| 00:02 | So welcome back. This is It's lecture 11 off neuroscience, and |
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| 00:11 | continuing discussing neurotransmitter systems and nurse transmitter types. If you recall, we |
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| 00:23 | Neuromuscular Junction and the discovery off Siddle in the Neuromuscular Junction, Vegas Still |
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| 00:32 | . Then we discuss some of the features off the neuro muscular junction at |
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| 00:40 | skeletal muscles. And now, most the time, we'll spend focusing on |
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| 00:47 | neuronal communication and neuronal synaptic transmission and review the major neurotransmitter systems that we |
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| 00:58 | where amino acids that included GABA glutamate glistening gabba being the major inhibitory neurotransmitter |
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| 01:07 | the cerebral and the C. N glutamate being the major excited during your |
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| 01:14 | in the CNN's glycerine being inhibitory neurotransmitter the spinal cord. But in the |
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| 01:22 | Broom. In the higher order lie scene is a co factor to |
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| 01:29 | receptors, so there exceptions to the . And as we discussed, the |
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| 01:35 | of the cell on how the cell to a given chemical depends on a |
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| 01:44 | and receptor subtype that that particular cell a means arsenal Colleen, dopamine, |
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| 01:54 | , histamine, norepinephrine and serotonin peptides the sister kind and die an |
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| 02:01 | And Kath, Elin and Macedo let's see the last fertility mate. |
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| 02:07 | a peptide. Why so matter? Substance B That trope in releasing hormone |
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| 02:13 | are active intestinal polyp that side the P. Then we talked about the |
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| 02:19 | that there's probably different packaging. As was a Zai hinted at you with |
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| 02:26 | homework question. What is the difference how neurotransmitters and Europe appetizer being |
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| 02:32 | It was really the question. What the difference between neurotransmitter vesicles and then |
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| 02:39 | ? Um, vesicles. And so get into in the second. And |
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| 02:45 | we're talking about these neurotransmitters, and is being packaged in the vesicles, |
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| 02:51 | a particular structure, vesicles having the hollow inside that gets backed with the |
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| 02:59 | . And then we said that there other neurotransmitters that we've already discussed, |
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| 03:05 | as a T. P. Is energy molecule and a dentist, and |
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| 03:10 | can also serve as a neurotransmitter, the core of the T. |
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| 03:15 | A. Delasin is also a neurotransmitter the brain on what we have. |
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| 03:21 | addition to these air mentioned the very classes off gasses. This is an |
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| 03:28 | oxide and carbon monoxide of conservative near . They're not being packaged into |
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| 03:35 | and then the substances that are living . They're also not being packaged and |
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| 03:41 | in vesicles. But brother, their or member insoluble, that can traverse |
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| 03:46 | cellular membranes and target their respective Carbonic acid. Endo cannabinoids there, |
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| 03:53 | Cassidy is a precursor. Also a off, um, degradation of Endo |
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| 04:03 | . And we discussed Ananda might into G and also discussed, uh, |
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| 04:09 | cannabinoids very briefly. And we'll have lecture on the story down in this |
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| 04:14 | expanding more about the cannabinoids and then cannabinoid system as a whole. |
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| 04:21 | so no, some of these important that we're making here on the slide |
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| 04:27 | As we learn more about synaptic neural , you'll understand that Gavin glutamate is |
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| 04:34 | being released. It's really very Very fast acting system means and tough |
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| 04:40 | often require higher levels of activity and levels of energy as a whole to |
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| 04:47 | be released, and that higher levels activity come from the fast activity of |
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| 04:52 | amino acid neurotransmitters that condemn organized networks cells that can start releasing a means |
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| 05:00 | baptized as well. So we discussed that we have to think about these |
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| 05:08 | the C. N s. Representing behavior. Settle Colin in the muscle |
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| 05:13 | a contraction of the muscle. It's output of your motor command. Your |
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| 05:17 | commands that I want to contract my muscle. So you contract your biceps |
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| 05:22 | the Seattle coolly and that comes from spinal cord from the motor and they're |
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| 05:26 | the spinal cord gives that contraction signal the muscles. But when you talk |
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| 05:32 | these neurotransmitter substances that are released in C. N s, you're now |
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| 05:38 | about emotional. You're talking about behavioral . You're talking about sensory information |
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| 05:44 | You're talking about abstract information processing and complex things that are associative but can |
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| 05:52 | be quite specifically associated with the specific systems and as well as the dysfunctions |
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| 06:01 | neurotransmitters. I learned and be specific certain neurological neurodegenerative disorder. So |
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| 06:10 | it'll call me dysfunction in the N s and the Colin Ergic circuits |
