
|
| 49:40 | membrane channel. Yeah, this is those trans memory channels appear on |
|
| 49:48 | Uh, Ionic channels are not So, Janek, channels are not |
|
| 49:54 | to just pass the Electra any any . Based on the concentration, there |
|
| 50:03 | quite a significant channel. Selectivity. can think of bionic Channel selectivity as |
|
| 50:12 | sort of ah, chemical and molecular that happens within the channel. So |
|
| 50:19 | is illustrated on the right is the loom, Um, off this trans |
|
| 50:28 | channel at the bottom. So you the sodium channel particularly illustrated here, |
|
| 50:35 | we're zooming in on the very inside of this channel. And there's a |
|
| 50:41 | solution even inside the channel itself off pro dam and you have sodium ion |
|
| 50:50 | of surrounded by water molecules and then most narrow part of this channel. |
|
| 50:57 | we call the innermost bloomin. Off channel, you have amino acid residues |
|
| 51:05 | have maintained and are exposing a certain this sodium channel will contain in the |
|
| 51:14 | in and negatively charged amino acid residue I mean no acid residue. The |
|
| 51:21 | space itself, the physical construction and channel is going to start stripping the |
|
| 51:28 | miles off the water. Some There will be very quick interaction and |
|
| 51:36 | sort of a propulsion that happens from negatively charged amino acid residue that will |
|
| 51:44 | and propel facility. Um, on on from the inside onto the |
|
| 51:50 | limit of the channel, would get by water. So hydration by h |
|
| 51:55 | molecules and passes on to the cytoplasmic side of the off the neuron. |
|
| 52:03 | this is very, very quick interaction is driven by diffusion all forces. |
|
| 52:11 | there is also very quick sort of electrostatic interaction very quick electrical interaction with |
|
| 52:16 | acid residues that allow for this channel be selected for sodium. If we |
|
| 52:24 | neuromuscular junction and we look at that coal and release on a muscle singular |
|
| 52:33 | alcohol and receptor has an eye equal million ions a second. What? |
|
| 52:40 | means I stands for current as in equals ir in alms law. So |
|
| 52:47 | conducts ah, 100 million ions per . It's a towel Colin Receptors and |
|
| 52:56 | Junction. Neuromuscular Junction is the junction nerve from the spinal commercial motor nerve |
|
| 53:06 | muscle, such as a quadriceps Uh, in contrast, an a |
|
| 53:13 | a. T p palm can deliver about 100 I on the second. |
|
| 53:19 | those air, they're slow operating and they will be contributing to slow |
|
| 53:25 | is and slowly rebuilding the member and . In this case, resting memory |
|
| 53:32 | are selected bionic shoulders so they selectively will select for sodium will select for |
|
| 53:40 | , will select for calcium, sodium is illustrated here, is stripped of |
|
| 53:47 | waters of hydration by in part by acid residues and enters in but larger |
|
| 53:55 | . Potassium is trapped and sent back . That statement means that obviously, |
|
| 54:03 | matters that if a an I honest large thio pet uh, smaller ions |
|
| 54:13 | ions that are interacting with the specific acid residue are going to be propelled |
|
| 54:21 | . Does that mean that potassium the larger so it has, um, |
|
| 54:31 | larger channel? Luminant passes through. does that mean that sodium, which |
|
| 54:38 | smaller in diameter, can pass through channels? So first of all. |
|
| 54:45 | we're learning in the course is about that are selected to the ions right |
|
| 54:51 | , with sodium to the potassium. are protean channels that allow the passage |
|
| 54:56 | multiple lines. So do you potassium calcium, such as glutamate receptor protein |
|
| 55:03 | . But in this case, it's something to think about it. So |
|
| 55:08 | you have a larger potassium channel, diving on what happens, that means |
|
| 55:13 | arms could go through again. That's that simple. Um, the smaller |
|
| 55:20 | diameter, the larger the waters of . Actually, so it's not. |
|
| 55:26 | not that simple, but there is to do with the size, and |
|
| 55:30 | of these rules do get broken, in very heightened levels of activity when |
|
| 55:39 | says any enters inside. Is this http starts working goblins inhibitor and |
|
| 55:47 | And that's the real licenses inhibitory in spinal cord, indeed. And it |
|
| 55:52 | in a enters inside Is this before teepee starts? Yes, its's before |
|
| 55:57 | is entering through the channel. So would be first the fact before the |
|
| 56:03 | would be in part rebelled by the p pomp. All right, now |
|
