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BIOL 4315/6315 Neuroscience Mon Wed - NEURO Lecture 11 Neurotransmission II
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00:02 This is lecture 11 of neuroscience, transmission too is the subject matter.
00:13 the notes are from €9.09. We set them into the presentation. You
00:27 you that in C. N. . We have two types of sin
00:31 . We have chemical signaling, we electrical signaling. So we talked a
00:36 about chemical neural transmission and that's what lowly discovered. But there's a lot
00:43 signaling that happens through the electrical. Oh that must have been somebody has
00:56 . Was caption and I don't want see if I can. So the
01:05 modes of communication through chemical and electrical are quite different through chemical synopses.
01:12 have neurotransmitter, bicycle fusion and release through electrical synopsis we have gap junction
01:23 and gap junctions allow for the transfer ions allow for the transfer of small
01:30 . They happen where there is this and the two cell membranes are coming
01:36 together to each other, forming the songs that form the gap junctions and
01:43 junctions are also present in glial cells in neurons and glial cells. We
01:51 an example of astrocytes and astrocytes have gap junctions where they can transfer increased
02:00 of ions and other chemicals through their networks. And neurons will use gap
02:07 in order to synchronize larger populations of because we need larger populations of neurons
02:16 in order to perform certain tasks. We talked about this very simple
02:25 the neuro muscular junction and the positive again. So there are certain features
02:34 this neuro muscular junction that we discussed we talked about How 1st of All
02:47 have the motor neuron, it projects the muscle cells that the axons of
02:54 motor neurons will ram if I. will form these very large pre synaptic
03:01 that are called motor end plates. these very large axons will contain acetyl
03:09 vein and the cecil co vein will released when the motor neurons are
03:16 The single synapse here, boston optically contain at the very close proximity to
03:25 pre synaptic side posson optically you have receptors. You need to acetylcholine molecules
03:33 open acetylcholine receptor channel. The opening acetylcholine receptor channels will generate this very
03:43 end plate potential which will always result activating volt educated sodium and both educated
03:51 channels that are located deeper within the all falls that will be necessary to
03:57 the cardia the muscle action potential. this synapse here is a neuro muscular
04:06 . The synapse series. We're talking skeletal muscles. We talked about how
04:12 in the heart will slow down the rate and that because it acts through
04:16 different ligand gated receptor channel and that is mascara nick and this receptor channel
04:27 the neuromuscular junction that we're talking about is nicotine nick, a civil code
04:33 receptor channel. Unlike voltage gated sodium that are formidable and selective to sodium
04:42 channels that are selected to potassium. ligand gated channels, a lot of
04:48 of sodium in which causes the deep through this end plate potential and they
04:54 allow for potassium to go out through same channel. So you have to
05:01 species that can travel through these acetylcholine channels. And we talked about how
05:08 vesicles will contain the quantum of the locally in molecules anywhere between 2000 to
05:15 molecules. And because of this, amount of molecules that always gets
05:21 you'll always have this very large post response. So it's a very reliable
05:29 and deep polarization and action potential release neurotransmitter results in the twitch of a
05:36 fiber. So only excitatory and a synapse is capable of producing an employee
05:46 of 70 million rolls. And then compared it to the central nervous system
05:53 . And we said that if at neuro muscular junction you can produce this
06:01 and plate potential that measures 70 million . And it will always guarantee that
06:11 the synapses activated, always produce the action potential here in the central nervous
06:19 synapses activation of one synapse, we it excitatory post synaptic potential or
06:28 P. S. P. And will only measure approximately half a mil
06:34 in size. So if you're talking reaching the threshold For action potential generation
06:44 would be -45 kilovolts here. All then, you know that in neuro
06:52 junction, you have this very reliable potential and you'll always get a
06:58 You'll always about the action potential. here you have to deactivate two synopses
07:07 be one middle of all 345678 and on and so forth. And the
07:15 synapses you activate. If you activate synapses and they reached the threshold
07:22 there's going to be an action potential the cns neurons. So you have
07:27 activate tens of positive excited inputs to this excitatory post synaptic potentially PSP response
07:38 is strong enough to drive the membrane . VM. To the threshold potential
07:47 for the action potential. That's why call this synapse a very reliable
07:53 And this initial deep polarization is and potential happens through acetylcholine receptor channels.