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| 06:15 | the in the frontal cortex and the result in memory loss result in many |
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| 06:22 | problems that are features of Alzheimer's So Colin Ergic signaling is impaired in |
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| 06:30 | CNS. In Alzheimer's disease, ergic signaling is impaired with discussed in |
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| 06:37 | neurodegenerative disorder, which is Parkinson's And we also said there is a |
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| 06:44 | disorder association with the opening and receptor and schizophrenia so they can have a |
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| 06:52 | disorder. You can have a neuropsychiatric neuropsychiatric disorder and not necessarily degenerating or |
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| 07:00 | the neuron. So they'll prolonged, , on extreme cases off schizophrenia. |
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| 07:07 | can result in the in the shrinkage self issues as well. Um, |
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| 07:16 | we will discuss more and more of neurotransmitters and neurotransmitter systems, and we |
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| 07:20 | pay more attention to some of them than others. And therefore there's will |
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| 07:26 | reflected in these questions on the quiz the exam number two. Uh |
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| 07:36 | And your homework question waas the difference the, um, secret Ori Granules |
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| 07:45 | neurotransmitters. And so, if you at it, it most of what |
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| 07:51 | gonna talk about neurotransmitters. Most of newer transmitter cycling in these yellow synaptic |
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| 07:59 | here in this pre synaptic external In this cartoon, most of these |
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| 08:06 | and their their their synthesis and a of their extra psychosis, of |
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| 08:11 | And then endorse. It does is fill ing. Recycling happens at the |
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| 08:16 | of the synapse happens at the level the synaptic terminal. So if you |
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| 08:21 | in into the neurotransmitter vesicles there of course, they have neurotransmitter molecules |
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| 08:27 | these red dots. Inside, they their own plasma membranes and there is |
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| 08:32 | transporter protein. There's gonna be a protein on the membrane of this off |
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| 08:39 | testicle, essentially bringing and reloading these vesicles with these red chemical. They |
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| 08:46 | transmitted molecules, uh, for baptize this sort of one of the reasons |
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| 08:55 | we were discussing and I just mentioned take longer Thio release require higher levels |
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| 09:03 | activity and energy because they are unlike transmitters, they're not synthesized and stored |
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| 09:12 | the synopsis and the synaptic terminals. instead there's a precursor peptides that are |
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| 09:19 | from the rough and a plastic particular through the Golgi apparatus processing in making |
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| 09:27 | secret er Granules that will contain these peptides are transmitters. And the interesting |
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| 09:35 | about these neurotransmitters, depending on the of activity in the system these |
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| 09:43 | these secret Terry Granules are not going took sternal terminal. So they will |
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| 09:51 | mawr, uh, less discriminatory. throughout the external extent throughout the external |
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| 10:02 | . It's a different kind of So you need really to have high |
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| 10:08 | of activity. Then the synthesis is at the level of the Somare rather |
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| 10:14 | the synapses for the peptides. And the release doesn't have this very specific |
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| 10:21 | , very special locations and spaces but somewhat gets released along the extent |
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| 10:30 | the Axiron by the fusion off the , the to the membrane. So |
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| 10:36 | will not concentrate on trying to understand the secretary gradual release and tapped I |
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| 10:43 | . But we will focus on this here on the neurotransmitter release. But |
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| 10:49 | is the difference that you should know the vesicles of Secretary Grandal's how they're |
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| 10:55 | . Obviously with respect to the secretary , also, you need to be |
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| 11:00 | supported, but they can also be along the external extent. And unlike |
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| 11:07 | of bicycles, they're not really stored in external terminals ready to be |
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| 11:12 | but rather produced on demand synthesized on and released on demand with high levels |
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| 11:20 | activity. So if you look at we're looking at here. Actually, |
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| 11:28 | is This is this is this is the neurotransmitter at the bottom, |
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| 11:33 | Looks like this is what the snow transmitted The bottom, right. Looks |
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| 11:39 | Looks like a Harry Harry Harry tennis that was laying underneath the couch for |
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| 11:46 | years and gruesome. Interesting protrusions off that was very complex so that the |
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| 11:54 | are quite complex and they have a off proteins and they have their own |
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| 12:00 | by which they can be activated and which they can, um, facilitate |
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| 12:07 | exhaust psychosis exercise. Hostess of the . So these air some some of |
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| 12:13 | very key, very important concepts that have to understand. Uh, everything |
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| 12:22 | we studied in the first section was action potential. And we said, |
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| 12:25 | potential that travels down the action reaches central terminal. And then I left |
