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BIOL 6397 Cellular Neuroscience (27770) - 02 CELLULAR NEURO NEURONS I
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00:01 so welcome back, Thio Cellular Neuroscience too. And as you see this
00:08 on the right, it's very colorful what different colors represent are different neuronal
00:18 . So it's really the image off pathways and the connectivity that you see
00:23 the brain from the brain stone into solemn list the area here into the
00:30 lobes and areas of the cerebral If there's a very top, and
00:37 is important because as we progress through information and the scores, it is
00:47 to be important to understand what individual neuron czar responsible for what individual units
00:55 glia are responsible for. Start understanding complexity of different subtypes of the
01:04 whether they're excited during inhibitory. In many features dynamic features of neurons,
01:11 in some of the glia that will over the next few lectures and the
01:19 connectivity sometimes determined some fundamental features of understanding of the outside world and
01:34 Aziz, you see on the macro here in different colors is one
01:39 But we will start from micro scale at what an individual synapse looks like
01:46 what no transmission of that individual synapse like and connectivity. It is
01:55 So a lot of the theme and course will be about plasticity, about
02:01 in synaptic plasticity, synaptic transmission structures the synopsis and these pathways. The
02:12 can be what I call hijacked by disorders and neurological conditions. They can
02:22 impaired by traumatic brain injury, and such, you can develop some very
02:29 syndromes, depending on what part of brain or what areas of the brain
02:36 gets affected by a specific disorder or . In general, the macro scale
02:46 says, and and connectivity between neurons total amount of what neuron bodies occupies
02:53 10% in the cerebral cortex and 90% glial cells. So everything you see
03:06 this in this network would be mostly cell. So I say that neurons
03:13 like chips in a chocolate chip On glia is like dough in.
03:20 reality, you need both to have cookie. Uh, well, you
03:28 have just a don't cookie, but would be very boring. And the
03:35 transmission synaptic transmission, fast communication decision , emotional intellectual processing is happening in
03:46 giving that necessary component for us to as normal human beings on a macro
03:55 . If we look at neurons, have excited Terry neurons, and we
03:58 inhibitory neurons excited to neurons will release during neurotransmitter, glutamate and glutamate,
04:12 the most part. But it really, that the response of the
04:17 to which glutamate is being communicated to , will depend on the receptors on
04:22 receptors that will be receiving would have their transmitters. But for the most
04:28 , Guido matter. GIC synapses are , Torrey and by exciting Torey the
04:37 , the electric potential within individual cells the release of litem. It promotes
04:47 and along the interconnected 1000 networks in brain. So excitation is up.
04:56 means mawr action potentials. Inhibition, the other hand, is mediated by
05:05 neurons and inhibitory. Neurotransmitter neurons contain neurotransmitters that we abbreviate as gabba gamma
05:16 butyric acid. They're traveling release off onto a J center. Interconnected networks
05:25 cause dampening of activity. We'll lower member of potential and will quiet the
05:35 away from being excited and will essentially the connectivity than between the networks.
05:43 might be excited. Both glutamate and are amino acid neurotransmitters, and both
05:54 them are involved in fast neural And, uh, you'll understand what
06:03 mean by fast neural transmission. But will also hear words like I on
06:10 Tropic and medical Tropic transmission, and on a Tropic and medical tropic
06:18 You will also learn that excited her inhibitory Neurons can co express and also
06:26 other neural transmitters that are not acid , such as a mean there are
06:36 . So, uh, modulators. can co release neuro peptides along with
06:47 off these classic amino acid neurotransmitters, and GABA. Is there slow neural
06:57 while when I say fast neural I'm really referring Thio I on a
07:03 blue dermatologic and GABA ergic. Signaling slow. A neural transmission involves measurable
07:10 receptors, which involved cellular pathways downstream the way to the transcription factors in
07:18 new clues, thus mediating slower Mhm. So the scales in nurse
07:28 is very important, and given neuron make a decision whether to produce an
07:36 potential. Within a matter of the action potential will have a duration
07:41 one too few milliseconds and neurons there will be synaptic neural transmitter release
07:50 the synopsis, which can then act the fast way through high on a
07:55 or in a slow way through a but tropic receptors and pathways. I
08:02 this picture because this picture gives you idea of what the brain looks like
08:08 the neurons very much supported by glial . And this is an overview,
08:15 we'll come back and talk mostly about sites and microbe. We,
08:21 on will also mention a legal down sides. But this diagram really depicts
08:29 happening in the brain. And what's in the brain is that you have
08:33 new neurons that are interconnected. They with each other. They have multiple
08:40 . As I mentioned, they may up to 100,000 synapses in a single
08:47 . That information that comes into neuron integrated, and here, at the
08:53 of the Axon, Neuron decides whether going to produce an action potential.
