VideoPoints

• ••• • •• • ••••• • •
BIOL 4315 & 6315 Neuroscience Mon-Wed 1-2.30 PM - Neuroscience Lecture 04 Neurons 2 and Glia 1
Help Tour
© Distribution of this video is restricted by its owner
Transcript ×
Auto highlight
Font-size
00:07 This is lecture four of Neuroscience and important things that we talked about that
00:12 continue talking about today where the organelles these cells. And in particular,
00:20 spend a little bit of time talking the cyto skeletal elements. And we
00:24 that there are three major different sub of cyto skeletal elements, microtubules.
00:32 let me zoom in. So everybody see better the microtubules, neurofilament and
00:40 and micro filaments. We discussed as smallest cyto skeletal elements also comprise of
00:47 smallest molecules. And we talked about ability of these cyto skeletal elements to
00:54 themselves and reorganize themselves, sort of a structural support lattice, like support
01:00 the overall structure of the cell, also for the outer membrane boundaries of
01:05 cell. And we spoke about how elements have the ability to polymerize themselves
01:10 longer chains and depolymerize and get broken into shorter chains. You can think
01:17 it as different structural elements by which can reconfigure a house uh using certain
01:23 of these elements. Now, we that the act in elements because they're
01:28 smallest ones are also gonna be located the outer boundaries of the south as
01:33 indicated by this label. And the labeled here in yellow will be mostly
01:41 the nuclear region. But also you see these what we call micro tullar
01:47 extending into the processes and essentially being for external transport of vesicles of
01:56 Um We further talked about axon that has pretty complex anatomy and different aspects
02:04 this anatomy talked about how the external . So once the goods get transported
02:10 , there's certain things that live there in the external uh in this uh
02:15 uh terminal, external terminal. And have mitochondria, you have vesicles filled
02:20 neurotransmitters. They confused presynaptic, you exocytosis. On the other side,
02:26 have postsynaptic dendrites or postsynaptic dendritic which is filled with postsynaptic receptors.
02:33 the chemicals from the vesicles will bind these possy nic receptors causing a possy
02:38 effect. So, we discussed also presynaptic versus the possy. And we
02:44 about how you can use different tracers even viruses in order to understand the
02:53 where the projections where the processes from . So must extend to how potentially
02:58 networks interconnect with each other. There also dyes that are called transsynaptic dyes
03:03 means that they're going to jump between and between synopsis. So you can
03:09 it across multiple connected synopsis. Uh we highlighted horseradish peroxidase as a,
03:16 a guy that you inject. And talked about herpes virus and rabies virus
03:20 are capable of this retrograde transport, from the periphery back into the SOMA
03:27 the anterograde transport, which was from SOMA into the peripheral regions. So
03:35 ended here on this slide last lecture our next slide begins uh our discussions
03:46 , well, it's not really the neurological disorder because we already have talked
03:53 epilepsy. And what we saw uh regards to epilepsy, is that fine
04:01 . You remember fas gauge, he traumatic brain injury and there was a
04:06 bit of discussion about traumatic brain injuries my other section. And re
04:11 I said that traumatic brain injuries can in other diseases. So in this
04:19 , we'll talk about another disease is and we'll talk about epilepsy, co
04:25 . We talked about epilepsy with regard traumatic brain injury that NAS gauge suffered
04:31 brain injury. However, he developed and actually passed not because of that
04:38 , but because he had status epileptic he had this massive uncontrollable seizure that
04:44 his death. And typically you have if you have epilepsy, which means
04:49 have repeated seizures throughout. We talked how following traumatic brain injury, epilepsy
04:56 a comorbidity may come about days weeks later, but sometimes years
05:03 And it's uh really interesting and on radio and on the news, you'll
05:08 that one of the US bases was by a drone and three of our
05:14 were killed and 25 were injured just . And the ones that were injured
05:22 , it's mentioned in the news from brain injuries. And so there are
05:26 types of traumatic brain injuries, brain or traumatic brain injuries that will cause
05:32 metal bar to penetrate through your A bullet to go a shrapnel and
05:37 are also brain injuries from being near explosive device, not even impacted
05:45 but a whiplash, a pressure wave other consequences. So this is really
05:53 because it's also traumatic brain injuries are related to epilepsy. They're also related
05:59 Alzheimer's disease and the condition that we will mention called chronic traumatic encephalopathy.
06:06 that is a condition that quite a contact athletes or football players especially may
06:14 if they have multiple repeated concussions and multiple repeated concussions are going to lead
06:20 CTE chronic traumatic encephalopathy, which shares lot of pathological hallmarks with Alzheimer's
06:28 I'm not saying that the main cause Alzheimer's disease is traumatic drainage.
