| 00:02 | This is like your 13 of neuroscience what you really should understand very well |
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| 00:09 | now. By this lecture is first all the seed of clothing uh system |
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| 00:16 | colon ergic system. And you can the colon ergic system and neuromuscular junction |
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| 00:22 | you only had one nicotine acetylcholine You had only excitatory synapse. Then |
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| 00:29 | produces employee potential. There's massive potential you should very well understand the synthesis |
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| 00:37 | degradation of acetylcholine in the central nervous . Synopsis and the fact that in |
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| 00:45 | CIA necesito Colin will target two types receptors and the tropic nicotine, a |
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| 00:52 | coming receptors and the metabolic tropic mascara acetylcholine receptors when we spoke in particular |
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| 01:00 | regard to the colon ergic signaling binding the civil code into the nicotine receptor |
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| 01:07 | cause deep polarization person optic neurons because would allow for influx of sodium. |
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| 01:13 | nicotine acetylcholine receptor channel is also permissible potassium. So unlike the channels that |
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| 01:19 | studied when we studied the action potential we specifically said this is both educated |
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| 01:28 | selective channel. This is vault educated selective channel. These channels allow for |
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| 01:37 | of sodium nicotine acetylcholine receptor and influx potassium. Most quranic receptors are linked |
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| 01:46 | the jeep road end. And if recall from last lecture the cascade from |
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| 01:53 | Munich acetylcholine receptor did you produce them downstream potassium channel and the effect of |
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| 02:00 | potassium channel will be hyper polarization on south. So in this situation and |
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| 02:06 | . Ergic signaling nicotine acetylcholine receptor is polarizing on parson optic nerves must carry |
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| 02:13 | is harper polarizing. We further discuss activities opposing actual activities that can be |
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| 02:22 | in middle but tropic signaling. When discussed that norepinephrine binding to beta receptor |
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| 02:30 | is linked to the stimulatory gee protein induce the production of cycling campion protein |
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| 02:35 | . Say on the other hand, of the alpha two receptor which is |
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| 02:41 | to the inhibitory G protein complex would in the reduction of the secondary messengers |
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| 02:48 | we can be in protein kinase. , so these are some of the |
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| 02:55 | concepts that we discussed how you can either this push pull mechanism through meadow |
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| 03:02 | , opposing actions the same molecule, two different receptors linked to two different |
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| 03:07 | of G protein complexes. We also how nicotine, nick and Mouskouri nick |
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| 03:13 | are opposing actions. This is where am, a tropic is opposing that |
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| 03:18 | a tropic action. And then we in great detail the glue, dermatologic |
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| 03:26 | gaba ergic signaling and in light of dermatologic signaling, we discussed the non |
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| 03:33 | . B. A. And bikini channels and also NMDA receptor channels. |
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| 03:42 | are both Tampa or known in India N. M. D. A |
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| 03:46 | channels are both isla tropic channels, special feature of an M. |
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| 03:51 | A receptor was that it has a block. So at rest it's not |
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| 03:58 | to glutamate and glycerine as a co to bind to the receptor to open |
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| 04:03 | . It actually needs to detect posson deep polarization and that possum topic deep |
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| 04:09 | will alleviate magnesium block in an and detects that far synoptic deep polarization because |
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| 04:17 | glutamate is released in the synopsis that buy into the emperor receptors and emperor |
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| 04:23 | can be activated, addressed. So early initial component of this G. |
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| 04:28 | . S. P. S due ample receptors and later prolonged component of |
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| 04:34 | Eps do tell MD. A receptors both obviously have their own agonist sampling |
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| 04:40 | M. D. A. And they also have their own antagonists |
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| 04:45 | and Q. Acts for example and PV or a P 54 an |
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| 04:49 | B. A. And M. . A receptor is referred to as |
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| 04:52 | detective because it coincidentally in order for to open and functional coincidentally needs pre |
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| 04:59 | chemical bonding glutamate and Pazin attic numbering polarization through activation of ample receptors. |
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| 05:08 | discussed this experiment where we started putting knowledge from the previous sections of the |
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| 05:15 | and previous lectures and of course such combination of voltage plan measuring reversal potentials |
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| 05:24 | experimental manipulations of the solutions or from psychological manipulations of the receptor channels and |
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| 05:33 | are recordings of an M. A receptor in normal physiological okay Magnesium |
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| 05:40 | where extra cellular magnesium is 1.2 million And at -60 million balls a few |
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| 05:47 | clamp this potential and you release glutamate your record from an M. D |
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| 05:52 | they will barely be opening if at . But when you de polarize it |
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| 05:57 | -30 of these receptor channels will be and conducting the currents. An MBA |
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| 06:04 | currents reverse zero millet balls, ample currents reverse zero million volts nicotine, |
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| 06:12 | receptor Channel Currents Reversers zero novels. the PSP reverses the zero. No |
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| 06:23 | And employed potential reverses its zero more . And that's the reason why you |
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| 06:29 | see any current of zero Millersville is potential in this diagram. And when |
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| 06:34 | de polarize the potentials to positive 30 60 you can see the opening and |
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| 06:38 | conductance through this channel that is relatively and stronger than at the hyper polarized |
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| 06:46 | . Now, if you remove magnesium the solution, we discussed that it |
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| 06:50 | two things basically allows for that an receptor to be activated addressed because magnesium |
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| 06:57 | is no longer there. But the magnesium concentrations and zero magnesium. We |
