© Distribution of this video is restricted by its owner
00:00 | um This is lecture 11 of neuroscience its neuro transmission to and last lecture |
|
|
00:09 | discussed that there are two synopses, types of the synapses in the |
|
|
00:16 | n.s. Give Me 1 2nd. have chemical synopsis and we have electrical |
|
|
00:25 | . Chemical synopsis is chemical neuro transmission fusion, neurotransmitter release and binding of |
|
|
00:32 | chemical neurotransmitters to the post synaptic receptors evoke a post synaptic response, electrical |
|
|
00:39 | gap junctions are formed when you have of the membranes of neurons to neurons |
|
|
00:45 | close in proximity about three nanometers apart each other. And if they express |
|
|
00:50 | gap junction proteins that connects on proteins will form the gap junctions. Gap |
|
|
00:56 | are permeable to ions. They're also to small molecules such as secondary messengers |
|
|
01:04 | as cyclic GMP. Gap junctions will able to feel immediately what the Jason |
|
|
01:11 | that is connected to these gap junctions experiencing. So the response is instantaneous |
|
|
01:17 | chemical synaptic transmission. There is a from vesicles fusion release of neurotransmitter binding |
|
|
01:24 | the receptor and boston attic response. may have anywhere between 5 to 20 |
|
|
01:30 | , delay. Gap junctions are instantaneous gap junctions will be found in glia |
|
|
01:38 | astra sites will take advantage of that they're buffering spatially buffering increases in local |
|
|
01:44 | of ions. They can Transported in the cells through these gap junctions connectivity |
|
|
01:51 | . And they're also gap junctions are expressed in neurons and the neurons. |
|
|
01:56 | very important so that you can engage number of neurons by stimulating one and |
|
|
02:01 | one neuron is interconnected to another few through gap junctions therefore you would only |
|
|
02:08 | to activate one neuron for all the 10 neurons to feel some sort of |
|
|
02:13 | level of activation. Only a fraction the stimulus that you see in sal |
|
|
02:18 | here, this large response electrical membrane , only a fraction of that will |
|
|
02:24 | translated through the gap junctions. But this is a really good tool in |
|
|
02:29 | to engage and synchronize larger populations of which is necessary in order to perform |
|
|
02:36 | tasks that we uh performing every day talked about neuro muscular junction and there |
|
|
02:44 | certain features of neuromuscular junctions that we out. So neuro muscular junction here |
|
|
02:50 | we talked about is the skeletal biceps triceps, hamstrings and we also |
|
|
02:57 | about the neuron or nerve to the junction to the cardiac muscle. |
|
|
03:04 | and the cardiac muscle and this cardiac acetylcholine was reducing the contraction of the |
|
|
03:11 | muscle was slowing down the heart That was Okelo, his discovery originally |
|
|
03:16 | he discovered acetylcholine now in the that same molecule acetylcholine has an excitatory |
|
|
03:26 | response on the muscles and it's the molecule acetylcholine but in heart it's acting |
|
|
03:33 | Mascarenas. Acetylcholine receptors. And then neuro muscular junction here it's acting through |
|
|
03:39 | acetylcholine receptors. Now these axons that from motor neurons in the spinal cord |
|
|
03:47 | ratify and form these large synopses that called end plates, motor end |
|
|
03:54 | motor employed region that will contain these large synapses with synapses will have |
|
|
04:00 | Each vesicles will contain 2000 to 4000 molecules. When there is an action |
|
|
04:07 | here at the motor neuron, it release the packet of these acetylcholine |
|
|
04:13 | 2000 to 4000. Acetylcholine will activate optical in nicotine acetylcholine receptors. These |
|
|
04:22 | receptors will generate and played potential. very large pasta fanatic potential that's always |
|
|
04:31 | the size of 70 million balls. very large deep polarization through acetylcholine receptor |
|
|
04:38 | is going to be sufficient enough to volt educated sodium channels and voltage gated |
|
|
04:44 | channels in the muscle fiber and cause contraction of the muscle by muscle producing |
|
|
04:50 | action potential. So, it's a reliable synapse. That action potential in |
|
|
04:55 | synapse means release of neurotransmitters. It'll means employed potential and means contraction of |
|
|
05:03 | muscle fiber. So this is what have for the neuro muscular junction and |
|
|
05:14 | only excitatory, it uses acetylcholine. , there is no inhibition here. |
|
|
05:23 | nothing that can inhibit the muscle once signal from motor neuron goes out into |
|
|
05:27 | muscle and it's an action potential, will contract unless there is some pathological |
|
|
05:34 | with the muscle or with the release Americans narratives that once you have this |
|
|
05:41 | membrane potential of about -65 syllables. have a threshold for action potential -45 |
|
|
05:50 | volts. This is VM. And this is resting membrane potential. |
|
|
06:01 | , when in the neuro muscular junction produce the employee potential, that template |
|
|
06:07 | is always going to measure. This potential is abbreviated E P P. |
|
|
06:15 | the post synaptic response. So if recall to acetylcholine molecules have to buy |
|
|
06:23 | this receptor. Okay, and when buy into this receptor, sodium ions |
|
|
06:30 | going to influx And positive charge coming , it's going to cause this massive |
|
|
06:37 | polarization that will measure approximately 70 million in size. And so because these |
|
|
06:47 | always have the quanta of 2000 to molecules that combine to 1000 or 2000 |
|
|
06:56 | receptors and activate 1000 to 2000. will always have this complete potential on |
|
|
07:02 | of which you will always be able evoke a very long cardiac action |
|
|
07:09 | So it's a very reliable synapse. only excitatory. And so the connectivity |
|
|
07:17 | between the motor neuron motor neuron and cells is only excitation by sid alkaline |
|
|
07:30 | binding to these nicotine IQ acetylcholine Okay, so these nicotine acetylcholine receptors |
|
|
07:39 | ligand gated receptor channels that will allow the influx of sodium for this deep |
|
|
07:47 | . They will also allow for the of potassium causing this ripple polarization during |
|
|
07:55 | athlete potential. Okay, so now is a neuro muscular junction and it's |
|
|
08:02 | different situation. It's a different situation the central nervous system synopsis and I |
|
|
08:12 | that everyone on zoom can see what's the board really well. If I |
|
|
08:20 | sharing for example, I think you have a larger screen so you can |
|
|
08:25 | your screen larger and hopefully take a of it and inverted and the power |
|
|
08:35 | or something along these lines. So let's continue on uh neuro muscular |
|
|
08:45 | And so the initial deep polarization is a single coding receptor channels and then |
