| 00:01 | There are science lecture 10. We're talk about neural transmission. The neurotransmitter |
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| 00:08 | . So for neural transmission we learn discovery of acetylcholine by Arnaud louis and |
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| 00:14 | neuromuscular junction stimulation of the vagus The cardiac muscle which slows down the |
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| 00:23 | trade. Electrical synopsis were also discovered we discussed electrical synopsis. These gap |
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| 00:32 | that are comprised of connections pass a of the passage of islands of small |
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| 00:38 | between the cells are quite specialized and have specialist functions and just allowing cells |
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| 00:44 | synchronize and they're very fast manner across ourselves. And then for the synaptic |
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| 00:56 | we talked about various types of synopsis dendritic access, somatic, excellent sonic |
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| 01:05 | even Dunder Hendrix announces that exist and of the anatomical features union observe and |
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| 01:13 | to confirm whether the synapse you're looking is excited to our inhibitory based on |
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| 01:22 | physical shape and also the symmetry symmetry the pre synaptic active reserves of |
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| 01:31 | attic densities. Okay, and for to understand your transmission in the neural |
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| 01:41 | , it's actually quite easy by reminding about neural transmission of the neuromuscular junction |
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| 01:49 | the reason for it is a couple things that are happening at the neuromuscular |
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| 01:54 | that make this a simple synapse relatively and also lays the foundation for a |
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| 02:05 | Colleen and acetylcholine neurotransmitter system which is complicated in the C. N. |
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| 02:12 | . In the brain such as in cortex. So as we know the |
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| 02:18 | neurons in the motor neurons send their their axons into the periphery onto the |
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| 02:28 | cells. This is the motor output that comes through the ventral side of |
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| 02:33 | spinal cord and the Axiron that comes from the motor neurons. It has |
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| 02:44 | large pre synaptic axonal terminals. Axon splits and we call this ratifies there's |
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| 02:54 | of this accidental endings throughout the muscle . But each one of these |
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| 03:02 | what are called motor and plates because the template of the motor neuron are |
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| 03:11 | large, a very effective And they 1-1 fidelity, meaning that an action |
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| 03:22 | in a pre synaptic external motor template in this external terminal will always result |
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| 03:35 | the busting up the contraction of the . It's a reactivation of a single |
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| 03:43 | . 1212 muscle cell, the neurotransmitter the action potential which reaches the external |
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| 03:52 | here. Would you have attacked of are these vesicles that are stacked with |
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| 03:59 | ? There's a synaptic cleft that separates motor neuron from the muscle cell and |
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| 04:06 | inside the muscle cell. You have very interesting folds that are called junction |
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| 04:14 | falls that allow for the deep imaginations imaginations toward the muscle. So these |
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| 04:28 | all falls will contain high densities of receptors and when there is a release |
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| 04:37 | the neurotransmitter, acetylcholine receptors will produce ant play potential. It's a synaptic |
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| 04:47 | At the level of the neuromuscular junction of one synapse Will produce a change |
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| 04:55 | the am playing potential of about 17 balls. That means that this very |
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| 05:04 | deep polarization by one synapse is going be enough to cause a contraction in |
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| 05:09 | twitch of a muscle recall. What's threshold for action potential generation? If |
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| 05:18 | go to the slide that we reviewed , this is a neuronal action |
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| 05:24 | This is not the employee's potential. neuronal action potential and a single synapse |
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| 05:32 | it gets activated, one excited there's means Half a million volta, one |
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| 05:39 | of all deep polarization for the So when we talked about, what |
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| 05:45 | it take for the resting member and to reach the threshold for action |
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| 05:51 | we said it takes a lot of to synapses. Why a lot. |
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| 05:55 | of all they're located distilling on the drives. Second of all inhibit their |
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| 06:01 | may be activated at the same time that will cause hyper polarization. |
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| 06:07 | one excited, there's synapse equals approximately a million volt in deep polarization. |
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| 06:14 | you can do the math of how synapses you have to activate. If |
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| 06:18 | resting membrane potential is about negative 65 involves And the threshold for action potential |
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| 06:26 | is -4500 revolts. It's a 20 of all difference once synapses, half |
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| 06:33 | ball. That means you need at 40 excitatory synapses to be active without |
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| 06:40 | from the inhibitory synapses to be active order to reach this value here in |
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| 06:47 | number of potential. The threshold value action potentials to generate the action |
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| 06:54 | What I have just mentioned to you neuromuscular junction. Is that a single |
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| 07:00 | here will cause an end play potential deep polarization? Not in half a |
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| 07:07 | evolve like you will have in the , In the CNN. But in |
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| 07:12 | muscle it's a deep polarization of 70 balls. Your thought processing may |
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| 07:20 | But if your motor output is this is obviously indicative of some sort |
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| 07:27 | a pathology developing. If you're telling arm to move and grab a microphone |
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| 07:34 | you have to tell it five times convince it for two minutes to move |
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| 07:39 | then you can barely move it. a problem. Everything we want to |
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| 07:45 | . It's done. It's 1-1 fidelity there's large depressurization that happens here. |
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| 07:52 | what happens in in these junction of is the following thing is you would |
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| 08:03 | uh let's see where is the Yeah. Something is frozen. Okay |
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| 08:18 | . So a single synods here will an and play potential. That's this |
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| 08:28 | . Okay, so this red is and flight potential that I'm showing you |
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| 08:35 | it is compared to the size of action potential. What does that |
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| 08:40 | That means that the muscle will produce massive deep polarization which is sufficient enough |
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| 08:48 | produce a cardiac action potential which is longer in duration and has a different |
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| 08:57 | . We won't be spending much time the ions involved. But you need |
