| 00:02 | This is our third lecture on Wiring brain cellular Neuroscience. And in |
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| 00:11 | we started talking about this period, period of development, critical period of |
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| 00:21 | . And what I want you to of understand when we're looking at these |
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| 00:27 | here, I hope everybody understands that dominance columns, the way that the |
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| 00:33 | , the way that you can deprive , monocular deprivation, you can restructure |
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| 00:40 | cortex, we can reorganize the inputs are coming from thalamus into cortex. |
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| 00:46 | you can ship that dominance with short a little bit with longer deprivation. |
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| 00:52 | can shift it a lot completely to the other is not available. It's |
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| 01:00 | good. So missing means that the is not responsive to that t any |
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| 01:06 | at all. So we know that this sweet spot here, this window |
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| 01:12 | which there is plasticity in which there recovery. But with more significant |
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| 01:20 | it does not recover. And when looked at this diagram, I saw |
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| 01:24 | lot of you either being tired or uh a little bit confused about what |
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| 01:30 | looking at here last lecture or maybe just misread everybody in the room. |
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| 01:37 | what this shows you is development in . And when we look at the |
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| 01:46 | dominance, we know that in the two months of life, we were |
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| 01:51 | looking at this in the road. the first two months of life. |
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| 01:55 | can have this reorganization of the ocular . You can have this shift whose |
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| 02:04 | now, you can repeat it at point that you know, four |
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| 02:09 | what is this something? 8, and 16. So when you look |
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| 02:17 | at eight weeks, you don't see much of the shift that you see |
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| 02:23 | four weeks, it's 12 weeks, don't see as much of a |
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| 02:28 | And then at 16 weeks, you are not shifting. There's no way |
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| 02:34 | can reorganize and shift these responses. here it's being essentially like use the |
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| 02:41 | shift in ocular dominance in these animals short term deprivation is being used to |
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| 02:49 | the levels of plasticity and criticality over time span. Here of of 16 |
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| 03:02 | , this would be equated to uh of maximal susceptibility of human binocular vision |
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| 03:11 | deprivation. It's similar in the order nine years. All right. Um |
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| 03:25 | influences. If you have a lo alius, norepinephrine, basal form |
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| 03:35 | acetylcholine, if you ha have these mono amine supply, you will have |
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| 03:44 | a shift. If you deprive an , the cortex will reorganize itself. |
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| 03:51 | , if you to fry or if cut so the the the locust and |
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| 03:58 | hormone inputs. If you deprive the cortex, now of these am |
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| 04:06 | then you do the same for deprivation , you do not see the, |
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| 04:12 | least you do not see the ship same way you would see in the |
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| 04:17 | of these amine transmitters. So you their input into the stride cortex, |
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| 04:23 | is your visual cortex. And now have shown that these neurotransmitters, acetylcholine |
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| 04:32 | norepinephrine are important and supporting the the correct reorganization. If you don't |
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| 04:40 | those during early development, you have deprivation, you do not have this |
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| 04:46 | , which also means that you will have recovery too. Now, we |
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| 04:52 | talked about some things that are happening birth and those are the retinal waves |
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| 04:57 | we looked at last lecture. So I hope we kind of come |
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| 05:01 | together, situate ourselves and this very environment. And that's what the critical |
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| 05:11 | of development is. It's the highest of plasticity that you observe. What |
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| 05:21 | some of the elementary mechanisms of cortical elasticity? And what are some of |
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| 05:29 | rules? What are some of the by which cells communicate and learn from |
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| 05:35 | other and modify their activity. So classic one is the ones that fired |
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| 05:42 | , wired together, the ones that out of sync do not link. |
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| 05:48 | talk about it a little bit more we talk about memory formation. What |
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| 05:53 | Ha was a famous or is maybe sorry, not sure. Uh Canadian |
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| 06:01 | and he came up with these uh of neurons and synopsis that are going |
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| 06:09 | be active, one is gonna release neurons and the other one is going |
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| 06:14 | produce a postsynaptic response. The ones fire together, they will end up |
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| 06:20 | strong synopsis, they will end up together. Remember we're looking at this |
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| 06:26 | process where we have too many too many synopsis or not too |
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| 06:33 | but more synopsis and more cells than have an adult. So you're going |
