| 00:00 | So this is electro 14 of neuroscience continue talking about neurotransmitter systems. This |
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| 00:07 | reviews different techniques that were used to expression of neurotransmitters as well as our |
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| 00:15 | . So on the top left, have, you know, history |
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| 00:19 | which is using antibody and the visible that's attached to that antibody. You're |
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| 00:26 | for the South that express a specific or a specific molecule of interest on |
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| 00:33 | middle. Here we have a picture in situ hybridization, in which case |
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| 00:38 | using a radioactively labeled probe that's comprised a particular sequence off Nick Clegg assets |
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| 00:47 | the strand of Amarna in the neurons complementary, exactly. Complementary to the |
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| 00:52 | , we'll show the minding and show stain expressing, showing only the South |
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| 00:58 | expressed this particular molecules of interest. third technique shown here is neurotransmitter. |
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| 01:06 | is on the functional side, meaning if you stimulate this acts on your |
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| 01:10 | glutamate in your recorded posson attic Be excited, Terry, plus synaptic |
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| 01:16 | . If you apply that glutamate through injection on toe this neuron onto this |
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| 01:22 | drive, you'll also should be able report an E. P s |
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| 01:25 | And in addition to this application, like application of chemical song Thio den |
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| 01:32 | our accents. We also discussed no . I'm Caijing molecule engaging, which |
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| 01:41 | you to focus in on very, small area, activating just single synopsis |
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| 01:47 | the time. So the most important that we've discussed is amino acid |
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| 01:55 | You know, Colin, serotonin, mean and and do cannabinoid system. |
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| 02:01 | , you know, I said, know that glutamine through blue dominates gets |
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| 02:06 | into glutamate. Mhm. And that gets converted into gabba through God. |
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| 02:14 | all of the inhibitory cells we'll have expressed Gap and we'll be able to |
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| 02:21 | Gabba. All of the exciting Terry will, uh, be releasing glutamate |
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| 02:27 | the civil. Colin. We reviewed pathways or tone, and we reviewed |
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| 02:31 | battling and Katou Colon means so for . It's very important, you |
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| 02:35 | the synthesizing and degrading molecules, the that you have a transporter or putting |
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| 02:42 | molecules back, synthesizing it at the of the cells here and then releasing |
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| 02:48 | prison topically so and Colin urging neuro , we distinguish the fact that you |
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| 02:54 | an endogenous agonist and endogenous acetylcholine, is produced by our bodies versus exogenous |
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| 03:02 | nicotine from nicotine ICC Channel receptor. this seal Colleen receptor is a channel |
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| 03:09 | must Quranic. It's also an exogenous , which is specific to most Quranic |
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| 03:16 | receptor. And it's a measurable tropic will discuss the functions of these |
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| 03:22 | and they also have exogenous antagonist such Cure Ari for nicotine IQ receptor and |
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| 03:27 | trap infamous Koranic receptor. So once have activation of nicotine receptor shown here |
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| 03:35 | the right, binding of acetylcholine molecules this nicotine receptor will allow the passage |
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| 03:41 | flocks off sodium and calcium islands D slightly the numbering but also affecting other |
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| 03:50 | . Key defectors inside the cells such intracellular calcium concentrations um, voltage dependent |
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| 03:59 | channels, both educated calcium channels. . Also some other downstream molecules just |
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| 04:07 | in tiny see so nonetheless binding of civil code into these nicotine receptors will |
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| 04:15 | the flux of ions through the poor exists in these channels. Medical tropic |
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| 04:23 | of acetylcholine receptor. It comes in different forms, but when acetylcholine activist |
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| 04:29 | tropic receptor, you have this membrane Jason G protein complex and catalysis of |
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| 04:35 | Jew protein complex could do several But in a shortcut pathway, activation |
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| 04:40 | aceto holding that over tropic receptor bacile , you can see that this receptor |
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| 04:46 | not conducting any islands, but instead receptor will send catalytic subunits of the |
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| 04:52 | protein which will in turn control the of potassium ions inside the cell. |
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| 04:59 | , so this is called the shortcut because directly from myself, during G |
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| 05:05 | you're affecting in nearby um channel Potassium in this case on what it does |
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| 05:12 | that binding off Siddle Colin too, Koranic receptor opens up with Cassie um |
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| 05:18 | when that potassium channel was open. happens is the potassium leaves the |
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| 05:25 | So these these nicotine receptors allow for charge to command sodium and calcium |