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| 09:03 | have voltage gated sodium channels d polarized produce the cardiac action potential. |
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| 09:14 | so here's a here's a thing. receptors, a single Colin will bind |
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| 09:34 | them in the cardiac muscle. We a type of receptor that slowed down |
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| 09:41 | contraction of the muscle. It's almost type of receptor in the neuromuscular |
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| 09:49 | The only subtype the cereal company and , the only subtype of this receptor |
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| 09:58 | nicotine nick and it is excitatory. , a ch binding to a ch |
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| 10:14 | causes employee potential. This massive deep . This deep polarization opens both educated |
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| 10:42 | channels. Plus what other channels, other ions are important for muscle |
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| 10:52 | would you have to make sure you enough of for muscle contraction household but |
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| 11:04 | not going to address the loan dynamics for the fact that you have to |
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| 11:08 | that the muscles but it's a cardiac or skeletal muscle produced action for town |
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| 11:15 | are much longer in duration. Gasol the CNS. Now, why? |
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| 11:21 | is a simple scenarios because it only nicotine acetylcholine receptor, it's only excited |
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| 11:27 | me, there's no inhibition of neuromuscular . So if there is a deep |
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| 11:36 | , if there is a deep there's always these acetylcholine receptors are strategically |
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| 11:42 | the closest to the active zones. optically and then there's activation and massive |
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| 11:49 | potential and down below in these grooves probably drive there was going to be |
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| 11:58 | densities of voltage gated sodium channels and gated sodium channels will get opened by |
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| 12:08 | ? What is gaining voltage gated sodium , voltage. What is opening acetylcholine |
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| 12:20 | ? Why is there deep polarization? it's a receptor channel? Okay, |
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| 12:27 | a single combing molecules that will get will bind to settle Colin receptors that |
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| 12:33 | also channels. And as you acetylcholine receptor channels are permissible to both |
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| 12:42 | and potassium Hiles. And this is synaptic potential. This is the synaptic |
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| 12:51 | but we call it and play potential it's not the sin absolutely into |
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| 12:55 | It's the end plate with the So it's the and play potential acetyl |
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| 13:00 | and the opening of these receptors and polarization flux of sodium through these ligand |
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| 13:07 | channels seal Colin recep their channels are by login. That means that the |
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| 13:14 | to open that channel is eligon is molecule. It's a Maciel Colin |
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| 13:19 | it's a molecule. But once these are active, receptor channels are active |
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| 13:25 | you have an unplayed potential. Now voltage is the key to the below |
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| 13:31 | voltage gated sodium channels, an opening those channels will initiate the action potential |
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| 13:38 | the opening of voltage gated calcium channels then subsequently polarization. So as opposed |
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| 13:46 | the cns synopsis. This is a highly functional effective high fidelity synapse 1 |
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| 13:54 | 1. So remember these terms. I will put a slide and maybe |
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| 14:00 | make a little better drawing without slide describing that. Now in general, |
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| 14:08 | we have is we have the whole system. It's not just neurotransmitters and |
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| 14:14 | is a subtle kobane and it has acetylcholine receptor. Macedo Colin also has |
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| 14:23 | any casino call intercept in the cardiac but in the CMS it actually has |
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| 14:30 | . There is a machinery that needs synthesize. The chemicals are neurotransmitters, |
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| 14:39 | enzymes, right? Most of the , most of the things in nature |
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| 14:45 | plants in your body cells, synthesizing making things. We have synaptic vesicles |
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| 14:55 | so this molecules that are made, need to be placed within the vesicles |
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| 15:01 | . That cell number is surrounded. al they have to be placed in |
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| 15:08 | . So you have transporters on the of the vesicles that will transport and |
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| 15:14 | up the vesicles for example, with , you agree update transporters once the |
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| 15:22 | is released in the synoptic left, don't get wasted. They get re |
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| 15:29 | taken back into the cell, they recycled back into the cell and the |
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| 15:34 | get refilled again. But in these and in the south and also in |
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| 15:41 | surrounding wheel cells a lot of You also have to have degradation enzymes |
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| 15:50 | the cells. You have synthesis going once the neurotransmitters are released. They |
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| 15:55 | hang on the synaptic cleft they either re have taken back or they get |
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| 16:02 | broken down what on the boston optic , the transmitter gated ion channels. |
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| 16:08 | when we're talking about synaptic or chemical we're talking about Lagan or transmitter gated |
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| 16:16 | channels because they are allowing for the of the ions and the flux of |
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| 16:22 | will change the number of potential causing post synaptic potential. There are also |
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| 16:30 | protein coupled receptors which are not ion and binding of neurotransmitters. So chemical |
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| 16:39 | the jeopardy in couple of receptors will into cellular secondary messenger cascades without opening |
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| 16:47 | channel crossing the ions through the actual protein coupled receptors. So they're g |
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| 16:57 | gated ion channels. Because those channels the cells have their own ju protean |
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| 17:04 | to the number that can get The subunits of that protein can get |
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| 17:10 | in effect other receptors or ion So there's ion channel gating and directly |
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| 17:20 | G protein coupled receptors in the cells most often g protein coupled receptors also |
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| 17:27 | secondary messenger cascades. We should slow that can then influence phosphor relation. |
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| 17:37 | falls for relation calcium release communication between other different things that many different molecules |
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| 17:49 | the neurotransmitter criteria for it to be neurotransmitters has to be synthesized and found |
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| 17:56 | the neuron. If you stimulate a that neurotransmitter needs to be released. |
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| 18:02 | the chemical released it must act in past synaptic receptor and cause a biological |
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| 18:10 | the effect on the person attic side dependent on the receptor it has. |