08:01 action potential, which is now portrayed happens through downstream activation of voltage gated
08:07 channels, calcium channels. Action potential which is not shown happens through opening
08:14 the voltage gated sodium channels. And potassium channels that we talked about.
08:24 , for neurotransmitter systems, we talked certain criteria for these neurotransmitter systems.
08:31 we also mentioned several major neurotransmitters. we talked about amina assets which are
08:40 glutamate glycerine. These are the major . And we talked about a
08:50 We started talking about the means here the neuro muscular junction and also in
08:55 neuro muscular cardiac cardiac muscle. And talked about the fact that what's really
09:06 is that if you were to take cartoon of the of the break.
09:12 you were to look at Gaba expression different parts of the C.
09:18 S. There would be neurons that be expressing Gaba scattered throughout. Okay
09:25 this is gonna be Gaba. If look at the expression of glutamate,
09:33 expression of glutamate is gonna be scattered . That means it sells the excitatory
09:43 projection cells. Excitatory cells will be in these different regions and there will
09:51 expression of glutamate. What and the that have Gaba and glutamate. They
10:02 also co express peptides. So when looked at that initial slide of the
10:09 and we talked about the hippocampal circuits the hippocampus. We also said that
10:13 are self specific markers that will allow to distinguish different subtypes of cells.
10:19 a lot of inhibitory cells for example also co express amount of statin.
10:25 can co express neuro peptide. Why addition to expressing and releasing Gaba.
10:32 we talked about how neuro peptides behave . They're synthesized differently from neurotransmitters.
10:39 there's a whole synthesis trafficking and cycling neuropathy tights that's different. So the
10:45 function for this Gaba and glutamate cells be to release glutamate and Gaba.
10:49 if their cells have a lot of coming their way apart from releasing glutamate
10:55 Gaba remember they'll start start synthesizing peptides transporting them and non specifically releasing
11:03 Okay. Through through kind of external Not as spatially specific as the neurotransmitter
11:12 . Now, a means are different there are only specific areas where a
11:18 cells that means cells that make the are located. And this is just
11:23 a cartoon example. So that means the neurons that synthesize the means will
11:29 located in specific areas of brain stem some other parts of the C.
11:33 . S so that they're confined spatially they're produced. And then the projections
11:40 these nuclei nuclei again by definition are types of the collection of cells that
11:46 responsible for the same for similar types functions. So from these nuclei that
11:54 acetylcholine or synthesizes norepinephrine, one of other molecules there is going to be
12:03 coming throughout the brain, communicating and going into the periphery as well.
12:13 just just to to to to for to form this understanding each one of
12:19 systems are very powerful system, amine nor but not friend acetylcholine in the
12:27 as we talked about these neurotransmitter they mean different state of being different
12:34 of alertness, uh different abnormalities. diseases. Talk about dopamine, you're
12:44 about diseases of addiction, you're talking Parkinson's disease. When you're talking about
12:52 choline and acetylcholine circuit dysfunctions. You're about Alzheimer's disease when you're talking about
13:01 for example, you're talking about depressive of disorders. Uh PTSD depression and
13:11 . So these have their specialized nuclei they are expressed spatial in a limited
13:19 but released throughout the circus quite globally the entire C. N.
13:26 And they're interconnected networks. And then addition to these molecules we discussed
13:38 these were ceo and and no we discussed endocannabinoid. This was to a
13:59 to a silver glycerol and anandamide. also introduced a molecule called a wreck
14:11 acid. And we said that all these molecules are different because they're not
14:22 into vesicles and they're not packaged in peptides storage compartments but they're actually membrane
14:33 and they can cross through plasma The neurotransmitters there in vesicles are
14:39 they need to be released. That they're in vesicles their package, they
14:43 to be released neuro peptides. If recall talked about neuro peptides, we
14:50 about secretary Granules, they will but from this more of the somatic cellular
14:57 synthesis with high levels of activity. . And so peptides are released through
15:04 secretary granule mechanisms and that's what makes different that what makes them different than
15:13 gasses. They have no vesicles. have no storage or canals and the
15:20 . They have no vesicles no storage or academic acid no vesicles no storage
15:25 . They are fat soluble lipid That means they cross through plasma membranes
15:33 acids and means. And and and . They still, despite the peptide
15:40 non specificity because of the Secretary Despite that you still have these molecules
15:53 the amino acids gaba glutamate and a signaling in the interrogate fashion. They
16:02 pre synaptic aly and they cause post effect. And these molecules the gasses
16:09 the cannabinoids or economic asset they signal retrograde fashion. That means they get
16:15 post synaptic li and then they affect synaptic terminals. Um We also talked
16:30 A. T. P. And so if you know A.
