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BIOL 4315/6315 Neuroscience Tue Th - NEURO Lecture 10 Neurotransmission I
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00:01 This is lecture 10 of neuroscience. gonna start talking about neural transmission and
00:07 also briefly review some of the things we started discussing at the end of
00:13 first section and in particular, we about the fact that when action potential
00:20 generated there is a forward propagating action that forward propagating action potential is generated
00:28 an initial segment is regenerated each note around the beer and the same dynamic
00:34 polarization, the same amplitude, the duration of action potential, the same
00:40 , the same attacks on terminal. purpose of this forward propagating action potential
00:46 to release neurotransmitter is to de polarize external terminal and cause the release of
00:53 . We then talked about the back action potential and we talked about this
00:59 anatomy of the axon initial segment and said that the low thresh told both
01:05 sodium channels these channels that are gated voltage that require a little bit of
01:11 positive voltage. In order to they generate the forward propagating spot but
01:16 1.2 which a high threshold voltage gated channels that require higher voltage, bigger
01:24 and positive current in order to generate back prop. Getting action potentials.
01:28 back propagating action potential is going to inform the cell and the inputs pre
01:35 inputs at the level of gun rights this cell is reacting to the incoming
01:40 . So the back propagating action potential really important in tuning this pre synaptic
01:46 , the inputs with post synaptic And if this activity is tuned well
01:53 tuned short temporal scales, milliseconds to milliseconds, it's really meaningful for the
02:00 synaptic cell, communicating this information to post synaptic cell and prostatic cell responding
02:06 informing the rest of the cell. yes, very positively attuned to these
02:12 . So a lot of learning, development, the strengthening of the synapses
02:18 happen because of the back propagating action and because of the communication that we
02:24 this pre synaptic post synaptic communication. there's some old information here on the
02:31 . The exam is not in two , but the quiz will be in
02:35 two weeks or so. My email is the same. My office used
02:39 be in this building, it's in one, but I'm meeting everybody on
02:43 , but if you're in half one whatnot, um let me know and
02:49 can arrange to meet in person if is absolutely necessary. So when we
02:54 about the brain, I often tell think about the space, when you
03:01 about the complexity of the brain, about the complexity of the space,
03:05 you're out in the field and you up in the sky and you see
03:09 of the stars and then you see of these super images coming from these
03:15 resolution microscopes from the space, showing the Galaxies, showing us the black
03:21 and we kind of understand some of things and some of the things we
03:25 understand, We see them but we can interpret it at the resolution,
03:30 resolution speed, resolution, whatever waves color resolution in imaging that we can
03:36 up. So we're still limited to And technologies keep holding and the brain
03:42 billions of neurons and those billions of are capable of making trillions of
03:49 So that's the complexity. It's like brain is like the whole earth,
03:55 billion people. Each one can have relationships or so in different levels.
04:03 that's one brain. If you took membrane area from the neurons that surrounds
04:09 of the neurons and remember they have extensive processes. And if you flatten
04:14 membrane area and you lay it out , all of the neuronal membrane area
04:20 four soccer fields. So from one , you take it out and unwrap
04:26 of the membranes, Four soccer Imagine a big kilt that has been
04:32 on the size of four soccer That's the fabric of our minds.
04:38 course the Monica hall was very important drawing neurons using golgi stain and he
04:46 not just drawing them out of He was reconstructing. It's called morphological
04:51 of neuronal anatomy, neural normal theology Sherington down into this understanding of trying
05:00 coin the term and explain the term the synapse a special place where the
05:04 synaptic synaptic neurons talk to each other was responsible for finding and definitively proving
05:14 neural transmission. We have the pre elements here. Pre synaptic lee when
05:19 action potential arrives here, this deep causes influx of calcium fusion of the
05:25 release of the neurotransmitter that these neurotransmitters bind to the receptor channel. So
05:32 gonna be talking about ligand gated receptor rather than both educated ion channels.