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| 07:03 | discussed as a model that is being for modeling epilepsy and seizures and a |
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| 07:09 | brain excitability and in the absence of a little bit of glutamate will activate |
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| 07:17 | strong conductance through an M. A receptor de polarize the cells and |
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| 07:20 | spiking activity and abnormal synchrony in the . So this is zero magnesium model |
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| 07:28 | actually one of the models of what be happening in the epileptic like where |
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| 07:33 | brain that is undergoing a seizure like And you can see that in the |
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| 07:38 | of magnesium at -60. They're very and NBA currents and opening of this |
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| 07:43 | channel. Again the reversal at zero adults. And then strong conductance is |
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| 07:48 | the positive potential. So then we ok now we're so smart, we |
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| 07:53 | how to use voltage clamp and the of the voltage clamps to lock the |
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| 07:59 | number of potential and different values and want to lock that potential because you |
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| 08:04 | to isolate individual current. You want see You want to calculate individual equilibrium |
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| 08:10 | potentials for one ion. How do calculate the wrestle potential from them? |
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| 08:15 | receptive to conduct several islands. You predict it but then you have to |
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| 08:21 | it after you measure it. Then have a mathematical format which you can |
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| 08:25 | it for computation or or anything like modeling. But you voltage clamp it |
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| 08:32 | different potentials and then you know that receptors responsible for the early currents in |
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| 08:38 | diagram that we discussed last time. are the ivy plots for both Tampa |
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| 08:44 | channel and the A receptor channel. voltage plots, vehicles. I our |
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| 08:51 | so everything in the negative PICO, range here, negative y axis is |
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| 08:58 | current, positive charge moving in everything on the positive people hamper access on |
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| 09:04 | top here is outward current so at what you see there is a reversal |
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| 09:11 | these currents. So both the early which is the linear component and the |
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| 09:17 | component here measured from the second line is non linear and M. |
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| 09:21 | A. Components, they both reverses millennials. And so we discuss that |
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| 09:26 | you do these kind of experiments you clamp. Now you can measure how |
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| 09:31 | is the current of the spurs dash , five milliseconds following the stimulus. |
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| 09:35 | the early component which is ampara and big is the current? 20 milliseconds |
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| 09:41 | the stimulus which is an MBA receptor . And you can see that that |
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| 09:47 | polarized potentials these closed circles at minus minus 60. There's very small amounts |
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| 09:53 | current, There's more in India current starts happening when it d. Polarizes |
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| 09:58 | -50 -40 -30. And then when reverses it is rectifying and it's conducting |
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| 10:05 | this direction. Very strong fashion. you identify these individuals early and late |
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| 10:12 | now you can apply the blocker for MBA receptor. And essentially these blue |
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| 10:18 | here this area, the blue area this curve year, the whole blue |
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| 10:24 | is what an M. D. receptor channel is responsible. So then |
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| 10:29 | receptor channel gets activated. Late is for this late gun but it's also |
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| 10:36 | Because you can see that the early here which is the white component, |
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| 10:41 | ends within 20 milliseconds. And then an M. D. A. |
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| 10:46 | gets activated only about five milliseconds But it is also prolonged and sustained |
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| 10:53 | through an M. D. Receptor. And if you recall the |
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| 10:57 | to an M. D. A channel so 2.5 times greater than through |
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| 11:01 | receptor channels. And then in the channels will also always conduct calcium which |
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| 11:07 | significant for secondary messenger. And to you a signaling cascades. So if |
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| 11:12 | apply this blocker here a PV and M. D. A receptor |
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| 11:17 | then you're looking at the curve here is in the open circles. It's |
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| 11:23 | flat line close to zero because a specifically blocks the late components. So |
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| 11:28 | would eliminate this blue area and we leave the white area here under the |
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| 11:34 | . And as you can see a milliseconds or so there is no more |
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| 11:38 | component. So the early components is in triangles. Is unaffected by this |
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| 11:46 | ap people offer but the late component into this flat line in these open |
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| 11:52 | light I. Ve plot. All right. And we talked about |
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| 11:59 | fact that it's very interesting how you these very large proteins that are complex |
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| 12:05 | but you can identify key amino acids these very long chains of amino acids |
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| 12:13 | one of them is removal of glutamine include I mean with arginine will eliminate |
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| 12:22 | conductance through ample receptor channels. So discussed that last lecture also. So |
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| 12:28 | call that not all ample receptor channels permissible to sodium and calcium only some |
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| 12:33 | them. And the ones that have . Will be permissible to calcium and |
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| 12:37 | ones that have argentine, they will longer have any calcium conductance. This |
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| 12:43 | from here, they will still have sodium conductance coming up on Tajani or |
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| 12:49 | development agenda. Receptor is founded early stages of the synapses and that's what |
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| 12:56 | called. Silence analysis because if you glutamate there isn't going to be personality |
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| 13:02 | that is significant and there is a receptor shift in India receptors during the |
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| 13:09 | . We also talked about how ample and an NBA receptors that can be |
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| 13:15 | from extra synaptic spaces into the So that's one way and to strategize |