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| 06:37 | the program cell death, you're growing synoptic development, but also synoptic loss |
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| 06:44 | synaptic strengthening of the active synopsis. a single synapse has little influence on |
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| 06:53 | rate of postsynaptic neuron. And that's a single synapse in the CNS on |
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| 07:02 | postsynaptic cell can induce a depolarization of half a millivolt, maybe just one |
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| 07:11 | . So you have to have co activity, correlated activity activity of a |
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| 07:16 | must be correlated with activity of many inputs, converging on the same postsynaptic |
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| 07:23 | . So one cell activating one synapse one neuron. A synaptic is not |
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| 07:31 | enough of the activity. So you to have correlated activity, you have |
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| 07:36 | have coordinating activity and a lot of being activated at the same time. |
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| 07:46 | , glutamate and we have two glutamate that are in the tropic and an |
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| 07:58 | A. And we also talked about receptor. So we talked about three |
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| 08:04 | groups of metabotropic. They were both and post synoptic. Here, we're |
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| 08:10 | at the postsynaptic receptors and what's happening in the immature synapse, you will |
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| 08:24 | at first have only an MB A . And so if this synapse |
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| 08:34 | pre synoptic terminal, it's going to released in glutamate. Glutamate can bind |
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| 08:39 | A and MD A and Luar. in early development are not there. |
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| 08:51 | if muna made gets released, there's that can help open an MD A |
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| 08:58 | . So, amper needs to, you recall to create an EPSP, |
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| 09:07 | early component of EPSB is alpha and lead component of this EPSB is N |
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| 09:17 | A. And so you need to depolarization, you need to have activation |
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| 09:24 | ample receptors and depolarization because if you and then D A receptors are blocked |
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| 09:31 | magnesium block, so they're not So in the early development, those |
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| 09:38 | will express an MD A receptor and are going to be called silence and |
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| 09:48 | , they're silent because glutamate is gonna released. But there isn't going to |
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| 09:53 | any possible response because there's no how during the development ample receptors we're talking |
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| 10:03 | within days post natally, for and, and rodents or prenatally in |
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| 10:09 | instances later, you'll have insertion of ample receptors. And once you have |
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| 10:16 | of the alpha receptors, now the are no longer silent. Now, |
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| 10:21 | there's release of glit amate, there's to be depolarization through alpha, there's |
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| 10:25 | to be depolarization through an MD A well. So there are other different |
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| 10:31 | that are driving uh the process of synoptic sorting or synoptic plasticity and different |
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| 10:42 | are driving this also. And in calcium and voltage gated calcium channels become |
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| 10:48 | important in the early development of these . So calcium channels in the sense |
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| 10:54 | influx of calcium not through an MB receptors, but influx of calcium through |
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| 11:01 | channels and also um increased activity oop to calcium influx by. So this |
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| 11:18 | just a review that an MD A will have a magnesium block, an |
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| 11:25 | will get activated first. So if don't have the ample receptor, you |
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| 11:30 | create a situation where an MD A is active and magnitude of calcium flu |
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| 11:39 | levels of pre synaptic and post synoptic . Why is that recy calcium is |
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| 11:51 | for neurotransmitter release? A synaptic calcium happens because you opened an MD A |
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| 11:58 | , some calcium is flexing in. calcium is actually a really good indicator |
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| 12:04 | activity. And you will see a of talks that address neuronal activity and |
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| 12:10 | looking at calcium imaging and that's because a correlation between levels of activity and |
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| 12:17 | amount of concentrations and spatial temporal patterns calcium. So, all right, |
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| 12:31 | we talk about plasticity throughout several important of plasticity that we're going to talked |
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| 12:43 | . First of all, there is term plasticity and then there is long |
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| 12:54 | plasticity. Short term plasticity is subdivided facilitation and depression. Long term plasticity |
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| 13:17 | subdivided into long term potentiation. Long synaptic potentiation, LTP or long term |
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| 13:28 | depression. Yes. So facilitation is that increases the signal, short term |
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| 13:39 | is something that did process. The decreases the amplitude of the signal short |
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| 13:46 | versus long term. So we will start talking about long term potentiation first |
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| 13:55 | it is kind of a easier to understand that at first. And that's |
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| 14:00 | your book explains at first too. me get into this detail here. |
