| 00:00 | So this is Tuesday. Neuroscience meeting 11. We're continuing talking about synaptic |
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| 00:07 | transmission, and we're continuing talking about systems and neurotransmitter system types. In |
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| 00:16 | case, we discussed that there are types of neurotransmitters such as amino acids |
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| 00:23 | as a means peptides. We also about gasses. We talked about quite |
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| 00:30 | neural transmitters such as, uh, deep and a Dennis Um uh, |
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| 00:38 | p being the energy molecule we talked lipid soluble, uh, neurotransmitters as |
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| 00:46 | . So a mean step tides, acid. What we discussed is that |
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| 00:52 | major excited during neurotransmitter in the N s is glutamate. The major |
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| 00:59 | neurotransmitter in the CNS is gabba, glycerine in the spinal cord is an |
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| 01:06 | neurotransmitter. But in the CNS and cerebral Google, I seen is actually |
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| 01:11 | co factor Thio excited to wriggle So again, the response off the |
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| 01:18 | does not depend on the chemical that released pre synaptic aly, but |
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| 01:22 | The pasta synaptic response depends on the subtypes that that neuron posson attic neuron |
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| 01:30 | because these chemicals combined two different receptors different receptor locations affecting them differently. |
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| 01:38 | Amina assets, of course, will engaged with excited to inhibitory. Fast |
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| 01:44 | that means we discussed are important acetylcholine dopamine, epinephrine, histamine, norepinephrine |
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| 01:50 | serotonin. And we also started talking how you know these demeanor transmitters, |
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| 01:57 | by glutamate inhibition by Yahoo. But neurotransmitters served very interesting functions. The |
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| 02:06 | could represent certain behaviors and certain behavioral and can be associated with neurological neurodegenerative |
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| 02:17 | . So in your list off your disorders, you have Alzheimer's disease. |
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| 02:23 | we mentioned that acetyl Colleen. We of all, talked about acetyl Colin |
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| 02:29 | the neuromuscular junction, so we talked how it was discovered in the vagus |
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| 02:35 | toe heart neuromuscular junction. Then we the functions off the neuromuscular junction |
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| 02:42 | whereas the tool Colleen de polarizes the and causes the production of the action |
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| 02:48 | by the voltage gated sodium channels and gated calcium channels. But in the |
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| 02:54 | . N s. We talked about disease, and we talked about Alzheimer's |
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| 03:01 | as having certain pathological features. You're pathological features, and we talked about |
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| 03:07 | plaques that form the tangles form inside cells, dying neurons and shrinking brain |
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| 03:18 | . And this system, the neurotransmitter that is affected in Alzheimer's disease. |
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| 03:24 | it is a fact that pretty significantly early on, this Colin Ergic system |
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| 03:28 | a seal Colleen signaling. And so is another type of pathology. Now |
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| 03:34 | looking at which neurotransmitter system is impaired these different neurological disorders, so you |
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| 03:41 | add Colin urging impairment or a seal impairment in Alzheimer's disease. If we |
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| 03:51 | at the dopamine, dopamine is very for certain motor functions and motor |
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| 04:00 | and dopamine dysfunctions would be associated with neurological disorder, Parkinson's disease. |
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| 04:11 | uh, in addition, dopamine receptor may be present in a neuropsychiatric disease |
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| 04:22 | , and so you can see that behaviors, for example, serotonin regulating |
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| 04:30 | and sexual behavior is different from memory learning and cognitive functions in the CNS |
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| 04:38 | are sub served by acetyl coleene. , that is dopamine that is |
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| 04:45 | Some of these motor functions and motor driving motor performance from the cortex into |
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| 04:51 | spinal cord and into your muscles. disorders. Neurological disorders such as Alzheimer's |
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| 04:59 | , Parkinson's disease but also neuropsychiatric Schizophrenia result in shrinkage of brain tissues |
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| 05:07 | and we discussed in severe cases of neuropsychiatric disorders. You do have degeneration |
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| 05:14 | neurons. You have information in the associated with this disorders as well. |
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| 05:23 | , we mentioned baptize, and we'll about some of these, uh, |
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| 05:30 | systems in greater detail than others, therefore they will be proportionately represented on |
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| 05:38 | test on exam questions and the Now, we talked about gasses, |
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| 05:45 | in general, we talked about these , means and amino acids packaged in |
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| 05:51 | ALS. We talked about baptize that go into the then score, |
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| 05:57 | vesicles. Okay. And then we that gas is, for example, |
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| 06:03 | not sitting inside these enclosed vesicles and the lipid soluble molecules such as their |
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| 06:10 | acid or under cannabinoids. They can travels through the neuronal plasma membranes. |
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| 06:17 | even if they've got somehow loaded into vesicles, they would just dissolve through |
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| 06:22 | membrane. And that's how they This they're signaling is not necessarily confined |
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| 06:29 | just specifically one location and the but it acts mawr in a lipid |
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| 06:35 | para crime fashion, finding the respective , which is the cannabinoid receptors, |
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| 06:41 | nitrous oxide. The sector's, um p was interesting because it's an energy |
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| 06:49 | , but it also serves as a in the core of a teepee |
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| 06:54 | Dennison is a transmitter as well. let me, um, and the |
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| 07:04 | of different neurotransmitters and peptides is really . Functions of the brain is really |
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| 07:15 | is expressed in certain circuits in the , so it's lighting up those |
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| 07:20 | When it's active, Macedo Colin is only certain circuits. Only certain cells |