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| 13:21 | cross in africa because if you recall glutamate cycle especially is controlled by Julia |
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| 13:27 | so there is not enough of a not to eliminate the person optic, |
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| 13:32 | assume a strategy of importing more glutamate to be as active as possible. |
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| 13:37 | those little glutamate coming from police are excited And then the receptors coincident detective |
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| 13:43 | very important for plasticity. Long term , long term potential Haitian and also |
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| 13:49 | term depression of the synopsis. Okay metal tropic signaling and glutamate. So |
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| 13:58 | is finishing you're talking about the glutamate really is through the hospital life |
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| 14:02 | C. Here PLC and split up pipe to into the number inbound G |
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| 14:09 | of protein kinase C. Or the triphosphate which bonds it. Three receptor |
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| 14:14 | that are calcium channels and release of inside themselves. Gaba a receptor channel |
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| 14:23 | of Gaba. Well, because the of fluoride and hyper polarization and we |
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| 14:29 | discussed how a lot of these and receptor channel is a target for pharmaceutical |
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| 14:37 | . Also it can be very much by illicit drugs. Gaba is also |
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| 14:44 | many pharmaceutical drugs if you want to inhibitory town in the brain if there's |
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| 14:48 | much excitation, very common seizure medications as benzodiazepines, uh barbiturates something sedatives |
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| 14:57 | will act to gathers up the There are steroids also we should involved |
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| 15:01 | uh inflammation control and ethanol alcohol will bind to these channels. So when |
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| 15:09 | have a over the hump happy hour you can tell your colleagues that it's |
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| 15:16 | Gaba receptors of the being inhibited right first and then after three or four |
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| 15:23 | will be completed disinhibited. So anyways do 34 drinks, it's not the |
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| 15:30 | yet. Uh Gabba activation will allow influx of fluoride and hyper polarization. |
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| 15:36 | , but deactivation which is littered with will allow for opening or potassium channel |
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| 15:44 | ethically also causing more hyper polarization. optical, It can control calcium channels |
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| 15:50 | you can control the physical release We look at this beautiful diagram, |
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| 15:56 | really like a diagram that if you understand if you understand the key to |
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| 16:01 | diagram if you understand what's happening when on top of things in this course |
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| 16:06 | a lumberjack synapses and inhibitory synapse. you have the gamble a receptor which |
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| 16:13 | chloride and inhibits this past synaptic And you also have person optical gabby |
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| 16:19 | which opens potassium channels and further hyper . So this is a very strong |
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| 16:25 | synapse. But this this ambient gabba can affect present at the Gabba B |
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| 16:31 | . And those present at the Gabba receptors will shut down influx of calcium |
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| 16:37 | will essentially auto regulate that's where their receptors they released from the same synapse |
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| 16:43 | they buy into the pre synaptic receptors auto regulate further gabble release. So |
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| 16:49 | pretty interesting right? Because the more there isn't more gambling spills and goes |
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| 16:55 | here around to present a topic side more control of Gaba release is going |
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| 17:01 | be there, its own regulations now if gabble levels are stronger than ambient |
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| 17:10 | and you have a nearby this blue sanat. And so you have excitation |
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| 17:16 | and this is an M. A receptor and ample receptor and you're |
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| 17:20 | excited to replace synaptic potentials here under influx of calcium and that calcium can |
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| 17:28 | calcium ca module. Um And that simple module and can interact with Jabba |
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| 17:34 | receptor an open potassium channels. So going to do here personality can actually |
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| 17:40 | polarized as excited place you know through mechanism that's completely gambling independent through into |
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| 17:49 | mechanism that's pretty neat through Gabba dependent to spillover. Gava combined to Gabba |
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| 17:55 | receptive piece unethically control calcium influx and glutamate abilities. So if there's so |
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| 18:04 | gabba that is being released that it over it actually can shut down glutamate |
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| 18:09 | to completely dominate this particular space or synaptic interaction here that has shown |
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| 18:16 | Yeah. So this is all of components kind of being placed together one |
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| 18:22 | time reminding you that Gaba A and reversal of Gaba A receptor channel, |
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| 18:30 | dares to gas. It conducts What is the reversal potential for |
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| 18:34 | A mr russell potential for fluoride. is about -70. Okay. Yeah |
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| 18:43 | would be conducts potassium, it controls channel, not conducts. But the |
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| 18:50 | controls potassium channel. Peace care to we're gambling be reverses the index potassium |
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| 18:59 | 80. Were potassium reversals. So A. You can see here after |
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| 19:05 | . You see a nice deep You see a very nice sharp |
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| 19:09 | P. S. P. But ePA species so sharpen it is being |
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| 19:14 | by inhibition of follows immediately so you glutamate, Glutamate is exciting. Gps |
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| 19:21 | . Yabba a draws this number in to -70. Then with some delay |
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| 19:28 | g protein coupled receptors you have activation potassium channel through Yeah baby. And |
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| 19:34 | draws the number of potential hyper polarizes tries to reach that equilibrium potential for |
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| 19:40 | of my Mercedes. Does that make ? And reversal potential for an |
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| 19:47 | D. A. Set of golden nicotine and amber zero. Why? |
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| 19:52 | you have one eye on sodium that's in positive 55. Another island was |
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| 19:58 | -80 3rd iron calcium positive 120 530 ratios of them. And kinetics and |