06:35 it is correlated. A lot of things are intertwined through some of the
06:40 network or semi cellular mechanisms and cellular . But let's talk about more specifically
06:48 Alzheimer's disease here. When you think Alzheimer's disease, what comes to mind
06:55 getting stuff memory loss is that, that all? So that's what
07:05 most of you know, that's what call the symptom of the disease,
07:11 ? Because when somebody's forgetting stuff, don't see what's going on in the
07:15 and have a sample or spinal fluid their blood. So you don't know
07:20 somebody comes in and has typically the of Alzheimer's is 55 years of age
07:26 older. And the patients with Alzheimer's and early loss of Alzheimer's disease will
07:33 developing memory loss, starting with a term memory loss. So they're usually
07:39 members will start complaining. It's how many times do I have to
07:42 you make a sandwich for me? know, you keep asking what am
07:45 supposed to do? So typically it's short term memory loss, not remembering
07:50 just happened. And then if the , uh le gets left unchecked and
07:59 , currently there is no cure for disease. It is a disease that's
08:08 a part of the normal age. a terminal individuals died from Alzheimer's
08:16 And if these symptoms progress and it for each person, how fast symptomology
08:24 progress. That means it's getting worse the disease is progressing in pathology
08:29 that means it's getting worse in the sense. So from short term memory
08:35 to long term memory loss and typically progression of Alzheimer's disease, patients may
08:42 their family members for quite a while then they will actually start forgetting their
08:47 members and the names of their own and who they are. Now.
08:52 and, and apart from the symptomology memory loss, there's a lot of
08:58 things that are um associated as symptoms Alzheimer's disease. There's a lot of
09:06 as disorientation and space, as disorientation time disorientation and space. If you
09:11 remember people's names, you don't know you found your way into this
09:16 So you're gonna forget how you found way. So every time you're gonna
09:19 to maybe get help or find your here. So that's disorientation, spatial
09:26 , memory also not remembering spatially where located. What happens if you don't
09:31 things? What happens if you don't keys for five minutes, minutes,
09:37 get mad, you get frustrated, get very anxious and what if you
09:41 find it for two days? You what if it is a common occurrence
09:46 whatever happened, you don't know where put almost anything and you don't remember
09:50 to find it or where it's It causes a lot of anxiety for
09:56 . So there's a lot more to symptomology and it is a terminal disease
10:02 at first, it's the inability of brain to remember things and ability of
10:07 brain to orient themselves, other psychological . And later, as is shown
10:15 , this is a progression of Alzheimer's with a severe stage of Alzheimer's
10:23 which essentially shows significant loss of brain . So you have neurodegeneration, neurons
10:32 degenerating, they're dying. And in , you can see significant loss of
10:37 gray matter in severe cases of Alzheimer's patients. So what happens in this
10:45 ? That means that your brain is not capable of performing all of other
10:50 functions and some of them are including functions. So, heart rate,
10:58 , breathing correctly and that causes the, the terminal and in Alzheimer's
11:06 . Um but if you look at pathological hall hallmarks, the pathology of
11:12 disease, we're gonna talk about two that are happening in and around the
11:17 . The first hallmark of the pathology Alzheimer's disease. The formation of what
11:23 call beta amyloid plaques or amyloid plaques senile plaques, you will hear or
11:30 plaques. Sometimes those are the aggregates the inappropriately cleaved protein that starts aggregating
11:41 of the cells. But as it aggregating and becoming larger and larger and
11:48 in other elements, calcification and causing like a ball of inflammation around that
11:56 . It physically starts infringing on the of neurons. It also has other
12:04 like I said within this chemically kind a inflammatory area that starts affecting neurons
12:11 in particular axons and axonal communication can impaired. So these are extracellular
12:20 Another typical pathology uh Hallmark of Alzheimer's of the formation of neurofibrillary tangles.
12:29 you have tau proteins that essentially on , they accumulate, there's overproduction over
12:39 of the K prodi it accumulates around selma and it causes these tangles.
12:45 so remember we talked about how the skeletal elements are very important for
12:53 So in the case of the what it essentially does, it destroys
12:59 normal structure of the cyto skalpel elements impedes with normal transport. Therefore,
13:05 cannot be transported in and out of SOMA. And the first case when
13:11 starts affecting the the cells from the , the amyloid plaques on the on
13:17 right here and they will start affecting axons. Axons will start failing to
13:23 action potentials. So on the the tangles impair the transport on the
13:30 , they start impairing axonal function and transmission, synoptic communication between neurons.
13:40 . So we'll come back and talk Alzheimer's disease again. Uh Currently I
13:47 there is no medication when we talk acetylcholine signaling, uh immune systems,
13:56 will talk about uh major Alzheimer's medications are based on acetylcholine signaling in the
14:04 . Yeah. Which one is the PP. Yeah. So there's
14:14 there's already amyloid precursor protein. It's a part of our natural brain protein
14:22 . It just gets cleaved inappropriately and it gets cleaved inappropriately, it produces
14:28 aggregates outside outside the cells. So will come back and talk about therapy
14:36 for Alzheimer's disease because the only medications are available right now, they can
14:40 down the progression of this disease. fact, open your news yesterday and
14:45 there is a discussion of potentially two medications coming online experimental for Alzheimer's disease
14:52 show the highest degree of slowing down the progression of the disease and there's
14:58 cure. It's just how well can control the progression of the disease from
15:02 few plaques to thousands of plaques from damage to the brain to severe damage
15:09 the brain structures? As is shown on a uh gross anatomical scale.