08:58 AK sants in the central nervous system encased by myelin sheets that are provided
09:06 glial cells that are called illegal dangerous . So a legal Dender sides have
09:13 multiple legs and processes that branch and each one of these processes creates
09:19 single mile and segment on neuronal ax . These violent segments are separated by
09:28 of ranveer. So the acts on segment this area here that's located the
09:35 to the Selma. The acts on segment will produce initial action potential.
09:42 action potential will get regenerated. Each over on here and that action potential
09:49 eventually re synaptic terminal and caused neurotransmitter . So in this case, glial
09:58 are providing the installation of legal dangerous . It's like an insulated cable.
10:08 have all of the cables insulated because electricity would leak out, and the
10:13 of ranveer contribute to the fact that action potential the fast, deep polarization
10:19 produced. Here is the same amplitude the end that the external terminal is
10:25 is at the initial segment of facts . Then we look over here and
10:31 see a very, very important player the Master Side, and we'll come
10:36 and talk about Lee and a couple lectures. This is a short introduction
10:40 place you within this neuro glial circuit is our central nervous system and as
10:48 sizes, you can see how the location their processes wrap around the synapses
10:55 the den writes off neurons. They communicated append them all cells here,
11:02 are also thought to be pluripotent cells formed the barrier between the interstitial space
11:15 , the brain and the cerebrospinal the ventricular, uh, compartments.
11:22 contains cerebrospinal fluid. So by this , it has interactions with the cerebrospinal
11:30 portions here of the brain. most importantly, Astra sides lay
11:36 They're called N feet or end process not only on the synapses, but
11:42 all over the micro capital, The brain is only about 3% of
11:53 total body mass in the brain consumes 20% of the total metabolic body
12:07 It is a system that I often is driven outside of the equilibrium.
12:12 a nonlinear system. It needs a of energy. It needs a lot
12:20 nutrients. What else does it The brain needs oxygen. Michael Capital
12:28 that are innovating the brain tissue. will find them closest space up Thio
12:36 micro meters. A typical soma is 10 micrometers in diameter. And so
12:44 isn't a place in the brain where is no blood vessel of micro capitalist
12:50 that separated Onley by few. Selma's this blood supply was in the blood
12:59 at all enter into the brain. being policed. It's being policed by
13:05 sides that comprise the structure that we to as blood brain barrier. So
13:14 sides not only control the synaptic interact with these defendable Selves, but
13:21 are responsible for what goes into the into interstitial spaces here by playing a
13:29 of being the barrier between the blood the brave, and, of
13:36 the micro vessels. So micro capitalists you see here will be carrying nutrients
13:41 be carrying different chemicals will be carrying . And if you recall from your
13:51 cell biology courses, there is two important things that neuron zones and sells
14:01 on oxygen glucose. Okay, so , an oxygen and neurons are
14:15 very much dependent on oxygen. So you cut off oxygen supply, which
14:25 called hypoxia, you don't have enough . If you cut off, oxygen
14:32 neurons may die within minutes, so why when people have, uh,
14:43 heart attack or stroke and they enter clinical death, that period is crucial
14:55 time period to when they get supply oxygen. It's crucial whether it's through
15:03 or through ventilation on. This is really relevant because coded 19 is really
15:13 out to be more or less. , vascular disease and infections and constrictions
15:25 blood vessels and micro strokes that are are very much contributing to the neural
15:35 . But this virus that's out there . So Astra Sides again play a
15:41 important role in policing what enters into the brain micro glial cells. Here
15:49 , we'll come back and talk some about glial cells, and I'll show
15:53 some very interesting videos. Also, glial cells are the repair cells.
16:01 the fastest, the most mobile real units on. They travel across
16:07 brain, and they clean up the and get activated during injury for repairs
16:15 you can see that there's different subtypes real cells that have covered here that
16:20 these neurons. But what will really on in this lecture is neurons and
16:26 you classify neurons and neurons are classified connectivity by excitability by specific markers or
16:41 molecules like neurotransmitters in Europe, vampires they express and also by the action
16:51 that they produce. So this is first published intracellular recording a picture Polaroid
17:00 on the Silla scope taken by Hodgkin Huxley in 1939. So as we
17:08 a little bit about the history of last lecture only 1939. We understood
17:17 those wires that Luigi Eagle Vonnie where electrical wires that those wires were
17:25 very fast potentials. And that's because didn't have equipment that was fast
17:32 A lot of equipment was developed, part of the Army and Navy
17:40 And in fact, a lot of cable still have the same connectivity that
17:45 would see in in some of the Uh um, devices and submarines.
17:55 so, 1939 there is electric physiological in the Silla scopes that air fast
18:06 to capture these very fast action potentials rest membrane is about minus 65 minus
18:16 million volts, and if the cell enough of the exciting terry inputs,
18:23 will dipaula rise to the threshold for potential will generate this very fast electrical
18:30 that lasts for about one too few . And then the number of potential
18:36 the celery polarizes again. So when talk about action potentials, different cells
18:44 produce different frequencies and different what we firing signatures of these action potentials.