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| 07:24 | the brain are therefore it can be and thought off The whole kind of |
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| 07:30 | behavior associated with these systems and the is pre synaptic and possum. At |
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| 07:36 | pre synaptic, you have to synthesize store release. Recycle as a pre |
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| 07:44 | side of the system has to cross synaptic cleft. Inside synaptic cleft. |
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| 07:48 | have a bio degrading enzymes transporters. the pasta synaptic side, you have |
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| 07:57 | synaptic receptors, different types of posson receptors. I on a Tropic Channel |
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| 08:05 | which essentially are ligand receptors that allow flow of ions through the channels versus |
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| 08:13 | tropical G protein coupled receptors. Postion in the response of the cell will |
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| 08:20 | on the receptors that expressed Parson optical secret Terry Granules that we talked about |
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| 08:28 | eyes something that where peptides are being , uh, packaged into So your |
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| 08:37 | old question last time, what was difference between the neurotransmitters and the secret |
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| 08:43 | Granules on DSO? The difference is all of them things that will be |
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| 08:50 | about synaptic neural transmission or the secular transmission, the synthesis of neurotransmitters the |
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| 09:00 | neurotransmitter molecules gets transported and loaded into vest ical on these red dots or |
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| 09:07 | neurotransmitter chemical molecules inside the vesicles. , uh, all of this is |
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| 09:16 | at the level of sternal terminal. you have synthesis of neurotransmitters loading into |
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| 09:21 | vesicles fusion release of the vesicles, is extra psychosis and recycling off the |
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| 09:27 | back into the present active terminal, is endo psychosis re update. |
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| 09:34 | if you look at the peptides, require mawr activities. So a lot |
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| 09:41 | times, uh, amino acid, transmitters would be responsible for fast excited |
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| 09:48 | inhibitors signaling, and you'll have heightened of a activity in order to start |
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| 09:54 | and releasing, baptized or under And then, in the case of |
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| 09:59 | , they will, but off from precursor peptide from rough into plasma Particular |
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| 10:05 | get processed through Golgi apparatus into the peptides neurotransmitters performed there and, |
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| 10:15 | forming the secret Tory Grandal's full of active peptides neurotransmitters and then being transported |
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| 10:23 | the external process and directed stored external . But the difference between peptides and |
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| 10:32 | secretary Granules and the neurotransmitter vesicles is your transmitter vesicles especially, will be |
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| 10:40 | find Thio the synopsis of synaptic whereas the peptide neurotransmitters secretary Granules can |
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| 10:49 | out through Axiron through different parts of Exxon. And different parts of these |
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| 10:56 | terminals are extra synaptic not just within very specialized synaptic region. And such |
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| 11:04 | also the case with endo cannabinoids and soluble. Our economic asset is that |
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| 11:10 | essentially are activity dependent, how much them will get produced and once they |
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| 11:16 | produced, they get released and they the plasma membrane. Secretary Granules will |
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| 11:23 | , not bind, but well views a membrane and release the content. |
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| 11:28 | this is a very different from the vesicles sort of quiet, confined to |
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| 11:35 | very specific, specialized in space areas synapses. So let's see how the |
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| 11:43 | release happens and what are some of prerequisites? The necessities for this neurotransmitter |
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| 11:51 | and fusion to take place up until second section of the scores. We |
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| 11:59 | about the action potential and we said when the action potential arrives at the |
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| 12:05 | terminal, it causes a very large polarization. And then what? |
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| 12:11 | it so happens that this priest dynastic polarization is necessary. So the flocks |
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| 12:18 | sodium and deep polarization of this pre terminal well open up voltage gated calcium |
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| 12:28 | . So the incoming action potential or pre synaptic deep polarization will open up |
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| 12:37 | voltage, gated calcium channels and calcium into the cell is necessary in order |
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| 12:45 | the vesicles to fuse to the plasma and caused neurotransmitter released into the synaptic |
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| 12:52 | . So if you want to block voltage gated calcium channels and you were |
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| 12:57 | producing action potentials and sending those action to the external terminal, deep polarization |
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| 13:05 | sodium is not going to cause a fusion and the secular the secular |
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| 13:14 | Okay, neurotransmitter release. It's not to do that. It's necessary that |
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| 13:20 | is present, and if you block channels. You can send all you |
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| 13:26 | . The action potential six terminal There will not be neurotransmitter release. |
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| 13:31 | synapses will not be actively releasing neurotransmitters be de Pol Arised. The reason |
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| 13:38 | it is the fact that calcium channels concentrated in these active zones. And |
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| 13:44 | you remember by these active zones, have the doctor and the prime vesicles |
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| 13:49 | are now ready to fuse their membranes the vest ical ready to fuse with |
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| 13:55 | membranes off the neurons in order to these neurotransmitters. So calcium channels voltage |
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| 14:03 | calcium channels. Influx of calcium activates protein protein complex and activates a protein |
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| 14:12 | that exists around this neural transmitter. . This is the bottom, |
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| 14:18 | Is what these neurotransmitter vesicles to look . They're very Harry old tennis balls |
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| 14:28 | have all of these bundles of dirt hair stuck on them. These are |