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| 05:32 | contributing to the deep polarization and activation masculine interceptor opens potassium channel. So |
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| 05:38 | the inside of the cell will be hyper polarized. So now you understand |
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| 05:43 | these air opposing action mechanism the sense this will de polarizes, sell nicotine |
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| 05:48 | must Quranic receptors can hyper polarizes but must quranic receptors and these G |
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| 05:53 | complexes are more sophisticated than just one . And this diagram shows and binding |
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| 06:01 | , locally, into the mosque or a receptor, you can have activation |
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| 06:05 | G I. G O Prodi. gee, inhibitory Prodi, um on |
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| 06:12 | is tied to a general cycle you know, the num brain, |
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| 06:16 | it can actually block the production of KNP, which is a secondary |
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| 06:21 | And if it's started to G Q team and these different subtypes of must |
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| 06:25 | receptors and one and two and three four and five, they're tied thio |
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| 06:30 | G type off G uh protein Another type of G protein complex G |
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| 06:37 | . There will be affecting the like Pacey back way and I still |
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| 06:42 | , as well as influencing the release calcium from the internal calcium store. |
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| 06:47 | you can see that both of these of the continent and muscular Nick will |
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| 06:52 | key effect is what you can see most of the factors, um, |
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| 06:55 | critics side are really related. Thio related to ju protean signaling and downstream |
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| 07:02 | from these G protein complexes that are with different subtypes, most Koranic |
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| 07:09 | So we also discussed can Nicola Means cycling of cattle Cola means we talked |
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| 07:16 | different pharmaceutical drugs and different illicit drugs interact with the neuro transmission and |
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| 07:24 | Cattle colonies are responsible for movement because know that dopamine and dopamine dysfunctional effect |
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| 07:32 | , and it's a part of movement such as Parkinson's disease. It also |
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| 07:36 | mood. It gives us positive boost stimulation attention. We focus in norepinephrine |
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| 07:44 | epinephrine. This is your fright or responses. Adrenaline off the brain, |
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| 07:48 | attention as well as it can influence . They're all functions, which is |
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| 07:53 | the periphery. Serotonin function is important mood for appetites. Sleep learning |
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| 08:02 | The system is very much involved, all of these processes and there is |
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| 08:10 | overlap between what these different neurotransmitters do aspire, is what behavioral functions they |
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| 08:15 | that now we have norepinephrine that we're about. It's all mentioned the actions |
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| 08:21 | norepinephrine and the brain. This is molecule norepinephrine. When it binds, |
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| 08:26 | can actually has two dominant receptors. data receptor, which is called the |
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| 08:31 | receptor, and the alfa two So these air the tune norepinephrine or |
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| 08:36 | origin ergic receptors, data and allergic refers to, nor adrenaline or nor |
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| 08:42 | Africa. Right? So this beta activation by norepinephrine and these molecules, |
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| 08:49 | like with nicotine nick and must Quranic , they could be located on the |
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| 08:55 | or Jason pieces of the membrane, competing inside the cell for both physiological |
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| 09:00 | downstream biochemical activity and functions. And activation of northern happen can activate these |
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| 09:07 | opposing action receptors on these air receptors will bind wanna Northern Africa data receptor |
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| 09:13 | activate the G protein and will activate general cyclists and increase the production off |
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| 09:19 | KMP, which will stimulate the production protein Chinese A and Chinese for small |
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| 09:25 | different molecules and channels and proteins. protein kindness production will increase the forceful |
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| 09:32 | channels. On the other hand, have foster cases, so kindnesses will |
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| 09:36 | a foster group p 04 and foster will detract that p 04 group. |
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| 09:41 | so there's a certain balance of these kindnesses and foster cases inside the |
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| 09:46 | in regulation of their levels and at of cellular to small regions of these |
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| 09:51 | receptor molecules that actually can very much the downstream functions as well as further |
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| 09:59 | off the signaling pathways at the level the receptors and inside the south as |
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| 10:06 | . So if you activate beta you increase the production of protein kind |
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| 10:10 | saying cycle people, if you activate tourist sector, it's lengthen inhibitory protein |
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| 10:16 | I and that will inhibit and then cyclists and will reduce and inhibit the |
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| 10:21 | of psychology and being inhibit the production 30 and dining saying so you have |
