| 00:02 | Welcome back, this is neuroscience electric . And we continue talking about the |
|
| 00:08 | transmission. Were very likely to go and talk about neural transmission into thursday's |
|
| 00:15 | as well. So don't worry about exact match with the syllabus. If |
|
| 00:21 | don't finish neural transmission today, it's important that we learned some very important |
|
| 00:26 | here and start forming this understanding of chemicals in the brain and how they |
|
| 00:33 | . And so please recall that we acetylcholine system as sort of a poster |
|
| 00:39 | system for what is happening in the systems with the synthesis with the release |
|
| 00:46 | the breakdown and also re synthesis and of these neurotransmitters. So acetylcholine is |
|
| 00:55 | with genocidal cory and Colleen chat together italy colon is loaded up in the |
|
| 01:01 | . So you have transporters for these . The secular transporters then Sudo colon |
|
| 01:08 | released. We talked about the fact neuro muscular junction is a very simple |
|
| 01:13 | that is only excited to it only excitatory acetylcholine receptors. Nicotine acetylcholine receptors |
|
| 01:20 | the central nervous system, neurons contained nicotine nick acetylcholine receptor channels that are |
|
| 01:27 | here in pink and mascara. would you protein coupled receptors that are |
|
| 01:33 | here in blue. So sid alkaline synaptic lee will bind to both types |
|
| 01:38 | these receptors on the post synaptic response be accordingly to the receptors that are |
|
| 01:43 | to now. Once the sigil Colin in the synaptic cleft is going to |
|
| 01:47 | broken down by Seattle calling. That's race into choline and acetic acid Colin |
|
| 01:53 | going to get transported. So there's , membrane transporters for these chemicals into |
|
| 01:59 | pre synaptic loft and in there they're re synthesized into civil Colin reloaded into |
|
| 02:08 | . And we released again and we about how different chemical systems neurotransmitter systems |
|
| 02:16 | different behavioral states. We talked about example, that a denizen levels go |
|
| 02:22 | in the evening and dennison makes you . That if you have a fight |
|
| 02:27 | flight situation that norepinephrine and nor adrenaline the brain kicks in if you have |
|
| 02:34 | sustained activity, physical activity, mental , light levels of stress that boosts |
|
| 02:41 | cannabinoid production. If you are having with chemical systems, distinct chemical systems |
|
| 02:51 | chemical imbalances in the brain are associated specific neurological dysfunctions and neurological disorders. |
|
| 02:59 | Alzheimer's disease, the colon, arctic that produce acetylcholine that are located in |
|
| 03:05 | brain stem, they all start dying there isn't enough of acetylcholine. So |
|
| 03:11 | main strategy for the therapeutic treatment on Alzheimer's page for the disease is a |
|
| 03:17 | industries inhibitors. What you're trying to is you're trying to make the sissy |
|
| 03:22 | investors more bio available. The one is still there that is still being |
|
| 03:27 | and released. A single called unnecessary will block the degradation of physical choline |
|
| 03:34 | the synaptic cleft and by blocking the that prolongs the amount of time that |
|
| 03:39 | is um the cleft and prolongs the of that molecule that is available to |
|
| 03:44 | bound to the post synaptic were However, as you understand, this |
|
| 03:49 | not the best strategy and there is cure for Alzheimer's disease. This doesn't |
|
| 03:55 | the progression of Alzheimer's disease. And only thing that this does is slows |
|
| 04:01 | the progression of the Alzheimer's disease so it doesn't advance as fast and it |
|
| 04:05 | advance maybe as severely as it would without having this therapy on this |
|
| 04:13 | We also talked that organophosphates are a colonist terry's inhibitors and those are nerve |
|
| 04:22 | . And if you inhibit a settle to rates and there's too much |
|
| 04:29 | it's the opposite. Then the muscle contracting and they start contracting nonstop and |
|
| 04:34 | go into what is called tetanus. lock up, they're still active that |
|
| 04:39 | just lock up in this constantly contracted . And if that happens to your |
|
| 04:45 | that moved the diaphragm, the breathing system. It's it's it's really a |
|
| 04:53 | situation. And so watch out as watching the news now what's going on |
|
| 04:56 | Russia and Ukraine under Russian attack, using all sorts of weapons vacuum |
|
| 05:04 | cluster bombs and there are reports coming of the chemical attacks coming out |
|
| 05:09 | There's obviously poison gas. You can this information online. I'm not telling |
|
| 05:14 | the sources or whatnot. But it definitely confirmed by the european union by |
|
| 05:19 | U. S. Military. The that's going on right now. So |
|
| 05:24 | nasty things are still on the war zones and the war play. And |
|
| 05:31 | is this is what they do. uh we deal with it although they |
|
| 05:38 | illegal nerve gasses for any warfare. they show up here and there and |
|
| 05:43 | show up in syria they show up Russia you're going to show up in |
|
| 05:48 | . Probably I hope not but just an eye and understand what's going on |
|
| 05:52 | the world. So we talked about excitatory synaptic transmission causes deep polarization and |
|
| 06:00 | . P. S. P. . And we talked about how in |
|
| 06:03 | neuro muscular junction this is a big and the neuro muscular junction. This |
|
| 06:08 | a -65 million volt number of potential produce this massive inflate potential E. |
|
| 06:16 | . P. That always reaches the for action potential here and always ends |
|
| 06:24 | generating a very large action potential in muscle cell. Okay so this is |
|
| 06:30 | the neuro muscular junction. This is neuro muscular journey in the C. |
|
| 06:35 | . S. Activation of a single causes the deep polarization of approximately 0.5 |
|
| 06:44 | bowls. So one synapse in the muscular junction 70 million volt e. |
|
| 06:51 | . p. Right? And then have one synapse activated in the |
|
| 06:56 | N. S. And that N. S. Produces a great |
|
| 06:59 | post synaptic response. Excitatory post synaptic . So if you activate two synopses |
|
| 07:06 | going to be double the size three five. And now you have to |
|
| 07:12 | on how many synapses you have to and half a million volt in order |
|
| 07:18 | reach this threshold for action potential If one synapse equals the deep polarization |
|
| 07:24 | . P. S. P of million volts. And the difference between |
|
| 07:30 | resting membrane potential And the action potential is about 20 million rolls. So |
|
| 07:36 | need at least 40 active excited. are synapses in order to de polarize |
|
| 07:41 | post synaptic neuron to produce an action . So the more of the synopsis |
|
| 07:46 | activate the stronger the ep sp response going to be the glutamate ligand gated |
|
| 07:54 | channels navigated by Liggins by chemicals will up these receptors and there are channels |
|
| 08:02 | will conduct sodium inside and de polarize cells also different from neuro muscular |
|
| 08:08 | Is that in the C. S. You have E. |
|
| 08:13 | S. P. S. And also have hyper polarizing potentials for |
|
| 08:18 | P. S. P. And I PS PS. A mediated |
|