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| 20:07 | going through this channel places that are zero value. Yabba is simple chloride |
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| 20:14 | -17 chloride reversal. Yeah baby Through program targets potassium channel. It tries |
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| 20:23 | reach the equilibrium potential for potassium if block Yabba a with bike succulent which |
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| 20:31 | specific receptor channel blocker for bike succulent of this trace and one this really |
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| 20:37 | E PSP that's followed by an P. S. B. By |
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| 20:43 | . Now in the presence of bike inhibition is blocked and that same stimulus |
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| 20:49 | produces the second trace which is prolonged deep polarization. So this should |
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| 20:55 | you how functionally within the synapses and in the previous slide. You have |
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| 21:01 | very tight excited to inhibitory synapse interactions glia also involved there and how you |
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| 21:08 | excitation followed by inhibition and inhibition a of times is keeping excitation and check |
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| 21:15 | running away. And if you block inhibition pharmacologically and manipulated this excitation becomes |
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| 21:24 | . What we call it is a . It can run away now because |
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| 21:27 | can spread through the interconnected neuronal network through the interconnected brain areas. You |
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| 21:34 | teams seven trans membrane uh receptors not . And uh You have a single |
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| 21:44 | muscular nick receptor subtypes. There's not one muscular receptor. Glutamate is 12-14 |
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| 21:50 | believe now. Yeah but be serotonin . The ratios of these receptors like |
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| 22:00 | D one D two ratio can influence of the underlying neurological psychiatric conditions. |
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| 22:06 | know norepinephrine and cattle and cannabinoids. talked about endocannabinoid is binding to |
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| 22:12 | B. One and neurons prison optically retrograde fashion. And CB two located |
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| 22:19 | the glial cells mostly on the micro cells. So can avenues control glutamate |
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| 22:25 | gaba balance through CB one receptor, transmission of men and gather and through |
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| 22:32 | two receptors and their cannabinoids and cannabinoids swallow processes like inflammation, An inflammatory |
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| 22:39 | release HTTP has its own channel 80 . A one A 2 A and |
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| 22:47 | . two Acts B. two y And a one channel is in the |
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| 22:53 | Channel. And the way a demonstration actually it's very similar to this dennison |
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| 23:04 | actually linked to the calcium channel. very similar to what is shown in |
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| 23:10 | Gabba. Sign up. So now this Gabby, this green guy with |
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| 23:16 | damazin receptor Dennison receptor is active calcium closed. The denison gets increased the |
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| 23:31 | in the evening. So I'm showing city as an example of Yeah |
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| 23:35 | But I can actually draw it out show it is an example of |
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| 23:51 | they want to. So, prison . Uh Okay. Oh. |
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| 24:07 | Yeah, I'm honorable. Okay. should work so preseason optically. Let's |
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| 24:15 | you're looking at glutamate synopsis here. . And Lieutenant is being released and |
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| 24:21 | happening, you can barely see Uh Okay, well, so imagine |
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| 24:34 | this guy would be receptor is in receptor that's and dennison increases in the |
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| 24:45 | and the democrats um will shut down but instead of Gaba has found a |
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| 24:51 | and antarctic synopsis. So um I think I can understand. Well maybe |
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| 24:59 | save that for next lecture a few is your plan working you say? |
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| 25:09 | . Oh yeah, I see what saying. Okay, yeah, this |
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| 25:20 | that? All right, Okay, . So you have glutamate and glutamine |
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| 25:27 | being released and you have this readiness receptor. So let's say it's a |
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| 25:35 | and dennison molecule binds to the receptor this receptor through the G protein coupled |
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| 25:47 | controls calcium influx. Okay. And it blocks the calcium channel. So |
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| 25:58 | dennison increases and binds to dentists and it blocks calcium channel and it blocks |
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| 26:06 | release of glutamate. So Jameson will in the evening time. Okay, |
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| 26:15 | increase in the evening time and then will go down in the morning |
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| 26:23 | It increases in the evening time. reduces excitation in the brain. So |
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| 26:32 | calms you down and it's just naturally have neurotransmitters and molecules in our bodies |
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| 26:41 | get expressed as a part of what call a circadian cycle. A day |
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| 26:47 | diurnal cycle. You have a whole that you learn about super charismatic nucleus |
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| 26:54 | express a certain transcription factors at nine chris transcription factors during the day. |
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| 27:00 | it affects our brain function with Mississippi the brain. one of the things |
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| 27:06 | Denison there are dentists and receptors blocking influx and blocking excitation blocking glutamate |
|
| 27:17 | So in this case this is a and we mentioned that caffeine. Yeah |
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| 27:29 | . I am also bind stood down same receptors but what it does it |
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| 27:40 | allows for the opening of the calcium . Actually binding of caffeine to denison |
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| 27:48 | inactive as the G protein cascade allows calcium to come inside the south and |
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| 27:56 | glutamate to be released, awesome opportunity serves. And so that's why Kathleen |
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| 28:06 | such us effect on the brain and lot of us dependent caffeine. It's |
|
| 28:14 | caffeine is a relatively strong chemical was strong addictive properties and Starbucks knows a |
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| 28:30 | about it because they buy three locations one intersection sometimes. Uh but it's |
|
| 28:39 | it's a very potent chemical, natural of it of course is coffee beans |
|
| 28:47 | also t and there's other forms of , there's synthetic caffeine too and this |
|
| 28:56 | of stuff. Again it's not it's stuff that gives jitters to people |
|
| 29:02 | and there's enough of natural caffeine in nature there. But essentially one more |
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| 29:08 | with dennison binding activists jeopardy in cascade shuts down calcium and shuts down glutamate |