18:50 we talk about self specific markers, talk about whether the cells have the
18:55 thio produce excited Terry neurotransmitters like glutamate inhibitory GABA or different neural peptides that
19:03 main codas well excitability, is Thio the synapse or to that
19:10 if the cell produces glutamate, is to goblets. Inhibitory connectivity is some
19:17 the south of projection sells. Some the South will project from one network
19:24 into another distal part of the brain from the retina into the columnist or
19:31 the column us into the cortex. then there are some cells that will
19:37 locally, so those most of the communication is by south, and we
19:45 Interneuron. So most of the sir inhibitory So you can think of
19:50 a local level neuron, sir, by both excited inhibitory inputs. But
19:57 inhibition has more control locally. Once neuron excited, Terry Neuron decides a
20:02 neuron that he's gonna fire an action . Or she, uh, it's
20:08 going to project a more distant distant regions, interconnecting, different parts
20:15 the brain. This is neuron that envision have four functional regions. So
20:22 some basics that I'm going to cover . Also, before I go into
20:27 heavy glutamate neural transmission to make sure everybody's on the same page and this
20:32 the material and please stop me if won't have any questions, um,
20:38 right a shot. Andi, If on a roll, I'll just pick
20:42 your question in a minute or Um, but most neurons independently on
20:50 shape and the declassification have four functional . They receive an import. Neurons
20:58 receive an input from another neuron Such a sensory neurons can receive information
21:05 , let's, say, the skin the muscles of the joints.
21:10 they can receive information from another modern . Local. Interneuron could be a
21:18 , it says Interneuron, but it be a projection cell, the neuroendocrine
21:23 . So there is again collectivity uh, C N s on and
21:31 blood and the whole body because of neuro endocrine system. This hormonal on
21:37 ecstatic regulation through neuron, the train through Endo Cannabinoid system. And we
21:43 discuss that look elaborate system later in semester. Input all of these
21:50 This is just, you know, inputs shown, but in reality,
21:53 neurons might be receiving thousands of Soma is usually the integrative part.
22:01 integrative, part integrative unit of the it integrates, calculates all of the
22:09 excited during all of the negative. polarizing things that push number and potential
22:16 to action potential or hyper polarizing The ones that dampen number and potential
22:21 make it less excitable. Integrate that very fast and then conduct all
22:29 So this is an ax on. say an ax on has been my
22:33 . That will conduct. And what it going to conduct? It's not
22:36 to conduct the neurotransmitter that it's releasing is going to conduct an electric potential
22:41 going to conduct an action. Potential potential will get regenerated each note of
22:46 here and when the action potential reaches output region. It will dipaula rise
22:52 region and cause on output in the of neural transmission or secretion. If
23:01 talking about a model neuron so you secrete neurotransmitter onto another neuron, a
23:06 neuron can release the subtle Colleen onto muscle cells. You can have excited
23:13 inhibitory into neurons interconnecting, and you also affect that as a construction of
23:24 a dilation off the capital. Reza's , and this is, Ah,
23:36 picture that I showed to everyone because really like the descriptions here that this
23:44 morphology. When Golgi stain was invented a row, Monica Hall used Golgi
23:50 to describe these different neurons. He some fascinating new ones. Um,
23:56 of this new concern unit polar, this is another classifications of neurons based
24:01 the morphology that needs to have a body, and I have one poll
24:05 from south to north. Some of are bipolar, so body is in
24:09 middle. It has a north pole has a South Pole pseudo una
24:15 because it actually has a peripheral Axiron goes to skin like in the dorsal
24:21 ganglion cell and then it Z integrative and then a central Axiron that goes
24:27 the dorsal part of the spinal cord contact motor neurons, pseudo unit,
24:32 self, most of the C. s cells in the cerebral cortex,
24:38 , which is really kind of the of this course. We have multipolar
24:44 and a cell that will study Thio extent is an excited. Her parameters
24:51 because it has a shape of the . It has basil dendrites coming out
24:57 the base of the pyramid has an pickle done right that comes off the
25:03 of this pyramid is accents that project these excited Terry Projections house and this
25:10 parameters cell of hippocampus. But you find parameter all cells in different parts
25:15 the brain. Hippocampus is a part the brain that's very important and is
25:20 in learning memory, emotional processing and exciting story. Cells communicate that information
25:27 of the hippocampus through the long range projections to the other interconnected areas of
25:33 brain on the right, here at bottom, what you see is probably
25:38 of the most morphological is spectacular cells the brain and these air per Kinji
25:45 of the cerebellum, where when we about thousands of synapses per Kinji cells