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| 14:06 | why is an MD A receptor MD A receptor service heavy of |
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| 14:12 | Remember they are coincident detectives, you to detect glutamate and depolarization posy |
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| 14:18 | So that posy calcium L through through MD A receptor channel triggers the biochemical |
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| 14:24 | that modify synoptic effectiveness. Long what is short term? What is |
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| 14:31 | term? What do you guys think we talk about plasticity, what is |
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| 14:38 | term milliseconds, seconds, minutes, , years, short term memory, |
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| 14:48 | you remember a phone and you carry for like 20 seconds really well and |
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| 14:53 | minutes later is gone. So it's , right? So really, really |
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| 14:58 | milliseconds, hundreds of milliseconds, minutes maybe, let's say, |
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| 15:04 | so what is long term, long is hours, days weeks, |
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| 15:10 | sometimes these are the actual modifications that at the sys the changes in |
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| 15:17 | in the efficacy of that s So you monitor synoptic strength before and after |
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| 15:24 | of strong and MD A activation. you have stronger MD A receptor |
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| 15:29 | there's going to be strengthening of synaptic or LTP. Don't worry, this |
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| 15:35 | just an introduction and it tells you uh these things are quite important. |
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| 15:43 | going on with my camera? There go, turn on the camera. |
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| 16:00 | how are these experiments done? And did we come up with this concept |
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| 16:06 | LTP or, or LTD or other ? And uh this is an example |
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| 16:18 | you said TIC stimulation and you can the number of fibers, these are |
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| 16:24 | . So these are fiber bundles, axons, you typically place a stimulating |
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| 16:30 | and you stimulate those fibers and you poop exci or a Posy potential |
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| 16:38 | How do you know? And then happens is that you're sampling this, |
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| 16:46 | sampling this, you're sampling this the these experiments are done. This is |
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| 16:51 | minutes. So you're sampling something for minutes and that sampling is difficulty every |
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| 17:07 | seconds. Imagine this is every 15 . You're measuring the amplitude of these |
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| 17:19 | EP SPS. So each one of is a stimulation, one through the |
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| 17:26 | 100 every time you stimulate, you a response in the PSP. And |
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| 17:32 | take that response an hour over 50 and you call this, your |
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| 17:37 | This is your baseline 100%. This the response that I'm getting. You're |
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| 17:42 | this every 15 seconds because it takes 12 seconds for the synapse when it |
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| 17:48 | neurotransmitters. But it's a fully reload the vesicles and neurotransmitters. You wanna |
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| 17:54 | a fair chance for the synapse to . We'll say that's a long time |
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| 17:59 | , synapse every seconds. But it's standard in elect to physiology and that's |
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| 18:03 | of the time it takes for the to uncover its release machine. So |
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| 18:10 | you've established this baseline that you this is my 100%. Does that |
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| 18:15 | that all of these EP SPS are be exactly the same size? |
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| 18:21 | they're going to be each one of if this is 100% why there's gonna |
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| 18:27 | some fluctuations. But you're going to up with the baseline response for 15 |
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| 18:37 | . Now, it says during the induction and your book doesn't really describe |
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| 18:42 | very well, but you are inducing LTP. The way you're inducing an |
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| 18:48 | is you pass what we call a stimulus. And during the induction of |
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| 18:56 | , you have activation of an MD receptor and you have a significant influx |
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| 19:03 | calcium. Bye. How do you that? What happens between this baseline |
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| 19:15 | the signal jumping up over here? typically the way these experiments were done |
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| 19:24 | they were done in the hippocampus and C A one area of the hippocampus |
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| 19:30 | the fibers were being stimulated and the were done from the perimeter cell. |
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| 19:37 | once every 15 seconds stimulate board, or stimulate or and then you're gonna |
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| 19:51 | the spot. So for us, , in the 1973 it was 100 |
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| 20:00 | stimulus that was applied. Does that that means that instead of sampling it |
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| 20:09 | 15 seconds? Boom. Hmm, gonna jolt these fibers now with very |
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| 20:18 | frequency trays. Each one of these has 100 Hertz. So I'm gonna |
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| 20:25 | it at 100 cycles per second and these strains of stimulation. You do |
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| 20:34 | for a minute, different protocols, say you do it for a |
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| 20:38 | So you repeat these about 10 right? That about uh and always |
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| 20:45 | 100 Hertz per cycle. And after finish this conditioning stimulus, you then |
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| 20:56 | the exact same stipulation that you do baseline. Now every 15 seconds, |