| 08:22 | Gaba. So when Gaba chemical is it will bind to Gaba receptors that |
|
| 08:26 | channels for chloride and that will allow of chloride inside the south causing the |
|
| 08:33 | polarization. This is metadata tropic So it's different when the ligand binds |
|
| 08:40 | the receptor and that receptor is a which means that receptor opens up and |
|
| 08:44 | conducts the ions and ion the However, if the ligand binds to |
|
| 08:51 | protein coupled receptor, that receptor is a channel never opens up catalyze is |
|
| 08:58 | G protein complex and G protein complex close and open nearby ion channels on |
|
| 09:04 | plasma membrane that are channels. So it can control open and close nearby |
|
| 09:11 | channels. It can also turn on enzymes in the south and also produce |
|
| 09:18 | messengers activate secondary messenger cascades. The tropic signaling can reach all the way |
|
| 09:25 | to the nucleus of the cell and the transcription factors in the transcription dynamics |
|
| 09:31 | the cell based on the activity. you have this E. P. |
|
| 09:35 | . P. That's glutamate and we the I. P. S. |
|
| 09:37 | . That's gathering will come back to and view it a little bit |
|
| 09:42 | But let's talk more about societal dura pharmacology. So this is acetylcholine |
|
| 09:49 | the central nervous system that will buy nicotine nicotine, a tropic receptor and |
|
| 09:54 | nick medical tropic receptor. They have own agonists. An agonist is something |
|
| 09:59 | opens the channel that agonizes the channel . It's something that blocks the |
|
| 10:05 | So tetrodotoxin was an antagonist that was as a reversal antagonist for voltage gated |
|
| 10:13 | channels. In this case you have and antagonists that are specific to anna |
|
| 10:20 | and miserable tropic channels. So an for nicotine nick acetylcholine receptor is nicotine |
|
| 10:27 | nicotine, yes, that substance in tobacco will bind to nicotine acetylcholine receptors |
|
| 10:33 | they are distributed now, musk urine buy into masculinity. Medical tropic zero |
|
| 10:41 | suffers and they all have their own secure our it. Which is a |
|
| 10:46 | antagonist that comes from little poisonous froggy and attribute. Okay, so some |
|
| 10:52 | these can be chemical agonists. Some them can be natural agonists natural meaning |
|
| 10:59 | derived versus synthetic nicotine is in So this plant derived and then you |
|
| 11:04 | have synthetic substances to that that that that you can use to control the |
|
| 11:11 | . So this is going to be activation of acetylcholine receptors for acetylcholine |
|
| 11:18 | Nicotine receptor gets activated. It's actually to produce deep polarization is going to |
|
| 11:23 | for the flux of sodium through this receptor channel and neurons in the muscle |
|
| 11:30 | the masculine nick receptor and activation of ethnic receptor often has completely opposite |
|
| 11:36 | So it can actually cause hyper So if the two are located on |
|
| 11:43 | same piece of the membrane nearby and Seattle colon gets released and it binds |
|
| 11:48 | catatonic and causes deep polarization for nicotine like it did. And then played |
|
| 11:53 | . And the sodium was flexing through acetylcholine receptor but in the neurons it |
|
| 11:58 | produce much smaller deep polarization right But then masculine IQ which is not |
|
| 12:04 | in neuro muscular junction was present in cns synapses not can complicate things. |
|
| 12:09 | it's not a straightforward if they're muscle to contemplate whether it should do something |
|
| 12:15 | you're telling it to do. That not be straightforward. And then you |
|
| 12:19 | say muscle lift this cup of coffee let me think about it. Maybe |
|
| 12:24 | should not. Maybe I should drop instead of lifting. Right? That's |
|
| 12:27 | wrong. The commands are not being . So this is happening here. |
|
| 12:31 | is a very simple command that goes the muscle. Now when we looked |
|
| 12:36 | the acetylcholine we also talked about other mean means remember mono means the means |
|
| 12:45 | the means are very important and this a cascade for the synthesis of epinephrine |
|
| 12:52 | starts out with tyrosine. We have hydroxy list which adds this oh age |
|
| 12:58 | entire scene and makes L. Di penalize valentin. Also known as |
|
| 13:05 | Dopa, L. Dopa with dopa box Alice you remove dick our box |
|
| 13:12 | this molecule. You remove the O. H. Group Citigroup. |
|
| 13:16 | dick or box elated, it becomes . Okay so when we talked about |
|
| 13:22 | different neurological disorders can be associated with chemical imbalances, we highlighted Alzheimer's disease |
|
| 13:30 | acetylcholine signaling. When you talk for about Parkinson's disease. When you talk |
|
| 13:36 | motor central motor neurological disorders that have motor dysfunction such as Parkinson's disease it's |
|
| 13:47 | that is mostly effect. When you about depression, anxiety it's serotonin |
|
| 13:55 | That is a fact. So the are not only your behavioral states but |
|
| 14:02 | balance of these molecules and interactions of molecules is important to supporting normal brain |
|
| 14:11 | and imbalance. Alzheimer's a pseudo Parkinson's opening anxiety, depression, |
|
| 14:22 | They are associated with distinct groups, of neurological disorders sometimes overlap. |
|
| 14:30 | And uh l dopa is a precursor dopamine. So dopa is also a |
|
| 14:39 | medication for both Parkinson's disease and schizophrenia well. So some of the psychiatric |
|
| 14:47 | , mental disorders like schizophrenia and not neurodegenerative neurological disorders can also involve imbalances |
|
| 14:56 | these molecules. From dopamine with dopamine hydroxy list, we produce norepinephrine, |
|
| 15:04 | , nor adrenaline. Norepinephrine, adrenaline the brain if you may. And |
|
| 15:09 | can see it's just one enzymatic reaction from producing a different chemical and that |
|
| 15:17 | chemical will bind to different receptors and a different effect. So and means |
|
| 15:25 | get up taken back. So when means are released into the synaptic |
|
| 15:31 | they will get up taken back. a lot of mono means will get |
|
| 15:38 | instead of synaptic cleft, they will get oxidized in these pre synaptic terminals |
|
| 15:47 | there is mono I mean oxides and is basically when you oxidize a lot |
|
| 15:53 | the mean you're rendering and an Mhm. And these mono mean oxidants |
|
| 16:02 | that are located on typically associated with membranes, that's where they're found. |
|
| 16:11 | so when you hear about mono amine inhibitors. They're typically drugs that are |
|
| 16:20 | in boosting mono amines. Because if inhibit the oxides Okay And oxidation, |
|
| 16:29 | inhibit oxidation. Therefore you have more that active mono amine and the prison |
|
| 16:37 | class that you can load up. there's a lot of strategies that you |
|
| 16:42 | see in therapies for amine molecules. again, it's a different neurological |
|
| 16:48 | different treatments, different drugs out But as a principle, you have |
|
| 16:54 | of this pseudo code line that gets down in the synaptic cleft, get |
|
| 16:59 | means that get broken down in the at the terminal, had these |
|
| 17:05 | The enzyme turnover and the body is two weeks or so. So if |