25:53 have up 250 of synapses because of of these incredible dendritic processes and ramifications
26:02 make it really look a single salad very complex tree or bush, this
26:10 the soma. This is a Faxon duh. Imagine having to draw these
26:17 when you first discovered. That is alcohol using the Golgi stain that all
26:23 these different cells, their morphology and location, of course, also have
26:29 properties. So, you know, salsa typically and vertebrates. Bipolar cells
26:39 typically sensory cells in the retina Epithelium in the spinal cord. Pseudo
26:48 ourselves in the spinal cord. Dorsal ganglion cells as well as McConnell
26:54 Thies again sensory information, off pain and pressure that goes into spinal
27:01 through civilian opponents. Unipol ourselves. then when we talk about glutamate,
27:07 gabble, allergic neural transmission in the . N s. And we're mostly
27:13 about multipolar Selves. And so let's at this other diagram, which is
27:22 cartoon that illustrates a economical network. is in the hippocampus on the hippocampal
27:35 C A one for him again. . Well, we'll get to the
27:42 of the some of the anatomy in couple of lectures to place you within
27:47 context of some of these systems and . But right now, the important
27:53 is to understand what neuron Oh, on the macro scale look like within
28:01 circuit. And what you see here an illustration off the hippocampal circuit where
28:09 have parameter all cells. Some of say CB blossom. Others say CB
28:17 . But these air excited Terry Peron cells and these arrows indicate that these
28:25 cells are actually projection cells that the from this region off the hippocampus in
28:32 C a one is going to come these excited Terry parameter all cells C
28:39 here stands for cal venden. So of the parameters cells are Cal Bend
28:47 positive, and some of them were been negative. Vast majority over 90%
28:55 criminal cells will contain there. So there so bodies in a layer that
29:02 called stratum to run the Dalai or Toronto cell layer. So 90% of
29:11 parameter will sell. Air cell bodies be in stratum parameter alley. There
29:17 be some dispersed in stratum, ready and in stratum, orients Blair's of
29:27 hippocampus. And so if the a lot of times, is referred
29:36 as archaic cortex because it has three layers. Stratum ready item stratum parameter
29:46 on stratum orients like neocortex in the cortex, which has six layers.
29:56 and this is quite interesting from evolutionary because neocortex, the Sixth Land,
30:06 cortical structure, neo stands for the . It's evolutionarily the most recent
30:18 the most evolving part of the And if I were to guess,
30:26 think hippocampus. It's trying from to , from this Arcade three layered structure
30:34 something even more complex. So this a part of the plasticity and also
30:43 plasticity. As humans, our brains circuits adapt to the outside environment,
30:51 natural environment or technological environment, and fact that we are co evolving with
31:02 . We change our synapses and connectivity a daily basis, but on a
31:09 term evolutionary perspective were also changing the , the layers on the columns that
31:18 be interconnected and the complexity of the circuits. So from archaic three less
31:25 , it may actually become something more , although on top here you also
31:31 another layer that's indicated striatum looking. molecule are also, but overall,
31:37 is start off as a three kind a large structure. So what surrounds
31:44 exciting Terry sells. These exciting terry are glutamate, sells their glue dramaturgical
31:51 , so they're excited enough. The that they will project out of the
31:56 will excite and interconnected brain circuit to they're communicating. These cells that have
32:03 an orange and red and purple on hand are all inhibitory cells, and
32:11 diagram illustrates some very important things. of all, that there is a
32:17 diversity, a much broader diversity off inhibitory cell subtypes they're supposed to be
32:24 to resell. Sometimes we only really one excited to resell. Sometimes the
32:29 is the location in which layer the is found and whether they have called
32:34 or not. But if you look the inhibitory cells, these inhibitory
32:39 they have their Selma's and starting for . These inhibitory cells have their Selma's
32:45 ready Adam and Looking. Also Milica Layers. Some inhibitory cells have dendrite
32:53 thick red projections of Denver rights that vertically oriented at this that have horizontal
33:02 projections. The yellow cops here and purple lines indicate axons and the yellow
33:10 , the synapses, some of the cells and the most powerful inhibitory cells
33:16 form inhibitory connections close to the Selma's the excited terry cells. Yet other
33:24 cells these yellow cops would be projecting the distal in a pickle. Dendritic
33:31 off these phenomenal cells and others yet try to modulate the output by contacting
33:38 the bottom regions of the summer. accents that are coming out of these
33:45 cells. So overall, this diagram a 21 different subtypes off inhibitory cells
33:55 ergic into neurons in the hippocampus Here, one you will say,
34:00 a second. This is supposed to good on the turgid Well, this
34:04 illustrates to you that most of the cell control will be happening locally and
34:14 of the cell diversity not just in , but as you'll see later.