05:40 Noah's story is cool. In the of easter saturday 1921 101 years ago
05:48 awoke, turned on light and jotted a few notes on the tiny slip
05:52 paper and then I fell asleep It occurred to me at six o'clock
05:56 the morning that during the night I written down something most important, but
06:00 was unable to decipher the scroll that was the most desperate day in my
06:06 scientific life. During the next nine , I awoke at three o'clock and
06:12 remembered what it was this time. did not take any risk. I
06:16 up immediately, went to the made the experiment on the frog's heart
06:21 below. And at five o'clock the transmission of nervous impulse was conclusively
06:29 This is from his 1953 from the of discoveries. And I love this
06:37 because uh you have a really great . Don't sit on it, you
06:41 to act on it in the very , you should take notes on it
06:45 think about how many times you laid bed and had a ha moments,
06:50 ideas. Musical compositions, images, is in your head and then what
06:57 going on Dreams? I was so figured something out during that dream and
07:01 I can't remember anything. So sometimes have to wake up and go to
07:06 lab and do the experiment. Don't too long or in the very least
07:11 good notes and taking notes is really . Even if you don't have a
07:15 phone or computer you can still So now the experiment that often all
07:20 did was pretty cool. He took hearts from the froggies and one of
07:26 hearts had a vagus nerve attached This is a cranial nerve that comes
07:30 the brain stem. The cranial nerve extensively throughout the body. And it
07:34 innovates to a large extent the heart a strong component going into the
07:40 So when you stimulate the vagus the heart rate slows down and when
07:47 stimulate the vagus nerve that is attached this heart, it's called the donor
07:52 . His heart is being bathed sitting a dish and although we removed the
07:58 surrounding that heart. Following the So he stimulated stimulated the nerve stimulated
08:04 norm into the heart. He saw there is a physiological effect the heart
08:09 was slowing down and he collected the from around that heart. He took
08:14 fluids and he applied it on to recipients on naive heart and that heart
08:20 not have a vagus nerve attached to . So there's nothing that is stimulating
08:24 heart and the way that the donor was stimulated. And instead when he
08:29 this fluid on the recipient heart the was the same, the heart rate
08:35 down. So he definitively proved that is a chemical in the fluid and
08:43 that chemical is responsible for regulating. this case the contraction of the cardiac
08:51 , the neurotransmitter that he's discovered was . And the fact of acetylcholine and
08:58 cardiac muscle is to slow down the . And they will say that sounds
09:04 because he told us about reflex, and acetylcholine from motor neurons that caused
09:11 excitation and cause the contraction of the . This is going to be one
09:15 the themes the response of the post cell. It's a muscle cell.
09:20 it's a neuron depends on the type the receptors that ligand gated receptor channels
09:27 those cells will have ligand. Acetylcholine be inhibitory in certain instances in certain
09:34 it can be excitatory and that depends what receptor is going to buy.
09:41 apart from the chemical synapses in the , we also have electrical synopsis or
09:47 we called gap junctions. Gap junctions comprised of these connection subunits that form
09:53 whole connect song on one membrane of neuron and forms a connection on the
10:00 of the adjacent neuron and reform this channel in between the two cells notice
10:06 For regular chemical synopsis the distance is 20 nm in space and for formation
10:15 these gap junctions, the membranes kind a cup closer to each other and
10:20 situations you don't understand exactly how and and when they do so if there
10:26 a partner connection on the other side form these gap junctions all channels.
10:33 when you stimulate one neuron this is stimulating electrode that it produces this instrumentation
10:39 square wave like policy that we discussed neuron will respond. This neuron will
10:45 containing this resistive capacitive properties. So job. And then what's interesting if
10:51 have an electric and adjacent neuron that interconnected through these gap junctions immediately without
10:58 delay, you'll see a fraction of current transferred to the other cell.
11:03 gap junctions allow for the flux of in between cells in between neurons,
11:09 between glia. You'll find gap junctions neurons and glia the major to major
11:15 subtypes of the brain cells. Gap will also allow the passage of small
11:21 such as secondary messengers. So cyclic . M. P, for example
11:26 cross through gap junctions from one cell another. That means that if there
11:30 a lot of positive current and one will cross into that. There's a
11:34 of cyclic GMP and one style it also cross into the other cell.