16:37 P. You know Denniston triphosphate and core molecule of it at denison is
16:43 neurotransmitter. That is interesting for us understand because it's linked to sleep
16:52 And because caffeine is an antagonist. from last uh section we started talking
16:59 agonist and antagonist antagonist is something that block the channel function. So it's
17:05 is a dentist and receptor antagonist and will promote the release of glutamate and
17:11 the dennison will reduce levels of glutamate therefore dennison will go up in the
17:18 and will go down a denison It's re synthesize will go up in
17:22 evening, it will go down when under constant stress. Not just the
17:28 hormones get altered and go through this H. P. A. If
17:33 recall from other classes hypothalamic pituitary adrenal , the cortisol signaling the stress hormone
17:42 through these access. But in addition stress you'll also be expressing. And
17:47 cannabinoid levels will go up. So molecules change as part of the external
17:55 . The stimuli that you're getting as of the circadian cycle goes up and
18:03 . Uh and they signal different different behavioral states. Norepinephrine. You're
18:10 alert. A lot of glutamate release cafe and you're very alert. A
18:15 of gaba release and the dentist and go up. You're getting sedated.
18:21 they all represent different uh functions, moods, different states of being an
18:32 . We talked about the fact that is necessary for the vesicular fusion and
18:40 because if you look at the this is what it looks like.
18:44 little hairy ball here and all of things dangling off of the podium uh
18:53 the peptides and things like that. it turns out that these vesicles
19:00 this is a simplified presentation of These vesicles have the secular protein complexes
19:07 the membrane has membrane protein comp. two complexes have to interact and interlock
19:15 each other so that the plasma the phosphor lipid bi layer of the
19:21 , confused with the phosphor lipid bi off the neuron and cause the fusion
19:28 to open and cause the neurotransmitter The calcium is absolutely necessary for that
19:36 . It turns out that on this complex there is a calcium sensor
19:45 One of them is synaptic tag men has to recognize influx of calcium in
19:52 for this vesicles protein protein interactions to place with the membrane proteins and for
19:59 exocet. Oh sis to take place then the two have to disconnect for
20:05 end of psychosis because this piece of membrane is not lost, it gets
20:11 . Endorse it owes back and refilled neurotransmitters. So for the pre synaptic
20:18 fusion and neurotransmitter release, you need potentials for deep polarization and that deep
20:25 and external terminal will open bolt educated channels and influx of calcium through voltage
20:32 channels. These are pre synaptic channels allow for this vesicular fusion to take
20:49 . Uh Now visualizing neurotransmitter release. really neat what you're seeing here on
21:00 left side our electron microscope pictures and of all you have on the top
21:08 calcium channel. So where calcium channels , they're located pretty sign optical.
21:15 so you're seeing these dots here, row of these dots running across and
21:20 looks like the surface of the But this is a single synapse you're
21:24 at. And these dots here there both educated calcium channels, interesting.
21:29 located strip digitally within these active pre synaptic active zones that have the
21:37 vesicles filled, docked and primed, to be basically docked fully and
21:46 And once you stimulate you can see there is an excellent exercise, exotic
21:52 pore forming. And now this is a vesicles that used from inside came
22:00 the membrane and now you're looking into inside of this bicycle. And this
22:07 crater that contains neurotransmitters. You can that this is a typical uh uh
22:15 for the synopsis where chemical synapses would about 20 nanometers. And where you
22:22 this narrowing of the membranes between the neurons. And if you have the
22:28 of these connects salons, they can the gap junctions. And this is
22:33 the large gap junction connectivity looks So speckles had been placed there.