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| 29:15 | calms the brain caffeine binding allows for to come in and for glutamate to |
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| 29:23 | release. Yes. So. Uh . Right. Finding a great question |
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| 29:39 | denison uh binding and cycling is related the sleeve disorders and any different sleep |
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| 29:47 | in in general. Uh It could related, could be one of the |
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| 29:53 | there could be other systems that are too. Um But it's a it's |
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| 30:00 | good way to think about it that you don't get enough of the dennison |
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| 30:05 | that you're not going into that calm in the evening. Well honestly I |
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| 30:12 | most of the time when you walk the pharmacy aisles and you look for |
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| 30:16 | aids you will find another natural hormone was melatonin that is used as a |
|
| 30:24 | sleep supplement. So I'm not sure can use it Dennis and something that |
|
| 30:30 | that sleep but pharmacological you can probably and you there are different agonists and |
|
| 30:40 | were dennison receptors to accomplish further different of excitability in those announces good way |
|
| 30:47 | think about it. And as I that you should think about these neurotransmitters |
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| 30:51 | neurotransmitter systems is states up and down downstate caffeine upstate under cannabinoids, happy |
|
| 31:02 | , serotonin, happy, good you know, norepinephrine and adrenaline upstate |
|
| 31:09 | . Um Yes mm. Uh Like a very very like me. |
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| 31:28 | I think you're thinking the right thing is that if you could use an |
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| 31:34 | and block did you program you could levels of excitability and I don't know |
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| 31:40 | there is any approved supplements or medications but I could look it up and |
|
| 31:48 | interesting for now because it's it's one the yes I'm interested in if you |
|
| 31:55 | about it, this is really the system that we stimulate every day and |
|
| 32:00 | is big business so and it's you we were very used to it it's |
|
| 32:06 | uh chemical and it's very habitual to it is cultural and it's cool and |
|
| 32:13 | everything you know from friday to bobo . It's you know, just the |
|
| 32:20 | part of our lives and brains. think we talked about this diagram also |
|
| 32:26 | wanted to point out that instead of segments you would have m trans membrane |
|
| 32:31 | we'll have said units will have the terminals that Kobach sea terminals that you |
|
| 32:37 | variations in these subunits. The arrangements these subunits and this in particular is |
|
| 32:43 | acetylcholine receptor channel. Okay and when look at the metabolic tropic you can |
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| 32:52 | that they are very different. Obviously don't have any channels And instead they're |
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| 32:57 | seven transfer numbering sub units here And one of our subunits here will have |
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| 33:05 | four And one through 4 segments. again neuro pharmacology. Maybe that's where |
|
| 33:11 | should have talked about caffeine and a because it's all mentioned here. Uh |
|
| 33:18 | way of looking at it things you to know settle Coley, nicotine, |
|
| 33:22 | must quranic nicotine, Moscow and cura opinion norepinephrine. You have to know |
|
| 33:28 | dolphin data opposing action and that we with respect to cycling can be. |
|
| 33:33 | never talked about supporter in all the antagonism you're not responsible. Tampon |
|
| 33:40 | D. A. No D. and and the agonists and qx 55 |
|
| 33:45 | gobble being know what they are. the only molecule here is by |
|
| 33:50 | Q. One which is blocker antagonist cabaret you should know 80 P. |
|
| 33:56 | binding to P. Two extra receptor as a T. P. But |
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| 34:00 | binding to a type receptor agonist for same A type or dentist and receptors |
|
| 34:06 | Denniston. And as you pointed out the antagonist is the caffeine. But |
|
| 34:14 | you think about now agonists and antagonists you thought about agonist it closes the |
|
| 34:20 | opens the channel antagonist closes the channel you're activating downstream G burning cascade or |
|
| 34:28 | blocking activation of that G. Burning basket. And now you have all |
|
| 34:35 | these different subtypes of receptors. Yeah every suffer sub units you have alpha |
|
| 34:41 | through six beta one through four gamma through four delta rho. So how |
|
| 34:47 | combinations. How can you can put gamma Some of them will have a |
|
| 34:53 | others will not. The ones gamble have DELTA. Are mostly located outside |
|
| 34:58 | the synopsis and have different functions. the receptor subunit channel subunit composition will |
|
| 35:06 | a lot of what variations of the function that it does inside the cell |
|
| 35:12 | different parts of the stuff. And general when we talk about the neurotransmitter |
|
| 35:19 | , it's a system that we call can amplify the signal because the neurotransmitter |
|
| 35:25 | 21 receptor can activate several Joubert in which can enter act with several downstream |
|
| 35:32 | the molecules secondary messengers and kindnesses and cases that will regulate the phosphor relation |
|
| 35:40 | defrost correlation of various channels And there's arrangements in the brain. There is |
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| 35:47 | through the system. There is divergence one transmitter combined 2123 receptors. This |
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| 35:56 | where one receptor subtype will have three intracellular factors X. Y. Z |
|
| 36:04 | . There is convergence where receptor B. And C. Which is |
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| 36:09 | by different transmitters will all converge on same system. So we saw |
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| 36:14 | alpha nor pan african. They don't up from conversion cycling campy. One |
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| 36:22 | them was pushing it another one was it redundancy. You have redundancy. |
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| 36:28 | a one receptor transmitter a one binding be interacting with effect or three. |
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| 36:38 | a different transmitter be binding to a receptor B will also converge and interact |
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| 36:45 | the factor three. So instead of molecules, you can have one or |
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| 36:51 | molecule and maybe one uh serotonin molecule through different receptors that will converge on |
|
| 36:58 | same molecule. And for cellular early of course you have these parallel streams |
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| 37:03 | are running one transmitter combined To a a two receptor. Um and this |
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| 37:11 | important. Redundancy, parallel streams, and convergence are all important. And |
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| 37:17 | our pathway signalling all the way from molecule no transferred all the way to |
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| 37:22 | nucleus. All right, so with we actually end the neurotransmitter systems and |
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| 37:34 | about how much we've learned about glutamate gaba if emailing in the brain and |
|
| 37:40 | . And now we're gonna move on structure of the CMS. This will |
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| 37:46 | our first lecture in the structure of cns. So if you put these |
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| 37:51 | here on the left and you look them to scale, this is the |
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| 37:58 | Miami about a couple of centimeters in , rabbit brain a few centimeters. |
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| 38:05 | brian, a few more centimeters human dolphin elephant wouldn't even be |
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| 38:15 | This is this is this is actual of the brains. So if criminologists |
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| 38:21 | still uh dictating the science and neuroscience the day and they said that the |