| 56:09 | onto reminding ourselves that we have to some basic concepts remind ourselves from basic |
|
| 56:15 | concepts and electrical concept arms law. , yeah. Arms law, the |
|
| 56:24 | I R. What does that stand ? The is voltage bolt and in |
|
| 56:32 | cells, neurons, the scales that relevant, our Miller vault. So |
|
| 56:38 | potentials that are measured as in you can see are measured in Miller |
|
| 56:44 | minus 65 a. M. The for Milly Volt. Okay, that's |
|
| 56:52 | minus 65 these tents for Miller These air relevant scales for us when |
|
| 56:58 | talk about neurons eyes current, which measured in amperes. And for |
|
| 57:06 | it's, uh, Nano and Paris million pairs thes air, the scales |
|
| 57:12 | neurons and relevant to neurons. Our for resistance resistance is measured in homes |
|
| 57:21 | cells have very high resistance, which measured in hundreds typically off mega owns |
|
| 57:30 | owns 1000 homes. G is the INTs which is measured in cements. |
|
| 57:43 | it's for us. It's nano and seaman's that are important for conductors of |
|
| 57:49 | channels or individual neurons with such so equals. I R G is the |
|
| 57:57 | off resistance. So okay, The the resistance, the smaller the conduct |
|
| 58:10 | . And then you can rewrite arms . I equals GV. Everybody can |
|
| 58:17 | that. So if you don't remember very well, that this seems to |
|
| 58:24 | confusing part that doesn't belong Thio your minds. There's no such thing as |
|
| 58:31 | part. There's no such thing as minds. This is neuroscience Ionic movement |
|
| 58:38 | . We talked about very basic We can remind ourselves. We take |
|
| 58:43 | box and we put a membrane. is plasma membrane. Imagine around. |
|
| 58:47 | this box on one side of the will put a lot of sodium |
|
| 58:51 | Another side of the box is just a quickest solution. Water. There's |
|
| 58:56 | any ions, and there's no so there's no flow of violence across |
|
| 59:00 | . You add sodium chloride channels and chloride. If users goes down, |
|
| 59:07 | . Radiant diffuses diffusion refuses down Radiant drives islands through the channels until |
|
| 59:16 | equal amounts of sodium and see on sides on the left side. And |
|
| 59:20 | rights of the remembering is the same fluoride. That's it. So for |
|
| 59:24 | for Ionic movement here, that's not the case and that's not really what |
|
| 59:31 | in the brain. But this is is important to understanding. That's |
|
| 59:34 | We have electrical potential, of and we have voltage and voltage is |
|
| 59:40 | thing. So it's not just, , electrical current, but it's also |
|
| 59:45 | sorry not only the chemical radiant, also the voltage or electrical currents have |
|
| 59:51 | that influence the movement of member of across plasma membrane. So wolf Bage |
|
| 59:59 | ion through channels as well. We that chloride, which is an |
|
| 60:05 | is gonna be attracted by a The positive end of the battery and |
|
| 60:11 | ion sodium is gonna be attracted by negative and of the battery here. |
|
| 60:18 | , so it's not just concentration, just the concentration. How much of |
|
| 60:22 | island is in there? But also is the charge? What are the |
|
| 60:27 | attractors? Uh, battery. How the battery across plasma membrane? So |
|
| 60:33 | of charge across the membrane gives rise difference in electrical potential. The fact |
|
| 60:40 | you have all this positive charge buildup the outside of the membrane and negative |
|
| 60:44 | the inside of the membrane. The both on the inside versus V out |
|
| 60:50 | that electrons inside the cell gives you difference, and that difference is 65 |
|
| 60:56 | volts. Gives you the V which is membrane potential. The M |
|
| 61:02 | the membrane stands for membrane potential, trust number in potential. The rest |
|
| 61:09 | equal. What you're recording internally The N, which is minus 65 |
|
| 61:15 | holes. Basic concept. To remind , set current flows Direction of net |
|
| 61:22 | of positive charge therefore, and ions opposite to current direction. Catanese move |
|
| 61:28 | current direction when you're tracing the current . But when you're doing all of |
|
| 61:34 | different recordings, there's a bit about on how you read electric physiological traces |
|
| 61:41 | as faras the directionality of the current or down positive or negative interpretation of |
|
| 61:48 | positive or negative reduction in charge. is deep polarization. So the more |
|
| 61:55 | separation there is, the more hyper there is across plasma membrane. And |
|
| 62:01 | this negative charge escapes out and inside the cell becomes less negative than the |