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| 10:27 | downstream activation, you have some membrane enzymes and then you have intermediary reactions |
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| 10:34 | these downstream enzymes and activation of downstream and activation of effect of molecules. |
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| 10:40 | this is referred thio push pull mechanism on one hand you have the stimulatory |
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| 10:45 | receptor northern efforts through that receptor, the system to produce more protein |
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| 10:54 | Um uh, more cycling campy and Alfa two receptors pulling the system away |
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| 11:01 | producing more protein kindness and cycling Okay, so all of these is |
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| 11:07 | shows you again. These receptors can located adjacent piece of the num brain |
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| 11:11 | wins data or Alfa two? it depends on the density expression of |
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| 11:17 | receptors how close they were located to release of norepinephrine bond such. But |
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| 11:25 | very important to now is the pre terminals for these molecules. For these |
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| 11:32 | and other signaling molecules such a serotonin steal Colleen or dopamine or histamine, |
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| 11:39 | have specific nuclear and 1000. These express these neurotransmitters. The difference is |
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| 11:47 | you will have GABA and glutamate neurons very widely throughout the cortex, the |
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| 11:54 | , the sub cortical structures and the assaults that resemble excited Torrey Salsa. |
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| 11:59 | all of this glutamate production in the of glutamate happens local, and it |
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| 12:05 | locally all over the brain and between cells and the glial cells. But |
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| 12:11 | production of these molecules so just norepinephrine happens in local civilians, and then |
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| 12:16 | projections from local civilians. Def usually into different cortical regions and sub cortical |
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| 12:23 | . Projected to the Syria about Sarah is well downstream into spinal cord, |
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| 12:29 | it will be a release of this throughout different parts of the brain, |
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| 12:34 | the receptors that are located, whether al forbidden in different parts of the |
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| 12:38 | or both, will determine the physiological and molecular functions downstream that these neural |
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| 12:46 | will now activate. But this spot a very spun special spot. Local |
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| 12:51 | from norepinephrine grafting nuclei would be producing molecules and serotonin molecules again well, |
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| 12:58 | there's a sprinkler system. The pre terminals will release the start owning |
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| 13:04 | Hey, and then serotonin receptors will located throughout the brains or ballon and |
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| 13:10 | in the spinal cord, so these will be affecting and causing a significant |
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| 13:15 | on different parts of the brain. the synthesis and the the the neurons |
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| 13:21 | express serotonin on Onley, located in Rafi nuclear, the projections of pre |
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| 13:27 | terminals our extensive but the so mus actually produce and code for this |
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| 13:34 | The genetic information for quoting certain in North Pole effort is located in these |
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| 13:39 | specific brainstem nuclei, Raffi for certain Locusts or alias for Nora. But |
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| 13:45 | Fran Magnus, cellular basal forebrain for coa union and particular Ponting and lateral |
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| 13:54 | segmental nuclear for a silicone so you see two green nuclear here to different |
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| 13:59 | of the brain stem brain stem, these will forebrain that are producing a |
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| 14:03 | column. It's the meanest producing that their family nuclear's. And then you |
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| 14:09 | dopamine that's produced an eventual take mental and substantial Migra. So all of |
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| 14:14 | different nuclei produced a specific neurotransmitters that discussing is very important. And the |
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| 14:21 | again, they're different because in the are generated inside the cells on demands |
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| 14:27 | the secular release, either glutamate or can turn on the production of in |
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| 14:32 | cannabinoids and a lipid soluble right. there are lipo Tillich. They crossed |
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| 14:39 | the plasma membranes and the retrograde They activated cannabinoid receptors on the pre |
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| 14:45 | terminals that elected you protein couple complexes can control calcium channels as well as |
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| 14:51 | release of glutamate and gamma. So agonists are endo, cannabinoids and |
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| 14:57 | um, I've been to a G electric gladly. Through this negative feedback |
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| 15:02 | , target cannabinoid receptors and control your as well as exogenous substance, which |
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| 15:08 | tetrahydrocannabinol, which is phyto. Cannabinoids in cannabis plant also binds to these |
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| 15:15 | and agonist to the CB one also controlling excited her and inhibitory neural |
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| 15:21 | . So, for the inhibitory we call deep polarization and do. |
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| 15:24 | of an ambition is the term for , for this whole process and deep |
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| 15:29 | and do suppression of excitation with excited blue dermatologic synopsis under cannabinoids function record |