22:42 I've been also very interesting when we out about membrane and what's going on
22:46 the membrane, very interested to know side of the membrane contains, what
22:55 it's a fossil lipid bi layer. it has to face is the face
23:00 the face. And in the old there was this technique of the freeze
23:06 . You stimulate the sound and you quickly freeze it with liquid nitrogen or
23:11 some other method. And then you place a little uh needle, you
23:18 , the membrane and try to cause little vibration with the table or
23:23 Something. So that needle hopefully would split the two faces of the membrane
23:30 because it's frozen as a defrost. kind of like a sandwich, hoping
23:34 the frozen sandwich that you, you , hit with a screwdriver flathead,
23:40 know, will fall apart perfectly into bottom and top face of the
23:46 So that's sort of on a microscopic that was being done, the frozen
23:52 you would see some of these trans proteins that's sticking around some of the
23:56 that would unfold and would be staying the extra cellular side, others would
24:00 on the side of plas mix uh then at the end of the
24:08 century, beginning of the 21st century developed dyes that are sensitive to different
24:17 . So we could actually image concentrations different ions and there are voltage sensitive
24:24 that are sensitive voltage or calcium sensitive that are sensitive to calcium influxes of
24:31 , sodium sensitive dyes, flexes of sodium potassium fluxus is just potassium.
24:37 imagine that there are molecules basically chemicals upon increases of potassium, they would
24:45 a much stronger fluorescent signal. And with these guys, uh roberta rodolfo
24:54 is one of the famous nurse scientists South America has shown that when you
25:01 at the calcium sensitive dives and this before the vesicular release, you can
25:08 that there are little peaks of calcium and you can see very clearly these
25:13 that could be correlated to these voltage calcium channels that are located close to
25:19 pre synaptic active zones. And then is during the stimulation. So the
25:25 that was being asked here is how calcium does go in and it was
25:35 Micro Moller. I don't know why is not showing up completely. Um
25:42 micromobility concentration of calcium that happens inside south and you see this organized tournament
25:54 spatially that gets now this disorganized and evolves into something more continuous and less
26:07 spatially. So it's not necessarily disorganized it's showing much higher levels of
26:13 And you see that there is like spatial specificity here that doesn't exist when
26:19 have the stimulation. So a lot vesicles could be stimulated and fused to
26:24 plasma membrane because we need a lot excitation a lot of the synapses in
26:30 to cause the vesicular release in order activate the downstream neurons. So in
26:44 central nervous system synopsis we have this ender zone that will but off the
26:54 that are filled with neurotransmitter. They close to the active zone. You
26:59 energy to be docked by these active and and primed. Almost used but
27:06 quite. We're sitting very close to plasma membrane and, pardon me,
27:12 need influx of calcium through both educated channels that will allow the diffusion of
27:19 particular membrane to the neuronal membrane. interestingly enough, sometimes it's not enough
27:27 and you'll only perform what is called partial fusion and only a little bit
27:33 the neurotransmitters will get leaked out of bicycle and it will get returned into
27:38 priming position again and wait for another until there is maybe more calcium.
27:47 if there is enough calcium then you form this full fusion pore you dilate
27:53 poor cause the full release of the into the synapse. Then the pieces
28:02 the membrane you can see like if fuse this membrane remember this will the
28:09 area is proportionate to the capacities in membrane. And if you've use let's
28:17 100 vesicles at once in one synapse capacitance properties of that cell. And
28:24 synapse will increase with this fusion because have more surface area. But then
28:31 piece of the membrane doesn't stay there it doesn't get exercise toes. It
28:37 surrounded by this Claritin it has like chemical markers that surround the vesicles membranes
28:45 recycle them back in with the help A. T. P. They
28:50 acidified so filled with hpE lots and of protons and then the neurotransmitter is
28:58 re uptake of neurotransmitter that's driven by high acidification levels. And so that
29:06 vesicles with the neurotransmitter can go back the dark crime and release positions again
29:15 in some instances it gets recycled it gets acidified but it gets recycled
29:22 for a longer process of re processing this early end. So it's almost
29:28 two temporal scales and can you exhaust vesicles. Yes if the neuron is
29:35 nonstop nonstop nonstop it will stop releasing . You will exhaust all of the
29:44 that it has and it will take 12 to 15 seconds for it to
29:49 completely. So if you have a sustained prolonged stimulus, active active active
29:55 last for longer than 15 seconds. very likely exhausting that's announced Of
30:03 So you won't get response from that . And you have to let it
30:07 10-15 seconds to recover for it to . Refill the neurotransmitter vesicles re dock
30:15 re prime them to be responsive fully . So alright so calcium the recycling
30:26 this this kind of thing by the that's partial fusion doesn't happen in the
30:31 muscular junction. So it's always reliable potential. And it does happen in
30:39 cns announces and that's why you need activate many many synapse. Not just
30:45 the response is small, 0.5 million but they're quite unreliable and sometimes they
30:50 not release the full content of the if the signal is not right or
30:56 calcium levels or the fusion of the protein complexes is not fully effective.