|
|
08:51 | action potential gets produced by these voltage sodium and calcium channels that are not |
|
|
08:57 | here. And we're not going to the dynamics of the action potential in |
|
|
09:02 | muscle for the purposes of this we talked about different neurotransmitter systems and |
|
|
09:08 | said that there are different types of and there are certain distinguishing features of |
|
|
09:18 | neurotransmitters and maybe I can save this uh raise part of the screen over |
|
|
09:27 | to add more information. Let's So we talked about amino assets and |
|
|
09:42 | talked about the means and we talked peptides, amino acids are the major |
|
|
09:48 | glutamate inhibitory gaba neurotransmitters in the glycerine inhibitory neurotransmitter in the spinal cord |
|
|
09:56 | neurons gliding in the cns is also co factor for glutamate ergic signaling of |
|
|
10:03 | signaling and we'll get to that in next lecture. So amines are acetylcholine |
|
|
10:11 | epinephrine, histamine, norepinephrine I any an amine serotonin. And if you |
|
|
10:19 | about glutamate, you can think about plus excitatory post synaptic response generating action |
|
|
10:27 | . If you think about gaba you about inhibition inhibits the cell membrane it |
|
|
10:34 | polarizes. It makes neuron less likely fire. When you think about the |
|
|
10:39 | you can think about them a little differently. They're regulating other features of |
|
|
10:45 | C. N. S. And features are related to our state of |
|
|
10:50 | our state of alertness. Our moods distinct dysfunctions in these systems can result |
|
|
11:00 | specific neurological disorders. So in Parkinson's and lot of motor cortical disorders who |
|
|
11:09 | have dough opening dysfunctions, Opening dysfunctions also be present and addictive disorders and |
|
|
11:16 | also implicated in schizophrenia dopamine receptor of . When you're talking about serotonin, |
|
|
11:23 | talking about regulation of mood and appetite when you're talking about dysfunctions and serotonin |
|
|
11:31 | , you're talking about depression, anxiety post traumatic stress syndrome disorder. And |
|
|
11:43 | you're talking about norepinephrine, you're talking adrenaline of the nervous system. So |
|
|
11:48 | there is a threat coming at you levels of North of northern africa are |
|
|
11:53 | to go up. A lot of substances are regulated during the day dependent |
|
|
11:59 | the external stimulus. So once again somebody is approaching you in an aggressive |
|
|
12:04 | and threatening you you're gonna engage your is called fight or flight response, |
|
|
12:10 | either gonna fight or you're gonna fly of the situation and to do that |
|
|
12:15 | need to engage the systems you have synchronize neurons. You have to do |
|
|
12:20 | split second really milliseconds to do And you would engage systems like norepinephrine |
|
|
12:28 | epinephrine which are the stimulatory systems. systems that mediate that fight or flight |
|
|
12:34 | and dopamine for example is a reward too. So when when you have |
|
|
12:40 | rewarding dopamine you get a shot of . So it's not just disorders, |
|
|
12:44 | also regular normal behaviors that are regulated by these systems and some of them |
|
|
12:51 | regulated by external stimuli. Some of are regulated by the day cycles are |
|
|
12:56 | diurnal or circadian rhythms. So some go up at night and go down |
|
|
13:02 | the morning and vice versa. Uh know from other courses of the stress |
|
|
13:09 | the cortisol, the stress hormones. you have hypothalamic HP a hypothalamic pituitary |
|
|
13:16 | axis. So when you're stressed you an increased level of stress hormones and |
|
|
13:21 | can be increased accurately. Or it be a part of the chronic stress |
|
|
13:26 | changes the system in a different But so this is also externally in |
|
|
13:31 | stimulus. Then in addition to what discussed here, we talked about the |
|
|
13:37 | that if you look in the in anatomy of the brain that I'm drawing |
|
|
13:43 | in a cartoon like fashion. Glutamate expressing themselves are going to be found |
|
|
13:54 | the C. N. S. . Gaba express themselves are going to |
|
|
14:01 | found throughout C. N. And hundreds of millions of neurons and |
|
|
14:09 | will be found in in the in spinal cord. So this is |
|
|
14:16 | Uh this is glued in a his . Also glycerine for the spinal cord |
|
|
14:25 | . But I mean systems are different immune system and I mean expression is |
|
|
14:35 | to specific nuclear in the brain. there's going to be nuclei and the |
|
|
14:41 | that express acetylcholine, they're going to south that express norepinephrine. And these |
|
|
14:53 | are the only locations where there's going be cells that are making those molecules |
|
|
14:59 | toning those amine molecules. Okay so nuclear are all I mean production is |
|
|
15:08 | on in these nuclei everywhere and they're in different places in the brain stem |
|
|
15:15 | and partly in the in the sub regions. So now the projections from |
|
|
15:24 | nuclei very wide and they go everywhere the brain and also into the |
|
|
15:35 | So it's a very different way of of the amino assets that you have |
|
|
15:42 | of millions of cells throughout C. . S. In different regions, |
|
|
15:46 | and cortex in the occipital lobe and lobe. You have glutamate and Gaba |
|
|
15:53 | . But when it comes down to means they're confined to these nuclei and |
|
|
15:59 | spatially confined their expression that means to much that produce these semi neurotransmitters are |
|
|
16:06 | in these nuclei. By definition nuclear of cells that are responsible for the |
|
|
16:12 | or similar type of function like producing synthesizing acetylcholine and then releasing that little |
|
|
16:20 | in through this very wide what we it a sprinkler like system, almost |
|
|
16:26 | non specific effect that you would have the C. N. S through |
|
|
16:30 | immune system's cells can co express amino and neuro peptides so cells can co |
|
|
16:40 | multiple neurotransmitters. They can remember that signaling is happening here at the level |
|
|
16:51 | the synapse. So the vesicles are in these pre synaptic terminals. The |
|
|
16:57 | are loaded here. You learn the are recycled and reloaded here at the |
|
|
17:02 | . They're primed and docked and ready be released. As soon as there's |
|
|
17:05 | action potential, there's going to be release of neurotransmitter. It's just not |
|
|
17:10 | to be causing this huge template potential going to be causing a much smaller |
|
|
17:16 | synaptic responsible get to that in a a few minutes. But neuro peptides |
|
|
17:20 | different because you need to activate the for prolonged a sustained period of |
|
|
17:26 | We have to jolt this neuron for while in order for it to start |
|
|
17:31 | peptides storing them in Secretary Granules and releasing them somewhat non specifically along the |