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| 15:36 | as well as the gasses and other . Or not packaging bicycles and neither |
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| 15:41 | small yours. Now, when we about glued a maid again, I'm |
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| 15:46 | you that you have glutamate and with Hassidic or box laced with God, |
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| 15:51 | have conversion into Gabba inhibitory neurotransmitter. let's remind ourselves that glutamate when it's |
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| 15:57 | , it will also find Thio I a tropical to make receptors and memorable |
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| 16:02 | glutamate subjects. Once in the synaptic , glutamate will get recycled back. |
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| 16:07 | glutamate transporters person optical and reloaded into vesicles for the subsequent XO psychosis and |
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| 16:14 | of the cycle or glutamate in this synapse, which is three parts pre |
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| 16:20 | neuron poss, synaptic neuron and glial . And this tripartite synapse glutamate can |
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| 16:27 | important into the glial cells and with synthesis converted into glutamine and then glued |
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| 16:34 | , in transported pre synaptic Aly and blue Tom minis and energy produced, |
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| 16:40 | upload is glutamate into the vesicles again subsequent mix of psychosis was very important |
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| 16:46 | the cycling and synthesis and production of it actually happens throughout, where the |
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| 16:52 | Terry synopsis and excited to neurons are throughout the brain and the Gabba. |
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| 16:57 | is the same way conversion of glutamate Gabba that is very juxtaposed to these |
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| 17:02 | specialized locations that are responsible for the off norepinephrine, serotonin or other |
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| 17:10 | So Jabba will have its own transporters transport into the pre synaptic site and |
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| 17:15 | into the vesicular glutamate will have its transporters eliminate. We discuss, binds |
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| 17:21 | types of eye on a tropic You have Ampara and M D |
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| 17:25 | And kinda to eliminate is an endogenous endogenous agonists for these three receptors and |
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| 17:32 | they have their own distinct chemical Ampara and India and China that will |
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| 17:37 | activate the specific receptor channels. We that the early phase of the |
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| 17:42 | P s P, the release of , will cause the opening off Amper |
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| 17:48 | . And so this initial deep polarization because glutamate. As soon as it |
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| 17:52 | the Amper channels addressing member in it will open up the channel cause |
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| 17:57 | influx of sodium causing the initial deep during this excited turn cost somatic |
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| 18:03 | But we discussed it, and then air receptors, which are this is |
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| 18:07 | on a tropic signaling so far in the Heiress chapters air different because they |
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| 18:11 | magnesium, blah and binding of It resting number and potential is not |
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| 18:16 | . Thio open an MBA receptors, then the air receptors have toe feel |
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| 18:22 | the Boston optic member and has been polarized through Amper receptors before magnesium leaves |
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| 18:28 | channel at the D polarized membrane So magnesium blocked leaves the channel, |
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| 18:35 | you have an influx of sodium and , and it's responsible for the lady |
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| 18:40 | phase of the PSP and then The flux through both of these channels |
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| 18:45 | A and An M D A channels be responsible for the re polarizing phase |
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| 18:49 | the secretary processing that control here. when we talk about non NMDA receptors |
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| 18:56 | really a grouping, Ampara and It's together because off their properties the |
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| 19:02 | that they're not blocked by magnesium also they conduct only about 20 people, |
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| 19:08 | through their channels and then D A conducts about 50 peak of cements, |
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| 19:14 | each one of these also ample kind have its own. Blockers are |
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| 19:18 | Such a seeing Q X and M A will have its own antagonists, |
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| 19:22 | as a P V and then A. Receptor is also more complicated |
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| 19:27 | Emperor receptor. So this is non receptor shows. Binding of Blue |
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| 19:32 | It will open this receptor channel on will flux through it. This happens |
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| 19:37 | Resting Member Central, but an M heiress after receptor is referred to as |
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| 19:44 | detector. Okay, so listen to part carefully. Why is it coincident |
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| 19:49 | ? Because, if coincidentally, has detect neurotransmitter release neurotransmitter release, which |
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| 19:56 | glutamate, glutamine has to bind to receptor. In addition to glutamate, |
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| 20:01 | have glide seen as a co so in spinal cord glisten was inhibited |
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| 20:06 | their transmitter. In the CNS gliding is a co factor. Binding |
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| 20:11 | glycerine together with glutamate will be better maximal activation of the glutamate channel, |
