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00:01 Okay, so this is our fourth in this course, and we're going

00:09 continue talking today about neurons and glia not certain if we will get to

00:14 neuronal Numbering addressed are resting membrane But I think as we talk about

00:22 material through the course, hopefully we'll up where we need to be with

00:26 material from mid term one. Now deep that I have is I received

00:32 message from Casa saying that you could a test long in exam. I

00:41 just a blow they very simple general that you would have toe answer and

00:48 would be able to test all of systems and taking the virtual Kosta

00:55 And the suggestion from cost A was you to take it this Friday,

01:00 would be September 4th. So you have to register for today and tomorrow

01:07 take it some time on on I also think that Friday's before Labor

01:15 I'm not sure it's the Rani our plans, but if they're I think

01:20 of you might be traveling by So, um not sure how to

01:27 this. It may be we uh, teach a little Ah,

01:33 all on chat. Uh, right , uh, I guess the question

01:39 , can you would you be willing take a very quick log in test

01:45 Friday, or should we piss opponents next week? Uh, giving you

01:52 time? Teoh, gather all of don't Charlie tools. So see,

02:00 a little illness. Sweetest fun. locating its foreign, it's who?

02:07 front. It's from his friends. , currents. Okay, So what

02:15 do is I will, uh you be able to actually go to Casa

02:22 register for the exam. And I coordinate with Casa today to make sure

02:30 everything will proceed smoothly on Friday for to take us again. You're not

02:37 grated, but this. So this ah purely for you. Test out

02:42 system. Make sure all systems ago that you don't have to stress about

02:48 having a Charlie tool to take the exam on the day of exam.

02:55 right, so we'll receiving this I will communicate, and we'll have

03:01 follow up email to you that all confirming this virtual trial test sample.

03:12 , for which you don't get the you're not getting graded for for for

03:16 Friday. All right, so I know. And one of the key

03:23 off neurons that we discussed. last time with Dendrite. It's and

03:30 particular, the dendritic spines. And talked about dendritic spines is being really

03:36 protrusions, that air coming off the branches in dendritic trees and that these

03:43 and the size of connectivity between neurons so the synapses and the Boston optic

03:50 in particular would be located on dendritic . And all of the information coming

03:57 these spines will be coming from other from other excited, very excited Torrey

04:04 , a turgid cells and synapses so inmates is excited to be neurotransmitters shown

04:11 in green all of the glutamate receptors arm, the down brides and around

04:18 storm off this particular south and the so will be receiving very strong inhibitory

04:27 . And these inhibitory and was mediated Gabba gamma immuno beauty recast it and

04:34 receptors on the image on the right shown in war egx. So everywhere

04:40 see, orange is gamma receptor cities dendritic spines that continue inhibitory receptors,

04:49 air the receptors that will bind inhibitory . And when gabba binds to the

04:56 receptors, cell activity gets inhibit, cells become less active, their activity

05:03 dampened. Uh, when gloomy excites green synapse isn't Boston optic densities.

05:12 cells get deep polarized, the cells more excited, and the cells produce

05:18 actual potential. So they produce more the electrical activity and they release more

05:24 the chemical neurotransmitters onto the other neurons the line. Now, what we

05:31 is that alterations and, uh, dendritic spine densities and the location along

05:41 dendritic tree and interdict shafts. And structure of these finds the morphology of

05:49 fines are very important. And on left you have an image off a

05:57 spine from a normal infant. And the rise you have an image of

06:03 dendritic spine from a mentally retarded in . And as you can see,

06:10 doesn't really expire in some, the are distributed differently, or maybe more

06:19 . In some areas are more dance the other areas that their morphology that

06:25 shape of the them did experience is different on the right is compared to

06:29 left. This is one of the of the sin Jones. So this

06:34 one of the, uh, autism like disorders or a SD Autumn autism

06:44 like disorders and fragile acts. this is a developmental mental red irrigation

06:54 one of the bath Allah, Jeez fragile X as well as the models

07:00 modelling. This autism syndrome like disorder these of normal morphological arrangement off dendritic

07:13 , because structure means function and function and structure and alterations and even the

07:22 will cause during early development alterations in structure of these parents. But once

07:28 structure has been altered, especially if is a long term change such as

07:34 term plasticity change long term depression, some spines over excitability and long term

07:41 ation, as we discussed in the lecture, then, uh, once

07:47 structure has changed, the functionality can permanently as well. And and if

07:55 doesn't change permanently, it may not . It's malleable compared Teoh normal den

08:03 and normal dendritic spines. So a of things to do when the spines

08:08 impaired will be influenced. The synaptic the calcium regulation expression of molecules at

08:15 levels of the dendritic spines and so important. Okay, so for our

08:22 section, we talked about Alzheimer's disease time, and we described the key

08:31 of newer pathology of Alzheimer's disease that adding one more disease now here.