|
|
17:38 | of the axon, not just external , so they don't have as much |
|
|
17:42 | the spatial specificity. So they're different but they you can see here that |
|
|
17:47 | same cell will co express neurotransmitters neuro molecules that we're talking about here. |
|
|
17:55 | in addition to these molecules we discussed his neurotransmitters and that nitrous oxide and |
|
|
18:05 | monoxide. We discussed endo cannabinoids to . G and anandamide and we'll come |
|
|
18:24 | and talk about this more in the election. Also later in this course |
|
|
18:30 | also talked about this molecule called our acid and our economic asset can be |
|
|
18:41 | precursor to cannabinoids and it also can a breakdown molecule of endocannabinoid. So |
|
|
18:47 | of these molecules that you're seeing here precursors for the other molecules and the |
|
|
18:54 | of norepinephrine and so on. So difference is that the gasses the |
|
|
19:03 | our economic acid, They're not stored vesicles, they are not stored in |
|
|
19:12 | , they're not stored in the Secretary . They're produced a lot of times |
|
|
19:16 | demand and they are lipid soluble or soluble and membrane soluble. That means |
|
|
19:23 | once they're produced inside the cell they float through the plasma membrane will be |
|
|
19:29 | and target their respective receptors and the will target cannabinoid receptors. Nitrous oxide |
|
|
19:36 | target nitrous oxide synthesis nitrous oxide The other interesting thing is that these |
|
|
19:43 | apart from being lipid soluble, so lipid soluble, no, that's a |
|
|
19:59 | can be synthesized on demand and they in a retrograde fashion. That means |
|
|
20:19 | they are actually released automatically and their are located preseason operability. Most of |
|
|
20:28 | other elements that we're talking about on the I mean assess their already released |
|
|
20:33 | optically released prison optically. These are specifically released specially those are released reason |
|
|
20:41 | released reason optically and these are all posten optically. So if you release |
|
|
20:49 | typically have an effect on post synaptic is called interrogate. If you release |
|
|
20:52 | cinematically have uh effect on pre synaptic is called retrograde activation. And then |
|
|
21:00 | also talked about 80 p. In to this and dennison and we talked |
|
|
21:11 | the fact that a denizen triphosphate is only just the energy molecule, it's |
|
|
21:17 | a neurotransmitter and it combined to a and receptors and the core molecule of |
|
|
21:23 | . T. P. A dennison also a neurotransmitter. Dennison has a |
|
|
21:28 | effect. It actually regulates glutamate So dennison activation of a dentist in |
|
|
21:37 | reduces the amount of glutamate reduces the of excitation in the brain and the |
|
|
21:44 | levels for example will fluctuate during the and they will go up in the |
|
|
21:48 | and at night to help you sleep calm the brain by reducing glutamate release |
|
|
21:59 | is an a dentist and receptor antagonist what it does, it actually stimulates |
|
|
22:05 | release so caffeine which we typically use the morning. Also we have a |
|
|
22:12 | with exogenous substances. Some substances exogenous use throughout the day and people have |
|
|
22:18 | systems that can accommodate things throughout the . For example like caffeine in the |
|
|
22:24 | of tea and some cultures people drink before they go to bed but it |
|
|
22:29 | has caffeine or in the evening And in certain cultures caffeine is typically |
|
|
22:36 | morning and lunch thing and after you because it keeps you awake and that's |
|
|
22:42 | if you're consuming coffee rather than But so we also form our own |
|
|
22:48 | with with different exogenous substances that interact our receptors such as caffeine will stimulate |
|
|
22:56 | release in the morning and during the at denison levels go down now glutamate |
|
|
23:01 | more likely to be released and then typically don't consume caffeine in the evenings |
|
|
23:05 | we need to pull an all So yes, some people basically stay |
|
|
23:10 | from, they say that some people be president not working. It's a |
|
|
23:17 | I think that what what I've experienced least I don't know the research on |
|
|
23:23 | . But culturally if you grew up as Children, we drank tea and |
|
|
23:28 | drank tea in the evening. So systems accordingly adjusted to to that substance |
|
|
23:33 | our receptors became plastic to that you know, so you are correct |
|
|
23:39 | we all individually adjust, We adjust part of color, part of the |
|
|
23:44 | and growing up most of the caffeine and most culture starts a teenage |
|
|
23:50 | that's when you still have a lot plasticity in the brain too. So |
|
|
23:54 | could be whatever cycle you're setting up of the cycles we're setting up in |
|
|
24:00 | , you know, teenage and early and late twenties are going to be |
|
|
24:05 | know, cycles potentially for the next 2030 years. So uh and that's |
|
|
24:10 | we're adjusting the systems and the the numbers of the receptors, How |
|
|
24:14 | they be activated? Somebody's a dentist is blocked for four days in the |
|
|
24:20 | and somebody else's for 12, I , for four hours in the morning |
|
|
24:24 | others for 12 hours throughout the whole . So it's it's yeah, it's |
|
|
24:28 | very interesting way to think about Um So all of the key elements |
|
|
24:35 | on here, I'd say. And hope that again, I'm gonna stop |
|
|
24:40 | chair to see what this looks I think you can see everything. |
|
|
24:45 | you're welcome on zoom too. Take screenshot. Uh We're going to lower |
|
|
24:53 | scheme. Mhm. Okay. So talked about how important this calcium in |
|
|
25:07 | and when the action potential life arrives , you have pre synaptic polarization, |
|
|
25:16 | have polarization and you require calcium So when this terminal gets d polarized |
|
|
25:26 | the action potential, you open voltage calcium channels and influx of calcium through |
|
|
25:33 | channels as necessary as we discussed vesicles have this protein complex. In |
|
|
25:39 | this is what the outside of the looks like. This very complicated hairy |
|
|
25:47 | of different proteins and things like that off of it, calcium is necessary |
|
|
25:53 | activate the protein protein binding protein complex the vesicles to neuron membrane and to |
|
|
26:01 | the fusion of the two membranes to protein protein interactions. So calcium will |
|
|
26:07 | some certain sides and up to tag as one of the calcium sensex sides |
|
|
26:11 | the vesicles. That tells vesicles that calcium. But we can proceed with |
|
|
26:16 | psychosis and following exercise psychosis, there's to be endo psychosis. The |
|
|
26:21 | the membrane organelles are going to be back and refilled with the neurotransmitters. |
|
|