15:14 very common comorbidity to Alzheimer's disease is . And what is comorbidity is that
15:21 is epilepsy? It's a traumatic brain . What is comorbidity? What does
15:27 mean? So you already have one that is going to shorten your
15:33 especially if you have a terminal disease Alzheimer's disease, it can shorten your
15:38 uh fairly significantly. And there are things that are happening because of the
15:45 pathology already mentioned, impaired external impaired synaptic transmission, uh which leads
15:56 many different problems which also has inflammation talked about. And maybe these are
16:03 of the common mechanisms that we know between the diseases that allow one disease
16:11 Alzheimer's disease due to the causes of inflammation to call upon sort of a
16:19 . A second disease, allow for second disease to express itself. And
16:27 you, in addition to Alzheimer's patients end up having epilepsy also and having
16:35 . And the second disease is on own, also going to shorten their
16:41 . But now you have two diseases are together co are shortening your lifespan
16:51 than right. Yeah. You just the, don't be the cause.
17:02 . Is it because they stop neuron and then not buy you them or
17:09 something else? Ok. So uh not only neuronal communication but it's pretty
17:17 complex processes that eventually leads to both and necrosis of neurons. But once
17:26 uh die or their axons degenerate in CNS, there's no way to regenerate
17:33 the periphery. If you have a nerve, there is a way to
17:39 and regrow that nerve, if not full, at least in a partial
17:44 of that nerve. But in the , there is no regeneration, there
17:50 some stem cells in adult brains, to a very small extent. And
17:57 e especially at older ages, like Alzheimer's disease, 55. And
18:04 there are a lot of mechanisms that allow for the brain to repair itself
18:10 easily, including a lesser number of progenitor cells, potentially uh stem
18:16 um an inability to control inflammation. inflammation sets itself up, it also
18:25 blood brain barrier, which hopefully we'll about today, which introduces other significant
18:32 . So it it it depends whenever injury in general, the best time
18:38 recover from any injury is in the childhood or early adult years. And
18:45 is from physical injury to the bones muscles uh to uh to a
18:53 for example, like a brain surgery you are not necessarily going to have
18:57 significant loss of function if you're a . But if that same amount of
19:03 brain in that same or similarity gets out in the adult or an aging
19:11 , there's potentially going to be a more of that function of lots,
19:15 lot less of the recovery and So we just are not as well
19:21 in older age to repair our bodies brains. So, you know,
19:29 there's this whole thing of uh really old people trying to uh stay as
19:35 as possible. So you'll see it Tik Tok probably too. You know
19:39 some 65 year old telling you I a body of a 45 year
19:45 like somebody should do a series of have a brain of a right.
19:53 uh brain health is somewhat related to too. So having a healthy body
19:59 important because a lot of that energy exercise actually uh benefits our brains as
20:06 . The lactate function. OK. move on to dendrites and dendrites.
20:12 already discussed the pretty complex. They the apical dendrites at the apex of
20:18 we typically consider an excitatory petal c is apical dendrites and then you have
20:24 dendrites and a lot of these dendrites have dendritic spines, they will be
20:30 , but there's also smooth dendrites and will not contain spines. So it's
20:35 necessarily that all of the dendrites will dendritic spines. Now, if you
20:42 trying to classify neurons from the very times of Ramonica reconstructions of all of
20:50 cells, you already started sorting through classes of neurons based on their
20:56 So when you're exposed to the cells the go stain, you have their
21:00 morphology, you can start comparing cells are similar morphological and see if you
21:06 find the same or similar cells in parts of the brain. So from
21:11 point on, we became interested in neurons and understanding how many different types
21:18 neurons there are what are some of features that will qualify one neuron to
21:24 a subtype A for example, versus D or E or so on and
21:29 forth. So, neuronal morphology, you can see here, these are
21:34 your typical parameter cells with these What's interesting about the dendritic spines?
21:41 already discussed this. But what's really about the spines is that if you
21:46 , they have the mitochondria, they smooth and the plastic reticulum, they
21:56 synaptic polyribosome complexes in the spines which them to be somewhat biochemically independent to
22:08 a certain degree and the ability to post translational modifications right there locally at
22:15 level of the spine, not necessarily the rest of the cell and the
22:20 to a limited degree and a lot energy is being consumed again because on
22:26 sides, on the presynaptic side where have the red pre synoptic terminals and
22:32 red vesicles there, you'll have a of A TP for release and recycling
22:37 the vesicles. And on the po side equally, you'll have a need
22:43 lot of a TP, you'll have there. Now, these spines are
22:49 about one micrometer in size and they the most dynamic units in the
22:59 And by dynamic, I mean is their functionality can change, they can
23:04 become stronger, their shape can become . So you can reorganize cyto skeletal
23:11 underneath make the synopsis or dendritic spines . Now, they can contain two
23:20 three po synoptic densities versus just one synoptic density here. For example,
23:26 have one pos synaptic density, 23 densities because this mushroom like shade spine
23:36 for a lot of surface area. a powerful synapse there. And you
23:42 also reshape and make those synapses and smaller. And when you make them
23:49 , they may just contain one pos density. Therefore, they're not going
23:54 have as much impact on the dendrite the whole pos synoptic neuron. So
24:02 strengthening or weakening of synaptic communication because the synapse is larger, has more