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| 14:34 | Prodi. It's these air calcium sensing . They're proteins that bind to other |
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| 14:41 | . And in very simple terms, have, uh, the secular snare |
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| 14:49 | that is associate ID with vesicles on top. Here, the snare and |
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| 14:56 | have the trans membrane. You have trans membrane, uh, snares And |
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| 15:03 | pro dance on the vesicles, the snares and the T snares on the |
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| 15:11 | of the neuron have thio interact physically each other in order to bring the |
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| 15:18 | on the proximity to the plasma And for that to happen, you |
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| 15:24 | calcium influx. So if you don't calcium coming in, calcium gets detected |
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| 15:34 | these vesicles. These vesicles have calcium sides. Such a synaptic tag |
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| 15:42 | The synaptic tag mint is going. essentially sense how much calcium is in |
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| 15:49 | . So when calcium concentration goes up calcium channels open and calcium channels open |
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| 15:55 | there is pre synaptic deep polarization in form of the action potential, only |
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| 16:00 | calcium channels open and there is significant of calcium Onley. Then this V |
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| 16:07 | t snare. This protein protein complex bring physically the organ. I'll this |
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| 16:15 | testicle. Use it with the membrane the neuron. Andi produce the exercise |
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| 16:22 | assis for release of the neurotransmitters, these vesicles will then be recycled back |
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| 16:32 | the pre synaptic terminal, so you see that these vesicles will contain a |
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| 16:37 | number of neurotransmitters they'll be loaded with certain number of neurotransmitters. We refer |
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| 16:43 | that as quanta. There's a certain number between 2 to 4000 off individual |
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| 16:51 | molecules that will be found in each lexical. And so when the vesicles |
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| 16:57 | is a neurotransmitter gets released, that maybe be a little bit of neurotransmitter |
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| 17:03 | in this vesicles. But now this of the membrane that fused doesn't get |
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| 17:09 | , it gets recycled back and the assist the process of under psychosis, |
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| 17:16 | these vesicles will then be refilled again primed docks primed and subsequent deep polarization |
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| 17:26 | action potential influx of calcium will allow to fuse back again. So it's |
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| 17:33 | important that we realize that this synaptic that we're looking at C. N |
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| 17:40 | and a single synapse If you activate single synapse, you're only causing 0.5 |
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| 17:48 | volt deep polarization. Very small, polarization by activating one synapse, 0.5 |
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| 17:55 | levels. And remember, we talked neuro muscular junction Neuromuscular Junction. We |
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| 18:02 | an and played potential by single synapse the size of 70 mil evolves. |
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| 18:09 | that the resting number and potential is minus 70 minus 65 and the threshold |
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| 18:16 | action potential generation is about minus 45 volts, so you have to dip |
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| 18:22 | . Arise the sell by about 20 volts. In order, Thio produce |
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| 18:27 | action potential if your central nervous synapse only 0.5 mil levels. Deep |
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| 18:37 | and you need 20 to 25 Also deep polarization. How many exciting |
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| 18:43 | synapses? Because excited terry synapses glutamate deep polarization. How many exciting Terry |
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| 18:50 | do you need to be active in to reach the threshold for action potential |
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| 18:57 | ? Well, if it's 25 million and a half a mil of old |
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| 19:00 | one synapse and it's 50 synapses that to be active in order to dipaula |
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| 19:07 | the Parson attic sell for it's a action potential thes air 50 Active, |
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| 19:13 | tourist synapses to produce essentially a response action potential in the Boston optic neuron |
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| 19:24 | then the neuro muscular junction. You have one synapse producing 70 mil of |
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| 19:29 | an action potential in one synapses. Junction equals a twitch of a muscle |
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| 19:37 | it produces such a strong, deep through acetylcholine receptors in your muscular junction |
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| 19:43 | the CNS, the deep polarization comes the glutamate receptors and in the C |
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| 19:49 | s, the size of that deep is zero only 0.5 mil of also |
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| 19:54 | half a mil of all. So you understand that you need tens of |
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| 19:58 | synapses just to dipaula rise apostle in neuron Those excited Torrey synapses, but |
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| 20:05 | that neurons will be receiving excited her inhibitory synapses there will be receiving |
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| 20:11 | A different parts of their Samata dendritic , some of them on the very |
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| 20:16 | ical top dendrites, others on the close to soma and this is Soma |
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| 20:24 | so on. So keep all of in mind that in reality you probably |
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| 20:29 | hundreds of active synapses and exciting Terry winning over the inhibitory synapses, maybe |
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| 20:37 | of active synapses onto one neuron in for that neuron to reliably fire action |
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| 20:45 | . And that's a big difference between neuromuscular junction of CNN s. And |
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| 20:50 | why I called the Neuromuscular junction on fidelity synapse 1 to 1. Once |
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| 20:57 | activated muscle twitch. One synapse activated twitch in the CNS one synapse |
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| 21:05 | Tiny and deep polarization. Justin ups one mil of all deep polarization. |
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| 21:11 | synapses activated, 10 mil of also polarization. Mhm. So once |
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| 21:18 | these are very important concepts to keep mind. Uh, this slide is |
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| 21:24 | , uh, showing us how we've trying to visualize neurotransmitter release and trying |
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| 21:31 | understand all of these necessary components. polarization of calcium calcium sensors on the |
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| 21:39 | complex protein, protein complex interaction between vest Iccho and the membrane on the |