26:28 | is the electron microscope pictures uh pre calcium channel. So we're looking from |
|
|
26:38 | on the cell into the plasma And these little dots you see like |
|
|
26:42 | line of dots. These would be presumed both educated calcium channels in the |
|
|
26:47 | synaptic active zones. And this is same pre synaptic active zones that have |
|
|
26:55 | started releasing the vesicles. So the came from inside of the south. |
|
|
27:00 | fused and it opened up. if you're looking in our little creators |
|
|
27:06 | these openings here, the craters that be the vesicles themselves. You're looking |
|
|
27:13 | the inside of the bicycle from outside the south. So this shows very |
|
|
27:18 | how this anatomy of the vault educated channels and he's beating like wines corresponds |
|
|
27:25 | very well with neurotransmitter vesicles fusion and . This is another image of electron |
|
|
27:35 | showing that where there is narrowing and at the two neurons, one and |
|
|
27:42 | together, close about three nanometers you will have formation of gap |
|
|
27:47 | So these are little dotted. Each is like a gap junction. This |
|
|
27:52 | what it appears like an electron microscope on both sides. So you would |
|
|
27:59 | it on on both sides of the the south and you see it also |
|
|
28:03 | the outside of itself. Uh as discovered different components of the membrane in |
|
|
28:10 | 1950s and 60s. It was really to kind of understand that the membrane |
|
|
28:17 | comprised of the phosphor lipid bi So there are two layers, there |
|
|
28:20 | an the face and there is a . And the science by chemists were |
|
|
28:26 | interested in finding out which phase how proteins and the trans membrane and the |
|
|
28:33 | with extra cellular face and the associated intracellular cytoplasmic side of the membrane |
|
|
28:41 | And so there was this freeze fracture is being used at the time. |
|
|
28:46 | neuronal membranes would be very quickly flash frozen in liquid nitrogen. And |
|
|
28:51 | a small needle would be placed next the membrane. A little vibration |
|
|
28:56 | tap tap on the table, sometimes the floor and hoping that that little |
|
|
29:00 | actually taps the plasma membrane perfectly, just splits it open in half. |
|
|
29:08 | the analogy is like you have a and you froze that sandwich has the |
|
|
29:14 | from the bottom side. And now put a flathead screwdriver to that |
|
|
29:21 | And you're hoping that if you tap light lit that sandwich to face, |
|
|
29:25 | going to break apart and it's going show you where the lettuces with a |
|
|
29:30 | and mayo and so on. So the analogy of that one on the |
|
|
29:35 | scale, that was really neat. and then in the 1990s and 2000's |
|
|
29:44 | had the ability to visualize fluxus and . So when we initially talked about |
|
|
29:52 | the south, we talked about Golgi , missile stain and the features and |
|
|
29:58 | of these stains on the south. these guys are sensitive to ions. |
|
|
30:06 | they're not necessarily staining a particular type cell. They are indicating to us |
|
|
30:13 | levels of concentrations of different ions are in this experiment. It's concentrations of |
|
|
30:20 | . And this experiment looked at, do these calcium micro domains look |
|
|
30:28 | If we image them, we'd like know here, The higher the concentration |
|
|
30:32 | calcium, the more red color, and red color you would be |
|
|
30:39 | And so when rodolfo llinas, uh other neuroscientists started using calcium sensitive dyes |
|
|
30:47 | questions as well. We see this , we see these calcium channels in |
|
|
30:53 | microscopy, they seem to have some specificity here. Can we image, |
|
|
30:59 | calcium have spatial specificity as calcium everywhere the synapse equally distributed. And indeed |
|
|
31:06 | the synapses are not very active. see these pyramid or very clear mountain |
|
|
31:12 | like structures representing calcium micro domains, calcium micro domains will be assoc with |
|
|
31:21 | pre synaptic vesicles that are docked and in the active zones. And then |
|
|
31:28 | second question was what happens to this specificity if you stimulate the cell, |
|
|
31:37 | that cell receives action potentials gets d , what happens to the spatial specificity |
|
|
31:43 | this calcium arrangement? And what is concentration? So the concentration was 200 |
|
|
31:50 | mall that's getting cut off here on slide we saw that the p concentration |
|
|
31:55 | way up during vesicular release and during deep polarization. So it's really like |
|
|
32:01 | what is calcium doing during this particular . And it's showing that it goes |
|
|
32:06 | this especially very specific locations magnus synapses being present everywhere. Pretty much pre |
|
|
32:14 | optically everywhere at least in these active synaptic zones and that the p concentration |
|
|
32:21 | . So you can see that there's more of the spatial specificity here. |
|
|
32:26 | there's a lot of calcium available in pre synaptic side of the neurons. |
|
|
32:32 | I had this image from neuron to . It's uh one of the older |
|
|
32:38 | that's still really good book to read you're into neuroscience. So in the |
|
|
32:45 | . N. S. Synapses versus junctions. The steam will continue. |
|
|
32:50 | actually going to continue on this drawing . But you have basically production of |
|
|
32:56 | bicycles. After early in this film have the filling of the neurotransmitter docking |
|
|
33:04 | these vesicles climbing of these vesicles with energy and other factors once there is |
|
|
33:11 | influx of calcium. So you must pre synaptic action potential and influx of |
|
|
33:16 | for the vesicular fusion to take But interestingly enough in the C. |
|
|
33:21 | . S. It's not not only response is not as big as in |
|
|
33:26 | muscular junction and non played potential. Sometimes the fusion pore opens only partially |
|
|
33:36 | for some reason maybe there wasn't enough . So the sensors and the protein |
|
|
33:41 | complex didn't activate completely to produce this fusion and the neurotransmitter vesicles and returns |
|
|
33:49 | this prime position and back into dark back into prime position. So this |
|
|
33:56 | called kiss and run. So you released a little bit of neurotransmitter. |
|
|
34:01 | you ran away. You didn't commit to the vesicular release here. But |
|
|
34:07 | there is enough calcium and if you this proper protein protein complex binding here |
|
|
34:14 | will have full fusion Uh dilation and fusion pore dilation and full release of |
|
|
34:23 | . Notice that when you fuse the you can if you're fusing 10 or |
|
|
34:31 | vesicles to the pre synaptic plasma remembering increasing the surface area of these cells |
|
|
34:37 | quite a bit. And as you're the surface area of these cells the |
|
|
34:42 | also gain more capacitance. So remember . The storage of charges depend on |
|
|