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| 18:14 | your cardiac muscle, your receptor is civil Colin receptor. If you are |
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| 18:24 | muscle you have nicotine in which is acetylcholine receptor, the response is very |
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| 18:32 | , slowing down the heart rate versus up the contraction. The molecule is |
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| 18:37 | same. Acetylcholine receptors are different and response is different after chemical is |
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| 18:44 | There's a machinery that it must be . Either it's really taken back into |
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| 18:50 | cell or it is broken down If chemical is isolated just like you know |
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| 18:55 | we did with a single Colin but of being applied to the heart from |
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| 19:00 | vagus nerve but it's isolated from a and applied onto another neuron that other |
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| 19:05 | should also have a response to. . Just some of the classical things |
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| 19:11 | this response to chemical but not too called neurotransmitter mimicry or synoptic military because |
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| 19:20 | mimicking being a synapse, you're mimicking excited to glutamate synapse. Instead you're |
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| 19:25 | squirting glutamate on another neuron just like the low we did on the |
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| 19:33 | These are some of the defining features mirror transmitter systems. We have major |
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| 19:41 | that we already learned about amino acids the most abundant and probably the subject |
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| 19:50 | the most studying the scores, particularly . She's an excited to amino acid |
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| 20:00 | but also gaba which is gamma immuno acid is a major inhibitory neurotransmitter. |
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| 20:06 | the cNS glisten we learned in the cord into neurons. It's an inhibitory |
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| 20:16 | in CNN's you will learn that glycerin actually a co factor in facilitating excitatory |
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| 20:23 | dramaturgical neural transmission for glutamate synaptic You will be learning quite a bit |
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| 20:32 | a set of Colleen. She already in the last couple of lectures a |
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| 20:37 | bit about dopamine epinephrine, histamine norepinephrine which is becoming one of mine |
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| 20:47 | More interesting molecules but I'm starting to about more and more all of these |
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| 20:54 | a means and they are different but also very very prevalent, not as |
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| 21:09 | excitatory neurotransmitters and their actions are all depending not only on the molecule, |
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| 21:16 | have different actions on different cells but in the receptor which they are |
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| 21:22 | You also have Captain dies call this the kind of morphine and careful in |
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| 21:30 | but that was about the status of at an M. B. |
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| 21:32 | P. Do you have to know of these? No you don't but |
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| 21:36 | gonna have to know some of the that we stress some highlights as as |
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| 21:41 | talk about neural transmission. Uh Let me um because this for a |
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| 21:56 | . So now we're back with the and basically in addition to amino acids |
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| 22:03 | means and tap tides. There's some traditional neurotransmitters such as gases and that |
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| 22:16 | mattress oxide and carbon monoxide. so okay. Always make this |
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| 22:32 | You can have a brain fart because have gas in your brain. Too |
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| 22:40 | gas. Just say too much about of the gas is not just talk |
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| 22:45 | carbon monoxide. Now that's that's really because we're talking about substances like gaba |
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| 22:52 | , acetylcholine, the stored in neurotransmitter and these gases, they're not starting |
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| 23:01 | vesicles and there are also a number soluble so that means that the traverse |
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| 23:09 | plasma membranes. Okay. The other molecules that I like to talk about |
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| 23:20 | course is ATP but Dennis and triphosphate not only the powerhouse or the engine |
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| 23:32 | , the fuel for the cells but also a neurotransmitter. And it combined |
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| 23:40 | http receptors are demos in receptors. Dennis and triphosphate binds to denison |
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| 23:53 | You know what else bonds to denison . You consume Most of you probably |
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| 24:01 | of you consume every day. This substance that binds the dennison receptors and |
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| 24:08 | gives you an upper boost. It's which is in coffee. T even |
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| 24:21 | teeth. It's made with green tea . Okay, so ATP uh binds |
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| 24:32 | denison receptors and uh there's a certain of a dentist and receptors a dennison |
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| 24:40 | dennison receptors as well. It's naturally molecule which is uh usually your sleep |
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| 24:50 | , it increases your sleep cycle and why caffeine has an opposite effect on |
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| 24:55 | Denniston weeks, you wakes you Um so that's a teepee and we'll |
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| 25:02 | back and mention a TP again and mention the dennison again. You understand |
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| 25:07 | the cycle how it actually activates the caffeine looking humanoids. Mhm. To |
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| 25:26 | G. And and and um I to our bodies produce natural cannabinoids called |
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| 25:37 | cannabinoid molecules. There are also produced demand when there is stress when there |
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| 25:44 | heightened levels of activity. And endocannabinoid just like gases are not stored in |
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| 25:51 | vesicles and they're also lipid soluble. means that they will traverse, they |
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| 26:03 | cross the plasma membranes, the fat and the cannabinoids to A G. |
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| 26:10 | a silver visceral and anandamide are becoming interesting for many different applications, pharmaceutical |
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| 26:22 | and many of these different molecules in mirror transmitter systems. You can think |
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| 26:27 | these neurotransmitter systems as different moods. can think of these different neurotransmitter systems |
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| 26:36 | different states and levels of activity asleep , stressed, relaxed, anxious, |
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| 26:47 | anxious. Get anxious serotonin starts flooding brain trying to calm you down. |
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| 26:56 | running for five km and you're smiling you think it's endorphins but it's |
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| 27:02 | it's there's no endogenous morphine molecules but are endogenous cannabinoid molecules and then actually |
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| 27:09 | a bliss and Sanskrit feeling of happiness happens naturally when you produce natural and |
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| 27:16 | noise in your systems. So think these things as different states of |
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| 27:24 | different moods, different processing functions in way and also different disorders that will |
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| 27:35 | associated with dysfunctions in these neurotransmitter systems seal, Colleen. Alzheimer's disease, |
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| 27:45 | Kleiman, Parkinson's disease, uh apple etc. Mhm. Serotonin |