34:18 in the cerebral cortex and the Most of the cellular diversity comes from
34:24 inhibitory cells. What does that That means that the complexity of the
34:31 processing is determined very much so by inhibitory cells and how they control the
34:38 properties of the exciting terry cells. what excited very cells are going to
34:43 onto the networks to the which their Even more so, you can look
34:53 a circuit in the cortex of what will see that these inhibitory cells that
35:02 located close to each other when you electrical activity from these inhibitory cells,
35:09 black stripes or black columns mean action . Each one of these cells,
35:19 one of these cells, has its pattern. Each one of these 21
35:25 of inhibitory cells and excited Torrey Selves their own patterns of action, potential
35:34 . Some of them will stutter. once they get excited or dipaula
35:39 that will produce trains discontinuous trains of potentials. Stop, stop, stop
35:52 So the empire and the stimulus and deep polarization is continues. But the
35:58 that the cell reacts to an it translates it into its own language
36:05 adjacent cell may be quiet during continuous stimulus and input h And then when
36:15 gets activated, it will. Instead the discontinuous strains, it will just
36:21 a continuous firing. These cells are cells, so they will have the
36:33 oil like deep authorizations that be 00 uh. What does that
36:51 That each one of these action potential signatures is really a different way
36:58 Processing the inputs and converting them into output that is now from the inhibitory
37:05 will affect the South on the local level and will allow or not allow
37:11 the exciting story south to which they're to to communicate that information further down
37:17 line to the adjacent normal circuits. the firing properties in this diversity and
37:28 electric behaviors of neural cortical cells, can think of different dialect we saw
37:35 encode a different dialect. It's a code, dialect or code, and
37:44 different code means something different to the cells and excited Torrey cells and
37:51 and network is then responsible for not in an individual cell but this whole
37:59 network that is responsible for producing an motor Command or in emotion, an
38:11 of these cells. And the reason they produce all of these different patterns
38:16 because they have different channels in their that conduct ions in a different
38:26 So they're different, and they speak dialect with same language. This is
38:36 illustration from my work that shows two that are adjacent to each other.
38:43 of them is an inhibitory cell. fire's very fast action potentials and the
38:49 cell is an exciting terry. Sell fires this much slower action potential.
38:55 so that's another feature that is That is different between excitation and inhibition
39:01 the fact that inhibition and inhibitory cells fire either over a very low frequency
39:11 or sustained very high frequencies of action . So some of the Interneuron some
39:20 the inhibitory cells can produce action potentials the order of 600 action potentials per
39:28 600 hertz. That's a non oscillation 600 times up and down with an
39:35 potential, and circuits can actually produce fast activity high frequency oscillations that also
39:46 circuits can Austin, late at a of hundreds of hurts, Aziz.
39:54 excited cherry sauce on that. The will typically go maybe as high as
40:00 hertz or 40 action potentials per And there isn't that much of ah
40:08 in the sense off, ranging from few action potentials to hundreds, but
40:14 ranging from a few action potentials to of action potentials in frequency. And
40:21 of these cells to sell on the and the ride are patched by an
40:27 . So this is a glass electrode we place under a microscope and the
40:33 Electra gives the exact same input to south, and you can see that
40:38 south interpret that same input differently. speak a different dialect, the different
40:49 during the experiment like this. This a typical wholesale electrophysiology experiment. You
40:56 inject the cells with the die. diet is typically called bios Iten or
41:04 Tim. And so maybe I will something quickly here. Okay.
41:34 So this is what gets injected during experiment. This die fills the cells
41:50 we're recording electrical activity from these This bayous, iten or neuro biden
41:57 fills the cells and this is typically that they're sitting underneath the microscope.
42:03 included. That picture of No, not. Yeah. Yeah. So
42:09 guys were sitting underneath the microscope and have micro electrodes and we record electrical
42:18 , and then we fill them with die. And after the experiment that
42:22 take the slice and we process using history, chemistry to communicate or cytology
42:32 . And we can reconstruct using this a sudden, you're a Biden.
42:37 can reconstruct the full anatomy and morphology the neurons from which we were taking
42:43 recordings. And so on the last , what you see is an example
42:50 or orients, Latinos a molecule ari into neuron of the hippocampus in the
42:56 orients that has a coma and the layer and the exciting to a parameter
43:02 cell in the stratum, pyramidal SP black extensions are the dendrites, the
43:12 on the basal dendrites. And the extensions are the Exxon's that air coming
43:19 of the cells. And so the a lemon to neuron has its projections
43:24 into stratum local north, um, local area. And that's why it's
43:28 in. Oh, a lemon to it has a body and stratum
43:33 but it projects in tow. Luminoso are s 00 l um And this
43:40 cell has an ax on that is this way. Coming This one.
43:44 actually coming at you and exits out the focal plane of the microscope out
43:50 the slice that is projecting into the regions. Uh, where hippocampus is
43:58 . Now that the important thing that these different classes off Interneuron XYZ that
44:06 Interneuron Czar not only have different so den drives, morphology, axons But
44:15 of them are, for example, cells that air TV that means that
44:21 providing and positive basket cells. Other cells are si ck or V i
44:29 . That means that those baskets cells two and 21 and two, for
44:36 , or one and four look They have the same location of the
44:42 almost identical dendrites projecting the acts on air here. But one of them
44:51 CCK like to expresses provide Alderman and expresses CCK CCK stands for color system
45:04 again. You don't have to remember and testicular kinda call a sister kind
45:09 then the vassal, immune present and on. The point I'm trying to
45:15 is that in the end, you have to know the internal markers that
45:20 into neurons expressed non just their morphology location in order to definitively distinguished,
45:26 example, with between a basket cell to provide them in positive and basket
45:32 number four, which is si ck . This is the O. Elam
45:38 seven. You see, this is ol um this is the soma in
45:42 Orient Slayer. And this is the and Latinos a molecule, Ari.