34:48 | large is the surface area to store charge. And this is what's |
|
|
34:53 | So during the the secular fusions if using a lot of vesicles, the |
|
|
34:57 | properties of the cell will also show . They will increase after the sexual |
|
|
35:04 | . There's endo psychosis process and this membranes get coated with the recognition particle |
|
|
35:12 | in and those vesicles are transported back pre synaptic side. The inside get |
|
|
35:20 | with age. Plus it becomes very . And with the help Of this |
|
|
35:25 | driven gradient and transport is new transmitters refilled back into the vesicles placed into |
|
|
35:32 | dark prime position, ready to be again. In some instances maybe the |
|
|
35:38 | needs a little bit more like a mile service versus just the oil |
|
|
35:45 | And in that case the vesicles can shuffled back into the early end, |
|
|
35:51 | , sat out here and and refill neurotransmitter. Go into the cycle. |
|
|
35:56 | can actually exhaust cns synapses from vesicular . If you have a sustained stimulation |
|
|
36:04 | sustained vesicular release for a few seconds will deplete neurotransmitter vesicles that have neurotransmitters |
|
|
36:13 | you will have to wait for about seconds for this recovery to take place |
|
|
36:18 | the neurotransmitter vesicles are reshuffled refilled and for subsequent release. Okay we'll come |
|
|
36:27 | to this in a second. But talk about the C. N. |
|
|
36:32 | . Synopsis and this is our neuro junction. But cns. Synopses are |
|
|
36:39 | and we'll get to talk about cns but cns synopsis can have either positive |
|
|
36:47 | negative synopsis. So positive is glutamate inhibitory input negative. It's got |
|
|
36:56 | All right. So this is different the you know muscular jungle that we |
|
|
37:01 | about. Because you're muscular junction only acetylcholine, it only has nicotine, |
|
|
37:10 | receptor, it's only excited her. no inhibition here. The only inhibition |
|
|
37:17 | have is at the level of the cord right with the spinal cord into |
|
|
37:22 | . The circuit that we talked about with the reflex arch. So when |
|
|
37:28 | have glue to late You have that's the same -65 no balls. |
|
|
37:36 | you excite one synapse one synapse will a positive deep polarization of about half |
|
|
37:45 | million fold. If you have this for action potential minus 45 you have |
|
|
37:55 | excite many many synopsis at the same . And if you excite them at |
|
|
38:00 | same time this response is deep polarization summit. So one synapse half a |
|
|
38:06 | volt to one million volts. For , two million volts eight synopses, |
|
|
38:10 | million volts, 16 synopsis eight million and so on. And only if |
|
|
38:17 | activate a very large number of these will you reach the threshold to produce |
|
|
38:25 | action potential. Okay this is the for the action potential here. So |
|
|
38:33 | the neuro muscular junction you just need synapse activation. You get em plate |
|
|
38:41 | of 70 million balls and you always the action potential in the C. |
|
|
38:48 | . S. Release of glutamate activation one synapse will cause the deep polarization |
|
|
38:54 | only half a mil a bold. so you need to activate tens of |
|
|
39:00 | excitatory synapses at the same time. proximity in time in order to reach |
|
|
39:06 | threshold in order for that neuron to action potential. And in addition while |
|
|
39:13 | is getting excited to a synopsis, same happens with inhibitor synopsis. If |
|
|
39:19 | synopsis get activated, you get If more and more inhibitors synopsis get |
|
|
39:27 | you get this member and potential more more hyper polarized. So you're drawing |
|
|
39:35 | with gaba. You are hyper polarizing numbers. These are excitatory post synaptic |
|
|
39:48 | . So when acetylcholine bonds the nicotine receptors, it produces this anti potential |
|
|
39:55 | your muscular junction it does something different the C. N. S. |
|
|
39:59 | there is a single calling signaling in C. N. S. And |
|
|
40:02 | the cns. The central cooling is going to produce this massive response and |
|
|
40:07 | is a neuro muscular junction. Mostly . S. P. S. |
|
|
40:13 | the strongest deep polarization that you will through glutamate. Okay excitatory post synaptic |
|
|
40:22 | and that is one glutamate neurotransmitter molecules buy to glutamate receptor channel that will |
|
|
40:28 | for influx of sodium. This will for influx of sodium. This is |
|
|
40:38 | this is out Mrs sodium. It also allow for the flux of |
|
|
40:48 | Yes. So again these are ligand channels. This is for E. |
|
|
40:54 | . S. B. And for . P. S. P. |
|
|
40:57 | . To produce this hyper polarization. , this is our neurotransmitter. Gaba |
|
|
41:07 | bind to Gaba receptor channels and Gaba channels. This is glutamate, This |
|
|
41:16 | Gaba. And Gaba receptor channels will for influx of chloride. So negative |
|
|
41:24 | coming inside the south, making the hyper polarized more and more hyper |
|
|
41:29 | more and more hyper polarized. Okay the comparison is that you have and |
|
|
41:43 | neurons cns neurons. If your recall can have an excitatory neuron, connect |
|
|
41:51 | neuron connect another excited turn neuron connected inhibitor neuron. I'm gonna call these |
|
|
42:03 | and those are gonna be connected to . Around here Gavin you're on this |
|
|
42:12 | neuron is going to be connected to Gavin neuron. Okay and this excited |
|
|
42:19 | is going to be connected to another neuron. So you can have inhibition |
|
|
42:27 | excitation excitation of excitation in the addition inhibition and excitation of inhibition as |
|
|
42:37 | So all of these different scenarios are in neuronal networks and they're absent at |
|
|
42:44 | neuro muscular junction and that's why we neuro muscular junction is a very simple |
|
|
42:49 | of understanding wondrous separate citation employee potential potential in the muscle but at the |
|
|
42:57 | of C. N. S. more complex. We have to activate |
|
|
43:02 | excitatory synapses to reach the threshold. G. P. S. |
|
|
43:06 | Is very small. So once the activation is just a fraction of a |
|
|
43:10 | of all you have excitation through glutamate channels and you have inhibition through gaba |
|
|
43:18 | channels. And we will build upon knowledge in the next lecture and will |
|
|
43:23 | the glutamate and gaba signaling Gaba A gaba B. Yo gabba, |
|
|
43:32 | And remember that show. The other is when we're talking about C. |
|
|
43:39 | . S. We have eye on tropic signaling and the and the tropic |
|
|
43:45 | . The tropic receptor channels are the to edge. You have a ligand |
|
|
43:50 | such as acetylcholine here you have a binds such as glutamate have a ligand |
|
|
43:57 | here such as Gaba and open the . So these are ion a tropic |
|
|
44:03 | channels. So they have their receptors they receive a molecule also channels because |