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| 12:30 | hanging. And then what happens? then what happens? So when action |
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| 12:38 | reaches the external terminal, deep it causes deep polarization. This |
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| 12:46 | synaptic deep polarization opens up voltage gated channels in this action potential. So |
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| 12:57 | flux of sodium and potassium and creating action potential. The deep polarization and |
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| 13:02 | arrival of action potential and external terminal up voltage gated calcium channels, those |
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| 13:10 | educated calcium channels that air very densely in the active zones where there's high |
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| 13:20 | off neurotransmitter vesicles, congregating, hanging , being primed and ready to fuse |
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| 13:26 | get released into the snappy clap. calcium comes in, calcium comes in |
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| 13:34 | calcium is absolutely necessary, and calcium are concentrated in the present optic terminals |
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| 13:44 | close to the active zones. Now about it the cells and neurons. |
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| 13:51 | said they have multiple different channels and have multiple voltage gated, different |
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| 13:58 | And we said each channel has its ivy plot. But we also said |
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| 14:04 | sub cellular early or within cells, channels and these receptors will be found |
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| 14:11 | very different locations, that there is strategy that neuron needs to strategize. |
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| 14:18 | it is the acts on our acts initial segment, it better have low |
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| 14:24 | sodium channel, so it's not going produce the action potential. It also |
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| 14:29 | I have both educated potassium channels or not going to re polarize and going |
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| 14:34 | this never, Uh, never, re polarizing state properly, never able |
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| 14:40 | open more sodium channels. So from channels is a whole lot of |
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| 14:47 | Gated calcium channels and acts on initial . Not so much. But if |
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| 14:53 | look now at the song all terminal two, these active zones in external |
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| 15:01 | will be loaded with voltage gated calcium because calcium is a necessary component is |
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| 15:07 | necessary signal in order for the protein that is affiliated with the synaptic classical |
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| 15:14 | the protein complex that is on the side off the pre synaptic plasma |
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| 15:22 | the calcium initiates the interaction of these to protein complexes, the binding of |
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| 15:29 | synaptic vesicles, the fusion to the membrane and release of neurotransmitter. So |
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| 15:41 | vesicles, they have calcium sensors. there is not enough calcium, these |
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| 15:48 | secular sensors such a synaptic stagnant So this is a simplified version saying |
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| 15:56 | you have a vesicular sneer, complex and complex, and you have trans |
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| 16:02 | snare complex and you have calcium channels the vicinity. And when there is |
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| 16:08 | of calcium, there is another sensor senses that calcium concentration has risen around |
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| 16:16 | synaptic vesicles, which now promotes for sneer proteins from the vesicles thio bind |
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| 16:24 | the trans membrane snare proteins. Bring plasma membrane lipid molecules physically in contact |
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| 16:33 | each other, which causes the fusion the vesicles to the plasma membrane and |
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| 16:41 | of the neurotransmitters in the snappy Finally, after this happens, no |
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| 16:50 | vesicles and these plasma membrane pieces, do not get just wasted. They |
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| 16:57 | actually fused the back and recycled back the present optic terminal. In number |
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| 17:04 | , you have end of psychosis. as you can see now, these |
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| 17:09 | are do not contain as much or of the neurotransmitters. So in order |
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| 17:16 | them to go from four into the , fully primed vesicles ready to |
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| 17:24 | they will have to get refilled with neurotransmitter of interest before they go back |
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| 17:31 | can do the cycle of exercise it fusion exercise. It assists and endo |
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| 17:39 | . And so to visualize new transmitter . There is very interesting techniques that |
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| 17:47 | used historically, and this is an microscope picture here on the left that |
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| 17:54 | these little dots that studied instead the number and the rows of these little |
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| 18:00 | . So these were presumed calcium channels the pre synaptic side, both educated |
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| 18:05 | channels. And indeed, you're seeing creators, what these greater size that |
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| 18:12 | looking actually into those vesicles to So you're looking into an opening that |
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| 18:19 | forming as the vessel Kalis using on other side of the plasma membrane. |
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| 18:24 | it's creating this opening this crater. so you have the exercise toda confusion |
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| 18:30 | . Everywhere you see these craters next the calcium channels. Thanks. This |
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| 18:36 | an electron microscope just to remind you a gap junction, remember where the |
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| 18:42 | Junction s? So we always have remember that visualizing synapses. We also |
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| 18:48 | to visualized electrical synapses here we're visualizing synapses. So tall diffusion of the |