|
| 17:10 | deplete some enzyme or something like you know, you have to rebuild |
|
| 17:14 | every two weeks. So then you asking yourself like why why do you |
|
| 17:19 | drugs and you some drug you take four hours? And another drug you |
|
| 17:24 | once a day and then another once week. And then he goes for |
|
| 17:27 | injections once every two months because they have different properties. It's really |
|
| 17:35 | It's not very simple and it's also to the metabolism of these molecules. |
|
| 17:41 | long does it take for body to something? How long does it take |
|
| 17:45 | chew up and analgesic in your you know, how long does it |
|
| 17:50 | to go through liver metabolism metabolized different , take different time period to do |
|
| 17:57 | . And so that's why you have of these different therapeutic regimes and |
|
| 18:02 | you know by the hour by the by the week and so on. |
|
| 18:08 | and cocaine will block the uptake of means. So if it blocks the |
|
| 18:17 | it's still still the same story. these mono means in the synaptic |
|
| 18:22 | they still have to be transported in prison at terminal. This is one |
|
| 18:26 | the strategies. If you block the epic that means you prolong you. |
|
| 18:31 | the motto means more by available right all of these kind of Colombians, |
|
| 18:36 | synaptic cleft, so cocaine which is to be a stimulant or upper will |
|
| 18:44 | the bio availability of the adrenaline of brain, norepinephrine, norepinephrine. This |
|
| 18:51 | we're talking about the illicit illegal drug and of course whenever we talk about |
|
| 18:59 | illegal drugs, there's always pharmaceutical therapies act through the same pathways. And |
|
| 19:06 | this is really what's what's what what know is that there will be many |
|
| 19:12 | . A. O. Inhibitors that pharmacological drugs and there will be other |
|
| 19:19 | amphetamines and gain illicit drugs that will on the same pathways maybe in different |
|
| 19:26 | of this pathway in this case. update of the molecules. I'm going |
|
| 19:33 | come back to glutamate and Gaba. I'm going to talk about serotonin the |
|
| 19:39 | function. You can see that major for got a column means are different |
|
| 19:44 | serotonin functions. But the principle is same. Serotonin is synthesized from |
|
| 19:52 | you dicker box sell it. I high hydroxide lit you put this hydroxy |
|
| 19:57 | O. H. On and then dick herb oxalate the five HTp into |
|
| 20:03 | five Ht. And serotonin gets released bind to the receptors will get transported |
|
| 20:11 | typically. And when you talk about common antidepressant medications, PROzac is I |
|
| 20:18 | is a brand name we're talking potentially blocking the re uptake of serotonin. |
|
| 20:24 | you can say okay I guess serotonin also happy molecule and I'm going to |
|
| 20:29 | that happy molecule more by available here blocking the transport of that back into |
|
| 20:34 | pre synaptic class in the pre synaptic , mood, appetite, sleep learning |
|
| 20:42 | overlapping functions between these molecules. Yeah for some reason I don't know what |
|
| 20:50 | but what happened to. Oh yeah talk about this for a second |
|
| 20:59 | took the fan anybody familiar with tryptophan a precursor to something that will make |
|
| 21:07 | sleepy and happy. And interestingly enough high levels of tryptophan in turkey. |
|
| 21:15 | like a bird and uh when you turkey for thanksgiving if you eat poultry |
|
| 21:24 | everybody is full and very relaxed and people think oh it's because I overrate |
|
| 21:32 | it's actually a lot of tryptophan in meat and you think about it. |
|
| 21:35 | is potentially one meal where you eat lot that turkey meat. Unless you |
|
| 21:41 | to turkey leg hot or something. think a big turkey legs but to |
|
| 21:48 | consume a lot of it that makes sleeping, producer, star tonin. |
|
| 21:52 | goes back to the same concept that levels is activity dependent and activity is |
|
| 21:59 | only how you move and what you during the day but also what you |
|
| 22:02 | what your intake as a food So a lot of the precursors for |
|
| 22:08 | cannabinoids and carbonic acid come from Omega and Omega six fatty acids and they're |
|
| 22:18 | as we discussed. And this is introduction. We'll talk more about the |
|
| 22:23 | system in general because it's a whole not just in the brain but in |
|
| 22:28 | body many different organs in the But this is this is different. |
|
| 22:34 | is why I want you to look this because we talked about neurotransmitter being |
|
| 22:40 | here. It acts on the receptor cycled back, reloaded release. So |
|
| 22:46 | happens to these molecules that are not in vesicles? Where are they? |
|
| 22:53 | they released place in africa and so happens to a lot of these lipid |
|
| 22:57 | molecules that we talked about our economic and they can an illness gasses nitrous |
|
| 23:04 | , carbon monoxide, they're not stored vesicles and there is typically a base |
|
| 23:10 | of these molecules that is present and increased activity or on demand, there's |
|
| 23:17 | production of these chemicals. So everything we're talking about except the first one |
|
| 23:23 | and other exogenous or pharmaceutical substances, are endogenous. So this is not |
|
| 23:29 | from cannabis. The plant cannabinoids from own cells in the body that produce |
|
| 23:35 | molecules and in neurons and the cannabinoids discovered and the cannabinoid signaling was discovered |
|
| 23:43 | the brain. The reason for it because we didn't know what are the |
|
| 23:50 | active ingredients in the cannabis or marijuana . Until 1960s, it was back |
|
| 23:55 | the same technique of liquid chromatography or performance liquid chromatography, where now you |
|
| 24:03 | able to take your grandma's concoction, it through the columns and say, |
|
| 24:09 | is something in here that I've isolated lot of it. There's something else |
|
| 24:13 | there that I've isolated. So we know about cannabinoids and cannabis plants, |
|
| 24:19 | knew about them, but we didn't the exact structures. Until 19 |
|
| 24:24 | we didn't know that we have endogenous until 19 nineties. So, when |
|
| 24:31 | talk about endocannabinoid system and the this is all the knowledge that we |
|
| 24:37 | built up Over the last 30 And the reason why it was neuroscientists |
|
| 24:43 | wanted to find out what endocannabinoid or do is because marijuana or cannabis has |
|
| 24:51 | psychotropic effect, it causes the high . So obviously probably it's not because |
|
| 24:57 | the bladder that you're feeling high, probably because it's affecting your brain |
|
| 25:05 | you're feeling high. So neuroscientists were interested to know what is the active |
|
| 25:09 | in cannabis. How is the active , which is the main psychotropic active |
|
| 25:15 | is tetrahydrocannabinol THC in the cannabis DELTA nine THC. The plants do |
|
| 25:22 | produce delta eight THC. When you delta eight is sold here. Delta |
|
| 25:27 | is here is a semi synthetic molecule is derived from CBD, which is |
|
| 25:33 | cannabinoid. So let's CBD THC delta come back to it and you'll learn |
|
| 25:38 | about it. The point being is there is substance is in the nature |
|