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| 38:31 | muscle can lift more weight and the brain structure can be more capable because |
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| 38:39 | of technologists would say that brain structure grow and cause a bump on the |
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| 38:43 | of your head. So, for would say that dolphins are in |
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| 38:49 | and when you're on the water, are in charge, No doubt about |
|
| 38:56 | . Of course you can be in boat. That's one thing. But |
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| 39:02 | you are in the water, dolphin in charge as a bigger brain than |
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| 39:08 | , I'm not sure sharks have bigger and dolphins or a few months, |
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| 39:13 | they would surely be in charge Uh you look at some of the |
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| 39:17 | species, rat and rabbit, you the surface of the brain is pretty |
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| 39:22 | . That's why there's the saying of brain. The surface of the brain |
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| 39:26 | smooth. And if you look at sophisticated, and of course, when |
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| 39:30 | finally look at the human brain, have a lot of ridges and imaginations |
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| 39:37 | ridges, Gira and self sign that's the surface area of the brain, |
|
| 39:45 | ? Yes. So we have certain and the planes a lot of times |
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| 39:54 | neuroscience and your anatomy. The description where you are in the brain. |
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| 40:01 | tell you whether you're looking at something , dorsal or ventral, lateral. |
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| 40:08 | so this is the interior ross troll front. This is posterior cardinal, |
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| 40:14 | is door. So, this is , and you can see in |
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| 40:19 | the CMS there is not much angle the brain and the spinal cord, |
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| 40:25 | in humans and to like a there is almost a 90° angle between |
|
| 40:31 | brain and the spinal cord which will down. But nonetheless, the back |
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| 40:36 | be the dorsal side and the front be the ventral side. Then the |
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| 40:42 | to midline you are, the more you are, the further away from |
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| 40:46 | line you are, that means you're more and more lateral, this is |
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| 40:53 | to coddle. And so if you the brain and you cut it in |
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| 40:58 | fashion here. Through this plane, call it mid sagittal cut, it |
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| 41:03 | be able to visualize what's inside of brain going from middle to the outside |
|
| 41:09 | or from lateral edges to the medial . Cut the brain horizontally. Or |
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| 41:15 | can produce corona all sections. And do you talk about mid sagittal horizontal |
|
| 41:22 | ? Because if you study your if you end up in Dental |
|
| 41:26 | medical school graduate school, that was anything to do with the neuroscience, |
|
| 41:32 | will see that this is a language the scientists speak, they will say |
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| 41:36 | you're looking at the corona sections through occipital lobe and that would be enough |
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| 41:43 | me to understand what structures that may looking at. But if somebody just |
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| 41:49 | me a slide and I didn't have good orientation of the whole brain, |
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| 41:54 | would be more difficult for me to to file though, would still be |
|
| 42:00 | . So now you have on the of the brain cerebellum brain stem spinal |
|
| 42:08 | features that are very similar. This mid sagittal cut. This is this |
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| 42:14 | right here Miss Agile which basically exposes inside the midline of the brain. |
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| 42:19 | you can see the structures that run the midline of the brain. So |
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| 42:25 | have cerebellum, serie broom and cerebral . Uh big distinguishing features. We |
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| 42:38 | lateralization and we have contra lateral sensor motor control of information in the cerebral |
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| 42:47 | hemispheres but at the level of the this is absolute lateral control of movement |
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| 42:55 | brain stem is where you have a of pathways that are going from cerebral |
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| 43:00 | cerebellum and from sarah Palin back two areas brain stem and we will be |
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| 43:08 | more and more into detail to these is mostly concerned with vital body functions |
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| 43:16 | as breathing consciousness, thermal regulation heart , this is all at the level |
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| 43:26 | the brain stem. Yeah, brainstem grain stone. Yeah. |
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| 43:49 | tired of all time. Yeah, in Lucia, the easiest, most |
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| 43:57 | way to prospect right here. right, a great bravo. You |
|
| 45:31 | know this guy pinky and the brain you're going to know more than he |
|
| 45:38 | but this is a good uh cartoon watch actually and there's other good material |
|
| 45:45 | one but everything that he was singing , you need to know about, |
|
| 45:50 | know where it's located in the So that pretty much after we're done |
|
| 45:55 | the next couple of lectures. So brainstem peripheral nervous system No time to |
|
| 46:03 | about it, voluntary motor sensory skin muscle, Somatic control of this. |
|
| 46:09 | control of the organs, economic internal , blood vessels and glands. And |
|
| 46:16 | the extent of the peripheral nervous system this course. Because we're really focusing |
|
| 46:22 | the C. N. S. what the Sienna says. I don't |
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| 46:24 | what this green line that were in repaired from. It's kind of annoying |
|
| 46:31 | CNN. S. Is protected by in in jeans. So you have |
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| 46:35 | major meninges. You have the dura which is the hard mother. You |
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| 46:40 | Iraq Noid which is this space Adenoid membrane space which is also referred |
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| 46:48 | as Supergirl space. And then you pia mater or the gentle mother which |
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| 46:55 | the last meninges. The softest one covers the brain, the closest and |
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| 47:02 | most inside of all of the And ng's You can see the blood |
|
| 47:08 | and micro vessels penetrating into the blood into the brain tissue. And if |
|
| 47:14 | recall the early days when we talked the brain trapper nations and he |
|
| 47:19 | why would you do these brand trapper ? Because you can have a subdural |
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| 47:26 | , subdural hematoma, blood clot formation of the blood blood clot formation, |
|
| 47:34 | on the brain. A lot of . How do you get and clean |
|
| 47:37 | up? You penetrate the skull. penetrate through them in NGos. You |
|
| 47:44 | out the one and you cover it . Vote for why did they do |
|
| 47:49 | ? Because you may have a recurring . The recurring information, you may |
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| 47:55 | this problem in multiple to three places the brain and that's why they were |
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| 48:01 | nations that were done in 23 places the brain potentially to access multiple blood |
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| 48:08 | and Irma thomas or large hematoma that to be cleaned out From 2 to |
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| 48:14 | points into the brain. So I believe that there was a clinical reason |