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| 18:55 | here we're simply visualizing these very large Junction pro dance. And as I |
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| 19:02 | before you see how there is a between the membranes were two cells come |
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| 19:11 | close to each other only 3.5 nanometers the two plasma membranes and allows with |
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| 19:18 | heavy channels These connects and connects on Junction heavy channels to form continuous Gap |
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| 19:26 | or electrical synopsis between the cells. remember the features of this electrical synapses |
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| 19:32 | very fast activating the only transfer a of that signal or that ion. |
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| 19:41 | they are also a lot for the of small molecules, like secondary messengers |
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| 19:46 | cycling, campy and a very important synchronizing in time. Large networks, |
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| 19:55 | cells through gap junctions, large networks neurons and also very important for special |
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| 20:04 | of potassium for Astra size of glial will also have these large gap junctions |
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| 20:11 | will allow them to siphon and uh, diffuse potassium. Essentially not |
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| 20:23 | for potassium concentration. Thio increase locally a long time, and that happens |
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| 20:29 | through the flow islands through the Judge to usual eyes this you know |
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| 20:34 | have to do some very interesting but we now also know. And |
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| 20:40 | known for 50 60 years actual structure the plasma membrane, that there's an |
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| 20:47 | face and that there is a P off the off the plasma membrane. |
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| 20:53 | inside faces off the this dual foster off the possibility of bi layer that |
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| 21:00 | can see some trans membrane proteins and is mentioned here. Freeze fracture |
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| 21:07 | So it was very interesting technique, what would you do if you wanted |
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| 21:11 | split the plasma membrane? If you to take the two layers and split |
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| 21:15 | apart, what would you dio? what they thought that they should do |
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| 21:21 | the fifties and sixties was thio stimulate fast to stimulate, or, if |
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| 21:29 | wanted to see vesicles, release or use freeze, fracture and freeze the |
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| 21:33 | membrane and place that frozen piece of plasma membrane and drive a little |
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| 21:41 | a little glass or metal needle electrode close to this to this piece of |
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| 21:47 | under the microscope and then walk around table and say a chance and do |
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| 21:56 | little bit of hope hocus pocus and jump in the room and hopefully the |
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| 22:04 | vibrate just enough so that the needle slip in between the two layers of |
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| 22:10 | fastball it as an open up the . So this is called freeze fracture |
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| 22:16 | . You will freeze plasma memory that fracture it if you're lucky enough and |
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| 22:22 | the right kind of jumping a I'm not joking because people have have |
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| 22:27 | very interesting superstitions when it comes to complex experiments. And this is an |
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| 22:33 | where you're trying to split possible number and to you have to use res |
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| 22:39 | and you have to fractured into. it was accomplished. Also down below |
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| 22:45 | shown here is that we talked about in the past and we said most |
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| 22:51 | the states that we discussed in the were to describe the anatomy off the |
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| 22:58 | . Golgi stain, missile stand, peroxide days. Okay, those |
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| 23:06 | the stains that we said they will us to visualize neurons that will allow |
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| 23:11 | toe understand the connectivity of the processes this neurons. In case of |
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| 23:16 | stain missile stain was used for the of architecture in the broad Manet |
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| 23:22 | And then, since about 30 40 ago, we've had states that are |
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| 23:28 | to ions. They're sensitive. Thio in ionic concentrations that you can observe |
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| 23:35 | the level of a single sour than level of a single synapse. And |
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| 23:41 | what is pictured here? These very colorful images, his calcium signaling and |
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| 23:50 | the left, these little mountains, mountains with yellow and red tops. |
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| 23:56 | they mean is the red color. there's a scale on the right. |
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| 24:01 | color indicates concentration of calcium. So lower the concentration, the more blue |
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| 24:10 | you're going to see. And then it gets green, it has mawr |
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| 24:15 | . It has more on if it red, that means locally in that |
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| 24:21 | area, there's a lot of calcium . So these die this particular |
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| 24:28 | and these guys were called calcium sensitive . You observe them through a |
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| 24:34 | so you need powerful microscopes. You to have either large synapses, a |
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| 24:39 | sensitive resolution microscope. You have thio that dye into the system and hone |
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| 24:49 | on a single synapse and then observed in this guy. So there's calcium |
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| 24:54 | guys. There is, uh, . Potassium sensitive dies, ion sensitive |