| 25:44 | the cannabinoids in the nature referred to phyto cannabinoids, phyto plant cannabinoids and |
|
| 25:51 | endogenous cannabinoids. A certain level of endogenous cannabinoids. When there is heightened |
|
| 25:56 | of activity. These cannabinoids, there's enzyme that will produce a lot of |
|
| 26:02 | cannabinoids calcium influx and these cannabinoids endocannabinoid cross their plasma membranes and also similarly |
|
| 26:12 | the nitrous oxide and carbon monoxide. will do a very similar thing and |
|
| 26:16 | will actually travel retrograde with. So is different. This is not a |
|
| 26:21 | synaptic molecule release. This is actually of past synaptic self and now you |
|
| 26:27 | this feedback loop It goes retrograde Lee cannabinoid receptors. CB one and CB |
|
| 26:34 | receptors. CB one receptors are dominating neurons and the cannabinoids will bind to |
|
| 26:42 | one receptors? CB one receptors are tropic g protein coupled receptors. An |
|
| 26:49 | of the jew protium complex will shut the influx of calcium will block multi |
|
| 26:55 | calcium channel. Remember that two things necessary for neurotransmitter vesicles release deep polarization |
|
| 27:03 | optically an influx of calcium through voltage calcium channels so that it can allow |
|
| 27:10 | fusion of the bicycle numbering to the numbering. So in this case you |
|
| 27:17 | either excitatory synapse or inhibitory synapse. these neurotransmitters are, let's see glutamate |
|
| 27:25 | gaba. And when there is a of glutamate and when there is a |
|
| 27:28 | of gaba and the cannabinoids are they freely cross through lipid soluble, |
|
| 27:35 | freely cross through plasma membranes. They lee activate pre synaptic CB one receptors |
|
| 27:41 | they shut down calcium influx and they or reduce the amount of that neurotransmitter |
|
| 27:48 | is being released. So D. . I. Stands for when the |
|
| 27:54 | found this concept, they first found in the inhibitory synapses and did |
|
| 27:59 | Stands for deep polarization induced suppression of . Deep polarization. When there was |
|
| 28:08 | lot of deep polarization prison optically a of deep polarization post synaptic lee and |
|
| 28:14 | of calcium. It's induced suppression of through this retrograde feedback mechanism. So |
|
| 28:24 | a second. Our first thought in was that controls inhibitory neurotransmitter release and |
|
| 28:29 | blocks inhibited neurotransmitter released through this retrograde feedback loop and shortly after it was |
|
| 28:37 | shown to be present and excited tourist . So when you think about in |
|
| 28:43 | phenomenon's there actually regulating if there's too activity prison optically and person optically if |
|
| 28:51 | inhibition it will be D. I. P. Polarization induced suppression |
|
| 28:54 | the condition. If it's excitation and is being released it's going to be |
|
| 28:59 | . People are deep polarization induced suppression excitation. So there's both D. |
|
| 29:04 | . I. And D. And what does that tell you? |
|
| 29:09 | this is a method of balancing excitation inhibition through this retrograde negative negative feedback |
|
| 29:19 | . So like I said if we talked about gabba and glutamate in the |
|
| 29:24 | it would be pretty boring, would plus and minus so black and white |
|
| 29:31 | all of these neurotransmitters and molecules, they do is they add all of |
|
| 29:35 | color. You can now have a of gray scale. You can have |
|
| 29:41 | lot of different colors too. Major and the brain are anandamide. And |
|
| 29:49 | Arco donald glycerol or to A. . So these are the major of |
|
| 29:54 | cannabinoids that we produce in our brains bodies. And the major phyto cannabinoid |
|
| 30:01 | this molecule DELTA nine THC. And reason why DELTA nine THC has an |
|
| 30:09 | is because DELTA nine THC also binds the same CB one receptors in the |
|
| 30:17 | . So by having endogenous regulation and talked about Melinda can avalos is one |
|
| 30:22 | . Exogenous lee these molecules can also neurotransmitter release excited during inhibitory neurotransmitter release |
|
| 30:30 | molecules because they will bind to the receptors. Exogenous phyto molecules will bind |
|
| 30:36 | the same receptors and endo molecules bind the same sides. Sometimes slightly different |
|
| 30:43 | . Because if you remember the receptor it is very complex, large ah |
|
| 30:50 | dimensional structures, five dimensional Penton eric and so on. All right. |
|
| 31:00 | then the last thing that we have look at is the black and white |
|
| 31:05 | . And Gaba glycerine is the third um You know I mean acid neurotransmitter |
|
| 31:13 | is here and if you D. Boxley glutamate which means you remove this |
|
| 31:19 | group C. O. H. get Gaba. So all of the |
|
| 31:25 | that will have this platonic asset Car box slaves enzyme God they're all |
|
| 31:33 | in neurons. Remember the cycling of of glutamate we haven't looked at but |
|
| 31:40 | also talked about how glee is involved cycling and glutamate. Now glutamate will |
|
| 31:46 | into the inhibitor inter neurons and they get converted into Gaba the major inhibitor |
|
| 31:54 | . So one step one reaction away major excitatory neurotransmitter. This is the |
|
| 32:00 | inhibitory neurotransmitter. All of the cells of the inhibit ourselves that express God |
|
| 32:08 | will be inhibited ourselves because there will synthesizing gamma and releasing Gaba. Alright |
|
| 32:18 | the phenomenons and what are the ways study neurotransmitters. So one of the |
|
| 32:24 | popular ways to study is with antibody . It's a technique called immuno history |
|
| 32:30 | you also don't need to use antibodies this technique called histone chemistry histology. |
|
| 32:35 | if you're using antibodies it's in you and you can create antibodies you can |
|
| 32:41 | inject the neurotransmitter candidates into a And you will see a lot of |
|
| 32:47 | if you're in the labs or if looking at the catalogs polyclonal or monoclonal |
|
| 32:52 | to the different antibodies and then you'll things like mouse anti rabbit rabbit anti |
|
| 33:01 | or something like that. What does mean? That means that all this |
|
| 33:04 | has probably taken from rodent injected into rabbit. And the rabbit now generates |
|
| 33:10 | immune response to that molecule produces antibody foreign in data and you can sample |
|
| 33:19 | and we have HP. L. . And all these wonderful other chemical |
|
| 33:23 | we can isolate that antibody you So now we have created the antibody |
|
| 33:28 | we we want against the substance that injected into an animal. Now you |
|
| 33:33 | a tissue slides and that tissue slides many cells in it. Unfortunately that |
|
| 33:39 | only too. But imagine there's 2000 and what you do is you have |
|
| 33:45 | antibody and this antibody is this y molecule here and it has a visible |
|
| 33:53 | on it. So wherever that antibody it's gonna show up under a microscope |
|
| 33:58 | that visible markers typically fluorescent mark. it will glow green green red yellow |
|
| 34:06 | on the weight line. So you the antibodies these black white molecules all |
|
| 34:12 | the slice that has 2000 or two . And only one of these cells |
|
| 34:19 | the antibody go in and stick inside there. So there's a whole procedure |
|