11:40 when we talked about astrocytes and I one of the functions of astrocytes,
11:45 cells or astrocytes is to suck up concentrations that are abnormal of potassium and
11:53 into itself. The cell has very of an extensive network of processes and
12:01 glial cells are also interconnected with other cells through gap junctions. So that's
12:06 way in which these local abnormal concentration get buffered and siphoned through space essentially
12:16 through the interconnected gap junction all So you say this is really
12:21 We'll spend most of the rest of time talking about synaptic transmission and different
12:27 and different neurotransmitter systems. But then should ask this question. So why
12:32 we have these gap junctions? And are they even regulated? Can you
12:37 these gap junctions? This is something regulates open and closing. So it
12:41 out that gap junctions are open and can either be more open or less
12:47 but they're never closed. So there's closure of these gap junctions. That
12:53 as a part of the physiological Of course we have the pharmacological agents
12:58 can be antagonists. It can be to gap junctions. In fact some
13:02 the anti malarial medications like chloroquine that's in sub Saharan africa. And some
13:11 the other countries that have malaria equivalent chloroquine mefloquine, their gap junction
13:20 So but they come again the They come from nature and which is
13:24 to be also another theme today. you need to have very fast
13:30 Gap junctions will allow for very fast . What do I mean by
13:34 There is no delay here. And you have a chemical synapse there's a
13:42 from the time the action potential arrives the bicycle has diffuse, your transmitter
13:47 to travel. 20 nanometers has to to the past synaptic receptor for you
13:52 see the response pass synaptic response. this delay is called synaptic all chemical
13:58 transmission delay. That's anywhere from five to 20 milliseconds from the time you
14:05 an action potential prison optically to the that you have a post synaptic
14:11 With gap junctions, it's immediate. they're really good not only for what
14:19 was telling you about the spatial buffering the chemicals through gap junctions, but
14:24 junctions serve another function in neurons. you want to synchronize larger networks of
14:33 And you have one neuron that's going be gap junction connected to 10 other
14:38 It's perfect because you only have to this one neuron and through gap junctions
14:43 immediately gonna engage 10 other neurons. we need these fast synchronization patterns in
14:51 brain in order to process information the that we do. We also hear
14:57 of a common theme here. Gap are very fast immediate. It's not
15:02 transmission has some delay, there's a temporal scales. One is immediate,
15:07 with small delay. The other thing you've learned, neurons are fast,
15:12 are slower. So there you have way of temporal control of physiology in
15:18 brain. Very fast through neuronal synaptic slower through these astro glial processes with
15:26 calcium waves with buffering of potassium and . So pre synaptic away you'll have
15:33 lot of mitochondria, you will have synaptic vesicles that are closed to what
15:38 call the active zones. Prison optically the post synaptic alie what we call
15:45 synaptic densities that contain large swaths of receptor channels. Most of the synapses
15:54 gonna be formed of dendrites and And if you form a synapse and
15:59 and soma you can influence this you can influence the integrative properties in
16:04 neuron because you can excite this and can say, hey I'm telling you
16:09 fire an action potential, it's an synapse, you can inhibit this neuron
16:14 will be less likely to fire. you're influencing integrative properties and in some
16:19 they're also acts of sonic synopsis But you think about axl sonic synopsis,
16:25 action potential in the cell. The has already made a decision, I'm
16:29 to fire an action potential produces this potential axon initial segment. So this
16:35 , this acts of song can no influence whether this other neuron is going
16:41 produce an action potential or not. can influence how much of that action
16:48 may reach this other cell. And call this is modular story properties.
16:53 here your influences integrated properties in the . Whether the cell is going to
16:58 or not and here you're modulating the of the to see what was going
17:03 influences. Yes, they can both all of the connections. Good
17:12 All of the connections between neurons. can either be excited and this can
17:18 be excited or inhibitory. So this just about the anatomy of accident critic
17:23 somatic. But if you think about to excitatory connectivity. Excitatory to inhibitory
17:30 and then you have inhibitor to inhibitor . You have three types of
17:35 ease in in the sense of excitation division that can happen. The other
17:40 that's interesting. If you look at electron microscope images, you see these
17:45 , you see the pre synaptic active , the pas synaptic densities and when
17:50 look at the excitatory synapses through these you see a symmetry that means that
17:57 post synaptic density side is much thicker larger than the pre synaptic active zone
18:03 and the vesicles and these excitatory cells quite round. However, if you
18:09 just without any stain, you don't if this is expressing glutamate or gaba
18:14 anything. But just if you looked saw another synopsis that had symmetrical differentiations
18:21 optical and fasten optically and had flattened a structure, actual anatomy of the
18:27 has flattened, those are the inhibitors . So observation alie you can start
18:34 the difference between excitatory and inhibitory synapses you still want to use the other
18:41 , sustains that we talked about. you know history, chemistry and
18:46 Okay, so since we talked about , we're going to continue talking about
18:53 muscular junction. So notice that the vagus nerve to heart is a neuro
19:02 junction nerve to muscles to cardiac The other neuro muscular junction is more
19:09 neuromuscular junctions that we are discussing and already alluded to is a part of
19:14 reflex sarge. And we talked about motor neurons that come out in the
19:19 basically in the spinal cord and can the muscle films. And when we
19:24 about that we said that acetylcholine will the contraction of these muscle cells.