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| 48:24 | brain triple A. Nations, not a shamanic, spiritual healing and subdural |
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| 48:36 | , abnormal fluid formations, normal cerebrospinal information. All of these things could |
|
| 48:44 | played a role in having done those and the prehistoric times. We have |
|
| 48:50 | ventricular system that's pretty massive and the system is responsible for circulating and generating |
|
| 48:59 | spinal fluid. So this cns this brain structure and the spinal cord is |
|
| 49:06 | by them in NG's and is sitting this flu this environment. So if |
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| 49:12 | hit your head, there is sudden or something, you actually have cushioning |
|
| 49:18 | the fluids and you have the support protection and cushioning from the meninges. |
|
| 49:26 | if dura mater is the toughest tough or hard mother, it's really tough |
|
| 49:36 | get through the ramada how tough you to press a scalpel really hard and |
|
| 49:42 | and exact a knife to cut through dura mater. So it is like |
|
| 49:49 | hide almost the consistency of your amata , but it's not easy to penetrate |
|
| 49:56 | it. Iraq noid is more like web, correct annoyed spider like web |
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| 50:04 | pierre is softer. So even injury the skull and penetrative injure into the |
|
| 50:14 | such as breakage of the skull You have still dura mater that may |
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| 50:21 | from an open wound forming into the and then the softening by the pia |
|
| 50:29 | and then the movement by the fluids allows for the soft tissue to bend |
|
| 50:34 | the side of the injury. Uh . What is the data? What |
|
| 50:43 | it mean? It sells uh what's exact cellular composition of the matter? |
|
| 50:53 | don't know that. It's a very question but it is definitely hard and |
|
| 50:58 | my experience of working with cadavers, is tougher than the skin for |
|
| 51:04 | And I would compare it to closest hide. But what types of sounds |
|
| 51:10 | ? That's very good question. Okay you have the circulation. That's another |
|
| 51:16 | of cushioning. But that's not only pia mater also provides nutrients. It's |
|
| 51:23 | and of course you have a lot nutrients and necessary elements for brain functions |
|
| 51:29 | come from the super spinal fluid circulates the ventricles circulates through the lateral ventricles |
|
| 51:38 | too circulates all the way into the canal into the cardinal regions enters into |
|
| 51:47 | subarachnoid space and the cord plexus is part where the cerebral spinal fluid gets |
|
| 51:57 | and it gets produced and it gets and gets regenerated and reproduced every |
|
| 52:04 | And so if you have a brain , a way that you would test |
|
| 52:09 | brain infection as you would sample through spinal fluid from the spinal cord from |
|
| 52:16 | spine because the infection would indicate that in the fluid. Yeah, |
|
| 52:25 | Could that have been another reason why trapper nations were done to hydrocephalus is |
|
| 52:33 | formation of the service spinal fluid, over production and drainage of service spinal |
|
| 52:40 | which ends up in the developing the skull is soft. We discussed |
|
| 52:45 | a little bit earlier that in fact will have to fusion spots and the |
|
| 52:51 | on the back in the infants. if you put your finger in the |
|
| 52:55 | head right here on the top. scary because it feels like you're putting |
|
| 53:02 | head on something very soft and quite because the skull the skull place have |
|
| 53:08 | fused together and they don't use for whole year, first year of |
|
| 53:13 | The background fuses before this one. , uh that means the bone is |
|
| 53:20 | . So if during these early because developmental person personnel developmental stages, |
|
| 53:26 | have abnormal formation of the fluid. ventricles are going to end gorge as |
|
| 53:34 | expand. They're going to start pushing the brain tissue as they push on |
|
| 53:39 | brain tissue. Brain place you starts on the skull because the skull is |
|
| 53:45 | so you can you can stretch it you can appeal that and push the |
|
| 53:51 | parts apart. And so that's why the case of hydrocephalus you would have |
|
| 53:58 | abnormal Children. This is really bad but with very large heads, you |
|
| 54:07 | almost like alien like heads. So can happen of course is just you |
|
| 54:15 | , some sort of abnormal development But hydrocephalus that I have experienced in |
|
| 54:23 | infant in the hospital, it was serious case of hydrocephalus here in texas |
|
| 54:31 | I see you there's a shaken Uh there is shaken baby syndrome from |
|
| 54:40 | shaking baby when parents are either not or cruel or stressed out and frustrated |
|
| 54:52 | the babies are crying, they are with them, they don't know what |
|
| 54:57 | do in them. Also to start and you stop crying, stop |
|
| 55:01 | And this can actually lead to So you can have injury. It's |
|
| 55:10 | just developmentally dysfunctions. It could be to injure, it could be due |
|
| 55:16 | traumatic brain injury. It could be to shaking. You know, |
|
| 55:21 | rapid shaking. It's not something that parents typically do and the father was |
|
| 55:29 | led away by police from nice to . It was very sad and the |
|
| 55:35 | had a drainage installed. So you put a needle or a tube insert |
|
| 55:42 | the ventricles and you will be training fluids, they want to control them |
|
| 55:47 | the floods. If it is something a child is generating, what |
|
| 55:52 | you know, doesn't require the child be. And I see you then |
|
| 55:57 | tube will go, drainage tube will into the peritoneal cavity. We'll get |
|
| 56:03 | up with a little bit of extra to grow so it can stretch while |
|
| 56:09 | fluids are being drained and just metabolized the body. So, could this |
|
| 56:14 | been another reason why the pyre? . Indians in peru were doing brains |
|
| 56:21 | ? Oh, probably yes, because , how do you access to fluid |
|
| 56:26 | the ventricle have to make a hole the skull. Now we have these |
|
| 56:32 | , you know, needles and tools things we can insert and leave. |
|
| 56:36 | at that time now, so I be surprised that there were maybe even |
|
| 56:41 | for draining the fluids from the Not just digging into the sculpt issue |
|
| 56:46 | I showed you earlier in the Mhm. And we will start talking |
|
| 56:53 | the development of the cns today in about neural tube formation. So, |
|
| 57:01 | you know, you have these three of uh developmentally and adam method ERM |
|
| 57:10 | actor. Durham. Three types of . You have neural, this is |
|
| 57:18 | neural plate and this neural plate where have here, victor. Durham shown |
|
| 57:25 | . Mr Durham that the endo Derm in yellow, then you have the |
|
| 57:32 | around the neural group here, you the folding of this plate into neural |
|
| 57:39 | . So these three layers of these are laying there. This is pretty |
|
| 57:45 | . This whole structure like self assembles from some code. All these self |
|
| 57:52 | three types of tissues come together, together and we have CNN's and think |
|
| 57:58 | developmental malformations in the brain are quite And how complex the structure is all |
|
| 58:07 | way from cns in the spinal We're talking about developmental malformations one and |
|
| 58:13 | maybe. And during the formation of process of neural tube formation, no |
|
| 58:19 | or the differentiation process. Later you this neural tube that forms from the |
|
| 58:26 | group that's in green that's surrounded by my voice, so mine's become vertebral |
|
| 58:34 | and skeletal muscles. So you can already the formation of what will be |
|
| 58:41 | spinal cord here and the skeletal muscles will come from these primordial cells, |
|
| 58:48 | crust formation here, we will follow this and the following stages and the |
|
| 58:55 | this tube falls, the more complex gets inside the tube. This process |
|
| 59:01 | relation process and new term becomes lining internal organs. Of the syrup |
|
| 59:11 | ERM is skeletal bones and muscles. . Actor Derm is nervous system and |
|
| 59:24 | . So the closest pluripotent cells to are actually skin cells. So you |
|
| 59:32 | take skin cells and you can can a blue of potent cell stem cell |
|
| 59:39 | you give it the right cues, can either develop into skin cell or |
|
| 59:43 | self. It's pretty, pretty, interesting. So this is the process |
|
| 59:50 | no relation. And then this gets complex and the cns goes through the |
|
| 59:55 | of differentiation. So the flat plate folded into a tube now becomes more |
|
| 60:03 | and the top of this to becomes cephalon which is the forebrain, the |
|
| 60:08 | of the maison cephalon or midbrain and settlement of the hind brain. So |
|
| 60:15 | are the three primary brain vesicles pros and roman cephalon. Mhm PMR. |