| 34:23 | immune artistic chemistry that's actually wash the . You have to puncture the cells |
|
| 34:28 | the detergent. The plasma membranes. called triton X detergent will puncture the |
|
| 34:34 | will allow for the antibodies to come and then you will do multiple washes |
|
| 34:40 | shakes and things like that. And if there's nothing that that antibody sticks |
|
| 34:45 | it will enter into this cell here the right to. But if there's |
|
| 34:49 | that that antibody sticks to like a of interest that antibody is gonna get |
|
| 34:54 | away from the songs. But if sticks to something it will remain inside |
|
| 34:59 | cells and only the cells that are that particular neurotransmitter of interest will show |
|
| 35:06 | and blow and in particular wave lines yellow, green or red depending on |
|
| 35:12 | tag. Another uh technique is in hybridization. In this case you have |
|
| 35:19 | strand of messenger RNA in the And this is a little bit more |
|
| 35:28 | but you have a radioactively labeled probe the proper sequence of complementary nucleic |
|
| 35:35 | So you make that pro because you the it's post genomic era. So |
|
| 35:39 | know the code. You make you tag it and if that strand |
|
| 35:43 | M. R. N. Is complementary and it will bind to |
|
| 35:47 | specific sequence. And the cells that you have these sequences will bind to |
|
| 35:54 | markers this case and radioactively labeled. you will see this punk Tate or |
|
| 35:59 | or stains only in the south that that particular moment. So these are |
|
| 36:04 | formal techniques that we study uh neurotransmitter . Remember that? We already discussed |
|
| 36:12 | that you can apply neurotransmitter. this is another way to study neurotransmitters |
|
| 36:17 | how the cells react to neurotransmitters using , electrophysiology. And we discussed that |
|
| 36:23 | you have this application of the fluid , you have problems with dialysis of |
|
| 36:27 | fluid everywhere because there's fluid everywhere around south. And so we said that |
|
| 36:33 | a better technique called engaging neurotransmitters. this is laser licensing of the |
|
| 36:40 | Did a little drawing for you And this is a class supporting lecture |
|
| 36:45 | on engaging neurotransmitters. So you literally cage neurotransmitters and chemicals and use very |
|
| 36:52 | lasers to license the cages to release chemicals. The advantage of engaging |
|
| 36:58 | you can really activate just a single a single dendritic spine and you don't |
|
| 37:03 | this dialysis. You only engage in spot where the laser is being directed |
|
| 37:12 | uh immunize the chemistry. It's not that you use only in the |
|
| 37:17 | you can use it during the You can stain the whole embryo. |
|
| 37:23 | important that these chemicals that we talk . There's also different chemicals that are |
|
| 37:27 | during early development. Trophic factors, factors in the brain that allow for |
|
| 37:32 | brain to be very plastic. And when they get we get older, |
|
| 37:36 | lot of these chemicals are no longer . So you'll still have all of |
|
| 37:40 | neurotransmitter receive means and such but some but some other milieu of chemicals that |
|
| 37:46 | be there. But it's but but no longer there and so the plasticity |
|
| 37:51 | go down to an adult that as . Mhm. But you can track |
|
| 37:56 | well in this case it's a 14.5 old mouse embryo, you're tracking in |
|
| 38:02 | particular case, Truck B. And everywhere you see a dark |
|
| 38:07 | there's a large expression numbers of that . So you can see this expressed |
|
| 38:12 | the brain and the spinal cord not much in the viscera. So a |
|
| 38:17 | of the molecules, a lot of that we talked about. MS serotonin |
|
| 38:21 | the central there's peripheral serotonin, how you measure central moses, peripheral |
|
| 38:30 | walk into Kelsey Seybold, they put needle in your brain for a little |
|
| 38:34 | out. You go home right every , we'll get put needles in our |
|
| 38:41 | now. But there's ways there's blood right, there's different ways of |
|
| 38:46 | but these molecules are circulating everywhere and also change as a function of |
|
| 38:52 | So this truck be maybe expressed very in the brain and the spinal cord |
|
| 38:57 | first two weeks, three weeks of and then later it just reorganizes itself |
|
| 39:05 | a different structure in the brain of structure in the body. The last |
|
| 39:11 | that we're gonna talk about this particular uh slides and will switch to the |
|
| 39:18 | lecture slides. Yeah the synaptic So synaptic integration as you know if |
|
| 39:27 | have one action potential boom it releases . It produces an E. |
|
| 39:32 | S. D. It's a small sp one synapse is not enough to |
|
| 39:37 | a post synaptic action potential. But happens if you shock the three fibers |
|
| 39:45 | the same time that are very closely to each other? Then the signal |
|
| 39:53 | PSB will summit. And this is spatial summation because it's taking the input |
|
| 40:03 | to input in space. That is at the same time. And now |
|
| 40:07 | can see that this response, it's times the size of the response that |
|
| 40:13 | saw when you activate it just And apps pretty logical. This is |
|
| 40:19 | summation. Double summation is if you that same axon but repeatedly that accent |
|
| 40:28 | a train of action potentials. Boom boom boom boom boom. When it |
|
| 40:34 | so and it does it at a frequency it augments the response. And |
|
| 40:40 | sort of a augmentation is called temporal . So it's it's some mating in |
|
| 40:47 | here in the middle of some mating spades adding it all together. It's |
|
| 40:53 | in time at the same time. it's summing over space here. It's |
|
| 40:57 | the same space. What is happening time. So we're summing over time |
|
| 41:01 | this would be the equivalent pattern of speed is augmented and growing ep sp |
|
| 41:07 | you will see has noticed this temporal will not cause as large of the |
|
| 41:13 | sp response. Right? Because it's all three synapses that are being activated |
|
| 41:18 | the same time. What what would the advantage of temporal summation? The |
|
| 41:25 | is actually longer. Okay, so is all if something else was happening |
|
| 41:31 | this this stage right here this sell be completely hyper polarized. But in |
|
| 41:38 | cell you can see there's still be deep polarization that something else could be |
|
| 41:43 | on top of them. There's a features and these responses based on the |
|
| 41:49 | versus special information. Now, if also recall the fact that and axons |
|
| 41:59 | have Myelin you have my elimination segments you have nodes of ranveer. Each |
|
| 42:05 | of ranveer have very high concentrations of gated sodium potassium channel so you regenerate |
|
| 42:11 | action. But there is no more in dendrites right? There's no violent |
|
| 42:19 | in settlements and that means that current going to leak. It's not going |
|
| 42:27 | regenerate but instead it's now traveling over and it's going to actually reduce over |
|
| 42:35 | . And so You have this maximal here of 100% of the current where |
|
| 42:41 | have your electrodes and then you can a second electrode and you can record |
|
| 42:46 | , what is that current? Five away From the side of the injection |