19:31 axons that come out of one spinal . They will form these what are
19:36 ramifications of the pre synaptic terminals and one of these ramifications will contain and
19:45 and plate. So this is referred as one single motor and play for
19:49 single synapse from that axonal ramification onto muscle fiber underneath you can see that
19:58 modern neurons will also have a lot mitochondria and vesicles and the vesicles are
20:05 of acetylcholine. So when the modern produces an action potential, it will
20:12 the release of acetylcholine and postion optically have these junction all falls inside the
20:20 fibers that close to the pre synaptic contain large numbers of nicotine acetylcholine
20:28 And deeper within these falls they contain gated sodium and calcium channels. And
20:38 reason why we want to talk about particular synapse and the certain features of
20:45 anatomy of the synapse is that maybe gonna try to draw it bigger than
20:53 . But this with suckers that are close to the prison optic side are
21:04 acetylcholine receptors. And so we abbreviate as N. A. Ch.
21:11 so here we have the pre synaptic . Okay this is the release of
21:17 single Killeen molecules. These are our junction all falls. Those deep functional
21:27 will contain voltage gated sodium channels, voltage gated calcium channels. So here
21:39 the pre synaptic side we have nicotine receptor. This synopsis is the
21:48 of the synopses as opposed to the slide. And when you ask the
21:53 , are these all excited or There can be different combinations in the
21:57 . M. S. These neurons receive excited inhibitory in the neuro muscular
22:04 and the muscle this input is only to him. There's no inhibition,
22:11 no inhibitor neurotransmitter between motor neuron and muscle cells. The synapses high fidelity
22:19 very reliable synapse. High fidelity means an action potential will cause a twitch
22:25 a muscle fiber, an action all of these will cause a twitch
22:31 of the whole muscle. So actually twitch of a muscle. There are
22:37 acetylcholine molecules that need to bind to receptors of civil calling receptors to acetylcholine
22:48 need to bind to receptors in order that ligand gated channel to open.
22:57 the deep polarization, the initial deep in the muscle cell is gonna come
23:04 nicotine acetylcholine receptors. Once there's enough the positive charge there's going to be
23:13 of sodium coming in. Once there enough build up of positive charge it
23:20 activate voltage gated channels and it will the muscle action potential. So you
23:29 to have this initial deep polarization through steel cooling channels. You wanna seal
23:36 channels. I don't know where it . Better to draw maybe sport
23:44 Uh then So this is our muscle . And let's say it's sitting at
23:55 million balls of breast. The threshold action potential is -45. This is
24:06 little balls number of the north pole for sodium Positive 55 million bowls.
24:17 this is of the muscle cells. muscle cell it receives input from a
24:24 synapse. This causes an end plate Of the size of about 70 million
24:38 . And this is referred to as motor and plays potential or E.