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| 21:46 | year and a you see electoral micro , electron microscope pictures and these dots |
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| 21:54 | that formed these lines that lined active are voltage gated calcium channels. And |
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| 22:04 | B you see these craters. And when you're looking at, you're looking |
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| 22:08 | the plasma membrane from extra cellular side the vest Nicholas using from cytoplasmic intracellular |
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| 22:19 | and is opening itself up. So looking into the inside of the vesicles |
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| 22:23 | outside of the cell. This is exercise Ozick fusion porn. You can |
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| 22:28 | that these fusion pores are forming very . Thio these high densities Walter skated |
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| 22:37 | channels, these air, our chemical and electron microscopes allowed us to visualize |
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| 22:47 | anatomy and the structure of the secular . Uh, the low. Don't |
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| 22:55 | that we have two types off synapses below here, his electric microgram off |
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| 23:05 | Gap junction. As you can there's a cell here on the left |
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| 23:09 | the cell on the right and the air separated about 20 nanometers until it |
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| 23:17 | point they come close together, about nanometers apart. And if you recall |
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| 23:24 | Hemi channels connect, Sense will A connects on will form a Gap |
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| 23:30 | on both sides from two cells. left cell on the right cell will |
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| 23:35 | , join these pro dance and formed Gap junctions that are electrical junctions. |
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| 23:42 | if you recall, that's when the of the ions happened, and also |
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| 23:48 | molecules such a secondary messengers, a campy can traverse through these gap |
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| 23:57 | These gap junctions air open, and also allow for fast synchronization of neuronal |
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| 24:05 | , right and the other function that know that these gap junctions served and |
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| 24:10 | of the material that we already covered they allow for potassium spatial buffering by |
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| 24:18 | sites. So Astra sites and Astra Networks interconnected one Astra site to another |
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| 24:26 | specially buffer potassium by slurping it up the region, where there was a |
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| 24:31 | concentration of potassium and distributing, and vastly through its network. In doing |
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| 24:39 | in a very fast fashion. Through gap junctions, so neuron is can |
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| 24:46 | their neuronal activity, can synchronize small passage and glial cells and have gap |
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| 24:55 | will allow for the spatial buffering off . Small molecules as well least keep |
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| 25:04 | of these things refreshed in your mind we talk about synaptic transmission. We |
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| 25:09 | have been trying to visualize the scientists trying to visualize the membrane. How |
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| 25:15 | this membrane look like? And I this very interesting, historically technique that |
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| 25:21 | used you would want Thio. What you do? What would you |
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| 25:26 | What would you dio if you have split the plasma membrane in half? |
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| 25:34 | would you do it? And so 50 60 70 years ago, The |
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| 25:41 | waas Well, let's freeze the membrane then let's try to fracture the plasma |
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| 25:53 | so there would be very quick freezing liquid nitrogen and very quick fracture that |
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| 26:04 | to take place so the experimental set would be set up. That would |
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| 26:09 | a frozen piece of a membrane or cell being a micro electrode coming close |
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| 26:17 | that cell. Do that membrane, then everybody would walk around the line |
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| 26:26 | stomp to be with hope that that bumped that piece of plasma membrane or |
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| 26:35 | right in between the two layers, to foster lipid layers and split it |
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| 26:42 | half. And indeed, this one us really understand that it's set a |
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| 26:50 | bi layer that there is an e and there's a P Phase two. |
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| 26:54 | membranes. If you zoom into these possible little violent membranes, eso trans |
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| 27:03 | proteins and that in and then we see which face. These trans membrane |
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| 27:09 | are associated with the face or the . What can be found on the |
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| 27:14 | on the inside versus the P It's ah, great uh, |
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| 27:22 | And really, there was a bit a superstition and mastery, and walking |
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| 27:27 | and vibrating the table and stomping in room to try to get these member |
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| 27:33 | the fraction in the correct way. you go Thio some of the labs |
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| 27:39 | they do very high level research. , um, um, people have |
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| 27:47 | own methods. They have their own . Sometimes they have things that they |
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| 27:54 | explain why, completely scientifically, but certain things in a way and way |
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| 28:03 | the other works. And that's why you have the best labs, |
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| 28:07 | We call the best labs because we do something better than others. So |
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| 28:11 | either have a better mousetrap. They a better piece of equipment or they |
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| 28:18 | had better techniques and using the same of equipment. So they just improve |
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| 28:23 | and and better lab. So this comes from trying really hard and then |
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| 28:30 | observing your environment. If you're doing quadruple recording from four South, you |
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| 28:37 | thio completely understand the vibration off the in your floor before you do that |
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| 28:44 | . Okay, so all of these play into whether you're gonna need the |
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| 28:49 | lab or get the best results because all interrelated. I find it really |
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| 28:56 | that, for example, when the makers make the eyes for world competitions |
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| 29:05 | skating, that the best ice makers they believe that playing certain music to |
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| 29:17 | eyes to the water molecules as their will influence the quality of that |