|
|
44:08 | conduct ions but also as you can they're non specific to an ionic |
|
|
44:14 | So when we studied action potential, talked about both educated sodium channels selected |
|
|
44:19 | sodium. Both educated potassium channels, potassium here we're talking about acetylcholine receptor |
|
|
44:26 | to allow flocks of sodium and potassium channels, receptor channels allow blocks of |
|
|
44:32 | and potassium here you have chloride activation Gavin. Uh And in addition to |
|
|
44:40 | ion a tropic channels these are a tropic channels. And then I |
|
|
44:45 | medical tropic channels the medical tropic channels when you have a receptor that receptor |
|
|
44:52 | not a channel. So I just . It's a medical tropic G protein |
|
|
44:57 | receptor, this receptor is not a . Instead it's coupled to G protein |
|
|
45:04 | activation of these G protein complexes can activate or inhibit downstream the other island |
|
|
45:12 | . But on their own G 30 couple of receptors on a channels they |
|
|
45:17 | allow the blocks of islands through In addition of affecting this is what's |
|
|
45:22 | the shortcut um pathway in addition to immediately adjacent ion channels on the plasma |
|
|
45:32 | . In addition to that, the activated G protein complexes can also interact |
|
|
45:39 | different enzymes and molecules and sinuses and messengers and the secondary messengers can have |
|
|
45:48 | the facts. Or they can have effects in regulating the transcription factors at |
|
|
45:53 | level of the nuclear scene. Same , little different effects in the same |
|
|
46:01 | s. Is missing. There there's aim sell different the fact in the |
|
|
46:06 | cell, same neurotransmitters. So in . N. S in C. |
|
|
46:11 | . S. You will learn that has nicotine IQ channels that we're talking |
|
|
46:18 | the same similar academic channels but they produce something potential in the CMS to |
|
|
46:22 | something different. And they also have tropic Mascarenas couple of her suffers and |
|
|
46:29 | two nicotine versus masculinity will have a effect on the same cell. It's |
|
|
46:34 | same neurotransmitter, acetylcholine. But if activates the receptors whichever one is more |
|
|
46:40 | or activated first will win. They have opposing actions to each other. |
|
|
46:46 | neurotransmitter, different effects on different So Siegel Colin is the same neurotransmitter |
|
|
46:51 | the heart that slows down the heart . Medical tropic acetylcholine receptors and the |
|
|
46:56 | muscle, it increases the contraction that's IQ. Acetylcholine receptors that are iona |
|
|
47:03 | different different effect on different cells but same chemical molecule. So the fact |
|
|
47:10 | depends on the type and the properties the post synaptic receptive to which these |
|
|
47:17 | bind. Okay, alright, we're talk a lot about acetylcholine system but |
|
|
47:26 | acetylcholine system will serve sort of as canonical system of what is happening in |
|
|
47:31 | amine systems in particular. And we'll be looking more into the amino acids |
|
|
47:36 | glutamate and gather. So with acetylcholine will find acetylcholine in the brain, |
|
|
47:43 | find acetylcholine and motor neurons and muscular . All PNS began Raonic and parasympathetic |
|
|
47:52 | . Um acetylcholine gets synthesized when the Kalay and choline come and chat |
|
|
48:01 | chat is an abbreviation for choline acetyl . And so yes you will be |
|
|
48:07 | for all of the details of this system produce acetylcholine acetylcholine, the common |
|
|
48:15 | is the neurotransmitter vesicles they'll have So if it's glutamate it will have |
|
|
48:20 | transporter for glutamate. If it's a colon will have a transporter for civil |
|
|
48:24 | will stop the testicle with the civil once the civil code in is released |
|
|
48:31 | can target in the cns both academic mastering acetylcholine receptors. But once the |
|
|
48:38 | colon is released and binds to these it gets broken down by Seattle |
|
|
48:44 | S turns so a single colony takes civil Colin, breaks it down into |
|
|
48:50 | acid and Colin. And choline from synapses. Acetylcholine Colin nestor is breaks |
|
|
49:00 | acetylcholine, it doesn't stay here for in synapse Colin gets transported back here |
|
|
49:07 | the pre synaptic terminal through the sodium transport. So there's another transporter here |
|
|
49:14 | will take the chemical from the synapse back into the pre synaptic terminal. |
|
|
49:20 | there with the help of chat with seal koei will form acetylcholine again. |
|
|
49:27 | loaded up and can repeat the When we talked about Alzheimer's disease. |
|
|
49:35 | the first section of the course, focused mostly on the cellular pathology. |
|
|
49:41 | hallmarks cellular pathology of Alzheimer's disease. in particular we talked about uh |
|
|
49:49 | inter cellular tangles. And we talked extra cellular plaques, uh senile plaques |
|
|
49:57 | amyloid plaques. We call them And we also looked at the gross |
|
|
50:02 | changes in the severe advanced stages of disease. And we saw loss of |
|
|
50:10 | tissue degeneration shrinkage, especially the gray where you have the axon where you |
|
|
50:18 | the selma's and you have the dendrites neurons and what I do for you |
|
|
50:26 | on the board, I also said amine systems in case of acetylcholine expression |
|
|
50:38 | these immune systems are going to be to specific parts of the brain to |
|
|
50:43 | specific nuclear. And I also said each neurotransmitter is you can think start |
|
|
50:52 | about each neurotransmitter as different behavioral different mood and a different pathology or |
|
|
51:03 | or neurological disease association for Alzheimer's It turns out the Colin ergic neurons |
|
|
51:11 | neurons that produce acetylcholine. We call Colin ergic norepinephrine, we call the |
|
|
51:17 | ergic serotonin, we call them serotonin . But those Colin ergic neurons, |
|
|
51:23 | neurons that synthesize acetylcholine, they seem be really vulnerable and are affected earlier |
|
|
51:32 | into the progression of this Alzheimer's And most of the medication. So |
|
|
51:38 | you can add on to your announced Alzheimer's disease that the pathology of the |
|
|
51:43 | pathology before you have this massive shrinkage loss of brain tissue could start selectively |
|
|
51:50 | out certain populations of neurons in this , that population as acetylcholine producing |
|
|
51:58 | Now you don't have enough acetylcholine, majority of alzheimer's medications, our little |
|
|
52:10 | Aries blockers. So now we're talking therapy and medications. Remember we started |
|
|
52:17 | about mechanisms symptomology a little that is developmental diseases, that aging uh more |
|
|
52:25 | to be prevalent in aging population. we're talking about more cellular mechanisms but |
|
|
52:31 | talking about systems, the neurotransmitter systems are more vulnerable. It's Alzheimer's |