24:46 . P. Y. Right? synapse activation of single synapse to change
24:58 70 million volts in the C. . S activation of once in s
25:08 it's excitatory inhibitory will cause a decolonization hyper polarization of only half a
25:19 That's why this synapse in the neuro drones. It's very reliable and that's
25:27 whenever a single building gets released you always produce cardiac sorry, muscle action
25:39 . I'm going to study the dynamics this action potential. You just want
25:44 understand that this synapses very reliable always 70 knowable globalization. So once an
25:51 activated action potential twitch of the fiber an app is activated in the cns
25:58 nothing little deep polarization, little hyper . This is the potential is this
26:07 . P. P. How's this . P. P. Generated through
26:12 channels. So acetylcholine ligand gated This is different when we talked about
26:21 gated channels. I give you the spiel about how voltage gated channels are
26:27 to one ion. So voltage gated channels selected to sodium voltage gated potassium
26:35 selected to potassium just like these channels here. However acetylcholine channels allow for
26:45 of sodium and the flux but potassium the same channel. So the rising
26:58 of this E. P. Is sodium coming in. Okay sodium
27:05 in acetylcholine receptors if they have acetylcholine to them to molecules and potassium going
27:18 . So the same channel is permissible both sodium and potassium flux. Doesn't
27:28 the one I own. It allows flux of two items and this underlies
27:33 employee potential. And because this new when they're released, the vesicles will
27:45 contain quanta of neurotransmitters. It's 2000 4000 molecules. He said, what
27:52 you mean? You want to? just said half or 1,
27:56 Well that's the nature but it's not or 2000. So these vesicles will
28:02 packed with 2000 to 4000 silicone in And that's why this TPP will always
28:13 about 70 million bones. Right? it was too packed in one neurotransmitter
28:21 to activate one channel 2000 in It's a very large number of channels
28:30 you can actively. So that's why synopses are very reliable. Very
28:36 It's nicotine, acetylcholine because nicotine will bind to these acetylcholine receptors and the
28:44 was dominated by the other subtypes. receptor must sarinic acetylcholine receptor and because
28:51 that you have a different effect on cardiac muscle from the same molecule.
28:55 the same as Sydell Colin molecule But receptor is different. Okay, so
29:00 you need to know and play potential . Always the change in 70 million
29:06 want to 2000 to 4000 released to this large change in the muscle cells
29:13 deep polarization and the muscle is through receptor channels. The production of the
29:19 potential is through voltage gated sodium and channels. Okay. Which we will
29:25 get into the ionic details of the action potential, it's a highly reliable
29:30 . So an actual potential is always twitch of a muscle. So now
29:38 we first drew the circuits remember I remember the cell's door. So the
29:43 man now you added just even more about that motor neuron that you studied
29:49 the previous section. And this is I said that it's not you don't
29:53 tested on the things in the first of the exam. But you build
29:57 knowledge upon the things you learned in first section, the second and then
30:02 the rest of your life. And have this image here and you're welcome
30:08 use this for notes. Again, can maybe take a couple of
30:15 Uh huh. If it helps it's of a little bit. Okay,
30:27 neurotransmitter systems, what do we mean system? So it's just a whole
30:32 . It's a whole machinery to have neural transmission and there are many different
30:40 , neurotransmitters have to be synthesized. there is a neurotransmitter criteria they need
30:46 be produced, synthesized and found in neuron. They typically will have synaptic
30:52 transporters that will load them up into vesicles once the neurotransmitter is released it's
30:59 going to linger in the synapse for long time even it's gonna get degraded
31:05 it's gonna get re up taken back the terminal and reload it back to
31:09 transporters into the vesicles, boston, going, we already discuss transmitter gated
31:17 channels. So ligand gated ion So the channels that open because of
31:22 binding of the Ligon as opposed to gated channels that remember how the voltage
31:29 and open reacting to the voltage boston optical, you also have G
31:35 coupled receptors and those are not they're linked to G proteins on the
31:40 of plasma side of the south. these G proteins can get activated and
31:46 subunits of these G proteins can I'll gated channels nearby on the synaptic
31:54 and we call the G protein gated channels. So some item channels can
32:00 be gated by G proteins. And you activate G coupled receptors you typically
32:10 secondary messenger cascades and those secondary messenger can be as influential as changing the
32:22 factors at the nuclear level. Secondary and secondary messenger signaling. Molecular signaling
32:29 be quite extensive as a consequence, consequences synaptic transmission and activation of certain
32:38 . Now this neuron produces a So if you stimulate this neuron this
32:44 should release the neurotransmitters when this chemical released it must act on something personality
32:51 it's not that we don't know what is exactly, It has to have
32:56 personality counterpart has to bind to something order to evoke a response after the
33:01 is released, it must be So there should be a re uptake
33:06 or enzymatic breakdown that we talked about the synaptic level. If this chemical
33:12 isolated. So you isolated this chemical first stimulated this neuron, you saw
33:18 response here. Then you isolated this . Then if you isolated this chemical
33:23 on the self it should have an response. Is if you stimulated that
33:29 that's experiment, he stimulated vagus nerve he took the chemical and applied it
33:36 another heart. Without stimulation. The classes of the neurotransmitters that will start
33:45 today and will maybe finish in a of uh slides the major ones that
33:53 already know about. The excitatory amino neurotransmitter glutamate in the C.