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| 21:03 | gonna sample the size of this And what it's gonna show you is |
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| 21:12 | there is an increase lasts long 30 minutes can go on 45 minutes |
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| 21:22 | go on for hours, can go for days like this great. So |
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| 21:30 | have long term potentiation and this was Hertz stimulation have a lot of influx |
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| 21:40 | calcium. And what's happening, cellular that you can see insertion of a |
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| 21:47 | more of ample receptors. So you this mechanism of additional ample receptors being |
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| 21:56 | into the synapse that is now Mm That means that if before the |
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| 22:05 | of the stimulus is exactly the same as it is, you're getting here |
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| 22:11 | 15 seconds, you're getting this But after this conditioning stimulus, all |
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| 22:16 | a sudden, you have an increase , let's say 150 or some. |
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| 22:25 | you are again, every 15 it's the same synapse going on to |
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| 22:30 | cell here. The same paradigm as baseline. But because of your conditioning |
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| 22:38 | have increased the response. We have that synapse, we have inserted more |
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| 22:43 | opper that synapse is way more responsive . And that responsibility that uh increase |
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| 22:50 | efficacy as I mentioned is long So if you have potentiation, |
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| 23:06 | it's the same electrode. But instead stimulating the fibers every 15 seconds, |
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| 23:13 | will produce these strains of very high frequency stimulations. Yeah. Mm Very |
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| 23:32 | . So that's, that's actually uh we talk about it in the next |
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| 23:38 | , the PLO paradigm of, you , dog salivating with the condition unconditioned |
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| 23:46 | . So this is kind of like stimulus. Hey, this is the |
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| 23:51 | and now the cell is so much ready to respond to that smell of |
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| 23:56 | hand or whatever the dog is responding . Oh, no conditioning pushes |
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| 24:08 | It's a necessary this this this increased of activity tells go into that synapse |
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| 24:15 | and you're gonna be much stronger. in that, that happens. If |
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| 24:19 | synapse is potentiating, it's being So there's also gonna be other |
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| 24:25 | Apart from the receptor insertion, you'll have sub sido Klem arrangements, the |
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| 24:31 | area of the spine is gonna grow so it can accommodate more alper recess |
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| 24:38 | inserted there. And that's just made synapse a lot more responsive to the |
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| 24:43 | amount of glutamate. So stimulation, they say, glutamate, say synaptic |
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| 24:49 | you have changed. Now, the would have so many more er |
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| 24:54 | right? And these blue guys, are alpha receptors, you can see |
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| 25:00 | inserted a lot more of them So if potentiation is sort of a |
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| 25:07 | paradigm too, it's a cellular substrate learning and bubbling. It's something that |
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| 25:14 | do a lot of something that you a little off 713743, the last |
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| 25:21 | digits and you, you forget But if you dial that number over |
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| 25:27 | over 7137432255225522, it goes, you conditions c through these repeated exercises. |
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| 25:40 | says 713743, you just finished You know, I don't know if |
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| 25:44 | not just, just made it So this is uh learning new |
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| 25:51 | memorizing new things, but a very important thing is to be able |
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| 25:56 | forget things. And it's not just that we drive the system always into |
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| 26:04 | synopsis, more efficacious growth. But fact that we have to forget |
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| 26:10 | we have finite amount of space in adult brains. We have finite amount |
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| 26:14 | synopsis in the adult brains. And cycle out the things we remember certain |
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| 26:22 | better, other things worse, you cycle back in certain things like with |
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| 26:26 | field of study or job or you'll remember it more. But LTD |
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| 26:34 | synaptic depression, then there's also likened forget it. Forgetting is a very |
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| 26:42 | part of human survival, right? have to forget. You have to |
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| 26:52 | . Sometimes you cannot forgive, you have to forget it because otherwise it's |
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| 26:58 | overwhelm you. So it's a really emotion and you have to have a |
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| 27:03 | mechanism of shedding the synopsis and changing plasticity. So what is the LTD |
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| 27:12 | that fire out of sync? Neurons fire enough really? Or fire out |
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| 27:19 | sync? That means that there's somehow firing in the correct order. And |
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| 27:23 | I say hello, somebody responds But if we change that order, |
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| 27:28 | mean, it's still OK. But some instances it's not, you |
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| 27:31 | like if you're buying something and I something and then the cashier says, |