31:05 so we'll come back actually to the and talk about the slide. Let's
31:13 a little bit more about E. . S. P. S.
31:17 already talked about E. P. . P. S. That are
31:22 by the excitatory synopsis. So this what can happening in the brain you
31:30 hide. I'm excited to see a cell side of our market plus.
31:41 I'll put glutamine here and this very synapse can contact and inhibitory cell
32:04 this inhibitory cell can contact another inhibitory and this is Gaba cells in the
32:13 and I will put a minus And this inhibitor herself. You can
32:20 contact another excitatory cell. And that to resell can contact another excitatory
32:42 So you can have excitation excitation exciting inhibitory neurons, inhibitory neurons inhibiting
32:50 cells inhibit the neurons. Inhibiting inhibitory . Okay so you have these types
32:59 the combinations. And so when glutamate released you get an E P.
33:05 . P O K E P. . P. Which stands for excitatory
33:10 synaptic potential. This happens where where this E. P. S.
33:15 . Happen? It happens in this here. Post synaptic aly would be
33:23 the electrode here. Okay now what if this inhibitory cell releases Gaba here
33:32 going to produce an I. S. P. Which stands for
33:38 pa synaptic potential Lumber that this is member in potential D. M
33:49 So this will be excitation excitation inhibition . More excitation. Now you know
34:01 this is probably a few synopsis. is potentially tens of the synopsis.
34:07 being some mated and activated at the time. This is all in the
34:13 . N. S. Okay so PS ps these are E.
34:18 S. P. S. Excitatory synaptic potentials these are inhibitory post synaptic
34:26 I. P. S. S. Mhm. So E.
34:32 . S. P. S. get produced because of the influx of
34:37 . So post synaptic alie glutamate will to glutamate receptor channels. And glutamate
34:46 channels will allow influx of sodium and potassium and also calcium and will be
34:53 for the E. P. P. When Gaba is released.
34:59 synaptic aly Gaba will bind to Gaba channels and Gaba gated channels will allow
35:12 influence of chloride. So sodium going the south, sodium going inside the
35:26 positive charge causes deep polarization, chloride and I on going inside the South
35:37 hyper polarization. So Gaba is driving membrane potential away from producing an action
35:47 in glue to me is driving a fees and driving the number in potential
35:57 to the threshold for the action When you talk about when we talk
36:10 these channels, these channels are called a tropic receptor channels and their direct
36:18 a tropic signaling versus metal. But . So we will very briefly introduce
36:26 concept that metal. But tropic channels we talk about glutamate binding to glutamate
36:34 channels. Their actual channels for Gabba binding to Gaba receptor channels their
36:41 channels And then in metabolic tropic signaling will bind to G protein coupled receptor
36:50 but they're not channels. The jew coupled receptors are just misspoke so will
36:57 to the g protein coupled receptors and of this jew protium can regulate channels
37:05 that are on the membrane can either or closed channels from those are referred
37:11 as G protein gated ion channels because gated from inside the south by the
37:18 of the juco audience activation of the protein can also activate secondary messengers and
37:27 breakdown and activation of certain molecules. uh uh same neurotransmitter can have different
37:36 in the same cell because it can to different receptors and different same neurotransmitter
37:42 have a different effect on different So acetylcholine will have inhibitory effect on
37:49 heart. It will have excitatory effect the biceps, different effect on different
37:55 , the same neurotransmitter. And in cns you will learn that cns neurons
38:01 co express nicotine IQ and muscular receptors you can have two different responses that
38:11 coming from the same chemical activation of same chemical. Alright, so this
38:17 what's happening in the brain, in C. N. S. We
38:25 nicotine IQ and masculine IQ nicotine receptor masculinity are G protein coupled receptors and
38:36 is for acetylcholine. So you will and will be responsible for knowing this
38:42 really well which is the synthesis to the breakdown transport of acetylcholine. You'll
38:52 it in motor neurons that we talked neuromuscular junction. Uh you all have
38:59 and the P. N. Began Raonic and parasympathetic nerve endings.