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| 29:24 | You can read articles about Olympic ice that actually use these different, |
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| 29:31 | techniques of producing sound and playing music eyes. There's people that play music |
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| 29:37 | plants to make them grow better, you have to pay attention. And |
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| 29:43 | no scientific proof, complete scientific But we know the sound resonates, |
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| 29:51 | if it's loud enough, it causes resonance. And then physical residents may |
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| 29:58 | with the changes phases from water until , for example. But has it |
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| 30:05 | been completely determined? Maybe not. hasn't even also being completely determined that |
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| 30:10 | have to walk around the table and on it together. Perfect crease |
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| 30:15 | But it happens, and people do and then reveal new things like |
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| 30:20 | And so this lost energy on the right is about calcium, and what |
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| 30:27 | discussed so far in the course are different dyes and stains. And we |
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| 30:32 | that for the purposes of the first , we really talked about the stains |
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| 30:37 | help us define the anatomy cellular Golgi stain the architectural off the networks |
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| 30:48 | structures you had missile stain or tracing neurons project from one side to |
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| 30:58 | We discussed horseradish, bere, This is all for revealing anatomical structure |
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| 31:07 | the cell structure of the networks and . You learn what there's other |
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| 31:14 | That same specifically acts on stew later the courts. But And about 30 |
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| 31:21 | years ago, there are scientists and in general started developing voltage sensitive dies |
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| 31:30 | ion sensitive dies. And what you here is a picture off and die |
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| 31:38 | it's sensitive to calcium. Well, does this work? So you have |
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| 31:42 | you have a microscope, and this is sensitive enough so that it visualized |
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| 31:47 | a single large synapse here, it visualizes synapse, and the pre |
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| 31:56 | neuron will get stimulated in the synapse before stimulation and normal functioning state or |
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| 32:04 | state, which, you see, these blue mountains on the left and |
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| 32:09 | blue mountains. Some of them have peaks, and some of them have |
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| 32:12 | peaks the blue and the red. represents here on the scale and be |
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| 32:21 | concentration, intracellular, calcium concentration. much calcium is inside the cell, |
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| 32:28 | it's important to know that just like see these presumed voltage gated calcium channels |
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| 32:34 | here in the electron microscope picture here the rose and active zones, you |
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| 32:39 | see that these moms of calcium have calcium concentrations and also distributed somehow and |
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| 32:48 | up together around the active zone here the synapse in the pre synaptic |
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| 32:57 | And only some of them reached the and red and the red represents 202 |
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| 33:03 | plus micro molar concentrations of Callison. so what, you're visualizing you're visualizing |
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| 33:13 | die and that die will produce different . Okay, depending on calcium |
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| 33:23 | So the more calcium there is, redder the signal is gonna be the |
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| 33:29 | calcium. There is the bluer the is gonna be. And in |
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| 33:34 | you're seeing an active synapse. And all of a sudden, these calcium |
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| 33:41 | that are sitting there and there is much calcium concentration around them because there's |
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| 33:47 | deep polarization on when you produce pre stimulation, you produce massive, deep |
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| 33:55 | and you produce massive influx of And now these peaks, blue peaks |
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| 34:02 | mountains. It looked like from my Kia. Uh huh, Clara |
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| 34:10 | This very special place in Turkey. , these look like Little Mountain |
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| 34:16 | All of a sudden they turn into valley. They turn into at least |
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| 34:21 | , a mountain peak starting Thio Pilar, a valley. It's really |
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| 34:27 | , and it's red because it is with calcium. So each one of |
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| 34:34 | mountains essentially represents a cluster of calcium , and when they get activated, |
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| 34:41 | can see that intracellular calcium concentration goes , way up to 200 micro mall |
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| 34:49 | in its levels. This work was and, uh, Rodolfo Llinas Laboratory |
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| 34:59 | the described US micro domains calcium, domains and calcium receptor micro domains that |
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| 35:07 | associated with these active zones and a that it's sensitive to calcium. |
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| 35:15 | we also have dies that is sensitive sodium thio potassium miles. We have |
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| 35:21 | that are also sensors that vault it's and because in this case, calcium |
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| 35:27 | does not represent as much of a change across plasma membrane as an action |
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| 35:33 | would we can visualize voltage guys, can visualize voltage as well, not |
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| 35:40 | individual high ons. But overall If you're interested from neuron to brain |
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| 35:45 | the later edition, we'll have some information. Really Like that book. |
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| 35:52 | you wanna Delvin and study more of , I would recommend that this is |
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| 35:58 | it all together. That what is Pre synaptic Aly, that you need |
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| 36:04 | , that you can monitor calcium influx that this calcium coming into the south |
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| 36:12 | necessary for the neurotransmitter release. And have two types off neurotransmitter release. |
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| 36:21 | have two types. One of them partial and then another one is complete |
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| 36:27 | the central nervous system. This is again that is specific to the central |
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| 36:33 | system, not the neuromuscular junction. Junction produced an action potential prison optically |