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| 28:00 | anxiety, food disorders. Uh That's really cool. And it's not |
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| 28:09 | in the cns you have those molecules the periphery. So I told him |
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| 28:15 | haven't cns and you have it in periphery and the cannabinoids added in the |
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| 28:20 | and neurons and clear can you have ? Almost every cell in your |
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| 28:25 | You have it in the bone marrow , glycerine all over the place to |
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| 28:32 | different functions. Okay, so now have these what we call traditional amino |
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| 28:39 | , neurotransmitters. Traditional means peptides and so traditional gases, lipid soluble molecules |
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| 28:48 | as into cannabinoids and also the energy ATP, which has its own |
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| 28:54 | And it's balancing with this a Dennis cycle which is the core molecule of |
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| 29:01 | but donaldson, triphosphate, baptize and . So that was a previous question |
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| 29:10 | the homework. And what you're seeing that there is a lot of neurotransmitter |
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| 29:16 | that you'll discover that happens at the of the synapse when the neurotransmitter vesicles |
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| 29:22 | with the synapse here with a membrane releases the neurotransmitter. The neurotransmitter gets |
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| 29:29 | into the synaptic terminal. The vesicles reloaded in the synaptic terminal. So |
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| 29:35 | the machinery is set up there for neurotransmitters, it's pretty much happening at |
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| 29:40 | level of this synaptic terminal and for peptides is different peptides are not always |
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| 29:51 | at high levels of neurons but they again are on demands of sort of |
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| 29:57 | similar to under cannabinoids. There is heightened increased levels of activity, sustained |
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| 30:04 | potential, firing a lot of neurotransmitter . That that died. You have |
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| 30:12 | precursors, you have the processing through apparatus, you have the secretary Granules |
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| 30:20 | encase them versus that that's the That in case the neurotransmitters and that |
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| 30:26 | high levels of a Kennedy. It out that the peptides are non specific |
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| 30:32 | those very specialist locations that the vesicles specific to the sin absence. And |
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| 30:38 | could have the secretion of top guys along the axon, not at the |
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| 30:46 | south. So it's a it's a a different, almost helped to save |
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| 30:54 | non confined in a way, para and these networks Because it is not |
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| 31:02 | that one specific neuron, that one synapse or 10,002 which you may be |
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| 31:07 | . But right, it it's spreading neuro peptide is part of the other |
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| 31:14 | that are usually slower functions. It involves activation of g protein coupled receptors |
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| 31:20 | an applicant and secondary messenger cascades. right, so what are you learning |
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| 31:26 | already? No transmission stops right Everything at the level of the synapse |
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| 31:31 | peptides and the cannabinoids, you need lot of activity, that cycle is |
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| 31:39 | . If that cycle affects ion person app quickly again it's fast. |
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| 31:43 | if you're affecting g protein coupled receptors that is a slower, slower processing |
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| 31:50 | for this analysis. So what are things required for the neurotransmitter to properly |
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| 31:56 | and release its content? The vesicles and release its content. It requires |
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| 32:03 | synaptic deep polarization. So we need potential. The action potential which is |
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| 32:11 | at the accent initial segment. If recall two types of channels and maybe |
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| 32:16 | point to an N. A. . 1.6 the low threshold channels generate |
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| 32:20 | action potential that's forward propagating that action regenerates its each note of ranveer it |
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| 32:27 | that the full amplitude external terminal. this is one of the prerequisites when |
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| 32:35 | reaches the external terminal. What the potential does, it opens up both |
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| 32:39 | calcium channel. So the pre synaptic deep polarization opens voltage gated calcium channels |
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| 32:48 | calcium entry is required into the In order for these vesicles to fuse |
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| 32:53 | the plasma membrane. No calcium, the secular release. So you can |
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| 33:02 | polarize the cell all you want to you can take the calcium from extra |
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| 33:08 | solution away or you can block these gated calcium channels and you will not |
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| 33:13 | the secular release. But if you influx of calcium and calcium voltage gated |
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| 33:20 | are concentrated at this pre synaptic terminals when the active zones of the pre |
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| 33:26 | terminals where you have these pre synaptic complexes and these neurotransmitter vesicles, these |
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| 33:39 | complexes of protein protein complexes. So vesicles protein complex, which is shown |
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| 33:45 | and abbreviated and simplified to the snare vesicular snare has to interact with the |
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| 33:52 | that are located on the membrane T . So trans membrane snares and for |
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| 33:59 | to happen, you have to have command when calcium comes in. Then |
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| 34:04 | protein program complex interaction can take place bring the two of us Philip it |
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| 34:11 | layers close to each other and help and when they fuse, the vesicular |
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| 34:19 | gets released into the synaptic cleft. on this vast cycle there's actually a |
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| 34:28 | cut, there's a calcium sensing One of them is synaptic stagnant is |
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| 34:35 | synaptic stagnant. And in reality this what the vesicles looks like. It |
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| 34:45 | like a pretty hairy beast with a of different things attached to little different |
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| 34:52 | glycoprotein, carbohydrate things hanging off around and once you have the fusion and |
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| 35:01 | particular release that piece of the number is very valuable so you don't lose |
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| 35:07 | bicycle, it gets pinched off here it gets recycled back into psychosis or |
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| 35:16 | it toes back into the priest in terminal. This is really neat. |
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| 35:23 | some electrical micrografx images visualizing neurotransmitter So now that you've learned about the |
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| 35:35 | . It can start visualizing that for , these are presumed calcium channels which |
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| 35:40 | pre synaptic. And when you when you stimulate, what happens is |
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| 35:47 | see these craters opening up near the channels. So I want you to |