39:05 when we're talking about acetylcholine here now talking about sarinic receptors. We're talking
39:13 C. N. S. So the brain and acetylcholine can synthesize with
39:20 coa way and choline come and And when they chat together chat is
39:29 for choline acetyl transfer rates. When chat, they form a single
39:37 So this is choline acetyl coa a have chat information of acetylcholine. These
39:46 will now have transporters and this is common theme if it's a glutamate vesicles
39:53 have a transporter for glutamate. If gaba will get have transporter for
39:58 Acetylcholine will have transporters for acetylcholine molecules will fill up the vesicles when there
40:07 the right signal and deep polarization. little college will get released into the
40:13 cleft it combined to both nicotine receptor and most protein coupled receptors. And
40:23 talk we'll talk about this response in little bit in a few slides and
40:28 even next lecture and after it binds acetylcholine receptors, acetylcholine gets degraded in
40:38 synapse. It gets degraded by a Alcala nestor race acetylcholinesterase chews it up
40:47 acetic acid and choline choline gets transported through sodium Crew transport us into the
40:55 synaptic terminals there. It chats with seal. Coetzee forms acetylcholine gets reloaded
41:04 goes through the cycle again. Acetylcholine will not stay long in the
41:12 , it will get eliminated by a Colin. S stories. It doesn't
41:19 linger there, it gets degraded and gets transported back reloaded, are you
41:26 be released again that's what we're going do now remember when we talked about
41:33 disease? We talked about hallmarks of . The intracellular tangles, the extra
41:41 plaques. And I said we're going learn more about Alzheimer's disease. And
41:47 looked at the advanced stages, severe of Alzheimer's disease where you have on
41:52 gross anatomical level shrinkage and loss neuro of a lot of brain tissue.
42:01 I also drew a cartoon for you that the amine neurotransmitters like acetylcholine will
42:08 produced in limited areas in these nuclei the brain. And so one of
42:15 features of Alzheimer's disease is loss of Colin arctic neurons, these certain groups
42:25 neurons that we're talking about and these neurotransmitter systems are more sensitive depending on
42:34 type of the disorder or disease that maybe is happening to an individual or
42:40 we're talking about and studying. So Alzheimer's disease there is a loss of
42:46 ergic nurse, that means there isn't of acetylcholine being generated by these nuclei
42:52 there isn't enough of acetylcholine being released the brain and most of the medications
43:00 majority of the medications for Alzheimer's disease a cd Alcala necessaries inhibitors. You
43:09 sometimes even hear commercials. Are you since it's called industries inhibitor C.
43:16 . N. Sometimes its the So settle colonist Aries inhibitors are drugs
43:24 pharmaceutical drugs that will inhibit a single asteroids. What does that accomplish that
43:35 the availability or by availability or the of this molecule in the acid locally
43:43 synapse. The logic here is if losing the cells that produce a single
43:52 and there are still the cells that a single codeine, let's have that
43:59 stay in the synapses as long as . So the Alzheimer's drugs, they
44:08 is no cure to Alzheimer's Alzheimer's drugs down the progression of the disease or
44:16 fast basically the deterioration of the severe of the disease happen. And it's
44:26 a very good strategy if you think it because you're losing the south that
44:34 producing a single choline, which means some point what's going to happen,
44:40 gonna have to increase the doses of blocker because you're gonna need more and
44:45 of that acetylcholine in the in the neurons that are still producing it.