45:48 , so this is the alarm cell have patched. We call it patched
45:54 electrode and reconstructed its morphology. This a parameter also, and we can
46:01 take the slices, uh, after experiment, not just reconstruct the
46:10 but we can stain them for specific so we can see that the
46:14 for example, this cell that contained and it stands for NB also assume
46:21 of Staten positive. And this adjacent provide them and positive. So you
46:29 thio typically in these communities, the techniques you have to use more than
46:36 or two more than two markers like them in some as a staten.
46:40 are beytin in order, Thio definitively and delineate the subtype of the
46:48 In this case, inhibitory salvage your from So so any questions? So
47:00 , everybody is following this pretty We're living in this circuit world of
47:07 and inhibition, and I'm trying to a point across that you have the
47:14 and these inhibitory circuits that will control locally and then exited Torrey projection
47:23 There's a glue dramaturgical cells. And now we're gonna go more into
47:27 Ergic signaling they will communicate that information range. Okay, Okay,
47:35 So I'll continue then. But before do so what I wanted thio kind
47:43 remind everybody that they have not taken in the last year last semester off
47:51 of the important features off neurons and General South that you you should think
47:59 and keep in mind that we are dynamic. Physiologically, we're dynamic
48:10 uh, bodies. A tool of is a tool. There's plasticity and
48:15 or spliced this city in the And there's plasticity that is in the
48:22 . A little bit by lair. a false Olympic. Byler, of
48:26 , is just the regular Byler that would see surrounding any cell that consists
48:32 the polar hydro filling head, which the Colin phosphate glycerol, and the
48:39 non polar tales which a fatty So the hydrophobic tails come together and
48:47 the inside of this by layer, then the outside. You have the
48:52 filic polar groups on both sides. first side is being the cytoplasmic side
49:00 the cell, and this other side the extra extra cellular fluid outside of
49:06 cell. And so the receptors transport receptors, receptor proteins and recognition
49:16 cholesterol, carbohydrates, sugars, Not all in that ed and
49:25 Some of them are trans membrane. of them are associated with extra cellular
49:30 , others associated with the cytoplasmic side the south. Then what you have
49:39 years, you have the side of elements that support the slew, the
49:47 out the faucet, Philip with Mhm. So let me, um
49:55 conveys the point that I'm talking about video. Christ. Okay,
50:41 he Wow. Yeah, that's so point here is I'm really trying to
51:16 also is that these proteins and trans proteins and receptor proteins, and especially
51:25 we talk about glioma tragic transmission that's ample receptors will learn about maybe
51:32 maybe a next lecture, depending on time a very dynamic they can travel
51:41 meters and milliseconds. So that's how how fluid this this mosaic is mosaic
51:49 is a different patches toe comprise this membrane. Okay, so let me
52:18 back the screen here. So picture is a very fluid this environment,
52:25 just because of the fluid, but of the ability for the plasma membrane
52:31 the proteins within plasma membrane thio travel plasma membrane and for these,
52:39 filaments and other structural components side of elements that actually reshape the membranes,
52:48 you'll see why this is important. the major side of skeletal elements and
52:54 is very important that you find and find that these elements are involved in
52:59 disorders. We find that a lot the tangling off the bed amyloid plaques
53:08 Alzheimer's disease or tau protein tangles Um, abnormal protein aggregations could cause
53:20 to side of skeletal elements is and damage can lead to banding ability for
53:26 membrane to be a slew. It as it isnot just in physiology but
53:31 in structure. So you have micro bills that are the largest, and
53:38 have these micro tubular highways to travel the accents that is surrounded by my
53:44 . We have neuro filaments, smaller , and then you have micro filaments
53:49 are acting molecules and especially acting. will be located at the distal parts
53:59 right by the membrane, and they form and prelim arise and dip.
54:05 arise into these different chains longer and chains changing the overall structure of the
54:13 membrane, Therefore, changing how this looks like on the outside of what
54:18 looked like. Aziz well, so . Features again is the fluid mosaic
54:27 that the receptors and the proteins are , that there is a lateral diffusion
54:34 this it is reshaped by activity. structure of the membrane is reshaped by
54:43 . The number of the proteins, of trans member and products, their
54:48 of cellular only get reshaped by activity depending on the demand of levels of
54:55 . And so a lot of times call this process activity dependent processes.