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| 35:52 | attention for example to how dense these channels are here. And you can |
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| 35:56 | these two very dense lines of calcium and obviously these two very dense lines |
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| 36:02 | voltage gated calcium channels are surrounding the zones with the neurotransmitter vesicles are sitting |
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| 36:10 | close ready to fuse and release because communication, once action potentials produced, |
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| 36:16 | takes a matter of about 5 to milliseconds across the synapse, the fusion |
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| 36:23 | release and the bar synaptic response. happens within 5 to 20 milliseconds depending |
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| 36:28 | the synapses and the machinery that is in them. But these craters opening |
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| 36:33 | is basically the bicycle using to the and opening up into you. What |
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| 36:40 | looking in as you're looking into the of that medical, from outside of |
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| 36:45 | cell. And the neurotransmitter is now out at you. You can see |
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| 36:54 | have a large gap junctions. This an electron microscope graph showing the uh |
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| 37:02 | large gap junctions where you have the coming together. So this is really |
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| 37:06 | to visualize those things and from the it looks like this. You |
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| 37:11 | you have the two numbers coming close and that's where you'll have the formation |
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| 37:15 | the gap junctions. And this is of an aerial view of what it |
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| 37:20 | like and a couple of interesting things that I want to discuss also is |
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| 37:30 | of all, the number Rain has studied quite extensively and we're not going |
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| 37:35 | go into the details of the member accept that you have the the face |
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| 37:41 | the p phase of this plasma membrane it's a bi layer, so each |
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| 37:47 | has its own name. And this shown here what is called priest |
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| 37:52 | So in the early days when the that I believe this was in the |
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| 37:58 | and sixties, they were trying to the composition of the plasma membrane and |
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| 38:02 | were literally like trying to see is a way that we can take two |
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| 38:07 | apart? And is there something that's with a cytoplasmic layer? Something that's |
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| 38:14 | only with extra cellular layer? Or something is there? And both of |
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| 38:19 | . How do we do it? do we look inside in two |
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| 38:23 | And so in those days they devised technique that employed liquid nitrogen immediately freezing |
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| 38:33 | cell as they were stimulating the south they just found larger cells in the |
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| 38:38 | . They basically freeze them immediately instant moon. We have to play around |
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| 38:46 | a lot of mechanics actually have to a little needle right next to that |
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| 38:52 | piece of membrane or that frozen And it was a bit of like |
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| 38:58 | science on the witchcraft. So people get together with the frozen membrane little |
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| 39:05 | to walk around and just try to the table when we stop there like |
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| 39:12 | to just barely vibrate the table. that needle point exactly in between the |
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| 39:19 | layers it would basically open up the layers. It would it would it |
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| 39:24 | spread it into the E. P. Face. So you can |
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| 39:28 | the trans membrane proteins, you can certain proteins that are left in the |
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| 39:35 | obviously where they're docked which face they're on. So that's that's that's pretty |
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| 39:43 | . And then we also want to what's going on at the synopsis. |
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| 39:50 | we can now actually visualize neurotransmitter vesicles . I don't have this image is |
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| 39:55 | you. But there is a very technique that's called every for us and |
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| 40:00 | that allows you to visualize individual neurotransmitter release for us of us for the |
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| 40:06 | . But this image which was taken another book which is a great book |
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| 40:10 | neuron to brain. And this research done by Rodolfo linas and dolph Alina's |
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| 40:19 | one of the great south american neuroscientists worked very much concentrated on synaptic neural |
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| 40:27 | and an understanding what is happening at core of the synaptic transmission. This |
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| 40:32 | some of the older work and when was doing this research, this guy |
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| 40:40 | incredible actually I think he's the first that took like an alligator head and |
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| 40:44 | it to artificial serve of final fluid kept the whole alligator brain and had |
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| 40:49 | life for like two days doing experiments it. And then um he just |
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| 40:56 | saw him talk and he was just huge intellectual and a visionary. Somebody |
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| 41:03 | you hear them talk it's like this is a visionary. They're not just |
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| 41:07 | the data and reporting on stop, trying to tell everybody was going to |
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| 41:12 | in the next 10 years or what's the next thing that should be done |
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| 41:16 | in this or what's the obstacle that in the way of something done you |
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| 41:21 | so and when he was doing this the dice came out that were specific |
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| 41:26 | islands. So you learn a little about voltage sensitive guys we'll talk about |
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| 41:33 | sensitive dies it is sensitive to voltage there are guys that is sensitive to |
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| 41:38 | . What does it mean? They're twice. That means that if there |
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| 41:42 | an increase of a given, I'll as sodium such as potassium such as |
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| 41:49 | . You can visualize that change. this is different from the dies that |
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| 41:57 | have so far discussed to date because all of the dies we've discussed were |
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| 42:08 | . That means that they showed us anatomy Golgi stain the processes the initials |
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| 42:18 | missile state learn there's a Weigert stay another state immunity is the chemistry we |
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| 42:26 | about um you know as the chemistry talk about the music and it's the |
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| 42:29 | today a little bit more. You , it's the chemistry antibodies they show |
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| 42:34 | where things are, they don't show what is happening. Alright. This |
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| 42:42 | of imaging is referred to as functional . So you have functional magnetic resonance |
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| 42:48 | in the clinics and the hospitals. functional imaging because it's showing you the |
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| 42:54 | the activity of the brain. Calcium imaging shows you the activity of calcium |
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| 43:01 | the fluctuations of calcium and the And what this image illustrates is that |