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| 25:02 | . There's also dies that a voltage dies. And so I will. |
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| 25:07 | will show you elect a movie What? Ah, voltage sensitive |
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| 25:13 | Signaling in particular looks like, uh another lecture. But let's look more |
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| 25:20 | at this calcium sensitive guy and the on a is neuron that is in |
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| 25:28 | steady state. That means it's not active. Dismembering is fluctuating, but |
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| 25:34 | is no massive physical fusion. Maybe you see one red peak. Maybe |
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| 25:40 | enough of calcium concentration to fuse one . But for the synapse to be |
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| 25:50 | , it's not enough for one Ethical diffuse and releasing neurotransmitters. Central |
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| 25:57 | system synopsis Unlike Neuromuscular Junction that we about central nervous system synopsis a |
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| 26:07 | Neuromuscular Junction one synapse produces a signal 70 million volts. Guaranteed action potential |
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| 26:15 | from rusting member and potential in order reach the threshold for action potential, |
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| 26:20 | only need a deep polarization of about million volts. It's different with |
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| 26:30 | Um uh, potentials. In the nervous system, a single synapse in |
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| 26:39 | CNS in the cerebral cortex produces a of only 0.5 million volts in |
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| 26:49 | and you still have to dip polarize sell by 20 to 25 million balls |
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| 26:54 | about minus 70th resting membrane potential to 45 25 million volts. The one |
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| 27:02 | only half a mil a vault. how many exciting story synopsis you |
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| 27:09 | Typically, you need to engage in to dipaula, rise and neuron to |
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| 27:16 | for action. Potential generation take 25 have also divide by half a notable |
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| 27:28 | synapses These exciting story synapses remember that are receiving excite interest synopsis and inhibitory |
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| 27:37 | at the same time. So that mean that maybe hundreds, maybe thousands |
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| 27:41 | synopsis, not just one here on image Here, where we're talking about |
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| 27:47 | , we see many of the calcium , but it's one synapse. But |
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| 27:52 | order for the synapse to produce a enough signal one synapse when it releases |
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| 27:59 | process in optical it all and causes million volt deep polarization pretty significantly, |
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| 28:08 | increases to about 200 micro mola be and on B, you're seeing an |
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| 28:17 | synapse. So in B, you're that all of a sudden these blue |
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| 28:23 | turned into Red Valley and this red represents increases in calcium concentration that is |
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| 28:33 | thio neurotransmitter fusion to the plasma membrane exercise Hostess of the neurotransmitters. Uh |
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| 28:43 | . And in fact, there is technique now dates back about 15 |
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| 28:49 | evanescent for essence, that will allow visualize the fusion of a single |
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| 28:56 | So here we're looking at the increases calcium fluctuation and on the left were |
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| 29:02 | at the fusion off many vesicles. there is a technique that will actually |
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| 29:07 | you to zoom in and study the of the fusion of a single |
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| 29:12 | And so, for this vessel call refuse to the plasma membrane. Calcium |
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| 29:17 | to come in. You have to the polarization. Calcium needs to |
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| 29:21 | Calcium will then promote the fusion off vesicles and exercise it assis. And |
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| 29:27 | the vesicles needs to be recycled. so for the synapse. If the |
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| 29:33 | gets jolted in a lot of neurotransmitter released. Lots of vesicles fuse for |
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| 29:39 | synapse to come back to normal. about 10 to 12 seconds in |
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| 29:47 | So while the signaling is very fast the order of milliseconds, you have |
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| 29:54 | potential. The last one to Synaptic DeLay, as we discussed which |
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| 29:59 | in the chemical neural transmission, is few millisecond delay, but then, |
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| 30:05 | the synapse to reset fully. If jolted it and released a lot of |
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| 30:11 | neurotransmitter, where to reset 100% for vesicles to get refilled, recycled and |
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| 30:18 | again to be released. You need minimum of 10 to 15 seconds in |
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| 30:24 | rate. So that tells you that a very strong activity, certain |
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| 30:30 | maybe an active for quite a long in neuronal language is quite a long |
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| 30:39 | . And here again, this is from a boat from neurons to |
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| 30:43 | from neuron to brain. I recommended work was done. Uh, Rodolfo |
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| 30:50 | ISS Laboratory, uh, then studying dynamics and the secular release and understanding |
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| 30:58 | exercise toast is visualizing exercise doses, not actual vesicles rather than ions and |
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| 31:05 | ionic concentrations that are correlated with the for release in the neurotransmitter system. |
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| 31:15 | also have something that doesn't happen in Neuromuscular Junction. You have a partial |
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| 31:21 | release. That means that you can either complete or partial neurotransmitter release. |