|
| 60:27 | can start from the top PMR. way to remember The pros in central |
|
| 60:33 | in four brain differentiate. And to us the phallic vesicles the still |
|
| 60:40 | So phallic vesicles will become cerebral cortex diane cephalon which will become the thalamus |
|
| 60:48 | hypothalamus in the brain. These are optic vesicles coming out here. These |
|
| 60:55 | vesicles will end up producing the retina the eye and that's why everybody in |
|
| 61:02 | department of optometry and ophthalmology is and because retina is a part of the |
|
| 61:07 | nervous system. Think so you have further shape taking for midbrain and hind |
|
| 61:18 | and this is showing you that optic optic stock information of the optic cup |
|
| 61:26 | this optic cup is what is going house the retina in the back of |
|
| 61:31 | eyeball coming off right here. Also of the essentially president cephalon and forebrain |
|
| 61:41 | . Then telling cephalon forms to So left in the right hemisphere this |
|
| 61:49 | to put things in perspective. You olfactory bulbs in the front. These |
|
| 61:53 | the optic cups which are the eyes bulbs. Remember we have this input |
|
| 61:58 | the nose we discussed that goes in front here for a factor information processing |
|
| 62:05 | , insightful um turns out and becomes and diane cephalon. Okay diane cephalon |
|
| 62:15 | into the thalamus here on top and underneath. Okay and then you have |
|
| 62:23 | the cerebral cortex and the basil tell stuff alone. The ventricles you have |
|
| 62:30 | ventricles. You have the third ventricle then you have the fourth ventricle that |
|
| 62:34 | into the spinal canal. The major bundle that starts forming to connect the |
|
| 62:40 | hemispheres is the corpus callosum. The hemispheres are interconnected with each other. |
|
| 62:48 | lateralization of brain function between left brain right brain but they communicate with each |
|
| 62:54 | with these massive fiber bundle called the callosum. So if you cut the |
|
| 63:01 | callosum you would destroy the internet in communication basically. And then you have |
|
| 63:10 | matter here coming out. It's called internal capsule and critical white matter. |
|
| 63:15 | there are projections that start forming between cephalon under cortex and vice versa from |
|
| 63:22 | cortex to die. And supple into us and hypothalamus and thalamus and cortex |
|
| 63:28 | the internal capsule in the white And the communication with the cortex will |
|
| 63:34 | processing all of the sensor information that into the cortex. Mhm. So |
|
| 63:42 | if we lay it out you have felon cephalon. Diane cephalon, mesen |
|
| 63:48 | , Romblon, cephalon. What is been cephalon? Which is what is |
|
| 63:53 | cephalon. Diane cephalon is the thalamus hypothalamus. Mesen cephalon is the |
|
| 64:01 | Midbrain is tacked on and take textile is the roof. So it's |
|
| 64:08 | the dorsal side to protect you from rain cerebellum. This is a part |
|
| 64:13 | Ramadan cephalon. Ramblin suffering becomes palms and medulla oblong gotta. And |
|
| 64:23 | yellow portion is the spinal cord. you can see that in the cerebral |
|
| 64:29 | you have the tool one and Or lateral ventricles. You have the |
|
| 64:34 | ventricle. You have the cerebral aqueduct the fourth ventricle. So the third |
|
| 64:42 | . We'd be going from the dance and the fourth ventricle will be found |
|
| 64:47 | the brain stem and finally the spinal the small canal that would go all |
|
| 64:54 | way through the spinal cord and supplying cerebrospinal fluid. So brain ship enterprise |
|
| 65:02 | versus apparatus, sauce i grooves gyro Rijs cortex is the reasoning and cognition |
|
| 65:13 | rats also have cortex. So what's special about us. Neocortex is only |
|
| 65:26 | mammals but there's a lot of mammals this earth. So are they capable |
|
| 65:34 | cognition rats. So we asked them cheese. Yeah. I don't |
|
| 65:49 | What do you guys think compliance Well you they understand the difference between |
|
| 65:58 | , religion and science. I don't right? It's like different, different |
|
| 66:06 | of knowing what these animals are capable . You obviously look at the human |
|
| 66:11 | and you're like, this is really compared to the, to the rat |
|
| 66:15 | . You also look at the rat and you say these are massive. |
|
| 66:18 | factor results. What are you I'm smelling all day long. That's |
|
| 66:22 | I'm doing. You know, that's his brain tissue is pertinent. That's |
|
| 66:28 | a lot of it is dedicated But overall, if you look at |
|
| 66:34 | structures that there are a lot of , brain stumps are about lone major |
|
| 66:42 | , Fourth ventricle ponds. You'll find here. But you can see the |
|
| 66:46 | is much stronger. It's almost 90° is compared to the rat. But |
|
| 66:52 | of the same structures about maduro bronchitis bouncing off cortex but there will be |
|
| 66:57 | sophisticated and because you have the dry salsa, you have an incredible amount |
|
| 67:04 | space area that allows you to increase you basically form these grooves and |
|
| 67:11 | This is a really nice representation of ventricular system in three dimensions. Inside |
|
| 67:17 | brand lateral ventricles, the third to in the brain stem and the spinal |
|
| 67:24 | and again the cortex is divided into lobes, frontal, parietal, occipital |
|
| 67:34 | , frontal and parietal are separated by central focus. Um, So |
|
| 67:42 | And it's another interesting thing that if go and catch an alligator and I'm |
|
| 67:48 | gonna walk national preserve down, I hear. And you cut into the |
|
| 67:54 | brain you will see the same it'll sell in the cortex that you |
|
| 68:00 | see in the rats cortex and you see the same criminal cell in the |
|
| 68:06 | cortex to so there's a lot of and cellular redundancy across the species. |
|
| 68:19 | lot of things that we know from of these studies from action potentials also |
|
| 68:26 | , they're not from humans, they're this all animal studies squared right brain |
|
| 68:35 | miles. Transgenic mayes, snail recordings what plasticity was discovered. So all |
|
| 68:46 | these things, there's an incredible redundancy , alligator. What do I do |
|
| 68:51 | day long I smell for food? my chicken bone from the swamp boys |
|
| 68:59 | me rat still. But you can that alligator actually is mostly driven by |
|
| 69:06 | by smell because of the very large that the factory balls occupy. And |
|
| 69:14 | find the structures and you'll find the largest structure and the mouse cortex and |
|
| 69:20 | right cortex in the in the And you'll find a six layer structure |
|
| 69:24 | the human cortex to so these simple of us or are the different simpler |
|
| 69:36 | of us were a lot of their and brain man and structures dedicated to |
|
| 69:42 | things. You know, imagine if had to smell for six hours a |
|
| 69:49 | to get by from a life and had no other dominant senses that you |
|
| 69:54 | barely see still here and smell. you talk to people that have |
|
| 70:02 | they lose sense of smell and taste a couple of weeks is the worst |
|
| 70:06 | ever. I'm eating cardboard. That's it's, that's what it feels |
|
| 70:11 | It has no taste at all. uh anyway, so this is sort |
|
| 70:15 | a little bit of a contemplated uh side note here about where his |
|
| 70:26 | what his thoughts, you know, animals understand intention? What animal species |
|
| 70:35 | understand intention, intention from other Or is it all reflects of reactive |
|
| 70:40 | driven uh mating driven, survival driven so on. So when we come |
|
| 70:49 | on Tuesday, which is actually on , when we come back on monday |
|
| 70:57 | will continue talking about the cerebral cortex you'll understand the anatomy of the cerebral |
|
| 71:03 | really well how different thousands are connect . So you'll know that what we |
|
| 71:08 | the canonical cerebral cortical circuits, how communicate in this and you'll know a |
|
| 71:16 | more about different brain stretches and their . This was sort of an overview |
|
| 71:21 | development. We're going to go into parts of the brain stem, different |
|
| 71:26 | of the um diane cephalon. It also study the 12 climate all |
|
| 71:33 | So for now I recommend you guys all of the neuro transmission material for |
|
| 71:39 | quiz on friday. But we should in two ways. The quiz on |
|
| 71:44 | and then I'll see you back here monday again. Yes. Uh |
|
| 71:52 | Yeah. Thank you, professor. welcome. Thank you. Yes. |
|
| 71:58 | new material is available. Yeah, was not. I checked before the |
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| 72:01 | . For some reason it was hidden you guys. Uh This is available |
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| 72:06 | . Thanks for asking. Mhm. Uh huh. Bang. Mhm. |
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| 5999:59 | |
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