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| 43:07 | you use this die and you visualize synopsis that are silent. They're just |
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| 43:15 | a little bit of input activity going . It's not a very active synapse |
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| 43:19 | is c are these little mountain formations And each one of these mountain peaks |
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| 43:26 | a yellow, the more yellow the red it is the higher concentration of |
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| 43:32 | guidance. This really shows you what call calcium micro domains that are located |
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| 43:40 | optically adjacent to these rows and voltage calcium channels. So now you're visualizing |
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| 43:51 | calcium micro domains and you stimulate the and you can see the concentration and |
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| 43:58 | blurring of these domains. This individual peaks becomes looks like one huge mountain |
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| 44:08 | or mountains syria and it gets very . That means that calcium concentration goes |
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| 44:17 | and this is a direct visualization of activity in salient or not. Such |
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| 44:23 | synopsis and very active synopsis. The of peak of calcium Inside here was |
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| 44:31 | up to 200 microphone. Okay, is really interesting because these are all |
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| 44:42 | imaging techniques to even electron microscope. do you see the opening of the |
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| 44:48 | ? It's not live. These preparations painstaking actually to isolate something. To |
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| 44:56 | it on the slide that the process rapid and para phone stored in the |
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| 45:00 | washing that come back the following You hope you have something so it's |
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| 45:07 | live. So you take an image the cell before you stimulated or stimulate |
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| 45:13 | and you see these nice rows of channels, You process that tissue and |
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| 45:18 | 2 3 days later you look at and then the day you're doing an |
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| 45:23 | you also stimulates themselves or you take of the membrane after you stimulated the |
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| 45:30 | and then hope two or three days you're gonna visualize this but it's not |
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| 45:34 | line. And so the difference with calcium sensitive guys and ion sensitive guys |
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| 45:40 | both of sensitive dies because the difference that they're tracking activity the functional they're |
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| 45:46 | the function the changes in calcium the changes in sodium levels, the |
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| 45:51 | in the member of potential levels and on. So for the neurotransmitter release |
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| 46:01 | this is the reason why neurotransmitter release the synaptic transmission at the level of |
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| 46:10 | in the cns is not as reliable neuromuscular junction is because you can also |
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| 46:16 | partial neurotransmitter release. That happens that happens in neuromuscular junctions have the early |
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| 46:24 | of stone. You know the budding of the vehicle that bicycle gets filled |
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| 46:29 | neurotransmitter that versatile gets docked. So need a teepee and other factors to |
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| 46:38 | those vesicles close to the active zones kind of keep pushing them closer to |
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| 46:44 | dark side and then priming the meaning they're just you just need a little |
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| 46:49 | of calcium and they're ready to fuse open up. That's when their prime |
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| 46:54 | there's other vesicles that are floating around up there and the ones that are |
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| 46:59 | close to the memory and the closest you right here calcium comes in boom |
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| 47:06 | . There's no transmitter fusion, but can be sometimes partial. So that |
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| 47:13 | a little bit of neurotransmitter leaks Maybe there wasn't enough of the calcium |
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| 47:20 | . Maybe there wasn't enough counseling Okay, maybe it just happens that |
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| 47:29 | have the fusion poor that is partial back around and goes into prime position |
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| 47:37 | sometimes it can go back into this position. Dark position, back into |
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| 47:42 | position sort of go through a different again because it hasn't gone through the |
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| 47:48 | fusion and full release but it needs be touched up in order to go |
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| 47:53 | to business. So this relationship was kiss and run. There's no deep |
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| 47:59 | here, just a little kiss will of neurotransmitter gone. Uh huh. |
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| 48:06 | there is sufficient enough deep polarization sufficient calcium activation of protein protein complex. |
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| 48:12 | a fuel fusion formation of full fusion dilation of that for release of the |
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| 48:21 | an end of psychosis which these green of Claritin molecules that will surround the |
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| 48:27 | vesicles plasma membrane and will indicate that cell that this is marked for recycling |
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| 48:34 | it can get now filled with high of H. Plus so you have |
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| 48:41 | filling it causing a certification. And is certification. Will then drive neurotransmitter |
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| 48:48 | of the vesicles, putting it back this position, docking, climbing and |
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| 48:54 | it ready for release again. This the end acidosis cycle and sometimes it |
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| 48:59 | to be rebuilt. So instead of just acidified and refilled, the neurotransmitter |
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| 49:06 | may get sent back to the early of south and go through the whole |
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| 49:11 | of rebirth at the level of thoroughly the south. Uh huh. |
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| 49:17 | Uh So cns synapses versus neuromuscular So this full fusion release of one |
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| 49:25 | , one synapse being active is equal half of Louisville. It's very small |
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| 49:31 | neuromuscular junction, very large deep polarization the form of hand flake potential and |
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| 49:37 | cns is called neurotransmitter of synaptic potentials very small excited harry potter synaptic potentials |
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| 49:45 | from a single neuron single synapses on order of half a normal quantum |
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| 49:53 | Mhm. There's certain quanta of neurotransmitters get released in these vesicles. What |
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| 50:02 | the quanta Between 2000 and 4000 What do you mean between this |
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| 50:14 | Quanta? Well it is a quanta there's a variation of nature and no |
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| 50:20 | a code will contain exactly 2,987 chemical next to each other. They'll all |
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| 50:27 | a slight variation With somewhere between 2000 4000 molecules. And if you talk |
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| 50:34 | the Seattle Colleen and you go back about nicotine acetylcholine receptors and the neuromuscular |
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| 50:41 | you need to acetylcholine molecules in order open one receptor mm We have 2000 |
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| 50:50 | to 4000 molecules. So how many can get activated? About 1000 to |