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| 36:40 | get a twitch of the muscle possum in the CNS synapses. Sorry. |
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| 36:49 | the CNS synopsis, we also discussed Quantrill release and in the Neuromuscular Junction |
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| 36:55 | have a certain number. I've never and needs to be other leads. |
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| 37:02 | in the CNN asset is different from Junction. You have neurotransmitters that but |
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| 37:07 | from the early end of sound we loaded vesicles that but off from the |
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| 37:12 | end of some loaded with neurotransmitters, get docked with some energy to get |
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| 37:18 | , which means that they're now very and proximity to that protein protein complex |
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| 37:24 | fuse. And if there is influx calcium following the polarization, two things |
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| 37:29 | happen. If there is a little of calcium, this complex may interact |
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| 37:36 | each other and bring the membranes off dust ical and the neuron close to |
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| 37:43 | other, but not open the poor . So the fusion poor will only |
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| 37:50 | up partially, and only a small of neurotransmitter would get released the air |
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| 37:56 | the synaptic cleft. So in this , the vesicles is not committing too |
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| 38:03 | . It's just giving a little puck the cheek. It's called Kiss in |
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| 38:08 | , and then it runs back into prime position, and it could get |
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| 38:14 | back up higher and refilled with more and go into docking position, considering |
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| 38:22 | prime ing position and say, I need a little bit more calcium |
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| 38:25 | here, in order for me, , you know, open up fully |
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| 38:29 | and do this whole fusion poor And so this is the kiss in |
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| 38:36 | scenario for the partial opening of the . And if you have enough off |
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| 38:44 | activated and enough of the calcium goes and significant effect on the protein protein |
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| 38:52 | between vesicles neuronal membrane, you'll achieve commitment and full fusion of this |
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| 38:58 | Ical to the cell and release of York Giants Mitt are fully into the |
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| 39:05 | left following that following the exercise it . You have the process of end |
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| 39:12 | psychosis and these membranes, these vesicles remember they're pretty hairy beasts, so |
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| 39:18 | have their own anatomy. They have own molecules. They get recognized. |
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| 39:25 | particular members get recognized by Claritin. Claritin molecule coach them and but |
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| 39:34 | um, but off from a plasma and coach them and by coding now |
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| 39:41 | now that it can now either get loaded up with program through the 80 |
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| 39:48 | energy drive and go back into the end or so where they will get |
|
| 39:55 | and reshaped, released and loaded with . And come on this end or |
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| 40:02 | go through direct physical is defecation without the early end of someone being reprocessed |
|
| 40:09 | same plasma number and of the It's loaded up with protons. Now |
|
| 40:14 | is a city Grady int, and is city. Grady int will drive |
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| 40:20 | optic into the vaster calls and these now filled with neurotransmitter, can go |
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| 40:28 | docking prime ing Partial or full fusion psychosis followed by Ando psychosis. |
|
| 40:40 | so this is the whole cycle and that some very important member and properties |
|
| 40:46 | we discuss will also change. So you just used 100 neurotransmitter of obstacles |
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| 40:53 | the plasma membrane. Look what happens your plasma membrane. The number in |
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| 41:00 | and the surface area of the plasma is increasing. So when you have |
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| 41:05 | circular fusion, you'll actually increase the property of the cell. Because, |
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| 41:11 | , great capacitors are have to have lot of surface area to store the |
|
| 41:17 | . And so, if you increase surface area by binding, allowing these |
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| 41:23 | transmitter vesicles to bind now, you're increasing the capacitance of the cell until |
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| 41:31 | of psychosis happens, and these additional a plasma membrane get butted off the |
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| 41:38 | get butted back off and recycled, felt for the subsequent release. So |
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| 41:47 | this whole timeline. We talked about being in milliseconds, action, potential |
|
| 41:54 | Within milliseconds, it reaches external Within milliseconds, it releases neurotransmitter within |
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| 42:05 | . A few milliseconds of synaptic Remember that is not present in the |
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| 42:09 | junctions, but is president of chemical . Within a few milliseconds of synaptic |
|
| 42:15 | , you will get a possum haptic . Now, if you released all |
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| 42:19 | these neurotransmitters year, it's not now to be a few milliseconds for this |
|
| 42:25 | of endo psychosis, refilling and docking prime ing to take place. This |
|
| 42:32 | is on the order of seconds 10 15 seconds, to be precise. |
|
| 42:36 | if you stimulated the synapse really you released a lot of neurotransmitter from |
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| 42:41 | synapse. In order for that synapse be fully fully at the same |
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| 42:51 | you have to retell all of these vesicles. And that will take about |
|
| 42:55 | to 15 seconds. These processes off Psychosis refilling docking in primary. A |
|
| 43:04 | are very important. All right, , also, you know, we |
|
| 43:12 | about these neurotransmitter vesicles and there will a fusion off neurotransmitter vesicles if you're |
|
| 43:18 | glutamate A If you're releasing Gabba There also be fusion of these neurotransmitter vesicles |
|
| 43:25 | you're releasing a single coleene. uh, when we talk about the |
|
| 43:32 | topics in this course, I always Thio correlate Thio what you're seeing in |
|
| 43:39 | what we understand about nature. And this segment is poisoning near transmitter release |
|
| 43:47 | interfering with neurotransmitter. Signaling is another to say, and it falls under |
|
| 43:53 | special interest bacteria, spider snakes and . So we're going to talk about |
|
| 44:03 | . Ready? Who is ready to about you? I am ready to |
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| 44:11 | about you and me and bacteria and and snakes. Do you have any |
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| 44:20 | specialist Spider Bacteria specialists? I have question for you. What is Clostridium |
|
| 44:31 | and why you invited to both ox ? Mm hmm. Okay. So |
|
| 44:45 | Chad. Answer, sir. On air arrived with Australian botulinum. Anaerobic |
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| 44:55 | produces the stock sick substance. And you recall, even in your exam |
|
| 44:59 | there was a question about tetrodotoxin and . Bluefish. And if you |