24:09 synoptic densities is receiving strong input, going to be re replying or responding
24:15 that input more reliably. If it's smaller input or smaller processing capability is
24:23 to be responding to that to a degree. So, strengthening or weakening
24:29 a part of what we call neuronal . In some instances, the spines
24:37 not just reshaped, they're not just and malleable, they're not just
24:42 but they can be completely driven away new spines can be created. So
24:50 is what we call activity dependent neuronal or activity dependent synaptic plasticity because the
24:59 is happening at the synopsis where two are communicating with each other presynaptic and
25:06 . And although we're talking mostly about dendritic spines of postsynaptic changes that can
25:13 equally. So the pre synoptic terminals also be more effective and larger in
25:20 versus smaller and less effective or not and causing the release of neurotransmitter at
25:26 for one reason or another. In , when we're born, everything is
25:31 lot more interconnected in our brains than is when we refine those connections through
25:37 growth process, through activity dependent process through all of the external stimuli that
25:43 getting as part of our early in particular postnatal development. So the
25:50 number decreases and the connections we find . If everything is interconnected. At
25:56 and later, there's only two or specific connections to develop in these more
26:02 , more developed neuronal macs. But spine number can change and synoptic number
26:11 number of synopses between one neuron to other. One neuron can have 10
26:16 onto the other neuron. It can more synapses have 15 soy naps
26:21 That means it's gonna have way more on this post synaptic neuron. And
26:27 so from the stem synopsis, it go down a number to 6754321 and
26:33 completely eliminate the connection with this And that happens because there is not
26:38 stimulation, there's not enough activity that this neuron or there is not enough
26:44 from this neuron, right? How can you talk to somebody and they
26:48 respond to you before you stop talking them? Pounds, right? So
26:55 will reshape spine level will reshape and of these things. A number of
27:00 and locations, the density of spines the shaft are very, very
27:06 It can be controlled by activity and by genes. And what happens if
27:14 have abnormal formations of the spine. here we're going to look at this
27:19 already third neurological disorder. So, about epilepsy today, Alzheimer's disease and
27:27 Fragile X syndrome, it's a syndrome you have single gene expression and missing
27:36 which is on X chromosome. So affects boys more and the X chromosome
27:42 fragile. Uh And what it does this is a early developmental disorder.
27:51 an intellectual disability uh with certain phenotypic . So that's, that's another interesting
28:00 for you to start thinking about. , first of all, there's
28:05 right? Symptomologies, I'm forgetting But if one individual, two older
28:11 or ladies walked in, they were 75 years of age and one of
28:17 was forgetting things and another one was , will, will you be able
28:22 tell that the ones that are They look a certain way, they
28:25 a certain phenotype, they have giant or something like that. No.
28:30 this is on the outside now. in certain neurological disorders, you will
28:36 phenotypic outward features and fragile X is of them. So a lot of
28:42 patients with that fragile x will have face shape and fairly large ears.
28:51 so obviously, this is not how neurologist would diagnose somebody with fragile
28:56 but this is just one of the of reference from them. Symptomology.
29:02 , if there is a phenotypic feature adds on, is there a genetic
29:08 because there's a genetic component to finally come up with a, with
29:13 with a diagnosis. It's a complex . It falls under autism spectrum disorders
29:20 it's essentially under autism spectrum disorders are considered a comorbidity because autism spectrum disorders
29:29 a very large umbrella uh disorders that a genetic component that sometimes don't have
29:36 component, behavioral component, uh it has to do with learning and
29:41 features. But obviously, this is and that's why sometimes it's a
29:48 Sometimes it's under the umbrella. That's interpretation of fraudulent acts. Now,
29:54 of the things that's important that relates what we're studying is this is a
30:00 spine from an input that has intellectual . And what was noticed is that
30:08 spines are very different. And it's not all about how long they
30:14 or how big they are. It's about the variety of the shapes that
30:18 come into their locations along the the densities where they're located in higher
30:26 versus smaller densities. And this is of the hallmarks, one of the
30:34 also for fragile X, it is and the spa. Now, if
30:40 look at this image here, what shows is that in green everywhere where
30:47 see a green God, we call a green punkt. You have glutamate
30:53 , you have an excitatory synapse and shown as glue R stands for glutamate
31:01 , those are excitatory receptors and these be excitatory synopsis on that c but
31:08 same cell also has all of these dots on it and these orange dots
31:14 plant are for Gaba receptors and Gaba . And Gaba synopsis are the major
31:24 synopsis in this neuron and also in brain. And what this illustrates is
31:31 single neuron will contain thousands, sometimes of thousands, sometimes even hundreds of
31:39 of synapses. A lot of them going to be excitatory. That means
31:43 there is excitatory inputs projecting onto the . But a lot of them are
31:49 to be inhibitory, which there's going be a lot of inhibitory inputs projecting
31:56 the cell. And the job of neuron is to take all of the
32:02 information. And sometimes you may have synopsis being activated at the same
32:08 In different ratios, there might be excitatory synopsis and 400 inhibitory in all
32:16 of different combinations. But so now happens if you impair the sri
32:23 if you impair the indri spines, if you impair the communication, that
32:28 you cannot process properly all of the or inhibitory inputs onto the south.