|
| 42:52 | occurrence. What is it? 10 away from the site of the |
|
| 42:58 | Can you still do it? Do still see any current? 20 microns |
|
| 43:02 | from the site of the injection. You inject the maximum current here. |
|
| 43:08 | 100%. And then what happens is a lot of this current will actually |
|
| 43:15 | ? We'll escape through open channels. . It will degrade. So by |
|
| 43:21 | time you get to this recording electrode going to have a much smaller deep |
|
| 43:26 | that you're recording as opposed to when started it right here. And this |
|
| 43:34 | from 100%. injection maximum current. of this V0. This v maximum |
|
| 43:47 | is referred to as the length the length constant or lambda. So |
|
| 43:58 | voltage λ is 37 of the peak at the site of the injection. |
|
| 44:07 | that means that neurons that have long constant will take longer time to go |
|
| 44:19 | and lose that current. And the that have short length constant will have |
|
| 44:26 | different currents if you were to. so. Mhm. Yes. So |
|
| 45:12 | would be a long one constant. would be a short Lanza. Uh |
|
| 45:23 | . The longer the lunch constant, longer that current can travel over |
|
| 45:29 | And that's important. And it depends the properties of the membrane, depends |
|
| 45:34 | the densities of the channels depends on number of channels that may be |
|
| 45:39 | They may be leaking that current mm hmm. There's another principle of |
|
| 45:47 | inhibition. So you produce an excitation in the den drive. You know |
|
| 45:52 | this excitation is going to die down the level of the soma. So |
|
| 45:57 | another reason why you need to learn dendrites. You need to activate 2040 |
|
| 46:02 | excited for synopsis. Guess what? typically closer to the summer and these |
|
| 46:07 | somatic regions you have inhibitors announcements. everything that is coming into these distal |
|
| 46:14 | here and the neuron has to actually the selma and has to still be |
|
| 46:20 | polarizing enough in order for the selma produced action potential. The good news |
|
| 46:26 | the threshold of action potential. Actually lower and lower and lower. The |
|
| 46:32 | you get to the axon initial So it's easier and easier and easier |
|
| 46:35 | the cell to have little deep polarization still generate an action potential. But |
|
| 46:41 | that little deep polarization to be present the summer, you have to have |
|
| 46:44 | lot of it in the distal regions you will lose this current will degrade |
|
| 46:52 | time depending on the length constant. the other thing that can happen is |
|
| 46:59 | happy excitatory current. He just thinks going to travel down the axon and |
|
| 47:04 | the style and then inhibitor synopsis gets close to the soma. And this |
|
| 47:10 | called shunting inhibition and this inhibitor cinemas now going to shout that current. |
|
| 47:15 | positive excited her current. That was to travel into the selma and activate |
|
| 47:22 | axon initial segment is now being shunted because you have negative current counteracting the |
|
| 47:29 | current and you have current leaks going . So if you have really get |
|
| 47:35 | for your input in the distance done it but close to selma you have |
|
| 47:40 | really good inhibitory input. Guess There's nothing in the soma. It |
|
| 47:46 | it out. So if you have an equivalent amount of inhibition the net |
|
| 47:54 | really no change at the member and level. So one or the other |
|
| 47:59 | to win. And if excitation when excitation has to win by a |
|
| 48:07 | And if inhibition is there you know will be driving down that potential hyper |
|
| 48:13 | that potential. And that's why when record from neurons neurons that are just |
|
| 48:18 | in the in addition or not being stimulated in the brain or not being |
|
| 48:23 | stimulated in the whole brain, they're very active. They will fire an |
|
| 48:28 | potential. You know d polarized hyper polarized polarized more hyper polarized boom boom |
|
| 48:36 | hyper polarized. It's not it's not you're gonna record from a neuron and |
|
| 48:41 | of a sudden it's gonna produce all these frequencies of stimulation they fired quite |
|
| 48:45 | frequently until they're directly stimulate and they to respond to that. The reason |
|
| 48:50 | they fire and frequently is because although may have a lot of excitation going |
|
| 48:54 | these neurons and condition will be canceling up. You have to have really |
|
| 48:58 | amount of excitation in order to drive sell to the threshold for action |
|
| 49:04 | Now this principle of modulation is also to the metabolic tropic signaling. |
|
| 49:11 | so this is another very last concept discuss. So when you activate this |
|
| 49:15 | protean complexes you can activate molecules such the general cyclists that will take energy |
|
| 49:22 | A. T. P. Can secondary messengers such as cyclic GMP is |
|
| 49:27 | very famous secondary messenger and cyclic GMP also cross through gap junctions. So |
|
| 49:33 | that gap junctions are not only electrical are islands that can cross but also |
|
| 49:39 | secondary messengers can cross through gap junctions then the cycle can be can activate |
|
| 49:46 | . So we inside our cells we kindnesses and foster cases, kindnesses will |
|
| 49:52 | channels. P. 04 and adding P. 04 group typically makes these |
|
| 49:56 | more active and phosphate. Asus will for Pharrell. It will take that |
|
| 50:02 | or four group off. So memorable signaling and downstream activation of these cellular |
|
| 50:09 | in a way to control the activity the level of the membrane through the |
|
| 50:13 | amounts of the kindnesses and prospectuses that activated at different times dependent on the |
|
| 50:19 | pathways that are activated. All But some of these slides are showing |
|
| 50:31 | the stuff that we covered, the that we talked about remember it's a |
|
| 50:35 | system. The transmitter is a whole synthesized release. Break it down, |
|
| 50:42 | busting out the receptors bind to the . And when you talk about |
|
| 50:46 | studying you can study different parts of system, you can study neurotransmitter |
|
| 50:52 | you can study receptor expression of the membrane. Some of these receptors are |
|
| 50:58 | be internalized sometimes inside the south. of them can be extra synaptic located |
|
| 51:03 | of the synopsis. These are all the methods immunities of chemistry and see |
|
| 51:08 | hybridization mimicry of neurotransmitter and as part the mimicry liquid dialysis, rejects the |
|
| 51:17 | with the photo license of the cage . All of these great techniques to |
|
| 51:22 | study neurotransmitter systems. This is a slide that overviews what we're talking about |
|
| 51:30 | on on top you're seeing the amino here, glutamate and Gaba. You |
|
| 51:38 | see that glutamate is converted into Gaba God, acetylcholine. No, the |
|
| 51:46 | synthesis with child and also degradation pathway the single column master is inhibitors until |
|
| 51:56 | asteroids which degrees are still common in inhibitors as therapeutics for Alzheimer's disease and |
|
| 52:05 | the by availability of single column. there a tone in battle trip to |
|
| 52:13 | 25 HDP tyrosine cata cola means to dopa dopamine and norepinephrine in the |