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| 27:34 | I buy something? You know, not making sense. The transaction doesn't |
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| 27:39 | . Can I buy something? can I buy something. So you |
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| 27:44 | opposite mechanism here, you have neurons are out of sync or not communicating |
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| 27:50 | , loss of synoptic ample receptors. you lose synopsis altogether? Yes. |
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| 27:56 | it's not just about strengthening synopsis or synopsis is you can lose them |
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| 28:03 | Uh This is potentially mechanism for the . We're talking about monocular deprivation. |
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| 28:09 | talking about reorganization. So you have have both structural and functional reorganization. |
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| 28:15 | , depressing the synopsis is a part driving those synapses away, both functionally |
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| 28:22 | anatomically with fewer ample receptors. Synapses influence over responses of cortical neurons. |
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| 28:31 | fewer synopsis, fewer ample receptors are as responsive cortex or the neurons that's |
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| 28:38 | to be communicating to cortex or between . So this is a monocular deprivation |
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| 28:47 | monocular deprivation you have here, we then the receptor activation by poorly correlated |
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| 28:56 | . And if you have poorly correlated , it can do the opposite instead |
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| 29:02 | inserting ut receptors. As we saw , can actually internalize the sample receptors |
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| 29:09 | it uh in internalizes the sound for have ace carrying activity. This is |
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| 29:16 | closed eye and the open eye is what it's doing just the opposite, |
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| 29:26 | ? It's inserting more powers after its it's flexing more calcium inside and it's |
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| 29:33 | strengthening this whole synapse. So it's win, some lose, some are |
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| 29:41 | , some were driven away. What you call this? I correlated |
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| 29:47 | Like I said, it doesn't make if somebody something is out of |
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| 29:51 | But how does that look like if 100 Hertz of this particular conditioning stimulus |
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| 30:01 | Pope? Is it the same conditioning ? And the same synopsis one that |
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| 30:09 | produce LTD? And the answer is it was first discovered in the |
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| 30:16 | it was one Hertz stimulation, continuous , one per second. And if |
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| 30:29 | 100 Hertz stimulation led to LTP and produce just one Hertz stimulation along the |
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| 30:38 | top, the response is you get . So how can you explain this |
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| 30:57 | ? What does this mean? So this first came out in the |
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| 31:03 | it was like, wow, we the code, found the code for |
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| 31:10 | things for LTV and for forgetting and things. LTD. And it's |
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| 31:15 | 100 Hertz boom, you remember one boom, forget. So TV, |
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| 31:21 | same sent out by the way, all in the C one area of |
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| 31:25 | hippocampus. That same diagram we looked when we're looking at the diversity of |
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| 31:30 | South and the Hippen campus, it's in the C one. So there |
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| 31:33 | are coming in the campus. wow, this is fantastic. We |
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| 31:39 | the right code for the brain to things and to weaken it. And |
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| 31:46 | course, when something like this gets in the seventies, then it's |
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| 31:50 | well, yeah, one hurts you . 100 Hertz you potentiate. So |
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| 31:58 | a second, what's going on? calcium, what's going on with the |
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| 32:02 | receptors? How can we have along same pathway? What is happening? |
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| 32:07 | the same synopsis. But one paradigm them strong and another paradigm makes them |
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| 32:14 | and excited than quick. But it a rate code. So this was |
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| 32:18 | of the big explanations for synaptic It's the rage code. This is |
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| 32:28 | long term plasticity. We'll look at term plus this in a second. |
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| 32:37 | short term plasticity as I described this and depression. So when you're |
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| 32:46 | when you're producing this train, this a train of stimulation. Let's say |
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| 32:52 | train is in 100 Hertz, you produce these trains at a, at |
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| 32:59 | Hertz very fast trains of stimulation. can produce some at 40 Hertz. |
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| 33:08 | can produce them at four Hertz or . You can vary this stimulation, |
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| 33:16 | Hertz, let's say to one this is the the conditioning stimulus that |
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| 33:26 | talking about that train of activity. guess what, during the strain of |
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| 33:32 | , there are also real responses. with each stimulation, even the 20 |
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| 33:39 | , you're gonna get an EPSB, going to be summing over time |
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| 33:45 | temporal summation. So the stimulus can grow in size certain frequencies and certain |
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| 33:53 | and cells will evoke this facilitation response the conditioning ST and this facilitation can |
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| 34:02 | for as long as that old stimulus , maybe for a second, maybe |