32:35 , again, the communication for of the interpretation potentially of the external stimuli
32:41 the communication between the south is going be different than these individuals. So
32:49 get back to classifying neurons. We to understand how neurons are. And
32:54 one of the simple ways again is look at their morphology, unipolar
33:00 bipolar cell and a multipolar cell. which case, multipolar cell has projections
33:08 in all directions and all the poles the bipolar cell goes north south and
33:14 , just sort of has one process bifurcates. So what are some of
33:20 cells? Morphologically uh unipolar cell would an invertebrate neuron, bipolar cell would
33:29 a sensory uh cell that will study the visual system called the bipolar cell
33:35 retina. When we look at the circuit uh pseudo unipolar cell. Oh
33:41 unipolar cell is a ganglion cell of root. Does that ring a
33:49 Remember we talked about how you have cord? So like a butterfly like
33:57 and this is the dorsal side and is the ventral side here. And
34:07 we have this bundle here and this where the SOMA are of the dorsal
34:14 cells, right? And they have axons going into the periphery.
34:21 So this is the peripheral axon and they have another axon is called the
34:26 axon. OK. And that goes the spinal cord. And then you
34:31 study that the synapse onto the cells . And from the natural side,
34:36 have multipolar cells. So this is unipolar dorsal root ganglion cell. Is
34:44 excitatory or inhibitory? It's excitatory. understand what that means. And then
34:57 neuron and motor neuron goes and becomes part of the same spinal nerve,
35:05 . You have spinal nerves here and is the motor output. Is it
35:12 inhibitory? It's only excited part and uses the C toline. That's something
35:23 you should have studied in the anatomy physiology. So, neuromuscular junction,
35:29 ? We'll talk about spinal cord OK. So we have dorsal gang
35:34 cells and this is something that's an thing. I usually tell uh my
35:41 that I will have questions about different class. There are certain things that
35:49 want to know about the set So for example, we already talked
35:55 the Raid all styles or SORU And so uh say we're gonna talk
36:09 motor neuron. What are some of things that we want to know about
36:18 style? So for example, I know, are they excited for,
36:22 the inventory? What is neurotransmitter that release when lo the world more would
36:33 out? What is their morphology? are great uh midterm one matching
36:45 And we'll learn about these cells over next uh uh couple of lectures,
36:51 and more details, but it's good start inquiring and understanding what those cells
36:57 and what they are. So a of rumors, for example, for
37:01 transit will release a see of the brown cells which are called to
37:08 lina well as gang against them. you should start making yourself like a
37:15 table like that because that is going ask you like for example, which
37:20 are motor neurons located on ventr or . And this type of note taking
37:26 general and even taking a sound or it, apical basal no rides
37:32 things like that. Even some basic sometimes can be very helpful. So
37:36 lot of the cells in the brain multipolar cells. The motor neuron is
37:41 multipolar cell. The theme cell is cell. This is a fini cell
37:48 the cells is a multipolar cell and contain all sorts of different shapes and
37:55 bifurcations in anatomies. If you can the spinal motor neuron, on average
38:00 contain about 10,000 synopsis. But a uh the tree containing cell like cell
38:09 contain 100 50,000 synopsis. So that's amount of information that a single
38:15 a single unit has to process. how else do we classify neurons?
38:24 , projection cells verses into neurons. projection cells versus into neurons. What
38:30 projection cells? Projection cells are the that are typically when we talk about
38:38 cells, we're gonna talk about petal . That means they are, they
38:43 excited cells release glutamate. That means project from one neural network or one
38:52 of the brain into the other area the brain. As opposed to inter
39:00 , interneurons are the cells that will located here in this neural network.
39:07 these interneurons typically are inhibitory and typically release Gaba as the major neurotransmitter and
39:18 can communicate to each other. They communicate to parameter cells but they will
39:26 have axons that project long distances into other structures. OK. So these
39:32 projection cells typically parameter cells and these interneurons. So that's another way in
39:48 we can classify the bad excitability, cells release glutamate inhibitory cells release
40:02 But is that all the chemicals? , we'll study many, well,
40:08 more chemicals in the brain at And uh it gets a little bit
40:13 complex than just excited or inhibitory neuropeptides. So what type of uh
40:23 they are? The projection cell, kind of neurotransmitter they release? What
40:29 of neuropeptides or cells? Specific They may contain cells, specific markers
40:35 call they may contain. This is first published in intercellular action potential
40:44 So in 19 thirties and especially during war two and after world war
40:51 the development of pretty sophisticated electrical circuits especially for the naval ships and the
41:01 uh for the navy and these oscilloscopes are really fast, they also developed
41:07 scientists start using these oscilloscopes in the thirties and forties later that they become
41:14 oscilloscopes and capturing really fast activity on fast activity is the action potential.