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| 31:28 | that's another difference between seeing that synopsis neuromuscular junctions. Quantrill release Quantrill Release |
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| 31:37 | to the fact that these vesicles will a certain number of neurotransmitter molecules. |
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| 31:43 | when I showed, well, this now, once it's end of site |
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| 31:50 | back into the pre synaptic terminal, doesn't seem to have many neurotransmitters, |
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| 31:55 | vesicles, and it's because there's a quanta certain number, their transmitters. |
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| 32:02 | supposed to be no vesicles that quanta between 2 to 4000 of molecules. |
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| 32:08 | so, in a way, it's release. If you have a full |
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| 32:13 | complete fusion and complete release off the , you will get a quantum |
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| 32:18 | And that's where we can say that excited. Her synopsis always equal to |
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| 32:23 | 0.5 million volts off deep polarization. optically, because the neurotransmitters will |
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| 32:31 | will contain a certain number. The will contain the exact they're similar number |
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| 32:38 | their transmitters, and if it is filled out, that will not have |
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| 32:45 | number. But let's look at So you have the early end of |
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| 32:48 | and the synapse you have neurotransmitters that uploaded into this vest ical and this |
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| 32:56 | This gets docked close to the plasma the plasma membrane. 80 p will |
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| 33:04 | the prime ing or bringing that medical closer. That's what you need. |
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| 33:09 | in the synapse. Issa's well calcium will now turn on the calcium sensors |
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| 33:15 | the vessel. Khan will say, , you ready to fuse protein, |
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| 33:20 | , complex visitors, T's nurse and in some instances, you only |
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| 33:28 | fuse, and the Fusion four opens partially. And then diffusion forecloses very |
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| 33:39 | , and this vesicles returns into a position, and from that prime position |
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| 33:47 | can be cycled back to go back chill out a little further, get |
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| 33:53 | with some 80 people, prime you because we've released a little bit of |
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| 33:58 | neurotransmitter, and now you need to partly reloaded before we can really release |
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| 34:04 | . So this partial fusion on partial of the Fusion poor is referred to |
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| 34:10 | Kissin Ram. It's really not much is just a little puck on the |
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| 34:17 | . It's not really committing to deep here. Just a quick puck on |
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| 34:21 | cheek, a little bit of still the nerve transmitter, partial fusion, |
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| 34:31 | I'm gonna run to get Dr Primed . So if it so happens that |
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| 34:41 | is enough of calcium and the factors of the time there will be full |
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| 34:48 | of neurotransmitter. In that case, fusion poor will fully dilate all of |
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| 34:54 | chemicals. The whole neurotransmitter quanta is to get released into the synoptic |
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| 35:04 | So this is committing Thio fully open fusion for fully dilate. To release |
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| 35:16 | transmitters into synaptic laugh. But no transmitter. Vast ical gets |
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| 35:24 | So these vesicles this plasma membrane and a vest ical gets coated with Clary |
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| 35:32 | . It's another coating molecule, and it gets recognized as an empty vessel |
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| 35:40 | . Hello? I'm empty so two can happen. Thio An empty vesicles |
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| 35:46 | by this green wheel off Claritin can on. Use a teepee and high |
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| 35:54 | . Grady in thio Get acidified on inside. Okay, so use up |
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| 36:02 | to drive protons inside the vesicles and that into the early end. This |
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| 36:09 | for re processing or it can be vesicles will be acidified again with a |
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| 36:21 | driving protons inside, making the inside the vest ical various city. And |
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| 36:29 | is certification is necessary for the neurotransmitter . To now load up or to |
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| 36:40 | or to re uptake uptake. These back into the vast circles not going |
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| 36:48 | early under zone, but going back the region where they can can be |
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| 36:53 | , primed and go through the exercise and end of Sighters. Aside from |
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| 37:01 | , yeah, so they're taking a from here is that there is partial |
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| 37:07 | complete neurotransmitter release that complete neurotransmitter released in the Quanta. A certain number |
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| 37:14 | their transmitter released that, uh, the fusion, the area of the |
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| 37:22 | membrane increases and this membrane piece of to the vest. Ical gets |
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| 37:30 | coded and recognizes an empty vesicles that gets acidified and taken back through the |
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| 37:37 | of Indo site owes exercise. It and and then cytosine. Okay, |
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| 37:44 | that's quite interesting. That's quite interesting how it is happening on. But |
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| 37:52 | , it is very interesting to think some electrical properties of the plasma membranes |
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| 37:57 | we talked about. So which variable electrical properties is very much dependent on |
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| 38:08 | membrane area of the south. We about resistance. We talked about |