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| 50:57 | receptors. So it's about 1000 or receptors in the muscle that caused the |
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| 51:04 | middle of old employee potential. Now can almost say what one receptor channel |
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| 51:11 | responsible for take 17 million balls divide 2000 and now you can actually say |
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| 51:19 | activation of one receptor channel neuromuscular junction pretty powerful actually just one channel not |
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| 51:25 | or not. So so quantum release so you have a certain package certain |
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| 51:32 | that's back there, it's not going be 2000 and 20,000 is going to |
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| 51:37 | 22,002 and a half 1000 But it's going to be all over there. |
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| 51:47 | 20 and 20,000. So there is is there is a there's a cycle |
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| 51:54 | re uptake and refilling and obviously there this kind of a interesting standard limit |
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| 52:04 | packing things in. Mhm poisoning your release bacteria, spiders, snakes and |
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| 52:14 | your books and it all right. a lot of stuff out there. |
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| 52:25 | I have some things written down Australian bucks align them. You're invited |
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| 52:30 | Botox party friday evening. Follow What it cost? 200 bucks the glass |
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| 52:42 | rose a champagne, you go into med spa clinic and you are doing |
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| 52:58 | . Why do people do Botox to young and beautiful again to the |
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| 53:06 | younger and younger and younger itself. well imagine you could be younger for |
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| 53:12 | not relevant, gets like 40s, , 60s and people pay so much |
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| 53:18 | care for anything color. So in case why do people use Botox? |
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| 53:29 | what is clostridium botulinum, anybody heard bunch of line um toxins. The |
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| 53:36 | botulinum and botulism. So you have toxins that form for microorganisms and |
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| 53:47 | Most of the things that are Again they're just like puffer fish that |
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| 53:51 | the microorganisms that produce ctx And so have these bunch of line on toxins |
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| 54:00 | form. There's different toxins. There's toxin that's mentioned here. Tetanus toxin |
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| 54:06 | not tetrodotoxin. It's not the same . To throw the toxin justice. |
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| 54:13 | toxin? We're talking about botulinum toxins . So botulism is a form of |
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| 54:18 | you can form and fox is toxic intoxicating disease if you eat bad old |
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| 54:25 | from camps, usually canned food that have some of the toxins leftover and |
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| 54:32 | you quite sick. So uh why you use that for Botox parties? |
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| 54:41 | that will make you sick and food you can isolate these molecules and you |
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| 54:45 | apply them in a controlled manner and controlled manner. And their function is |
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| 54:51 | botulinum toxins. But these Sharky's and are different subtypes of botulinum toxin B |
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| 54:57 | E f g A N E C and this is our protein protein |
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| 55:03 | Remember that the vesicles have the protein here and that the secure we call |
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| 55:08 | the snare has to interact with the or t snare trans membrane protein |
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| 55:14 | And this interaction is necessary calcium influx necessary and this interaction is necessary for |
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| 55:21 | vesicles issues with the plasma membrane And these guys do these little sharky's. |
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| 55:27 | don't let the protein protein complexes to with each other And by jumping up |
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| 55:35 | here, these linkages between the physical the plasma membrane. They prevent the |
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| 55:42 | release and in this case the Botox injections are usually done around the eyes |
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| 55:50 | forehead chin because with the aging and movement of the muscles. You have |
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| 56:00 | formation. It's just normal because your is stretching and shrinking and stretching |
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| 56:06 | you're gaining weight, losing weight over . It's the muscles are moving. |
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| 56:11 | forming wrinkles. And what the Botox do is they actually prevent the release |
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| 56:21 | the Seattle Colleen and prevent the contraction the muscles. And in addition to |
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| 56:32 | , people also typically used for beauty fillers, which fills up, it's |
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| 56:40 | a toxin. In this case it's little like fluid, it's like filler |
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| 56:45 | fills up around the lips and around eyes and makes you I think you |
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| 56:51 | better more youthful for me. I find it really interesting how Almost always |
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| 57:01 | about 10 ft away you can tell person that had a plastic surgery versus |
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| 57:06 | person that didn't have a plastic surgery on their face, No other body |
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| 57:15 | face. If you look at the you can tell there's because there's certain |
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| 57:21 | and there's a certain I guess desired or something, you know, so |
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| 57:26 | full perky lips, you know, like filled up around the eyes. |
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| 57:30 | usually stretch face so that there's nothing stretch stretch to answer that there's nothing |
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| 57:38 | . Um While it's a huge So Botox, you know, in |
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| 57:43 | case it's being used for for beauty with Botox injections actually have a therapeutic |
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| 57:52 | also approved. Anybody knows when FDA Botox approved for treating huh pain. |
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| 57:59 | it sweaty hands. Is that learn something new every day but from |
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| 58:10 | , this is great. But from disease perspective, it's for my grant |
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| 58:17 | . So when you think about these that you're taking advantage of the |
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| 58:22 | you're learning what the nature is controlling it. Now, you can |
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| 58:27 | for beauty purposes. And so when people get injected with Botox and fillers |
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| 58:33 | if you watch uh like the people on tv after these surgeries, they |
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| 58:41 | barely talk like whatever the housewives stuff city without difficult on talking and looking |
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| 58:51 | seeing because the literally muscles are not and moving the lips like it would |
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| 58:57 | the single Colin is not being But now there is no wrinkles and |
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| 59:01 | look fuller. So, beauty neurological treatment disorders neurological disorder treatment |
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| 59:08 | So if anybody is interested to look why, why would there be, |
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| 59:13 | know, Botox treatment for something like migraine? Yeah, there's other molecules |
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| 59:19 | nature and they can affect different parts this pathway. The release of recycling |
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| 59:28 | Black widow veteran, we'll take the Colin release. Black widow spiders. |