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| 34:06 | two seconds and then it goes So during the actual stimulation, you |
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| 34:14 | the signal, you can also have complex response where the signal first gets |
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| 34:21 | and then it gets depressed. This happening on the order of seconds. |
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| 34:26 | this is likened to short term memories short term plasticity. This is the |
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| 34:36 | synopsis against C three to C A in the hippocampus, you have A |
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| 34:43 | an MD A and you're causing facilitation you can change the frequency and you |
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| 34:53 | have facilitation and depression. You can the frequency. You can have one |
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| 34:57 | followed large response, followed by decreasing which would be short term depression. |
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| 35:05 | during the actual conditioning, we have short term effects and following that |
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| 35:14 | we can have LTP long term effects LTD. It's the same experiment basically |
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| 35:28 | if you use 100 Hertz or long potentiation, use one Hertz, you |
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| 35:35 | end up with long term depression. alper receptors, that's a pretty good |
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| 35:45 | . Anything else is going on or other explanations for this? How can |
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| 35:52 | same synapse generate LTP and LTD using same N MD A and calcium |
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| 36:05 | An MD A is the coincident So we already saw how well you |
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| 36:11 | internalize ample receptors, you can weaken , you can insert more ample |
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| 36:16 | so you can strengthen it. But is happening like to do that? |
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| 36:21 | . What is the signal glutamate lack glutamate and calcium. You love the |
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| 36:30 | slice. We love calcium imaging because neuroscience, hear a lot about brain |
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| 36:37 | and calcium imaging too. So high stimulation of hers, high frequency |
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| 36:47 | you have a lot of 1000 high concentration of classroom internally, over |
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| 36:54 | micromolar and you have production of a of protein Kass and those protein kinas |
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| 37:05 | cause phosphorylation. So add it to four groups. Yeah, finances. |
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| 37:21 | also long, long term association of , long term depression and those will |
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| 37:30 | involve the transcription factors. So what low frequency stimulation? Low frequency |
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| 37:42 | This is low frequency stimulation is one . So this is low frequency |
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| 37:49 | This is a high frequency stimulation, frequency stimulation. If you produce it |
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| 37:57 | the same synapse, but you change paradigm into boo boo boo. You |
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| 38:04 | very small amount of calcium and lower of calcium influx in inside the South |
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| 38:11 | promote production of phosphatases and they will deflux correlation that's pretty good. And |
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| 38:32 | always feel so happy in neuroscience or any science. When we find an |
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| 38:37 | , it's calcium of course, or micromole or one micromole LTP versus |
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| 38:44 | Not that simple, but we're all to explain these things. And we |
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| 38:49 | explain though with inserts because we can them with increases in calcium and calcium |
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| 38:57 | a secondary messenger. So, so reported activity to secondary messenger that can |
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| 39:02 | facilitate human calcium, full module CNAs correlation on this low calcium facilitate production |
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| 39:12 | high basis sort of like an explanation missing from maybe. But I I'll |
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| 39:19 | it, you know, if it's , once we put fate things to |
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| 39:23 | the cers and channels with the four that that can be long lasting? |
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| 39:28 | it the post coral can also we the activity of channels or syrus? |
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| 39:33 | fact can be also long lasting. how does calcium itself relate to kinas |
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| 39:39 | phosphatases in the sense of where is real like concentration where it switches? |
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| 39:46 | it 1.2 micromolar? And you start uh interacting with more Kassis where, |
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| 39:54 | , where is that? You it's, it's a little bit arbitrary |
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| 39:57 | calcium, low calc. Yeah. . You said one stimulation can produce |
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| 40:08 | to a greater impressive and better than can get by having no stimulation to |
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| 40:14 | at all. Um No, actually this kind of a baseline recording. |
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| 40:23 | you did nothing, the cells in brain slice stay alive for about eight |
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| 40:30 | and you can get stable recordings around just around 100 baseline. If you're |
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| 40:37 | doing any simulation, it will stay for a long, long time. |
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| 40:41 | long as the slice and the cells alive won't change much. So this |
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| 40:47 | activity dependent processes and you need to that conditioning stimulus. So you need |
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| 40:52 | have a change in activity, uh activity in order to to have a |
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| 40:58 | know, confirmational synaptic change or insertion the receptors strengthening and weakening. So |
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| 41:08 | is pretty cool too LTV WLTP I like this explanation. So first of |