33:59 S. The major excited neurotransmitter. major inhibitory neurotransmitter in the cns Gaba
34:07 major inhibit their neurotransmitter in the spinal glycerine. You will also learn that
34:14 the C. N. S. is not an inhibitory neurotransmitter because it
34:20 different receptors and it actually can influence signaling. So hang on to that
34:27 well we'll address it. I'm gonna it louder. Uh The davinci like
34:39 here okay this is the brain Okay and when you're talking about these
34:54 acid neurotransmitters they'll be expressed everywhere everywhere everywhere, excited to everyone. And
35:02 inhibitory ones. They'll be expressed everyone selves everywhere throughout extensively throughout the cns
35:12 different cells and many different circuits, yourselves in hippocampus in the cortex and
35:18 colonists everywhere. You will see expression Gaba everywhere. You'll see expression of
35:24 of these amino acids everywhere. You'll expressions of slicing. But when it
35:30 down to a mean neurotransmitter systems, special and there are only certain locations
35:39 the brain and this is just as example, it doesn't mean that I
35:44 you to replicate this. There are certain places in the brain are certain
35:51 in the cns nuclei defined as collections cells that are responsible for the same
35:58 similar function. Only these nuclei will acetylcholine and then the projections will go
36:10 from these nuclei and only dopamine only is expressed in these specific locations.
36:21 there's a difference here in the spatial of these molecules. The other interesting
36:28 is the cells like inhibitory cells that Gaba and express Gaba can also co
36:37 some of these peptide neurasthenic marriage. you can co express I mean acid
36:44 in europe. So the cells that some inhibitor in your hippocampal cells will
36:49 gamma and they'll have neuropeptide y so are peptides and we're gonna talk a
36:57 bit about these uh peptide synthesis and . It's supposed to neurotransmitters. These
37:08 are very important for our brain Acetylcholine dopamine norepinephrine, histamine norepinephrine serotonin
37:19 we will study them more and more more over the next few lectures.
37:24 you'll really understand acetylcholine function of the really well. But you can start
37:30 about these neurotransmitters and neurotransmitter systems as behaviors, different states of being different
37:42 associations. If we're talking about you will learn that it is Alzheimer's
37:50 where you have a loss of colon neurons and neurons that produce acetylcholine.
37:57 about Parkinson's disease, we talked about of dopamine and dopamine arctic lands,
38:04 talk about depression, antidepressants as R. I. S. You're
38:09 about serotonin. So these systems have functions to represent different moods, different
38:16 of alertness, norepinephrine or adrenaline in brain, you're alert, the bears
38:21 at you. That's what kicks in you want to go to sleep.
38:24 other neurotransmitters kick in and help you asleep. All of these molecules that
38:30 looking at here are endogenous. That that we synthesize them neuron, synthesize
38:37 of these molecules that we're talking especially that means you will find them
38:43 in the body. They're not unique the brain. So you have
38:47 central serotonin, you have serotonin the in the gut serotonin levels in the
38:52 system. So they are in the also and they serve different functions depending
38:57 what synaptic receptors their target. I'm add to this list some cool things
39:05 a reason. So first of all box here, I reserved for
39:15 nitrous oxide and carbon monoxide can be . Always make this joke. It's
39:23 but somebody tells me they have a part have too much or you know
39:29 too much gas and are out gassing they can serve as neurotransmitters. What
39:38 can serve as a neurotransmitter? T. P. What does
39:43 T. P. Stand for? tried to prostate? And we said
39:49 wait A. T. P. a major energy molecule in the cells
39:54 the brain cells but A. P. Can also be a neurotransmitter
39:59 it combined the receptors that are called receptors. And so we have another
40:07 called the denizen which is the core the denizen triphosphate molecule. The denizen
40:14 for example go up at night. some of these neurotransmitters will be synthesized
40:19 and differently during the diurnal cycle. so a denizen levels will go up
40:28 it will make you sleepy in the and the dentist and levels will start
40:33 down in the brain to help you up in the morning. So there
40:38 some of these regulated by external stimuli behaviors. Some of these neurotransmitters in
40:44 regulated by the circadian written by the cycle. Okay dennison. You should
40:51 very well because most of you have a dentist and receptor this morning by
40:58 coffee, chai, tea, bobo . Uh Yeah but martin which all
41:10 caffeine right? So caffeine interacts with dennison receptors action and you learn more
41:18 how it does it when you understand present african post synaptic regulation. So
41:23 should know caffeine caffeine stimulates the release glutamate and dennison dampens the release of
41:30 helps you fall asleep. Caffeine stimulates release of glutamate. What else is
41:35 does not only wakes you up if have too much coffee, what does
41:39 do? My my heart is Right so why? Well there's there's
41:45 a dentist and receptors and the art . So it's a common theme.