|
| 62:07 | , deep polarizes Ah, that means the cell the inside of the cell |
|
| 62:14 | is less polarized compared to the outside the south. Each ion in each |
|
| 62:25 | has an equilibrium potential that will Librium . Here is now that as e |
|
| 62:33 | equilibrium potential is exactly the interaction between chemical forces and electrical forces that we |
|
| 62:42 | that you have diffusion alone and electrical where you have a Colombian potential are |
|
| 62:52 | an opposite to each other. And no non ionic movement. So you |
|
| 63:00 | in the first case just by simple fusion. If you have plus minus |
|
| 63:07 | minus equal amount what it shows you diagram on the on the bottom in |
|
| 63:13 | middle of the screen. It shows that the sides of Saul, the |
|
| 63:20 | of the side of Saul on the experts element of fluids are neutral in |
|
| 63:26 | , and the charge separation is really across plasma membrane. Negative charge concentrated |
|
| 63:31 | the inside positive charge on the outside the plasma membrane. So if you |
|
| 63:38 | flexes off ions across plasma membrane, can cause voltage fluctuations. And because |
|
| 63:45 | channels can flux thousands and millions and per second, you have quite large |
|
| 63:54 | fast voltage fluctuations that happened across plasma and then milliseconds, such as action |
|
| 64:02 | . So you have net ionic difference exists only at the membrane. |
|
| 64:08 | And if you look at example on ride? Yeah, potassium ion on |
|
| 64:13 | inside of the cell. You have lot of potassium on this. A |
|
| 64:16 | charged us, uh, pro dance have negative charging the cannons, cross |
|
| 64:22 | member, another proteins in the outside so or some other ion for which |
|
| 64:27 | don't have a channel. Either you look at it came. |
|
| 64:30 | is the target here of the So you add a potassium channel. |
|
| 64:35 | happens is that you have a lot potassium on the inside is illustrated by |
|
| 64:40 | large cave and little of potassium on outside, as is illustrated by the |
|
| 64:45 | case. Now, when you have potassium channel, potassium will start long |
|
| 64:52 | the channel so this big potassium concentration be switching. Potassium will be flowing |
|
| 64:58 | the outside of the south from the because there's a lot of potassium |
|
| 65:02 | This a miner's does not. It not cannot cross the plasma members. |
|
| 65:08 | not affected. Now listen. What at some point, as potassium goes |
|
| 65:14 | inside of the salt of the outside the soldiers. Positive charge buildup from |
|
| 65:18 | same potassium on the outside of the membrane. That positive charge, the |
|
| 65:25 | charge becomes a repellent and electrical And despite the fact that there is |
|
| 65:31 | larger concentration on the potassium on the of the cell and still smaller concentration |
|
| 65:37 | the potassium on the outside of the now the combination off electrical charge pushing |
|
| 65:45 | and the change in chemical Grady int the net movement. So in this |
|
| 65:51 | , you reach an equilibrium potential. Ionic driving force is essentially it doesn't |
|
| 66:00 | exist because it's equal. It's it's and opposite to each other. So |
|
| 66:08 | we know the only concentrations, we calculate reversal potentials or equilibrium potentials. |
|
| 66:16 | will use this into change of equilibrium for Russell potentials for individual ions. |
|
| 66:22 | so we will pick up here for next lecture. Mhm. I want |
|
| 66:26 | say there's graduate students that I did have enough time to prepare with your |
|
| 66:32 | for today, so we will reschedule for the following week. I will |
|
| 66:37 | out another email. Um, if have any questions, please write to |
|
| 66:43 | over chat. Great. Good. is ahead of the learning curve |
|
| 67:03 | Fantastic. Great to see. it looks like you don't have any |
|
| 67:07 | again. A reminder. If you problems with Casa, virtually let me |
|
| 67:13 | ASAP. Number two, please. on the videos on blackboard to make |
|
| 67:20 | that you're seeing everything. Um, three. Uh, let's see. |
|
| 67:28 | number three? Wow. I guess continue this electoral material as we get |
|
| 67:36 | next week on Monday, Let me real quick. There's no office |
|
| 67:42 | The video points elections on video I will post that information on the |
|
| 67:47 | syllabus now. And I think we're to go. Okay. Fantastic. |
|
| 67:54 | a good, great the rest of week. And I will see you |
|
| 67:59 | week. Take |
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