55:01 , outside of skeletal elements that if have normally functioning side of skeletal elements
55:09 normally, uh, prelim arising diploma acting molecules, the smallest alum asses
55:15 you will be able to maintain the shape off the off the whole Saleh's
55:21 as its micro protrusions like dendritic Very third very important feature of neurons
55:29 other cells don't really possess. A spines. So this is an electron
55:35 image off reconstructed them dendrite shaft, that then drive shaft has the spines
55:46 are coming off of it. That's these spines, our postion optic and
55:53 marketeers. Pasta? Nah, pick . Boston optic densities is Boston optically
55:58 you will have collections off protein receptors on the pasta synaptic sides. This
56:05 a down dried mitochondria in and on pre synaptic side, juxtaposed to this
56:14 here in red is an ax and that Axiron contains these round vesicles
56:21 are neurotransmitter vesicles, sort of filled neurotransmitters. And so a lot of
56:27 transmission and excited Terry Trans synaptic transmission happening here at the level of these
56:33 spines and that experience also have a own Paulie Reiber Somo complex and they
56:41 my mitochondria. And so they are off some biochemical machinery and re engineering
56:51 the local level at the level of synaptic spine. And of course,
56:57 you know, most of the assembly these part of the river Somo and
57:02 new materials and proteins will be happening closer to the Selman organelles surrounding the
57:11 of the Selma. So they're these spines come in different shapes and these
57:18 spines to the most dynamic, structurally , they can change their shape.
57:28 this is both structure and function. the shape, change the function,
57:34 enough function results in the change of shape. These didn't really expanse conform
57:41 spines can form. Today you're forming spines. Is your learning this
57:48 You encoding new information, building new or strengthening the ones that you've already
57:54 with your previous neuroscience learning. So building out these new shapes new dendritic
58:01 and increasing the firing and excited Terry and inhibitory modulation off that excited her
58:10 as we speak. And these side skeletal elements underneath, especially the active
58:17 , are very important because the shape the structure depends on the underlying side
58:24 skeletal elements off inside the bodies. then these inside can very much affect
58:35 , then drives. Integrated spines are with adjacent pre synaptic terminals and how
58:41 processing the information from these pre synaptic activity, environment dependent plasticity. So
58:54 more active you are, the more the stronger your synopsis of becoming,
58:59 they may even change their shape. less active the synapses are, the
59:06 they're becoming, and they actually may just completely go away and be
59:14 And guess what? For? Getting process of forgetting you shape and you
59:20 new synopsis as you learn new But then you forget things. You
59:27 certain things that are long term those things that you keep recalling certain
59:32 that encode in long term memory. it's difficult to forget because of that
59:39 psychological aspects that may be affiliated with memories. But then, forgetting is
59:47 normal part of human existence. Forgetting protecting ourselves. If you couldn't forget
59:56 bad experiences, you have to relive constantly and replay them across the
60:02 It could overwhelm you. And it happen so too many, especially those
60:08 suffer from post traumatic stress disorder. you may now you have to change
60:15 synapses. There has to be a plasticity, different environment, different activity
60:20 which this plasticity depends. So short memory and things that you forget is
60:31 form a few synopsis connections. This are active. You recite information for
60:36 couple of months, you take the , you go in the spring break
60:40 you're like, Whoa, what was ? Why was it learning it?
60:47 a lot of information that at your you have tow, memorize and take
60:52 . That's just a part of a grind. Just take it as a
60:55 of the normal grind. Uh, know, you should memorize crab
61:01 Come on. Should know it by at nine. But then you should
61:08 think of what does that crab cycle mean? And so more of
61:12 integrative approach to science and more of practical approach to science is very much
61:18 . And so that's why I say . Okay, look, at these
61:21 in them that expires. When you you shape more spines, you form
61:25 spines. New connections strengthen the You forget stuff. The spines go
61:31 . Normal processes forgetting things. We remember things. Plus there's finite amount
61:38 space, and still we have billions trillions. But we don't have hundreds
61:43 trillions of synapses. We cannot go billion of neurons. So it's a
61:50 space on those synapses. Not necessarily have to go away with interplay and
61:57 of these synapses. And these don't explains can be used by different forms
62:02 activity throughout life, the ones that demanding most activity or the most that
62:08 in your environment. So again, you look here on the right,
62:16 you see is you see a neuron blue and you see green synopsis stained
62:26 glutamate receptor these air glue, dermatologic and then orange. You see gob
62:34 synapses, so a neuron can receive or an inhibitory inputs. This isn't
62:44 could be an excited Terry neuron, you can be an inhibitory in your
62:49 . Both excited and inhibitor. Endurance receive both excited inhibitory synapses, so
62:55 excited Grampus is they come in. will try to dip polarizing Durham and
62:59 and tell it fire in action I want to exciting and this inhibitor
63:05 they're gonna saying Go down, dampen . Ignore these incoming excited turning inputs
63:14 then this There are, in the of milliseconds decides. I think I'm
63:22 enough de polarized enough firing action. or not, it's a very complex