41:49 find them in the brain and find in different organs in the body.
41:55 what we have is we have a of caffeine dispensaries. You think about
42:02 ? It is caffeine is an addictive . It's more addictive than some of
42:06 drugs on the D. A. . And we have sometimes three dispensaries
42:12 one intersection caffeine. Right? Three on and one dunking donuts in the
42:19 corner. So what do you $67.08 dollars nine frap frappuccino something.
42:32 . It's like, wow. Most it is water. Just a little
42:35 of caffeine. Some 20 or 40 or something like that. That molecules
42:45 I want to discuss. Our endo and the two major endocannabinoid czar to
42:56 G. S. An abbreviation and will talk about them some more.
42:59 this is today is an introduction to of these molecules just forming a general
43:06 of it and then we'll go into details on some of these systems.
43:11 just like a teepee at denison gasses . Endocannabinoid there endo they're endogenous molecules
43:19 synthesized by your body and brain Mm bo is endogenous cannabinoids is equivalent
43:28 cannabis plant. So phyto cannabinoids or cannabinoids will be found in cannabis plant
43:38 endocannabinoid will be synthesized by your bodies brains and it turns out that almost
43:44 cell in our bodies has an endocannabinoid system. Now all of these neurotransmitters
43:53 for them to be a part of system, they have to have
43:56 So the same way as a denizen molecule interacts with the dentist and receptors
44:02 have caffeine exogenous molecules from the plants with your receptor same way. Andrew
44:10 that have cannabinoid receptor CB one and two. What's really interesting is cannabinoid
44:17 are the most abundant g protein coupled in the brain. They are the
44:23 abundant most prevalent receptors in the brain and the phenomenal receptors CB receptors and
44:31 cannabinoids are also emerging as sort of molecules that are generated inside our
44:39 And for a long time there was debate that talked about endorphins and what
44:46 called the runner's high and people would oh you know this runner's high is
44:51 feeling and actually it's really good You run for long distance or or
44:56 for a while you have this feeling happiness you know and it's not certain
45:02 you're it's because you've exercised and you better about burning some calories or something
45:07 is going on. And it was to endorphins. Endorphins which would be
45:13 like morphine molecules, morphine is an substance. What we're talking about here
45:19 the cannabinoids, endogenous molecules and then fighter kannapolis has been interactive endogenous since
45:26 year and the science has shown that is then the cannabinoids that give that
45:32 high, that blissful feeling and in ancient language from mls Ananda stands for
45:43 . So it's a bliss molecule. is internal molecule that's a bliss
45:48 And it makes sense that the recent is showing that these runner's high or
45:54 feelings that may come about and dodge are stemming from the activation of the
46:01 . Because under cannabinoid production increases with physical activity and repeated stress. Either
46:07 or strong stress on the body and brain. Yes, to a G
46:15 , for now it's that but it's Erica O'donnell literal it's in the subsequent
46:21 but like I said, I'm introducing for now and then we'll talk some
46:26 about more of these molecules. The molecule I'd like to put on here
46:32 a wreck a tonic acid that is as a neurotransmitter and also conserve as
46:40 precursor. So you'll see that these like an economic asset can be a
46:46 to endocannabinoid. And you'll see also of the uh like dopamine and epinephrine
46:53 their precursor to another molecule. That that there's an enzyme that takes one
46:58 that makes another molecule out of The reason why I actually like to
47:04 all of these molecules on this side because all of these neurotransmitters are member
47:14 . Everything that you see here, means amino acids, neuro peptides,
47:21 not member insoluble, but the gasses through membranes and the cannabinoids are fat
47:27 insoluble or economic acid as well. reason is you'll see that most of
47:33 signaling from these molecules is retrograde signaling unlike these molecules that get released pre
47:41 aly and target post synaptic receptors. molecules get released post synaptic aly and
47:48 retrograde fashion target tree synaptic receptors. you understand more about this in the