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| 20:18 | it's not enough. So coincidentally, has to detect pasta Matic deep |
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| 20:24 | and when Posson optic deep polarization that's when magnesium leaves this should receptor |
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| 20:31 | and allows for the flocks of sodium calcium through this channel and then the |
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| 20:36 | through of potassium. Through both of channels, so and then D a |
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| 20:41 | in that sense have slower kinetics. have to wait until the cell number |
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| 20:45 | is deep polarized through much faster Amper . They have to detect pre synaptic |
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| 20:52 | and they have to detect plus synaptic in the form of deep polarization in |
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| 20:57 | to be fully functional. And so fact that an M. D. |
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| 21:01 | receptors are so prominent and the fact NMDA receptors not only conduct a lot |
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| 21:06 | carne, but also a lot of , which causes intracellular, calcium and |
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| 21:11 | messenger cascades, it has a profound on many different functions and many lasting |
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| 21:18 | . And India receptor is very important many different forms of plasticity in |
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| 21:23 | ltp, long term, potentially ation of depression that we discussed and plays |
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| 21:28 | significant role in being able to basically coincidentally detecting tune activity. The pre |
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| 21:36 | neurotransmitter release of pasta napping, deep of posson optic activation on in the |
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| 21:43 | receptor also has binding sites for PCP engage the one and we'll discuss this |
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| 21:49 | the next round, actually, because running out of time. But these |
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| 21:53 | some of their interesting molecules of binding the receptors. And needless to say |
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| 21:58 | also, there are metal but dropping receptors. So and then the receptors |
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| 22:04 | not gonna be a tropical that made Celtics, and then the receptors conduct |
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| 22:07 | channels. Okay, they conduct items their channels. So you have metal |
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| 22:12 | tropic glutamate receptors that linked the Jew signaling cascades that act very differently. |
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| 22:19 | the distinguishing feature here is an ample be open. Addressing member of potential |
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| 22:24 | the president's off glutamate and M d will not and in the presence off |
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| 22:30 | magnesium concentration, this is an experiment the left you have a regular intracellular |
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| 22:35 | concentration of 1.2 mil Imola and in presence of glutamate of minus 60 million |
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| 22:41 | . You're recording an M. D card, but you don't see much |
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| 22:44 | that current because Ludin eight is not to open that channel. So when |
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| 22:48 | dip polarized and set your holding potential the voltage clamp to a D polarize |
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| 22:55 | starting middle of all the value. you have the polarized the cell. |
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| 22:59 | you see the openings of police an D A. Channels. Then you |
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| 23:03 | a reversal of current through an M H zero Miller balls. In a |
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| 23:08 | , this is an equilibrium potential for M D, a channel that conducts |
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| 23:12 | ions. In the first, our of the course we learned about our |
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| 23:18 | equation, calculating equilibrium potential for each and Goldman equation. Calculating membrane |
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| 23:25 | which takes into consideration permeability for sodium potassium and their relative concentrations and electrochemical |
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| 23:33 | . But here you have actually a of conduct several ions, and if |
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| 23:38 | clamp it, zero no of also no current flow. And when you |
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| 23:42 | polarized to plus 30 when you hold a really high positive potentials, which |
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| 23:47 | non physiological, you will see very opening, often MBA channels and flow |
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| 23:53 | current in the opposite direction after it's . Zero No vote, and on |
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| 23:58 | right, you have an experiment where you have taken the magnesium out of |
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| 24:01 | extra cellular solution. You applied and it proves the point in the |
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| 24:06 | of magnesium and if you have glutamate neurotransmitter NMDA receptors will be opening addressed |
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| 24:14 | they'll be opening at 30 minus And there will be opening a possibly |
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| 24:20 | potentials as well. So the take message is that if you eliminate |
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| 24:25 | glutamate will open the channel. Because , what happens is you have a |
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| 24:29 | of glutamate. You have a block magnesium and the glutamate binding and deep |
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| 24:35 | will then open up this NMDA receptor . So we will take a hard |
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| 24:40 | here. We will finish talking on transmission on Tuesday. I'm wishing you |
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| 24:46 | luck on the quiz. Please Thio Kosta. And you can take |
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| 24:54 | quiz is gonna be 10 minutes. luck to you and I will talk |
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| 24:59 | you next |
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