|
|
52:37 | acetylcholine system that is really vulnerable and see the loss of these kahlan ergic |
|
|
52:44 | and. So the medications that block single colonist Aries. If you block |
|
|
52:51 | then you're prolonging the amount of you're increasing potential in the amount and |
|
|
52:59 | prolonging how long it'll Colin can stay the synapse and combined to these past |
|
|
53:06 | receptors. Alright, so that's overwhelming and therapy of Alzheimer's disease. There's |
|
|
53:13 | cure for Alzheimer's disease. The therapy down the progression of the disease at |
|
|
53:19 | best. But think about this, this really effective when you're thinking about |
|
|
53:28 | ergic neurons that are dying that are lost? What happens that you had |
|
|
53:37 | pollen ergic neurons? Now you have colon ergic neurons. What do you |
|
|
53:41 | is going to happen to medication? it still going to be effective or |
|
|
53:48 | you more likely now to have to the concentrations of these medications because you're |
|
|
53:55 | losing more and more of the choline ergic neurons and you have to increase |
|
|
53:59 | medication to make this remaining acetylcholine just available as possible? Right, so |
|
|
54:10 | what happens if there is no more nurtures producing neurons? Is that medication |
|
|
54:20 | ? No, probably not. Um happens when you raise levels of pharmaceutical |
|
|
54:28 | or or or things over the counter that you're in taking, you start |
|
|
54:35 | other parts of the body. That's when you're reading directions for ibuprofen or |
|
|
54:42 | , It says, you know, on your age or size, take |
|
|
54:46 | tablets? 400-800 mg maximum every six . So you cannot take 100 tablets |
|
|
54:55 | six hours because why? Well you not die but it may cause all |
|
|
54:59 | of complications of your on your other . A lot of the pharmaceutical over |
|
|
55:03 | counter drugs and even botanical corporations are through the liver. You can overload |
|
|
55:10 | liver and cause liver toxicity and it's an older person. So you're gonna |
|
|
55:15 | tent and more drugs and compromise the of other organs or systematic failure |
|
|
55:22 | Now you have to weigh that. , what else can you do? |
|
|
55:29 | to come up with a better strategy treating Alzheimer's disease. I use that |
|
|
55:35 | that came up I think a year two ago in my class, somebody |
|
|
55:39 | why don't you just eat acetylcholine? don't you just feed a single coding |
|
|
55:43 | Alzheimer's patients? And of course, know, if you eat something, |
|
|
55:47 | digest it. I don't know how of it would get into the |
|
|
55:53 | but precursors? Right, that's that what that student was thinking about. |
|
|
55:58 | can't you give some sort of Why can't you make more subtle |
|
|
56:04 | So what do you need? Maybe need somehow to stimulate the enzymes. |
|
|
56:09 | you need to stimulate chat. Maybe strategy is not as good. Maybe |
|
|
56:14 | need to stimulate transporters and trying to it as back as much as possible |
|
|
56:19 | fast rather than trying to keep it . So what about receptors? Maybe |
|
|
56:25 | make receptors a lot more sensitive so a little bit of a single cone |
|
|
56:29 | doesn't take two molecules, it just one and it's active. So all |
|
|
56:34 | these are strategies that when you're thinking neurotransmitter systems, neurotransmitter dysfunctions and in |
|
|
56:42 | when you think about neurological disorders, of the neuro drugs they will target |
|
|
56:47 | that will be blockers for receptors. will be uh agonists for receptors uh |
|
|
56:54 | will be antagonists for receptor channels or for voltage gated channels like sodium channels |
|
|
57:00 | potassium channels when you're talking about this transmission and the cycling within the |
|
|
57:07 | Now you can think of all of different strategies that could potentially be employed |
|
|
57:11 | the future to try to preserve these systems, like a mean system in |
|
|
57:17 | case Cullen ergic acetylcholine system if it so vulnerable. Okay so you can |
|
|
57:25 | think about that transporters synthesis was post response degradation of the neurotransmitter in the |
|
|
57:34 | cleft. Uh there's other medications for disease that not a single building base |
|
|
57:41 | the overwhelming majority are Qala necessaries inhibitors sometimes some commercials for other drugs you |
|
|
57:47 | hear for especially older population are you since So it's not like online doing |
|
|
57:55 | . But are you taking Colin estrus ? C. I. M. |
|
|
58:00 | that's that's what it stands when you the little text. Sometimes in these |
|
|
58:04 | on tv actually or online. So is Alzheimer's system. It's a it's |
|
|
58:12 | sorry Siegel polling system. You should all of the details that we're talking |
|
|
58:17 | here and you should add some notes you save space for Alzheimer's disease or |
|
|
58:23 | keep the information here. Come back this slide here. I wanna talk |
|
|
58:29 | poisoning neurotransmitter release. It's a special from your book bacteria, spiders, |
|
|
58:37 | and you. So there's a lot different elements out in nature. We |
|
|
58:44 | talked about different microorganisms producing toxins and fish uh in shellfish harboring in certain |
|
|
58:55 | . These microorganisms and producing these You also have spiders have snakes. |
|
|
59:02 | have venoms. Uh And uh you have also heard of clostridium botulinum or |
|
|
59:12 | . The botulism is uh not a common disease but it can occur when |
|
|
59:19 | is canned food that wasn't prepared canned properly or stored properly or has |
|
|
59:27 | expired, started warm temperatures, Clostridium will produce these botulinum toxins a |
|
|
59:38 | Okay, so clostridium botulinum uh microorganism if you consume this bad canned food |
|
|
59:46 | can kill you. So we'll talk little bit about how it can kill |
|
|
59:50 | . But so this is a bad news if you have botulism but you're |
|
|
60:00 | invited to a Botox party and clostridium and the toxin that it produces botulinum |
|
|
60:09 | but first was taken advantage by the and aesthetics industry. So Botox injections |
|
|
60:18 | what do both ox injections do? in general, what does this toxin |
|
|
60:22 | ? It turns out that this toxin forms of the B. D. |
|
|
60:26 | . E. C. Interferes with protein protein complex, the protein complex |
|
|
60:32 | the classical physical polling and the So it targets specifically this protein protein |
|
|
60:38 | on acetylcholine signaling and vesicular fusion. why would the beauty industry want to |
|
|
60:45 | it if you can get poisoned and from consuming these toxins? How can |
|
|
60:51 | toxins be used for aesthetic purposes? what happens when you are aging and |
|
|
60:59 | speaking and you're flexing your fingers and and stuff like that. You get |
|
|