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| 59:35 | actually prevalent in texas too, can deadly. And unfortunately I had one |
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| 59:40 | my acquaintances, father who was gardening got bitten in the neck by a |
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| 59:46 | widow Spider past three days later in hospital and it was pretty fast at |
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| 59:55 | from the swelling from a bump into kind of a pussy thing and they |
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| 60:00 | save him. So quite potent. why you need controlled environment and that's |
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| 60:06 | little tiny things, you know, can kill you too. You |
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| 60:12 | mosquitoes. God they carry all sorts stuff. Right? The viruses, |
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| 60:18 | west Nile, you know like uh a Phil itis. Uh people get |
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| 60:28 | from a mosquito bite because they get a flight is there's mosquitoes carrying, |
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| 60:33 | sorry, ticks that carry encephalitis and a politic ticks. Mosquitoes carry |
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| 60:40 | takes cancer politis very powerful little Taiwanese cobra has a substance called alpha |
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| 60:47 | toxin and it affects the process synaptic of the civil code. And we |
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| 60:53 | talked about personality because we concentrated the release today from the pre synaptic |
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| 61:00 | Human synthesized organophosphates. You have human organophosphates that interfere with the Seattle cooling |
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| 61:11 | . Actually said. Local industries inhibitors organophosphates which are used in agricultural purposes |
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| 61:22 | quite often used for suicide purposes I just learned about that a few |
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| 61:27 | ago and it's pretty scary but not nature, but humans also synthesize |
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| 61:33 | Some of them are good. Some them are bad gonna false face can |
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| 61:39 | gases such as sarin and soma Nerve they're called nerve gases if you heard |
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| 61:47 | , you heard of 1990s attack and Subway in Japan nerve gases poisoning of |
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| 61:55 | people. Okay. And then you weaponize other substances into gases. Uh |
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| 62:02 | can weaponize fentaNYL into into gas. chechens have done it in Moscow. |
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| 62:11 | about 15 years ago or so putting to sleep. So substances that are |
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| 62:20 | there and we'll come back and talk these substances. You understand actually the |
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| 62:26 | of actions of organophosphates because you understand silk protein synthesis degradation pathway. And |
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| 62:32 | understand that these substances are also very to the most common Alzheimer's medications that |
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| 62:38 | on the pharmaceutical market. So E E. P. S. |
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| 62:45 | Is different from employee potential. What's talk about employee potential because that was |
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| 62:52 | the neuromuscular junction and it was huge million bills and always caused a muscle |
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| 62:58 | contract an E. P. P. Is not that an |
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| 63:01 | P. S. Be activated A single synapse will cause this deep |
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| 63:06 | about have a similar law. And you have an excited tourist synapse you |
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| 63:12 | have glutamate release and glutamate will bind glutamate receptor glutamate gated channels and will |
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| 63:21 | an influx of sodium which will cause deep polarization. That will also allow |
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| 63:26 | the potassium to leave, which will the re polarization. So this is |
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| 63:30 | excited to replace synaptic potential, abbreviated D PSP. And you can see |
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| 63:36 | the duration of the synaptic potentials Is the order of 5 to 10 times |
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| 63:43 | in duration than the action potential. , they are graded responses. Action |
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| 63:51 | is all or non E. S. P. S. Are |
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| 63:55 | if you activate just announces you get mole of all four synopsis to 2010 |
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| 64:02 | . It's greater action potential if you the threshold always drives it to the |
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| 64:09 | potential for sodium. Idea species are paseana. If there is release of |
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| 64:20 | or gamma amino butyric acid inhibiting or gabble will bind to channels that conduct |
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| 64:28 | . So they're receptor channels. Gabba will open up chloride channels and influx |
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| 64:35 | and I am chloride into the south cause this hyper polarization in the form |
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| 64:43 | the inhibitory synaptic potential I PSP. so neurons are constantly receiving E. |
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| 64:52 | . S. P. S. receiving inputs from excitatory synapses and generating |
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| 64:57 | SPS inhibitory I. P. P. S. If they receive |
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| 65:02 | of the excitation and excitatory synapses, E. P. S. |
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| 65:07 | Will reach the threshold for action potential produce an action potential. So what |
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| 65:19 | talking about is I am a tropic metabolic topic, neural transmission or direct |
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| 65:30 | indirect neural transmission and acetylcholine synthesis and . But I think what I will |
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| 65:36 | actually is I will end here and we come back on Wednesday will restart |
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| 65:42 | talking about synthesis and degradation of a colleague. Uh huh. And then |
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| 65:50 | into talking about the indirect and direct because there are two types that I |
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| 65:57 | a tropic direct signaling receptor for gated and metabolic trophic indirect signaling G protein |
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| 66:06 | receptors channels. G protein coupled receptors now channels. Okay so there's gonna |
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| 66:13 | a lot of interesting information coming and malaria to from mosquitoes. Yes, |
|
| 66:20 | you for pointing that out, horrible cause massive headaches. Uh what is |
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| 66:28 | that people take when when I went Nigeria, I took flora Quinn. |
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| 66:33 | believe the substance uh that is sort preventative for malaria but there's also I |
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| 66:44 | that quiNINE which is an tonic It has an anti malarial properties. |
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| 66:51 | a stimulus substance. Glory Queen Queen blocks gap junctions actually. And so |
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| 66:59 | chloroquine. And so this method of is an equivalent of chloroquine. So |
|
| 67:03 | another thing you guys got dresses one . I don't know about junctions, |
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| 67:07 | junctions in the brain. So So uh what quiNINE is supposed to |
|
| 67:14 | when people go sometimes to some tropical where they have mosquitoes and malaria, |
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| 67:20 | drink a lot of gin and It's an excuse I'm consuming quiNINE of |
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| 67:27 | , you know, to stay safe malaria. Anyway, so this cheerful |
|
| 67:32 | . And today's lecture, I'll see on Wednesday. We'll have our quiz |
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| 67:37 | week and I will tell you about more next Wednesday. This Wednesday. |
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