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| 41:19 | , it was rate code. Second all, you'll find in your |
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| 41:22 | this article that talks about neuromodulation of timing dependent plasticity, STD P. |
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| 41:34 | does everybody understand this that this is term, this is during the |
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| 41:39 | the responses can facilitate, it can . It depends on the frequencies. |
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| 41:44 | depends on the synapse here. Long effects would seem to be in the |
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| 41:51 | synapse but have a rate code that frequencies cause potentiation, calcium and low |
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| 41:59 | cause depression, decrease calcium too. it was pretty happy with that for |
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| 42:08 | 20 years. This you may have of this bad water. So there |
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| 42:27 | into play a spike to dependent So this is something that you |
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| 42:34 | And uh undergraduate school, you uh studies to learn how to search for |
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| 42:44 | . And uh then your first year studies or second year of graduate |
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| 42:52 | you learn how to read the You know what section is, |
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| 42:58 | why would you look at methods? then the 3rd, 4th, fifth |
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| 43:05 | you get into the trends in the that you're studying. And all of |
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| 43:10 | sudden these things come out of your . A little moving pool on the |
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| 43:15 | coast did this and you know, only for select group of people, |
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| 43:19 | really means something. But that means you're getting really specialized, you're getting |
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| 43:25 | uh an expert, becoming an expert AAA field. And it's, you |
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| 43:33 | , an important field that a lot neuroscience relies on was the city |
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| 43:39 | But so then you kind of start your graduate or postdoctoral studies really having |
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| 43:45 | of a segmentation. This group did , this group did this and this |
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| 43:49 | introduced this, you know, uh throwing out the names. And uh |
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| 43:57 | , so that happens. OK. what does spike timing depend on |
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| 44:05 | And um what do I have to with it? OK. In |
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| 44:10 | what do I have to do with ? I didn't even tell you what |
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| 44:13 | have to do with plasticity. I'll you about the next lecture just as |
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| 44:19 | remind of LTP and LTV because we're connect with, remember I was telling |
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| 44:24 | about these zones and the animals remember in the rodents developing rev junius |
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| 44:33 | you better be taking notes because I'll you questions on these, on these |
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| 44:37 | , on the, on the on the quizzes. But so like |
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| 44:43 | said for 20 years or so, was pretty happy. We got the |
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| 44:46 | code C and Kate and A B or in search. And this is |
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| 44:52 | cool. And then people do they have a cell with the AXON |
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| 45:03 | this is called you sign up and is ac with the SOMA and an |
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| 45:12 | and this is called Awesome. So in some electrophysiology lab, after being |
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| 45:25 | , it's like we stimulate these tired response, we give this frequency recorder |
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| 45:31 | and we stimulate get baseline, we on TV and stimulate you get a |
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| 45:37 | . Somebody was sitting in the I said and said, OK, |
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| 45:42 | gonna stimulate this. We synoptic and going to induce back propagating spike, |
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| 46:03 | back propagating spike, remember and spike propagates back. So this is gonna |
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| 46:11 | 13 and then I'm gonna get a . It's post, it's gonna be |
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| 46:21 | pre, post free, post, post fine genius, right? So |
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| 46:28 | if I did post free? What I stimulate its two first? You |
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| 46:36 | , it probably went to the bosses said, let me do pose before |
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| 46:42 | and they're like, you're out of , man, you know, you'll |
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| 46:46 | the papers again. So, but was really interesting. Three was stimulated |
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| 46:58 | post and when this stimulation won and post response happened within very short time |
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| 47:08 | and the short time window is about milliseconds to 20 milliseconds. So pre |
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| 47:15 | three P three P three P even milliseconds or so, simulation response, |
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| 47:22 | response, simulation response 10 milliseconds, response. Now if we do the |
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| 47:28 | experiment when we sample the fibers, we get the same baseline. But |
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| 47:34 | of conditioning response of boom, boom, slow stimulation, we now |
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| 47:41 | pre post, pre, post, free, post free and we link |
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| 47:47 | within a very short period of But we see that all of the |
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| 47:51 | that were pre post, if they within 20 milliseconds, if they're even |
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| 47:56 | 30 milliseconds, the response remains theta the pre is evoked and the post |
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| 48:06 | evoked 40 milliseconds later. There's no . This guy saying, let's go |