61:06 | , things get worn out. Skin stretched, it gets stretched and |
|
|
61:10 | A lot of times you form wrinkles your face and chin and lips and |
|
|
61:17 | people don't like that so they want look youthful. So this is where |
|
|
61:21 | take advantage of the toxin molecule and modern science and modern medicine, you |
|
|
61:27 | localized injections. And when you do injections that actually relaxes the muscles that |
|
|
61:35 | causing these wrinkles because it blocks the release. And sometimes these procedures Botox |
|
|
61:44 | also used together with filler injections so something a little bit different. That's |
|
|
61:50 | you want your eyebrows or eyes or to look fuller and bigger. So |
|
|
61:58 | would be some fluid injections that are like warm that could be basically for |
|
|
62:06 | purposes, making it look different. And sometimes after Botox injections when people |
|
|
62:13 | around their mouth. They may have like completely moving their lips properly. |
|
|
62:19 | that is because the colon reception releases and they're not properly activating the |
|
|
62:26 | It's similar to like when you have and you have anesthesia and a little |
|
|
62:32 | of swelling after dental work. It's kind of a little bit of that |
|
|
62:36 | . But so this is what people with Botox now. So this is |
|
|
62:41 | beauty industry and aesthetic industry cut onto Botox now is also an FDA approved |
|
|
62:49 | Botox injections for the treatment of migraine case you didn't know migraine is a |
|
|
62:55 | disorder. It's not a headache. is a neurological disorder. And Botox |
|
|
63:01 | seem to alleviate some of the And it's improved uh d a food |
|
|
63:08 | Drug administration approved medication for treating So this is an example of how |
|
|
63:15 | can take something that poisons and kills . You can look at it in |
|
|
63:20 | lab, isolate the toxin and see this toxin does understand the mechanisms of |
|
|
63:26 | of that toxin, which is the binding of acetylcholine. Use it for |
|
|
63:31 | purposes locally to get rid of wrinkles such. Use it for clinical purposes |
|
|
63:37 | treat migrants. Uh There are many parts of the system here. This |
|
|
63:43 | the pre synaptic system. But remember we talked about the pre synaptic and |
|
|
63:48 | synaptic components of this system and there different molecules that can affect different parts |
|
|
63:54 | this pre synaptic synaptic system. Black spiders to produce this toxic venom, |
|
|
64:03 | will release acetylcholine, I'm sorry they interfere with acetylcholine release. But a |
|
|
64:09 | from Taiwanese cobra toxin will have an on post synaptic acetylcholine receptors. So |
|
|
64:18 | toxins will target pre synaptic pasta, pick sides. Okay some of them |
|
|
64:24 | be deadly. Black widow bites can deadly and we have black widow spiders |
|
|
64:30 | in this area actually even though the case of a person that that past |
|
|
64:36 | days following a bite on the Uh so they're very powerful. We |
|
|
64:42 | about toxins being used by roderick Mackinnon they had binding properties and roderick Mackinnon |
|
|
64:49 | studying the structure of the potassium Was looking to see how it affects |
|
|
64:53 | flux of potassium and gating of potassium using these toxins. Uh then we |
|
|
65:00 | human synthesized toxins. Organophosphates that will target this acetylcholine system. Organophosphates are |
|
|
65:12 | for agricultural purposes and they used for purposes. Organophosphates that are also produced |
|
|
65:20 | illegal warfare purposes. So chemical warfare and nerve gasses such as salman and |
|
|
65:29 | . And there are famous instances of nerve gas is being used by terrorist |
|
|
65:36 | and attack and Tokyo Metro and Japan the early nineties uh nerve gasses released |
|
|
65:45 | a couple a few years ago, can't remember exactly in syria. Uh |
|
|
65:50 | bad guys around the world will take we know from the mechanisms of action |
|
|
65:57 | will also make weapons out of this and weaponize these different molecules. And |
|
|
66:04 | way that organophosphates work is nerve When there is a lot of nerve |
|
|
66:10 | injection, inhalation or intake. Uh happens is they act as a Theological |
|
|
66:19 | inhibitors so they act as Alzheimer's So it's so great. So they |
|
|
66:25 | be great for Alzheimer's nerve gasses. if you have normal levels of of |
|
|
66:31 | , remember that these substances are not affecting your brain. Acetylcholine is also |
|
|
66:36 | muscular junctions. Acetylcholine will also be to the diaphragm contraction as you're |
|
|
66:44 | So if you activate the muscle too , too much of a single coding |
|
|
66:49 | organophosphates will block acetylcholine esters. There be a lot of acetylcholine and the |
|
|
66:54 | . What happens when you activate muscle . If you activate the muscles |
|
|
67:00 | they enter into what is called a state, the muscle tetanus where they |
|
|
67:05 | polarized and they're no longer producing action . That means they're locked up and |
|
|
67:12 | you can imagine is when you have muscle cramp, If you have it |
|
|
67:17 | than 10, 15, 20:30 it's painful and if it's all all over |
|
|
67:25 | leg you can't move the leg now that type of muscle cramp on your |
|
|
67:32 | muscles. That means you can no breathe. So most of the |
|
|
67:37 | S. Medics and other advanced army would carry some of the antidotes and |
|
|
67:44 | to re stimulate the block and we and put some adrenaline into the hearts |
|
|
67:49 | the hearts of stopping to to recruit soldiers. A few years ago, |
|
|
67:54 | had a special forces medic taking the from the U. S. Army |
|
|
68:01 | he did a tour of duty in and he encountered nerve gas attack in |
|
|
68:08 | . And so he told his story what happened and because he was the |
|
|
68:15 | , what transpired and how he had get off the guys off the rooftop |
|
|
68:20 | rush them down below. Uh for number of reasons to get them |
|
|
68:25 | So it's not something that doesn't It does exist. And you can |
|
|
68:31 | stories, the most recent stories you know, these nerve agents, |
|
|
68:37 | gasses, look at the story of trying to kill the main opposition |
|
|
68:44 | Now, volley by it's an incredible actually. It's a movie by placing |
|
|
68:49 | of these nerve gas agents into his . And uh failing, failing basically |
|
|
68:57 | this, at this uh you killing mission of the of the opposition |
|
|
69:01 | at the time. So, these exist and you will hear about them |
|
|
69:06 | the news almost in the yearly whether they use on a single person |
|
|
69:12 | instance by bad guys or they're just by crazy people on a larger |
|
|
69:17 | Alright, we'll end on this interesting here. I'll see everyone on Tuesday |
|
|
69:24 | we will try to finish, neuro transmission. No transmission. Three |
|
|
69:28 | . Take care. Everyone. Thanks being on zoom, |
|