41:20 neurons produce action potentials that are about to 23 milliseconds in duration and about
41:29 millivolts in amplitude. It's a very electrical potential in neurons, action
41:37 And so if before 19 forties, , we understood the shapes of the
41:45 because we had all of these dyes we have microscopes, then it was
41:51 for us to understand the activity of cells. Can we correlate certain
41:57 Do petal cells have a certain what we call pattern of action
42:04 So, firing signatures. So action is like firing because it's so
42:10 Uh do they thermal cells have different potential patterns from the interneurons? Or
42:19 they all the same across the So you can be a parameter cell
42:24 inter neuron, dorsal ganglion cell or neuron. And you will always produce
42:29 same action for Schultz and the same . And with these experiments, we
42:36 start unraveling the different cell subs have patterns of actual potentials. And that
42:42 can indeed correlate these patterns to specific uh genetic expression. Once we have
42:53 tools to analyze cells genetically, now can start and generating antibodies, for
43:02 . And we're talking about the second of the 20th century, you're generating
43:06 , you're tagging cells, you're doing to chemistry, you're revealing different
43:11 different neurotransmitters across the brain and also . Once you have the genetic
43:18 you can study what unique subsets of that are on these cells that are
43:26 what unique proteins or receptors that are in these cells. And we realize
43:33 these subtypes of cells are different because express slightly different subset of genes.
43:39 there might be 100 different subtypes of , they all neurons, but they
43:45 have a variation in the subset of genes that they express. And the
43:50 and molecules that they carry. Although have the same code, like every
43:56 has the same code DNA, but every cell is going to utilize all
44:04 the time, the same pieces of code. And that's what makes cells
44:09 by expressing that code differently, having abilities to uh to differ morphologically and
44:18 . OK. Now we are doing like single cell RN A sequences and
44:24 throughput. How many 100,000 cells a where we can analyze uh all of
44:31 trusts it's called can't pronounce it trans pretty cool stuff. So now we
44:43 that neurons and we can visualize them infrared microscopy. We can put electrodes
44:49 we find two cells here. This for my reporting at the beginning of
44:56 21st century. Uh So you have cells and they have two micro electrodes
45:02 them and we give them the same stimulus. So the cell on the
45:07 and the cell on the right, see the exact same stimulus from that
45:12 . And what you see there, one of these lines, every one
45:15 these six is an action potential. these are action potentials. So each
45:28 of these sticks is like an Each one uses a natural. And
45:43 can see that the cell on the once you give it more and more
45:48 the stimulus which would really inject more more positive current, it responds with
45:54 very fast pattern, very fast frequency action potentials and it sustains that very
46:01 frequency. And the cell on the , it gets the same input from
46:06 electrode. So the same stimulus or of the same stimulus, but it
46:11 with a much slower pattern of action . And also that spaces itself what
46:18 call accommodates it goes from faster frequencies slower frequencies during the response of the
46:26 . So we understood pretty clearly that cell subtypes will differ functionally. Both
46:38 these cells speak neuronal language of action . But I call this a different
46:46 . So the cell on the left different dialect from the cell on the
46:52 , this is a functional output of cell action potential is going to cause
46:57 release of the neurotransmitter. That's why functional output of the cell that eventually
47:03 cause a certain pattern of communication. certain pattern of neurotransmitter release very fast
47:09 sustained pattern from one cell versus very and less sustained pattern from another
47:18 So it all influences neuronal communication of direct these recording. So we can
47:24 really smart and we can place a that is called neuro, sometimes also
47:29 biocyte and neuro and dye once it's inside the cell. So during the
47:37 , you have an electrode and it have this neuro and dye and this
47:42 will enter into the cell and it expose all of its beautiful morphology.
47:49 as we do these recordings, we the cells using infrared microscopy. There's
47:54 stain, we give them electrical stimulus re record their functional electrical response or
48:02 documents. Then during the recording, fill the sauce with the dye after
48:10 recording, we process the dyes and reconstruct the precise morphology of these cells
48:21 finally, we can crossing them. , apart from this dye after or
48:28 the process of processing and then revealing dye in the tissue concurrently before or
48:34 there's different ways. But you can use antibodies to see if those cells
48:43 specific markers. So immuno chemistry and we do all of this, we
48:52 the morphology, we know the We know the location of the
48:57 what network they're located, we know markers they stay for intercellular. Then
49:03 really good at refining and defining that cell subtype. And of course,
49:12 you have the ability to suck up cytoplasm inject the dye but also suck
49:18 the cytoplasm. You could do single RN A analysis on that also.
49:25 this is being now replaced by some the high throughput uh RN A sequences
49:31 are available. This is an example a patch of a cortex and then
49:39 patch of the cortex. This is small patch of the cortex. Number
49:43 single cells, about 10 micrometers in . Many of the cells were
49:49 We called it patch. The cell a microelectrode were recorded from different cells
49:55 this um cortical circuit here and all these cells received an identical input and
50:04 can see that certain cells responded again these fast sustained sequences of action potentials
50:14 . So, although these cells here receiving exact same input, but they
50:20 respond, all barns will go the on top beat called stuttering cells because
50:35 can give them a continuous input, stimulus and they will stutter. So
50:41 will produce these stuttered trains of action that cells like it's not continuous as
50:49 would see here. And so now I demonstrated it, I want you
50:55 to pick your favorite um run it just for a good vocal exercise.
51:02 on. You don't have to be . It's just like boom,
51:10 boom, boom, boom. At point, I have a TED
51:15 I I should have done this. I said it's like because that's what
51:20 potential sound like when you actually can them from electrical signals into an
51:27 But I like this illustration. So but but you're getting the um the
51:34 flow here in the sense that these all different dialects. And now you
51:41 expect that because these cells speak different . What would you expect? There's
51:46 to be different about those cells, morphology, there's cellular gene expression,
51:54 , certain proteins and channels that are be different? OK. What else
52:01 neurotransmitters that they release may be different they are projection cells versus interneurons?