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| 38:21 | We talked about current, talked about mountains. We talked about capacitance. |
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| 38:30 | talked about RTZ f We know it you increase. Somebody knows that |
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| 38:47 | The area. Yes, the more . The south Uh, yes, |
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| 38:58 | higher his resistance, the smaller that . But it's the opposite for |
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| 39:06 | So once you actually think about you take plasma member in these vesicles |
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| 39:13 | you're fusing hundreds of these vesicles, increasing the surface area of the plasma |
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| 39:19 | . You know how can hold more . So you're really very much affecting |
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| 39:24 | capacitance properties. Uh, capacities properties the off the plasma membrane on bicycle |
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| 39:32 | would actually very much equate to changes capacitance if you were to measure capacitance |
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| 39:39 | thes active cells. All right, now we are again learning a lot |
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| 39:49 | very interesting topics in this course, I starts a little. I'm liking |
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| 39:59 | course more and more as I start introduce more and more interesting material to |
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| 40:08 | course, Uh, every year, semester, almost, Uh, and |
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| 40:15 | , you know, this course is just you're not just covering basic neuroscience |
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| 40:21 | learning. Oh, these air the . This is how this works. |
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| 40:25 | remember RTZ F minus 90 is potassium . It's also not just understanding the |
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| 40:36 | , the physiology, understanding some which will come back to more and |
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| 40:41 | anatomy toward the end of the second , will place it back all within |
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| 40:46 | context. These circuits in this communication themselves. But we're also learning about |
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| 40:53 | neurodegenerative disorders. Okay, so you your notes on neurodegenerative disorders. You're |
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| 41:01 | learning about toxins. And you had or three questions on exam one on |
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| 41:10 | toxins that we covered in class during first section. I'm sure you remember |
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| 41:17 | Simpsons and why we watch The Simpsons see how easy it is. Ttx |
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| 41:22 | fish. Okay, what else? sacks. A toxin? Okay, |
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| 41:26 | way will not come back to questions those particular toxins. But it's very |
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| 41:34 | that we keep talking about these things are in our bodies and how these |
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| 41:45 | in our transmitter systems are related to neurological disorders. We're constantly coming back |
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| 41:53 | toxins because it's something that's outside in , and it's a good things that |
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| 42:00 | out there in nature, and we draw on these toxins. Remember talking |
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| 42:04 | spider talks and some potassium channel on MacKinnon and how you need these? |
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| 42:11 | blockers, toxins and antagonists which are and agonists, are another type of |
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| 42:19 | that opens the channels okay or opens receptors. We need these in order |
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| 42:26 | understand the structure of the channels. you also we'll learn that there's other |
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| 42:34 | that thes toxins do, and then can taken advantage of them in a |
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| 42:41 | therapeutic applications. So what? We're to discuss this bacteria, spider snakes |
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| 42:47 | you You're ready to discuss you? , it's time you turn on the |
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| 42:55 | and discuss you. Okay. Joking , we're gonna talk about Clostridium |
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| 43:06 | Uh, does anybody know what Clostridium is? So let's see your |
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| 43:21 | Botox. Wow. Okay. Yeah, Botulinum toxin. So the |
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| 43:35 | botulinum botulism botulinum toxin can be Its ah, Clostridium botulinum. It's |
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| 43:46 | . Yes, causes spasms and the . A glass of paralysis. Same |
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| 43:53 | grows in food. Very good. causes botulism. Very good. Which |
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| 43:58 | Yeah, which can paralyze you can can be really bad. Now. |
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| 44:07 | does it come about us in the ? It's in the water and the |
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| 44:14 | . If they are multiplying, we produce the toxin. So remember even |
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| 44:19 | back to fugu fish? It wasn't fish itself. It's making ttx |
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| 44:26 | It's the bacteria. It's a micro that are invading the fish and invading |
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| 44:33 | liver and ovaries and producing. In case of Ttxt TX this case you |
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| 44:40 | Botox, and so you have the . And if you don't preserve the |
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| 44:46 | , especially can the vegetables Then you have formation and canned food off Clostridium |
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| 44:53 | lineup. Uh, you seafood equally needs. Also it is more |
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| 45:02 | Thio have the studio botulinum and homemade , preservatives. Uh, because maybe |
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| 45:14 | people prepare their their jams or um, pickles or whatever, the |
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| 45:22 | of the pressure may not go high before they jar them before they can |
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| 45:29 | . And so you may have formation the studio botulinum. Um, so |
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| 45:37 | the solution is to heat the and that's again not the best way |
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| 45:46 | doing it. But we don't ah, great way of preserving food |