47:56 couple of lectures alright, so we'll back and talk about these molecules some
48:02 and like I said, the seed Colin is something that you're gonna know
48:05 well and will then continue the theme Alzheimer's disease. How most of the
48:12 Alzheimer's medications are actually targeting acetylcholine systems what part of the system they're
48:18 Unfortunately quite an effective one. And is a homework question that was on
48:24 previous three sides before this is the to the homework question, This is
48:29 peptide three courses. So in order activate the neurotransmitter vesicles and action potential
48:34 polarization. There's gonna be a fusion this Mexico there's neurotransmitter molecules that are
48:40 the synaptic vesicles historic pre synaptic precision optical, we have energy
48:46 You have transporters to deal with the in the terminal neural peptides in order
48:53 call upon synthesis and release of neuro . You need to have sustained activity
48:58 the south. So one too few potentials is not going to do the
49:03 of neuro peptides. Instead you sustain inputs onto the cell. The cell
49:09 them biting off the precursor peptides from in the plasma particular crossing is processing
49:14 through the gold, your products fitting out within the secret torrey Granules.
49:20 the vesicles but super dura Granules and so much activity now in the cells
49:25 super Granules. These neurotransmitter vesicles are spatially specific there in the synapse,
49:32 connection between pre synaptic and possible. they stay here and we're being recirculated
49:37 the pre synaptic cell. But when Europa thighs are active and they start
49:41 down the axon they can start non using and releasing along the external terminals
49:51 and and the whole extent of the . So that's another interesting thing is
49:57 are very spatially confined and precise signaling peptides introduced. This nebulous like communication
50:07 not exactly certain how they exit through where exactly they're gonna exit and it's
50:12 going to be just in one peace in africa. So these are
50:16 big differences how they synthesized, how transported and how they are released.
50:23 of the neurotransmitters are synthesized here and here and released in the axon
50:29 And europe appetizer has to come the from the soma to synthesize them and
50:36 them in a fashion that is not specific. This is going to be
50:41 last slide. I'm gonna go over very quickly because I want to save
50:44 lecture. Apologies for starting late today the technical issues. But remember when
50:50 talked about the accident, initial segment a lot of voltage gated sodium and
50:55 channels. Nose of reindeer have a of voltage gated sodium and potassium channels
50:59 they can reproduce action potential regenerated. then when we come to the external
51:04 , when there is a the action here, the deep polarization and external
51:09 opens voltage gated calcium channels. And voltage gated calcium channels are necessary to
51:16 open in order for the vesicles diffuse the plasma membrane and have the vesicular
51:23 . If you take out the calcium the exercise cellular solution, you block
51:28 release. So you need both. need deep polarization and action potential influx
51:34 activation of voltage gated calcium channels and of calcium in order to cause neurotransmitter
51:41 . And the reason why calcium is important is because these neurotransmitter vesicles will
51:48 a protein complex that's referred to as secular protein complex. The snare and
51:54 membrane of the neuron will also have complex. It's referred to as trans
52:00 snare complex and these protein complexes between vesicles and the membrane, they have
52:06 interact to bring this bicycle close to membrane so the fossil lipids fuse and
52:14 the formation of the fusion for and of the neurotransmitter into the synaptic cleft
52:20 the absence of calcium, there's nothing these proteins can do. So calcium
52:26 is necessary for this protean protein complex the vesicles, all membrane and neuronal
52:32 to form to cause the fusion on secular release. So, we'll come
52:38 and study more everything that we've talked in the next 23 lectures again,
52:44 reminder. We don't have a lecture Tuesday. We don't have it on
52:48 . We don't have it in And I will see everyone a week
52:54 today on thursday. So, thank very much for being
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