52:11 . So there's many different methods and gold standard of defining a neuronal
52:20 right? There could be a There's 100 no there's 100 40
52:23 there's 100 4347 and so on and forth. You could have this
52:29 the moving target for the gold standard the subs of the cells. It
52:32 moving as the technologies are improving. , but we can do our best
52:37 trying to uh very clearly define them much as we can using as many
52:43 tools as we have to or as as we have available or have
52:48 Or this was my setup at George University where I did my second postdoctoral
52:55 which was on epilepsy. And in , in my study, I was
53:00 to know what cells start, epileptic , which subtype of cells. So
53:07 wasn't enough for me to know Oh, this cell started, I
53:11 to know what subtype of the cell it that started these seizures. And
53:15 answer that question. And to this , actually, if you want to
53:20 to the resolution specificity on electrical activity individual cells, you still have to
53:26 the single cell patch lamp or electrophysiological . And if you wanted to know
53:34 one starts, which cell starts you need at least two cells to
53:39 that. And it is better if have three cells and it is best
53:43 you have four cells, you can from concurrently. If you're mad
53:48 I think world record is seven and is somewhat automated at the same
53:52 very difficult long experiments. But they us some very interesting activity in the
53:59 tissue that we published. And two three years later, the same type
54:06 activity was discovered in human living human . So what you find in the
54:12 is another lesson. It's not only said, well, Goji just
54:16 I'm just gonna bring the stain and it on the brains. You can
54:19 a lot of innovation, academic so to speak. But uh also
54:26 you find in the lab. A of times it's like, what does
54:29 have to do with me with my ? Well, a lot and a
54:37 of things that you find at first simpler models in simpler organisms. We
54:44 a lot of genetic similarity. We homology of proteins with many different species
54:51 this world. We can learn a of things and from these types of
54:57 , we learned that the inhibitory cells the ones that start seizures. It
55:02 very surprising and it took us about years to prove to the scientific community
55:06 reviewers that that is the case. after we did it then just a
55:11 later, there was a human study living brains showing very similar patterns of
55:17 from inhibitory neurons starting seizures as So it's really, really gratifying um
55:24 , to know that your work can an impact uh and be applicable
55:30 to society classifying neurons. This is example of a really famous circuit really
55:36 started circuit in the brain that we the hippocampus. OK. And the
55:42 mainly consists of the three layers. the top layer is stratum radium.
55:49 have it labeled here on the la , then the white stratum ravalli bottom
55:57 ST or so for the most they count all structures of three layered
56:03 . And what is portrayed here confuses uh a lot of students and uh
56:12 asked me two or three times, do they need to know for the
56:16 ? But this is a publication from . So when you talk about something
56:22 is still relevant, this is still relevant. Of course, there's
56:27 refinements and improvements. Single cell RN uh high through blah blah blah.
56:32 molecular analysis have been refined and played the subtyping of the cells. But
56:37 still illustrates how one really can know many subtypes of cells there are.
56:44 this is the hippocampal circuit. And the circuit charges show these cells in
56:49 blue and these are the parameter cells are projection cells that means that they're
56:56 with the axons are going to exit of the cans. Communicate that information
57:01 the other platforms. Exci cells to glu they mostly live in strata from
57:10 , some of them live in the two layers. Morphologically, the subtypes
57:15 the cells the three that are shown identical. So the location of the
57:21 where you find their CS in Galla Ra Island is a little different.
57:26 else is different? The only thing CD which stands for called be turns
57:31 that some parameter projection cells express cal and others do not. And this
57:39 fairly simple for the excitatory projection cells the hippocampus. That means those cells
57:46 super important for communicating information to the networks uh of the brain.
57:54 you see surrounding these petal solace, , all the way through 21.
58:01 are inhibitory interneurons that are staying in circuit locally. They're inhibitory because they
58:10 Gaba, they're interneurons because they do have axons that leave the hippocampus and
58:18 to other parts of the brain. about 80 to 90% of all the
58:25 in the hippocampus are excited or petal . So if you look at this
58:34 that and hippocampus, 80 to 90% the cells are pinal cells which leads
58:45 to 20% of all the cells as neurons. And there isn't that much
58:52 variety. And as far as the , despite the fact that interneurons only
59:00 for up to 20% of all of cells of the campus, there's at
59:05 21 different subtypes of those interneurons. there is a lot more complexity in
59:13 network processing, especially local network processing stems from the inhibitory cells. Those
59:24 , some of them live in others live in red is the orange
59:30 red. We have dendrites, some their dendrites will be extending vertically.
59:36 will be extending horizontally, those yellow and those purple processes. These are
59:44 and the yellow cuffs of synopsis. it shows that certain neurons will form
59:49 right on the c of the projection and other into neurons will target the
59:56 dendrites of the parameter cells and yet will target the basal dendrites and even
60:02 axons of the parameter cells. So about this network pretty complex where you
60:10 21 different players. These players will different dialects, ta ta,
60:16 ta, ta, ta, ta bla bla bla bla bla,
60:17 ? They're all speaking with each other this network. They're speaking to the
60:22 cells, they're controlling parameter cells at apex on the SOMA on the base
60:30 on the output to this inhibitory neurons a lot of control of the petal
60:38 and they will determine what kind of gets projected into the adjacent network.