|
| 52:24 | So the question is, do you to know the enzymes that lead from |
|
| 52:30 | opening into norepinephrine such as dopamine beta list? The answer is no. |
|
| 52:35 | you need to know the major classes these? If I were to ask |
|
| 52:39 | is L dopa or norepinephrine um a colony and they'll say yes, is |
|
| 52:49 | an amino acid? And they'll say . So, you know, |
|
| 52:52 | And I'll say Gaba is a mono , you know, it's an amino |
|
| 52:59 | . So these are all very good But no longer to the details with |
|
| 53:03 | enzymes except for one God, because the most important. We have to |
|
| 53:10 | understand glutamate and Gaba. And that's be really the focus of probably the |
|
| 53:16 | half an hour or so of our is limited. Gabba, little motor |
|
| 53:22 | signaling these neurotransmitter systems that we talked ? A little Colin Colin. Odjick |
|
| 53:28 | pharmacology do protein receptors. So this what mascara nick do protein receptors uh |
|
| 53:39 | like their function And it's referred to this case as shortcut pathway because you |
|
| 53:46 | acetylcholine metabolic tropic acetylcholine receptor activists catalyze the G protein complex and the G |
|
| 53:53 | complex can open potassium channel. So it's called shortcut pathway. That |
|
| 54:02 | that there's no chemical and immediate intermediaries G pro dam and another secondary messenger |
|
| 54:09 | or something like that. That G goes directly into the potassium channel. |
|
| 54:14 | what happens if you open potassium channel the plasma membrane to the number of |
|
| 54:21 | potassium is going to be leaving the and the membrane will be hyper |
|
| 54:27 | And this is how nicotine acetylcholine receptors will conduct sodium in and cause deep |
|
| 54:35 | through the ion a tropic channels and . Tropic acetylcholine receptors will actually cause |
|
| 54:41 | polarization by opening potassium channel near one is going to be faster than |
|
| 54:49 | and the tropic is going to be than metal. But tropic because for |
|
| 54:52 | reaction to take place, you're looking tens of milliseconds of delay, sometimes |
|
| 54:58 | milliseconds on the tropic activation to assist interceptor model. Two molecules behind acetylcholine |
|
| 55:05 | boom, it's conducting open formidable advise medical tropical receptor activation. G |
|
| 55:13 | G protein has to move and open channel in this case potassium channel. |
|
| 55:18 | now you can see how the same acetylcholine on the same cell can have |
|
| 55:25 | effects excitatory through nicotine IQ and inhibitory mass karina civil colon receptors. Who's |
|
| 55:33 | to win? Maybe nobody. Maybe controlled in time. You always get |
|
| 55:38 | positive response from a single colony. it has nicotine receptors and if you |
|
| 55:42 | more security it's followed by a negative for hyper polarization but who wins? |
|
| 55:48 | it's only nicotine IQ muscle wins. on who wins. It's almost masculine |
|
| 55:54 | . Almost always masculinity or if it only mascara nick in neurons hyper |
|
| 56:01 | So the expression of the receptors in cells will determine the post synaptic response |
|
| 56:06 | that same model. And often the receptors located on the same cell to |
|
| 56:12 | same molecule, responsive to that same will have an opposite effect physiological effect |
|
| 56:20 | . The tripartite synapse will introduce this that glutamate of courses in excitatory |
|
| 56:26 | it gets released. It will bind iron, a tropic and medical tropic |
|
| 56:31 | receptors. It will get transported with neuronal transporter back into the south. |
|
| 56:37 | will get uploaded back into the glutamine and it's going to get released. |
|
| 56:43 | the same cycle that we talked But in this case there's no degradation |
|
| 56:48 | glutamate and that's not the class and no degradation of glutamate in neurons. |
|
| 56:56 | there is this our third player in tripartite synapse, glia ostracized, have |
|
| 57:02 | glial glutamate transporter, they will slurp the glutamate, they will have glutamine |
|
| 57:09 | and glutamine synthetic taste will produce glued in astrocytes. Then astrocytes will give |
|
| 57:17 | glutamine, it will be transported into pre synaptic neurons and with glutamine AIDS |
|
| 57:23 | 80 p energy is converted into glutamate uploaded back into the last circles. |
|
| 57:31 | who is partly in control of we are they're on synthesized them, |
|
| 57:41 | them up, release them. But will actively control those glutamate levels and |
|
| 57:47 | a good thing because if there's too glutamate neuron is overloaded with its function |
|
| 57:53 | kicks in and says I'll help let me take some of this glutamate |
|
| 57:58 | it, I'll give it to you in a few seconds or so. |
|
| 58:02 | so you have the tripartite synapse and you realize that glee actually is in |
|
| 58:07 | of the activity especially the excitatory synapses that's what we refer to as tripartite |
|
| 58:14 | , pre synaptic neuron, post synaptic and the third player is Gloria. |
|
| 58:24 | of these slides repeat because maybe we'll at them again sometime later. |
|
| 58:32 | This is another way I just told that I am a tropic receptor might |
|
| 58:38 | d polarizing effect, metabolic tropic may hyper polarizing effect. But guess |
|
| 58:43 | There's also different subtypes of metabolic tropic . And depending on what cascades I |
|
| 58:49 | in intracellular lee will have an equivalent . So let's look at norepinephrine, |
|
| 58:56 | and neurons has two receptors data. be beta and nora P alpha alpha |
|
| 59:04 | receptor when norepinephrine binds to its metabolic . These arm edible tropic receptors. |
|
| 59:12 | doesn't have iron, A tropic Metal tropic receptors activate the G protein |
|
| 59:18 | convert GTP activated metal cyclists convert ADP cyclic GMP and will produce a lot |
|
| 59:28 | protein kindnesses and cause a lot of relations. So basically boost the activity |
|
| 59:35 | these pathways and boost the production of Chinese say oh but right next to |
|
| 59:42 | better receptor There's a subtype of Meadowbrook norepinephrine receptor, alpha two and alpha |
|
| 59:51 | is linked instead of to the which is stimulatory G protium. It's |
|
| 59:58 | to G. I. Which is G protein. And then inventory activation |
|
| 60:05 | this G protein complex will do the will reduce activation of identical cyclists, |
|
| 60:15 | reduce the production of cyclic AMP That will reduce the production of protein |
|
| 60:19 | essay. So this system memorable tropic . Now I told you an example |
|
| 60:26 | I am a tropic versus Meadowbrook I am a tropic de polarizing, |
|
| 60:30 | tropic hyper polarizing for acetylcholine receptors. , medical tropic receptor subtypes can be |
|
| 60:37 | varied and they have very different And this is an example of two |
|
| 60:42 | tropic receptors that have a very different intracellular early and we'll also have a |
|
| 60:47 | effect physiologically. So one of them pushing the system the beta stimulatory is |
|
| 60:53 | the system to produce more protein, saying more phosphor relation And the other |
|
| 60:59 | , the Alpha two is pulling it from producing that protein kindness and having |
|