|
| 45:07 | puffer fish does not produce the talks that's what we talked about. It's |
|
| 45:11 | micro organisms and it's bacteria and the that produces thes toxins and a bunch |
|
| 45:18 | line. Um uh, The studio can produce the botulinum toxins and the |
|
| 45:25 | botulinum has found in the water, it's found in the soil. And |
|
| 45:31 | it comes with seafood. It comes meat. It enters into the food |
|
| 45:37 | , and it's also in the vegetable because it is in the soil so |
|
| 45:45 | can be generated Because of food. have bean stored improperly, and most |
|
| 45:52 | the time it comes from outdated, , expired camp food or canned food |
|
| 46:00 | wasn't prepared properly and at home. , a lot of times this happens |
|
| 46:07 | when people are making their jams and big ears or whatever, they're making |
|
| 46:14 | days and their in their jars that food items meat, seafood, |
|
| 46:25 | If you don't prepare them properly, may contain with studio botulinum, which |
|
| 46:30 | produce much line of toxins. and so what do we dio with |
|
| 46:40 | ? And how do we usually consume that we want to preserve for a |
|
| 46:46 | time? We heat it and what ? Thio. Different proteins. When |
|
| 46:56 | raise the temperature, anybody, the , that's right. So what |
|
| 47:14 | S's okay to preserve it like Right? But you are heating, |
|
| 47:22 | you are now debating the nature in pro teams. So the proteins are |
|
| 47:27 | that, um, dietary substance on value that their value may be |
|
| 47:37 | but there's nothing could do. You thio heat you can in the food |
|
| 47:42 | you can see that a lot of air moving toward fresh food, especially |
|
| 47:47 | co vid. Even on TV, can see the commercials for fresh delivered |
|
| 47:54 | or fresh frozen food that you have . Mix yourself. This is really |
|
| 47:59 | and new in the future. Wave the food, consuming a lot of |
|
| 48:04 | . A lot of fresh foods called called processing, is becoming very important |
|
| 48:12 | for antioxidant and vitamin and nutrient rich . Protein rich foods especially. So |
|
| 48:21 | is how we deal with it. , so why you invited to both |
|
| 48:27 | spotting and what is botulinum toxin does bunch of line, um, |
|
| 48:31 | Here we have a demonstration where this ical synaptic vesicles is acetyl Colleen, |
|
| 48:39 | you have the protein complex and and tag mints. And after grabbing them |
|
| 48:44 | vest ical that the circular protein Then you have the trans membrane protein |
|
| 48:51 | 25 some tax on here. And you can see again this protein, |
|
| 48:57 | conflicts between Mexico and the plasma membrane to interact in order to cause the |
|
| 49:02 | of the testicle. On the release the neurotransmitter, I noticed that with |
|
| 49:07 | Sharkey's are these Sharkey's air botulinum toxin actually toxins. And in fact, |
|
| 49:13 | see here tetanus toxin Tetanus toxin is to be confused with tetrodotoxin. Bates |
|
| 49:22 | toxin is not tetrodotoxin. It's a types of toxin. It is not |
|
| 49:28 | fugu puffer fish talks and that we about. But you can see botulinum |
|
| 49:34 | is different. Sometimes B D f or here below e or here |
|
| 49:40 | one will target either the trans member or the circular proteins will target this |
|
| 49:47 | protein complex. And in the presence these toxins, you will basically not |
|
| 49:55 | the release of the neurotransmitters. So will prevent the fusion of the festivals |
|
| 50:00 | the plasma membrane, or you will lock the release of the neurotransmitters. |
|
| 50:05 | so what happens in botulinum with with toxins if you get poisoned by botulinum |
|
| 50:13 | . Anybody knows paralysis was right. you don't have You don't have activation |
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| 50:26 | the muscles and that can be deadly if if it's yeah, exactly. |
|
| 50:34 | you don't have activation of the So you don't have activation of the |
|
| 50:38 | muscles, decrease of the activation of cardiac and and so on, |
|
| 50:46 | cardiac receptors again, it will depend the receptor. So we discussed it |
|
| 50:51 | be expressed in these different parts of body and different organs. So this |
|
| 50:56 | our Botox. Okay when we talk other poise instead of their black widow |
|
| 51:05 | and the venom that they released contains other toxin that will also influences the |
|
| 51:12 | , coal and release. And it's , very poisonous venom. Think about |
|
| 51:19 | people get bids. Small fraction die they're not treated properly and fast enough |
|
| 51:28 | with things that acetyl Coley and things , uh, encourage proper Colin Arctic |
|
| 51:37 | . So blocking the release is also . Now, the other reason why |
|
| 51:42 | is here there's actually two types of before I talk about other toxins is |
|
| 51:48 | two types of parties. Why do have a boat office party. I |
|
| 51:52 | to ask him. So you come and you get a a glass of |
|
| 52:01 | and you sit down because you're here Botox party. What is a Botox |
|
| 52:10 | ? Why would you have a Botox that sounds like flaccid paralysis on its |
|
| 52:18 | ? It ISS. So Botox, you injected locally, will paralyze your |
|
| 52:24 | locally. And there's two types of going on with Botox. Think |
|
| 52:29 | One of them is a party because of them is a cosmetics party and |
|
| 52:33 | to improve your looks June inject the and then prevents the release of neurotransmitters |
|
| 52:42 | the contraction of the muscles. And contraction of the muscles is when you |
|
| 52:50 | formation of the wrinkles. So Botox can alleviate their parents or the formation |
|
| 52:58 | the wrinkle slow down the formation of wrinkles. And of course, |
|
| 53:01 | lot of times is also being used fillers and people that get injections in |
|
| 53:07 | lips with fillers and the Botox smooths and fills out the lips. But |
|
| 53:13 | also may have difficulty speaking on pronouncing because difficult fund moving muscles around the |
|
| 53:24 | right after the injections and the second is treatment off migraines, actually. |
|
| 53:35 | Botox injections are approved for FDA approved treatment off off migraines, you |
|
| 53:47 | also seeing comments about spasms and the six eso if you have some kind |
|
| 53:57 | ah lockup of the muscle or enough of the activation. Uh, |
|
| 54:03 | much sorry. Activation of the muscle spasm information because of the too much |
|
| 54:09 | the neurotransmitter release. That's exactly what is if you constantly d polarized the |
|
| 54:14 | that muscle constantly contracted. How long you contract your biceps muscle continuously? |
|
| 54:22 | for that long. And then then happens if locks up into into spasm |
|
| 54:28 | behavior and to tetanus muscle tetanus and cannot activate and contract that muscle |
|
| 54:35 | So in effect, the breathing can many different things can affect the |
|
| 54:39 | the muscle function itself. So we're about the continuing its talc alone in |
|
| 54:45 | chapter is Muslim. So now there other things that will affect posture, |
|
| 54:52 | everything that we're talking here with black and with black widow venom and studio |
|
| 55:00 | bunch of line, um, We're talking about pre synaptic vesicles release |
|
| 55:06 | Taiwanese Carver will contain ALPA Bouguereau which can affect parts synaptic aceto Colin |
|
| 55:13 | process unethical it will be affecting the . Remember, the whole system consists |
|
| 55:19 | pre synaptic synthesized neurotransmitters, what happens the synaptic cleft and then passed synaptic |
|
| 55:27 | . And then we also have organophosphates are synthesized by humans is not only |
|
| 55:35 | , but there's a lot of synthetic that humans introduced for both purposes for |
|
| 55:43 | purposes and also for destructive purposes for purposes, weapons of mass destruction that |
|
| 55:53 | affect the breakdown if it's foul calling the synapse. So I'm gonna jump |
|
| 55:58 | a couple of slides and explain this you. So in order for us |
|
| 56:03 | understand this, we actually have to the synthesis and degradation and recycling of |
|
| 56:09 | Seattle cooling. Still, Colleen is and colon Arctic neuron, so there's |
|
| 56:16 | , then have the ability thio to the seal. Colin Colin Ergic neurons |
|
| 56:22 | synthesize Coleene, still calling from Maciel Coetzee. When the too common |
|
| 56:28 | together, that's the way you They chat, they talk to each |
|
| 56:33 | and they form a pseudo Colleen. child is calling acetyl transfer rates seal |
|
| 56:40 | through its The steel calling transporter will loaded up into these popsicles once in |
|
| 56:46 | vesicles, and there's deep polarization to . Colin will get released into Sonata |
|