60:45 can actually completely because they inhibit they can completely quench and suppress any
60:51 and nothing is going to project from A to network B. They can
60:58 a certain pattern, a certain dialect will dominate, which will influence this
61:04 cell to communicate through this network in specific pattern. Allowed I communicate
61:10 I don't communicate. So you have level of complexity at the local circuit
61:18 that is introduced by the inhibitory There are much more diversity in the
61:25 cells morphologically synaptic. And also if finally do this cellular analysis of molecular
61:33 of cell specific markers, it's not you to memorize this. But some
61:38 the in your cells like two and look identical. So what's the difference
61:43 two and four? They may even the same dialect. But two is
61:48 basket cell that expresses pro provide and is this basket cell that expresses another
61:55 to kind of a different marking side it which qualifies it as a different
62:01 of the cell given other uh features things that go to the analysis.
62:07 what do you need to know for exam about this is that in the
62:12 , which is predominantly three layered you have a lot of inhibitory
62:16 Uh Now how you tell the difference inhibitor excitatory cells know that the exciter
62:21 are projection cells, inhibitory cells are because they release gaba the local circuit
62:28 . But there are also a lot variety of these cells. So they
62:33 really impact and determine what kind of gets communicated out of that network into
62:38 adjacent and contribute a lot to allowing the adjacent networks to communicate and synchronize
62:46 or not communicate at all and get of sync, right? And that's
62:55 important for neuronal plasticity and learning and . So, Ramon Kahal, when
63:04 was drawing different subtypes of cells, can see he drew around, he
63:08 drawing with PC, he also glu lose glia. So he also stained
63:20 in human cerebella. So on the in B are different types of Astros
63:27 the time, he named them as glia smooth for the plasm with as
63:34 for V Astros that have be marketing with an app pretty remarkable,
63:42 So he already sept died, not neurons based on their morphology because he
63:47 record action potentials. He did not immunochemistry available to him or a high
63:55 with RN a sequence, right? But he also started defining morphologies of
64:02 glial cells. And in this he was a pioneer in this area
64:08 well. So for glial cells, have four major subtypes of real cells
64:14 we will discuss in the sports radial , oligodendrocytes, microglia and astrocytes.
64:22 glia is very important for the development neuronal processes, neuronal migration and
64:29 What does that mean? Neuronal Where are neurons migrating? Were they
64:33 guided to they're migrating because they are in specific areas of the brain.
64:40 neurons are not born you layer cortical neuron and occipital lobe is not
64:45 in layer six and occipital lobe. born in specific zones around inside your
64:54 . Actually and then from those specific , they migrate into their final destinations
65:02 to migrate to their final destinations, need guides that will get them to
65:07 final destinations. And radial glia have their physical guides to those final destinations
65:14 the neurons. Oligodendrocytes are important for and supportive neurons. When we talk
65:22 insulation, we talk about oligodendrocytes wrapping the axons and forming myelin sheets around
65:30 axons of neurons Microglia is the most mobile elements in the brain that
65:38 involved in injury, cleanup, scavenging an injury and repair and immune
65:47 So, microglia released cytokines and you have heard when COVID-19 was in full
65:54 . Even National Public Radio was talking the cytokine storms. You know what
65:59 side? It's not like, you , gulf storm is different cytokine
66:04 It's like you have microglia that control that release cytokines to call upon the
66:11 response. It's normal response if you an infection, inflammation, injury in
66:16 brain. But if it goes out control, the cytokine release goes out
66:21 control. And you have these cytokine including promoted by microglia, it can
66:28 more damage than a positive response in brain and can perpetuate the process of
66:36 . As Tracy, you can see Asy there and you can see that
66:40 end and processes of the ostracizes of top, right is wrapped around the
66:46 , wrapped around the dendrites and the process form the feet on the
66:53 on the blood vessels. So, is very important in synoptic plasticity and
67:01 release in synaptic formation. We call of synaptic formation, synaptic genesis.
67:09 astrocytes are also very important because there checkpoints. They are one of the
67:13 checkpoints at the blood brain barrier. the barrier between the blood and the
67:19 . So they will patrol and monitor that can enter or not from the
67:25 into the brain. So a lot functions that glia is responsible for.
67:31 I said, you won't have a if you have, don't have the
67:35 and glia will influence neuronal migration growth neuron, synaptic formation, synaptic
67:44 homeostasis of the brain as a as whole, in particular microglia, ostroy
67:51 controlling these processes of inflammation of chemicals even energy and neurotransmitter release, especially
68:00 the excitatory glutamate cells. This is of glial cells that are involved in
68:07 development of neuronal processes. So glial literally have this process here that gets
68:17 by neurons. And what neuron does neuron climes along this process. So
68:25 actually have cytoplasmic continuity between neurons and glial cells. And neuron will use
68:34 radial glial cell like a rope like lattice to migrate and to find its
68:40 destination. Hopefully, this link will . Hopefully there's no commercial in
68:57 This is an example, it's working my screen, but it's it's not
69:01 on your screen. It's not showing of it. Folks are dropping
-
+