| 61:05 | kindnesses. It's referred to as push medical tropic signal through the do protein |
|
| 61:13 | and once they're activated you will see downstream activation of secondary messengers of enzymes |
|
| 61:21 | all the way down to the transcription of the nucleus in the cell. |
|
| 61:29 | , so this is this is what talking about exactly when we talked about |
|
| 61:35 | . You can see that norepinephrine is in locus Aurelius, the blue nucleus |
|
| 61:41 | the brain stem. You can see projections from norepinephrine going widely distributed throughout |
|
| 61:47 | cortex of cortical tissues and also going spinal cord. If you talk about |
|
| 61:52 | , serotonin is produced by these green that I referred to as Raphael nuclei |
|
| 61:59 | and purple. The green ones will their tone into spinal cord and periphery |
|
| 62:06 | the purple ones will transport the serotonin over throughout the cortex, basal ganglia |
|
| 62:12 | cortical structures and such. And so can see that for each one there's |
|
| 62:18 | as local Sibelius, rafi nuclei this is the production of a single |
|
| 62:25 | , podunk younger pontin and lateral dorsal nuclear in green there's another spot of |
|
| 62:32 | a single choline, okay, which located here, magnus cellular prefrontal cortex |
|
| 62:40 | . And so these different means. different neurotransmitter molecules that we're talking about |
|
| 62:47 | will be confined. So most of that produces molecules will we find only |
|
| 62:52 | these new cleaners and the cannabinoids will widely distributed throughout the brain. And |
|
| 63:00 | is the case with amino acids, that synthesize gaba and glutamate and |
|
| 63:07 | they'll be found everywhere. There's so throughout the brand. But these sprinkler |
|
| 63:13 | are quite specific and quite unique to mean neurotransmitters that we're that we're studying |
|
| 63:23 | . The cannabinoids will be produced I just spelled out some things that |
|
| 63:27 | talked about. Tetrahydrocannabinol delta nine, Delta eight. You know how you |
|
| 63:33 | what the plant produces? Or doesn't look for enzymes, there's there's |
|
| 63:41 | If there's something that synthesizes in the , then you know, it comes |
|
| 63:45 | the plant. If it's not, means it's semi synthetic. Maybe it's |
|
| 63:50 | derived or maybe it's fully synthetic. . Yes, I was. Which |
|
| 63:58 | part of THC makes it psychotropic, uh typically is linked to hallucinations in |
|
| 64:11 | . Psychedelic terms means mind altering. I want to ask you a |
|
| 64:17 | Just copy all through your mind about . Does it alter your mind listening |
|
| 64:25 | music? Does it alter your We have a lot of psychedelic |
|
| 64:29 | We're talking about things that are Sometimes DELTA nine THC is going to |
|
| 64:34 | called intoxicating. Uh So my question this alcohol intoxicating? No. |
|
| 64:47 | Absolutely. Yeah. Can you die alcohol much much easier. Can you |
|
| 64:54 | from delta nine THC. No, no there's no deaths reported from natural |
|
| 65:01 | nine CHC. And that's very different synthetic cannabinoids. Find spice cushioned the |
|
| 65:06 | shops and the smoke shops. That nothing to do with the plant has |
|
| 65:11 | to do with the physiology we're talking . They're very dangerous molecules and quite |
|
| 65:16 | 1000 times more potent than natural delta THC. So those things that are |
|
| 65:21 | unregulated and controlled and illegal. But somewhat under the radar of the regulators |
|
| 65:26 | find their way into the smoke No. Which part of delta nine |
|
| 65:32 | is psychotropic compared to CBD if you mind. Let's hang on to that |
|
| 65:36 | , we'll have a whole lecture of cannabinoids. We'll look at some of |
|
| 65:40 | structures. It's the binding properties of to CBD. They're different structures so |
|
| 65:45 | will bind to different parts of the one receptor THC is a strong |
|
| 65:51 | Two CB one receptor. CBD is the negative Alistair IQ modulator of CB |
|
| 65:59 | receptor, meaning that it actually has different binding side from THC. And |
|
| 66:04 | of activating CB one receptor and is and cascade, it will be taming |
|
| 66:10 | down modulating it in a negative It's still binds it, it still |
|
| 66:15 | levels of activity but it controls or reduces those levels of activity. That |
|
| 66:23 | be generated by THC. So I spelled out here, deep polarization induced |
|
| 66:29 | of an ambition D. S. . And D. Polarization induced suppression |
|
| 66:33 | excitation. So these are the retrograde for controlling both the glutamate and gaba |
|
| 66:41 | president. How was camp. How's hemp? Different hemp is a |
|
| 66:50 | that contains Up to 0.3% THC in matter. Delta land THC and it |
|
| 67:00 | contain CBD or other non psychotropic So the help again. We'll talk |
|
| 67:08 | it at the end of the course is a federally legal crop. There's |
|
| 67:14 | on what products can be consumed from or how it D. A. |
|
| 67:18 | example doesn't improve CBD tinctures but that stop the pharmacies and the stores and |
|
| 67:25 | stores selling it because it's really non . So people, you know, |
|
| 67:30 | regulators don't go after things that are that dangerous typically. And there's a |
|
| 67:37 | in the D. A. And to completely clear and legalized the CBD |
|
| 67:42 | . So uh it's a whole science it. uh but this percentage of |
|
| 67:54 | THC it's something that is said by , Meaning that is their Canada's planted |
|
| 68:02 | plant that always produces 0.3 or Sure, you can have genetics that |
|
| 68:07 | be approximately keeping that THC level synthesis the plants to 0.3. But nature |
|
| 68:13 | alive and the sun can get hotter the humidity and certain features can make |
|
| 68:21 | plant raise those levels to 0.4. although genetically we have identified cannabis sativa |
|
| 68:31 | hound plans that have 0.33C in the States In Italy. That is defined |
|
| 68:38 | 0.6% THC as hell. And in is defined as 1% THC in |
|
| 68:47 | Why? Because it's it's nature. there's really the cut off line is |
|
| 68:51 | the regulatory cut off line. But the fact that the products that are |
|
| 68:56 | from help should not contain more than or 33 mg program of THC then |
|
| 69:04 | finished product, we'll get to that because that's pretty interesting. You can |
|
| 69:09 | a five g hemp product five times mg of THC. It's 15 mg |
|
| 69:17 | THC in colorado. It's called an from the dispensary, not from a |
|
| 69:24 | . So it's it's a whole debate going on. The lines are a |
|
| 69:28 | bit blurred. I think the main , things like fentaNYL and things that |
|
| 69:34 | cause death because they're deadly dose is close to an effective dose. The |
|
| 69:40 | why there's no deaths from THC or , there's overdoses but no deaths is |
|
| 69:46 | the deadly doses like 1000 joints in minutes. So I don't think you |
|
| 69:52 | , snoop can do that. But know maybe Anyways we'll end the lecture |
|
| 69:58 | today, we'll finish up on the and Gaba. We'll look at the |
|
| 70:02 | and glutamate synopsis and we'll move on the C. N. S. |
|
| 70:06 | will release your tests, I I will release your test so you |
|
| 70:10 | see all the questions you got and of that. We can discuss it |
|
| 70:13 | thursday. So wishing you have a week. Stay sane. |
|