44:51 the concentration is gonna go up. know that whenever you're increasing anything in
44:57 concentrations, it's not good. You , that's why you cannot take 16
45:03 in one day, you're limited to eight or so besides the brain,
45:09 also have organs like liver for example you can overload it and cause systematic
45:16 to organs. Because if processing and of a lot of drugs would be
45:22 place through the liver. So you to raise the concentration. So you
45:26 a systematic effect on the body. then at some point, there is
45:33 more salt producers little Colin. So medication is I guess it's just
45:40 So you have to start thinking about are some of the other strategies,
45:48 are some of the most ideal strategies you could think of? You could
45:55 a still uh choline system and that could come up with a different way
46:02 treating alzheimer's disease. It's quite limited these colonists terry's inhibitors. And I
46:12 that there is also medication that treats M. D. A. Receptor
46:19 , dramaturgical signaling in addition to colonists . But there aren't that many choices
46:27 are available. So think about what things could you do? Somebody said
46:35 don't you just need to seal cloning know and you have a lot of
46:39 in your body you know it's like it's the same thing you eat something
46:45 digested you know? But then it's a crazy idea because what the person
46:54 maybe thinking was precursors and we somehow the precursors or what is what's going
47:02 ? Where's the breakdown? Can we specifically try to save acetylcholine sounds?
47:09 we have other cells start expressing a coding that didn't do it before.
47:16 now they will because we'll turn on switch and and the genes or
47:22 So all of these are good things think about. This is a very
47:27 theme for a lot of the neuro that you're seeing that uh there will
47:33 an effect of the drug on either synapse and by the by availability of
47:39 substance in the synapse or it will uh controlling or blocking the transporters in
47:46 to prolong the availability of that Um and and this is like I
47:52 , is a is a common Now let's go back to actually this
47:59 uh cartoon here and talk about our interest bacteria, Spider snakes and you
48:15 you are very important and there are of these little animals that produce all
48:24 of different toxins and venoms. And talked about puffer fish, microorganisms and
48:31 fish and uh you have uh spiders are tiny spiders but their bites can
48:40 deadly when we talked about spider how they can specifically bind to the
48:46 channels. And roderick Mackinnon did the and some of them will buy into
48:50 channels. Tetrodotoxin movie antagonize the both sodium channels and so on. So
48:59 may have also heard of clostridium botulinum botulism disease. And it's not very
49:10 , but it is typically caused by that is found in poorly canned or
49:19 kept and poorly preserved canned food. the nasty thing is uh in there
49:29 is clostridium botulinum and what the boche line on toxins do. The botulinum
49:42 are here depicted as these little sharky's what these little sharky's do they interfere
49:50 the protein protein complex and they interfere the binding of acetylcholine neurotransmitter vesicles all
50:02 the plasma membrane. So they essentially the release of a single coal.
50:11 you can think of a lot of things happening. If you limit napoleon
50:16 the heart, the heart rate is to go up. If you limit
50:19 the muscles, you won't be able move the muscles. If you consume
50:24 of it, where it starts affecting muscles of the diaphragm through canned
50:30 you basically suffocate and kind of breathe . And then we have this thing
50:39 Botox that everybody may have heard right? And Botox first emerged in
50:49 beauty industry. And Botox are the that it's for aesthetic reasons,
51:01 Uh in some cases, for medical for skin therapies and things like
51:07 but mostly for aesthetic reasons. And injections. It's not a scary
51:16 right? Nobody's dying. Nobody's eating canned food. They serve you champagne
51:23 . Have you sit down in the and inject the areas that have wrinkles
51:30 around the eyes or the face or lips, why is that? Why
51:36 wrinkles form on the face because we our hands things and we can see
51:43 hands aging and the same happens with face with with movement. It starts
51:49 forming wrinkles and when the Botox gets and actually prevents these muscular contractions from
52:00 place. So there's two things. of all, there's typically Botox injections
52:05 are done followed by the filler Now Botox is one thing Phil there's
52:11 thing filler is something that fills filler something that makes uh lips really big
52:17 you inject it in the lips. , Botox though, after Botox injections
52:25 if they had it around their lips for for for a year, they
52:30 difficulty speaking. Guess why? Because blocking this little colon release and the
52:38 the activation of the muscles. So almost like when you have a local
52:44 and then you're a swollen have difficulty . It's kind of like similar to
52:50 . But here you're blocking the release a single colon now. So that
52:56 that was big and it still is big Botox injections and Botox parties.