| 56:53 | in the Neuromuscular Junction that we in particular the skeletal muscles. We |
|
| 56:59 | have nicotine nick acetylcholine receptors, which receptor channels in the heart. We |
|
| 57:08 | that there is a must carry nick , acetylcholine receptors in the central nervous |
|
| 57:16 | . We have both nicotine nick channel receptors and must Quranic, which are |
|
| 57:23 | protein coupled receptors that do not conduct . They're not channels that will discuss |
|
| 57:29 | in greater detail in the future So once that's a tall Colin gets |
|
| 57:35 | , it will bind to the will discuss the fact once that binds |
|
| 57:39 | these receptors, and in the cleft, acetyl Colin will get broken |
|
| 57:46 | by a C H E. A Colin Nestor race seal colonist arrays would |
|
| 57:53 | seal. Colleen will break it down Citic acid and Kohli and this Colleen |
|
| 58:00 | will then get transported through sodium and transporter back into the pre synaptic terminal |
|
| 58:12 | once in the prison uptick terminal with help of Chat, it will form |
|
| 58:18 | Seal Colin from Colin and the Civil . A. Okay, so this |
|
| 58:22 | the cycle. Then the Siegel Cohen get loaded up in the neurotransmitter bicycle |
|
| 58:28 | and released once again. So when put here is actually most of the |
|
| 58:36 | now we're moving on to yet another of Alzheimer's disease. You are two |
|
| 58:41 | today about Alzheimer's disease. Colin Ergic number one number two. The Mechanisms |
|
| 58:49 | Action of Alzheimers medications. Most of Alzheimers medications. Most of the Alzheimers |
|
| 58:56 | block at the towel Colonist Aries. they block, it's a towel. |
|
| 59:02 | Esther is called Qala necessaries inhibitors on for different medicines and especially drug and |
|
| 59:10 | interactions for certain pharmaceutical medications, you hear if you are taking sense. |
|
| 59:16 | , I m. Cullen ergic inhibitors za towel calling Nestor race inhibitor. |
|
| 59:23 | if you had taken Colin ergic that's a tactical investors inhibitors that block |
|
| 59:28 | a towel. Colin s stories. increases the presence of a subtle called |
|
| 59:34 | the synaptic cleft. We also refer it as bio availability. How much |
|
| 59:39 | this acetylcholine is available, And so you block the degrading enzyme acetylcholine esta |
|
| 59:47 | . Then you prolong the duration of . Go Colin stays in the synoptic |
|
| 59:53 | , and you also increase the concentration the Seattle Colin in the synaptic |
|
| 59:59 | Mhm. So a solo colonist Aries that are Alzheimers medications can only slow |
|
| 60:07 | . The progression of the disease they do not is not a cure for |
|
| 60:14 | disease. It's on. Lee slows progression of Alzheimer's disease, and it |
|
| 60:19 | not very effective. It's quite a medications, multibillion dollar industry. Think |
|
| 60:27 | this. Just look at the What else can you do? So |
|
| 60:32 | these Colin Arctic Narrows? What happens you don't have acetylcholine? And you're |
|
| 60:37 | the brains with acetyl cholinesterase inhibitors? no single Colin Extra production of |
|
| 60:49 | Call him. That's one way to , Terry. Maybe transporters, maybe |
|
| 60:58 | it faster, maybe doing something This is just to fix the seal |
|
| 61:05 | problem. What about the plaques? about the tau tangles? And that |
|
| 61:11 | exactly a problem with a lot of neurodegenerative neurological disorders. There are multi |
|
| 61:20 | . You have the plaques that of and affecting uh, Exxon's. So |
|
| 61:27 | got to go and bust the How you gonna bust the plaques? |
|
| 61:30 | calcified black sitting there in the How you gonna target them? How |
|
| 61:36 | gonna drive some medicine to drive to plaque to busted? But you |
|
| 61:40 | You guys will. You will create medicines. How do you untangle the |
|
| 61:47 | tubules? You know, maybe some we'll be able to rewire the micro |
|
| 61:54 | , restructure the micro tubules inside Wa wa. That would be really |
|
| 62:00 | . So you're still getting all of transport? Maybe now it's reduced the |
|
| 62:06 | or the severity of the disease. cells, David, This ultimate |
|
| 62:12 | maybe new cells that produce a single , specifically program. Now you have |
|
| 62:21 | deal with. Okay. Now let's that cell into a network and make |
|
| 62:27 | that the brain and the immune system recognize it as a foreign invader and |
|
| 62:34 | that part of the brain altogether. do you have the stem cells, |
|
| 62:39 | ? Hook up, form the synapses not change your mind? Right. |
|
| 62:45 | Adam is one thing. How you is another thing. We haven't gotten |
|
| 62:51 | yet. Do stem cells change cognitive ? MHC is introducing the surface. |
|
| 62:59 | . I mean, this is how think about it now, just But |
|
| 63:02 | let me ask you this this So guys know something about Alzheimer's disease |
|
| 63:09 | I mean, it's not a It's kind of like a statement, |
|
| 63:12 | I read it. All right, thinking you're thinking about pathology. The |
|
| 63:18 | . I know something. When you this course you thought is dementia and |
|
| 63:21 | just forget things. Now you know behind it. You know some symptomology |
|
| 63:28 | it, you know, molecules You know, medicines that are used |
|
| 63:32 | treating Alzheimer's disease. You know that is not very effective and it's |
|
| 63:37 | The progression of the disease is but it would be nice Thio find |
|
| 63:41 | cure some day and that may come a completely different angle. So before |
|
| 63:46 | talk too much and run over our , just want to mention that if |
|
| 63:50 | look at the system, then you affect acceptable cobian release. You can |
|
| 63:55 | the civil code in Boston optically you can affect the levels of a |
|
| 64:00 | Colin and the synaptic cleft. And is what the organophosphates do and the |
|
| 64:06 | medications equally so. But organophosphates, nerve gas is that being produced and |
|
| 64:13 | in warfare have been used on humans being used not so long ago. |
|
| 64:18 | is a real problem they used by that are used by Russians to poison |
|
| 64:24 | opposition. Any political opposition very well by Germans, they can determine what |
|
| 64:30 | and Russia making some of these nerve and nerve gas is they used |
|
| 64:36 | 19 nineties Tokyo nerve gas subway attack killed dozens of people and poisoned many |
|
| 64:45 | organophosphates. When get released, there's construction of the muscles. There is |
|
| 64:49 | blockage breakdown, a style polling. a constriction off the pupils, and |
|
| 64:56 | that construct contraction basically and spasming nonstop you prevent from the proper contraction and |
|
| 65:07 | after dark rang and attacking off the system. Attacking off the style Coleene |
|
| 65:16 | in s stories and leading thio death it is not treated, uh, |
|
| 65:23 | it is not treated immediately and so lot of military standard issues to have |
|
| 65:31 | antidote for nerve gas is ah, which is basically anti colon ergic and |
|
| 65:41 | . It's a combination I will actually toe link about that. It's a |
|
| 65:46 | of drugs that allowed to alleviate this up from organophosphates, but it has |
|
| 65:52 | be delivered within a couple of And I had honor of teaching |
|
| 65:58 | um, Special Forces medic in my that served in this class neuroscience collapse |
|
| 66:06 | served in Fallujah and had a situation organophosphate poisoning and Fallujah and rescuing soldiers |
|
| 66:14 | having the standard issue antidote injections and saving their lives. Because if you |
|
| 66:23 | are affected, only sometimes you're Before you realize that you have that |
|
| 66:27 | answer could be very fast. Once go into a situation where your breathing |
|
| 66:33 | , the fact that your mates can help you get out of it. |
|
| 66:38 | , organophosphates. They're also used uh, pesticides. Surprisingly, it |
|
| 66:45 | be used for suicide purposes and in Americans. Very strange thing. |
|
| 66:50 | but that is it. So you all of these interesting nature components that |
|
| 66:57 | the seed locally in system signaling human , medical components, Alzheimers medications, |
|
| 67:09 | weapons of mass destruction, warfare components and industrial applications. So you can |
|
| 67:18 | that those are kind of a world co evolved. They really should not |
|
| 67:24 | across each other special purpose. And focus should be on this. How |
|
| 67:30 | I help and solve the problem off disease? So I'm sorry for running |
|
| 67:36 | time. A little bit. I'm to stop here today. Thank you |
|
| 67:40 | much for being here. I will you. Um, on Thursday. |
|
| 67:49 | Look at your questions that you missed the exam. We'll discuss your exam |
|
| 67:55 | you will have mawr information on the . Thank you very much. And |
|
| 68:00 | talk to you on |
|