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| 45:50 | you can try to get rid of Clostridium botulinum completely in the food if |
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| 45:58 | preserving. But then you know, the food, using food, |
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| 46:05 | using acidification of food. And so why a lot of times you will |
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| 46:10 | on the food label on will say contains this and this and this and |
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| 46:14 | wondering. Wait a second. Is the food I'm eating or this is |
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| 46:19 | nitrates. Um, preservatives, uh, this and not and process |
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| 46:25 | heat Thio. Guess what happens to in vegetables from food when you he'd |
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| 46:33 | when you hit them a lot, , kind of a change. Their |
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| 46:39 | . Somebody, I think responder. people know even more than ideal. |
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| 46:44 | see the nature break. Of There you go. So you can |
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| 46:53 | now on. I will say that is very important. Especially now you |
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| 47:00 | see now the world is changing and moving toward fresh foods and we're moving |
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| 47:08 | plant based foods. In Germany, of meat eaters are switching to plan |
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| 47:16 | meets to alternative plan based meets or grown in the lab. Such |
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| 47:25 | uh, the meatless burgers that you find the meatless sausages that you can |
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| 47:31 | a plan based meets number one. two people are going for a lot |
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| 47:39 | fresh foods. And so you will that, in my opinion, the |
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| 47:45 | and that increases in marketing and commercials fresh food deliveries for fresh frozen |
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| 47:54 | Deliveries are everywhere in the newspapers and and on all of the sorts of |
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| 48:03 | . So that's important, you But in reality, you also have |
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| 48:10 | of population that cannot afford fresh Fresh food is more expensive, then |
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| 48:17 | food. And also there is not great where preserving fresh food unless you |
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| 48:23 | it. And then you're talking you know, countries and states like |
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| 48:28 | having high temperatures and very high bills keep something frozen for a long. |
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| 48:35 | anyway, so what's the line Toxins are shown here on the |
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| 48:42 | and they're showing his little Sharkey's. you have a bunch of line, |
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| 48:46 | , toxins. B D F When you have another Sharkey botulinum toxin |
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| 48:51 | and E. And then you have Sharkey here, Botulinum toxin C one |
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| 48:57 | they're illustrated. The Sharkey's here because they do is the complex that we |
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| 49:06 | talking about. Sinatra tag mint, Brevin snapped 25 syntax. And you |
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| 49:12 | this is protein protein complex that forms synaptic vesicles on the plasma membrane. |
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| 49:19 | so you have the calcium sensors, we we said we simplified it to |
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| 49:24 | artists near a particular proteins and trans proteins, so that particular proteins. |
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| 49:31 | complex is a targeted by vocal item . Bye, Botox. It's also |
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| 49:37 | by tetanus toxin that is shown Tetanus toxin is not to be confused |
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| 49:42 | tetrodotoxin. And you should say, course not because tetrodotoxin binds to voltage |
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| 49:51 | sodium channels. And here you're talking a particular protein complexes. I know |
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| 49:57 | the stocks in is different from boxing and tetanus toxin, but most |
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| 50:03 | , that focus in a bunch of toxins will target both of this succulent |
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| 50:08 | the trance memory protein complexes preventing the all of a sudden off, preventing |
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| 50:15 | fusion off the neurotransmitters to the plasma . Okay, so you have paralysis |
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| 50:22 | you cannot have a Seattle Colleen You have a binding thio, the |
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| 50:28 | complex that allows for a cedar uh, neurotransmitters for the for |
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| 50:35 | for the vesicles to release the So why are you lighted to about |
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| 50:43 | parties? So a lot of which linemen can lead to paralysis because |
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| 50:47 | are nerves are not functioning. The , so not being released in the |
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| 50:53 | . Enough contracting. So it can bad if you don't have contraction off |
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| 50:59 | muscles that help you breathe, for can be deadly. Now what is |
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| 51:05 | Botox party? Why are you invited a Botox party? So what does |
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| 51:11 | have to do? Is Botox and is it a party? Actually, |
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| 51:18 | it's. There's two reasons why it's party, So the first party is |
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| 51:23 | cosmetic party. In the cosmetic Botox is injected around the eyes and |
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| 51:29 | the lips and what it does. stops the release of a seal culling |
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| 51:35 | the muscles and stops the contraction of muscles and therefore prevents information or a |
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| 51:43 | temporarily alleviates the parents off the wrinkles the face. Also make sure this |
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| 51:51 | , and they recover difficult. Oh , have junction in your words, |
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| 52:01 | A |
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