63:30 that has to happen. That computation at the level of these dendritic spines
63:35 these individual synapses and the summation of of the activity across different synapses and
63:41 different parts of the cell. The that are the closest to the SoMa
63:46 have the highest impact on what the does and whether the self generates an
63:51 potential the synapses that are located more . You have to activate a lot
63:56 of these synapses because the dendrites are perfect. Conductors, like accents are
64:02 of the information excited or inhibitory from regions will actually not reach. The
64:08 will actually be lost along the way there is no installation on done
64:13 so that's a feature that we discuss myelin nation. A specific Thio
64:18 uh, not done drives How London Drink spines. This is an
64:26 of a done drive from a normal and done drive from the mentally retarded
64:32 ah, in autism spectrum disorders and fact, fragile. X syndrome is
64:41 of the autism spectrum disorders fragile X , one of the models and one
64:46 the path of physiology. Ease or that you see and these diseases are
64:55 spines. You can see that they Elon gated, that there shape so
65:02 different the densities they're regularly distributed across then dried. This process again is
65:14 by both, obviously very strong by activity and environment dependent component nature,
65:24 is genetics as well. So both , the nurture. Uh, but
65:32 is an important, important component. important unit in neurons. You have
65:40 start to get to know has been explains in sin absence. This is
65:44 neuronal communication happens. So once that decides to produce an action potential,
65:51 action potential within a matter of milliseconds get regenerated each note of ranveer and
65:58 the target through different synopsis one neuron neurons. Different parts of this
66:06 Selma's and don dries as well. once this neuron reaches the terminal,
66:13 happens is you have the release of . But for us to understand the
66:20 of the neurotransmitter, I wanna make that we understand what neuron does to
66:24 that, and in particular, neuron an action potential at resting number in
66:34 . This is resting number of It's about minus 65 million balls.
66:40 the cell integrates all of this excited input and the membrane potential reaches minus
66:49 million balls, you have massive influence sodium, both educated sodium channels open
66:56 . And during this rising phase of action potential, you have massive influx
67:01 sodium ions sodium ions and are regulated the dynamics of the sodium channel,
67:10 starts closing slowly and you have now flux of potassium. So during the
67:16 phase of re polarization, you have e flexing, meaning potassium is going
67:22 inside the south to the outside of south, and finally you rebuild this
67:28 . Potential doctor rest by using an K pumps or an a k a
67:33 P. A s so as you , polarize the plasma membrane. There
67:38 some influx of sodium mawr, deep , more sodium. And that's why
67:43 have this very fast rising phase of action potential, uh, followed by
67:50 descending phase of the action potential. also shows here that during the actual
67:58 face and the peak of the action up to here and during the re
68:03 , you have an absolute refractory During this period, you cannot produce
68:08 action potential. Now, following this factory period, you have this phase
68:13 hyper polarization below resting number and potential then re polarization back to resting membrane
68:23 . And this period is called relative period. That means that if you
68:28 strong enough input, you can dip the cell again to the threshold for
68:33 potential. You can produce another action and so different neurons, depending on
68:40 speed by which they can reproduce action , have different refractory period's and the
68:50 tal cells have longer refractory period's, that's why they fire slower frequencies and
68:57 action potentials and the inhibitor Interneuron Czar be much faster because they have much
69:03 refractory period's, allowing for the action to be produced a soon as another
69:11 that is re polarizing and reaching close the resting membrane potential. So
69:18 M here isn't Mila vaults. This zero Mila vaults resting membrane potential minus
69:26 action. Potential threshold is minus 45 by sodium and flocks, followed by
69:34 e flex and re polarization through sodium poems. During the actual action
69:41 you are what is called in the refractory period. You cannot produce a
69:44 action potential, and following that you're the relative refractory period. Given the
69:50 enough stimulus, you can produce another . Potential action potentials are referred to
69:56 all or not meaning that if you the threshold level of minus 45 million
70:02 here, you will generate an action . Okay, so all or
70:08 if you don't reach this level here member and will re polarized and we'll
70:13 form or inputs excited to input stickum , reach the threshold and produce an
70:18 potential in the way, this is digital code off the brain. This
70:25 are non response and everything that is . Some threshold to this actual potential
70:31 is sort of like an analog So you have both analog oscillations and
70:38 digital spikes 01 spikes that are all none. So when we come
70:45 we'll delve into the neurotransmitter release, we'll actually start addressing neural transmission,
70:53 dermatologic neural transmission, synthesis of glutamate the major glue Dermot Urgent pasta,
71:00 receptors and their functions. So I'm you all a good, uh,
71:09 . If you have any questions, welcome to ask questions. I forgot
71:13 part. I was not enrolled in class for like the first day of
71:23 . Eso I know in neuroscience like the original neuroscience like we had,
71:28 the master students had, like an assignment like here in this class.
71:31 don't have that right, because
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