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| 48:14 | . This guy says, yes, , yes, yes. They're like |
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| 48:20 | stretch that time window to 4050 milliseconds . Yes. But yes, that's |
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| 48:31 | no change in the synoptic strength. use that example with, with |
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| 48:36 | you know, say hello to You expect an answer within seconds comes |
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| 48:40 | 15 minutes later, you get you know. So what happens? |
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| 48:45 | this is prepose, prepose potentiation. great in this order is potentiation, |
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| 48:50 | you have to have it within a time window of the two cells. |
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| 48:56 | . What happens if that genius I'm gonna do post free. If |
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| 49:01 | do post pre, this responded fire , respond to fire did really, |
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| 49:10 | fast. It actually causes pretty significant within that short time window. The |
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| 49:18 | between the postsynaptic and pre again, you stretch that time window post, |
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| 49:28 | that's doesn't change anything. It's no longer around for neurons to be ideally |
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| 49:35 | . It tells you that the pre post synoptic side has to be tuned |
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| 49:40 | this 5 to 10 millisecond window. fact, some have described the sweet |
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| 49:44 | as about seven milliseconds or ideal, potentiation or depression of these synopsis. |
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| 49:56 | was driving today, I was how do we know which one is |
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| 50:00 | ? Which one is post you stab cells in the tissue? You were |
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| 50:06 | it's coming from this direction to that you know the circuit well, |
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| 50:10 | almost you you can do that. this is three we synoptic action credential |
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| 50:18 | synaptic back up what you expect. is bussing backward life followed by |
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| 50:25 | So this is three post, this post brief. Oh You can change |
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| 50:43 | , you can change these post, pre post. How do you change |
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| 50:49 | ? Temple requirements for A CD PS P is malleable. The magnitude of |
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| 50:55 | spike timing dependent plasticity. So it's spike timing dependent plasticity. Because the |
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| 51:00 | of the spike, if the two happen within a certain time window, |
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| 51:06 | correlated and it can either be positive or negatively correlated. A spike |
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| 51:12 | dependent plasticity versus rate code rate code 100 Hertz one Hertz spike timing dependent |
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| 51:24 | . What do I have to do it? We destroyed it. So |
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| 51:31 | first saw that we can stretch these different levels of amplitude. And then |
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| 51:38 | did my post doc, my first doc was in Johns Hopkins University and |
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| 51:44 | really, really uh top experiments, tough and rigorous environment. When I |
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| 51:54 | wanted to present as a postdoc to Journal club. I was so |
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| 52:01 | so nervous because like any one of professors at Johns Hopkins opened their mouth |
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| 52:06 | you just feel so small and like want to urinate in your pants very |
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| 52:11 | and it's just really like very, stressful, but it's an incredible experience |
|
| 52:17 | , to learn from some of these . Uh And my work was that |
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| 52:23 | looked at spike timing, defendant plasticity the visual system. And what we |
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| 52:30 | here is the temporal requirement for this . Independent plasticity can be modulated. |
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| 52:38 | sometimes you will get differentiation, pre or post free and you get de |
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| 52:44 | , pre post or post free. do you get that in my |
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| 52:49 | We were studying norepinephrine and nor epinephrine these what we call classical rules for |
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| 52:56 | bomb dependent plasticity of classical curves. have outdone these curves into extending them |
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| 53:02 | depression or potentiation depending on the a . In this case, norepinephrine that |
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| 53:08 | had present. Again, stressing the of a means in regulating the plasticity |
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| 53:15 | like we saw with ocular dominance columns . In this case, with timing |
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| 53:19 | plasticity, it's almost like in the of a certain substance. The order |
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| 53:25 | matter what matters is the timing So in one substance that timing |
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| 53:32 | pre, post or post free it always cause potentiation. You spill another |
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| 53:38 | on that synapse. The order doesn't as long as it stays within that |
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| 53:42 | timing, short window, it will depression. So when we come |
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| 53:47 | we'll actually finish some more slides. And I'll just tell you very briefly |
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| 53:54 | this slide when we come back and some of this ltpltd work with early |
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| 53:59 | when we're looking at the development of synapse. So, all right, |
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| 54:06 | can also watch it next time I'm send an email about the, |
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| 54:12 | it was tomorrow. So everybody is and aware a lot. Oh |
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