53:04 there's also another way in which Botox being used and not as an FDA
53:12 treatment for migraines and some of these of action. We don't understand very
53:25 , but we don't understand very well Botox injections would be helping with acetylcholine
53:34 and the migrants in this case. in modern medicine you have to show
53:39 some substance is safe and effective. can treat a disease. You don't
53:45 have to know the mechanism satisfaction before put it on the market and make
53:51 a you know, multi billion dollar drugs. So uh but you have
54:00 the camps, bad food, bad controlled environment injections locally. No problem
54:10 aesthetics, controlled environment. Clinically injections Botox for migraine treatment also. No
54:20 . So again, a common There's a lot of stuff out there
54:24 the nature that's bad. Too poisonous kill us. We can turn it
54:28 our advantage for scientific purposes for clinical therapeutic purposes as well. Uh There
54:40 other venoms here that I mentioned. widow spider venom will interfere with the
54:48 Colin release. Also Taiwanese cobra will a venom called alpha bungalow toxin.
54:57 will interfere with post synaptic binding of civil code. So remember these systems
55:04 , we're just looking at this prison component of the system. It has
55:08 synaptic receptors, it has the post component of signaling. And then we
55:15 have substances that are human synthesized and organophosphates and organophosphates are used in uh
55:30 industry. Uh organophosphates also synthesized in you have potentially learned about as nerve
55:44 though, names like Salman star in a nerve gasses that basically are like
55:55 medications, they are a CDL coal inhibitors. So too much of acetylcholine
56:06 kill you and cause over contractions of muscle of the same diaphragm muscle or
56:13 lungs and when the muscle over contracts too much acetylcholine, the person can
56:20 having seizures that cNS driven in the can start suffocating. And these man
56:29 substances, there are illegal substances, war substances And they're being used.
56:37 all the time. Um there were attacks with nerve gasses is the famous
56:45 metro terrorist attack in the 90s. the Chechen takeover of the theater in
56:55 involved nerve gasses as well. Then bad dudes around the world always store
57:04 and use them uh in different conflicts its Middle East or or other territories
57:12 the world. So we can also these good things, learn about them
57:17 turn them into into pretty deadly chemical that are outlawed. But you
57:25 Syria is not listening to anybody and they have Putin as their friend
57:37 So all of these good things here alkaline metal, but tropic to tropic
57:43 . So let's go in and talk more subtle choline and then we will
57:47 back and talk about these other Okay, so let's see what time
57:55 is now. This is the reason I mentioned that the nerve gasses will
58:01 like Alzheimer's medications because it's a steel industries inhibitors. So uh, when
58:10 over stimulate the muscle with acetylcholine in muscles can enter into a state what
58:17 called tetanus, a titanic state, means that it will lock up in
58:23 contract ID in, in in in position where it is flexed or
58:33 So you can imagine you can you flex something for 10 seconds, 20
58:37 and then what happens starts being very painful. And if you lock
58:42 the muscles that control breathing through diaphragm can over activation. and this tetanus
58:50 up of the muscle can lead to too. So uh now do Alzheimer's
58:58 do that. No. Uh and a whole, you know, effective
59:06 of using these medications and preparations and that are around them too. But
59:11 parral also very important that we understand nature, endogenous substances other nature that
59:21 their own endogenous substances gonna interact with system, spider and snake venoms and
59:27 like that. I just recently listened a program actually because we have uh
59:34 , we have quite a bit of on the gulf coast. Uh and
59:40 question was, who do you call you get bit by something unknown,
59:47 you guys know who do you Ghostbusters? No, but who do
59:53 call? Mhm. Uh so that most of the people answered
60:03 but apparently they're not as first and don't understand these bites as well.
60:09 there is uh like a whole um prevention center poisoning and something toxicology prevention
60:19 , it's a long number and that's one you're supposed to call because they're
60:25 going to walk you through and help if you call 911, they'll just
60:29 sit tight, we're gonna get you know? But apparently in that
60:34 which was on NPR you're not supposed do all of the myth things that
60:38 tell you, you're supposed to you know, like stuck on
60:41 try to suck it out, spit out, urinate on it,
60:44 you know, rub it on It's like, no, you're supposed
60:48 basically get advice and quite often not anything and even sometimes tightening something
60:56 can make it worse than, than . So you really have to know
61:00 it is and take the advice and to get to profess national system as
61:05 . All right, on this, , interesting note. We'll end here
61:10 and we'll continue and probably finish your , transmission three and next lecture.
61:16 , I'll see you again on Thank you for being here. I'm
61:20 for a student. They can come in. Um, but I'll see
61:26 on zoom on monday again.
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