08:36 acts, which is a part of family of the diseases. They're called

08:41 syndrome like disorders, and the neural feature of fragile X is have

08:52 um, dendritic spine morphology and arrangement as well as, uh,

09:00 It's mental interrogation. So this once again, I want to reiterate

09:06 this process of spine development during early spine establishment, which is really establishment

09:14 this sin abscess, is very much on activity. And that's where we

09:21 that this is an activity and environment plasticity. Because duty and environment,

09:28 during the early development, are someone nurturing environment, active environment, stimulation

09:40 different census stimulation of social interactions. are all important things that play into

09:48 Nuremberg pathology and the normal normal anatomy well as a neuropathology off. This

09:56 is, well, US genetic so they can be familial that becomes

10:02 from the family that they can be , which means that they just occur

10:09 , do to the environment. And why so this environment, opportunity and

10:14 could see Jean uh, processes that influence the final structure information of the

10:22 and then further, once the structures activity, I even environment that changes

10:29 change the plasticity of these structures, the synapses, weakening the synapses SARS

10:35 shown on the right this spinal contained Colorado Distomo complex. And that indicates

10:43 the dendritic spine, which is adjacent it's on the Ryan adjacent to the

10:48 tone along the last that this dendritic is an independent by a synthetic

10:55 a zone. By possessing this part so more conflicts. Also, it's

11:01 surprising if in some of the synopsis many synapses would also see um,

11:06 p. A special in the pre side is is one of the energy

11:11 that is necessary for the exercise doses . So, uh, moving on

11:19 neurons if we already talked about certain things about neurons first, we said

11:27 neurons can be roughly divided or are into two major classes and those air

11:36 two year olds and inhibitory neurons. then we said, in with them

11:41 excited inhibitory neurons. And general, over 100 50 different stuff. IVs

11:47 different. So how do we describe neurons and where some of the features

11:53 are common amongst these nerds So most have more functional regions, which is

11:59 inflict region on the top with and have an integrated region. Then you

12:05 to conduct our region and you have output region. The input region is

12:09 that particular neuron receives its temper and component complementary component or input words coming

12:17 So ah, neuron a neuron. model Darren is contacting another your on

12:23 its SoMa, which serves in his units of many synapses. Potentially

12:30 different little neurons contact the soma, then the solar decides whether it's the

12:36 unit and integrates excited during inhibitory Onto this narrow and the overall

12:44 what is happening? The levels of and decides next the computation, whether

12:50 going to produce an action potential, an action potential is going to get

12:56 , and the axle on hillocks which located between the Ronel Soma in the

13:01 segment, the first violin aided segment the axle, then conduct all unit

13:07 a shown here and Blues Mile. she's a wrap around the accents that

13:13 as a conduct I'll units that conducts electrical potential change. That actual potential

13:18 is gets generated. A level of axe. Our killer. It conducts

13:23 but propagated conductivity into his outfit which is a synaptic terminal in this

13:31 , Axe Onal Terminal. And there a secretion o. R or release

13:36 the neurotransmitter. And not, but so in the, uh, second

13:45 from left arrived, you have a neuron, so you have an input

13:49 the skin, so we already know kind of neuron this would be.

13:54 example, we already discussed the anatomy the spinal cord, and we said

13:59 is divided into the door. So car and central motor part, and

14:06 send that the door so sensory since out then picks up the signals

14:10 the periphery. This would be a axe on, then picks up the

14:16 in the river and conducted into the So you have here different arrangement where

14:22 have the peripheral Axum is conduct all . Then you have the dorsal root

14:27 there, the spinal cord that will the integrity of, uh,

14:31 calculation. And further, you will it through the central AC so onto

14:36 neuron. So from the sensor in , um, let's say from the

14:40 through dorsal root ganglia, and you contact the motor neuron and spinal or

14:47 zones. And of course, the neuron will release the neurotransmitters inactivating the

14:54 neurons. Now, motor neurons here contact, uh, other motor

15:02 Or these implantable comes from the sensor can activate a motor neuron and that

15:08 neuron will conduct it's information actual potential gets generating the solar here and well

15:16 neurotransmitter onto the muscle, causing the of the most now local into neurons

15:24 the Interneuron is that don't conduct signals long distances. But you have a

15:31 Interneuron step interconnect with each other, most of the local interference of the

15:36 are inhibited, turned into neurons, in fact, most of that diversity

15:41 the subtypes of the brain comes through diversity of that inhibitor ended. There

15:46 Interneuron PSA Grain. Then you have into neurons. This is a

15:53 but these are some of the rear neurons that will inhibit our engineers That

16:00 project the longer distances on. And you have narrows that actually are contacted

16:07 then you're and a cream cells, they can actually release an influence

16:13 as a constriction of acid elation at level of the capital ary with in

16:20 , despite the fact that you can other neurons and humanitarian excited story that

16:26 can announce contact must also cost muscle that, because, uh that Kabila

16:34 a constriction of acid elation in the , Um, and overall sort of

16:40 apparent crime like secretion from the neurons Korean systems in the way you have

16:45 huge diversity of these sounds, but of them Happy's four functional regions.

16:51 we just discussed here. Okay, now let's look at some of the

16:58 and let's start learning increasingly more so these different cells. So morphological ease

17:07 way in which you distinguish these We want to stop. Classify them

17:13 , what's to stop classifying them into 150 different. Sometimes we have to

17:17 a lot of the information. we have the morphological information that so

17:22 you live, you have ah, polar cells and those. It's also

17:27 a cell body and have one So North Pole only. And you

17:33 accents projecting into dem rights. And projecting in one direction of visa difficult

17:40 neurons, Bipolar or so, such as bipolar. Sell off the

17:47 . We'll have dem drives. Then have so volume will have an accelerant

17:53 Jackson. That's bipolar because it has holes. It has a very clear

18:00 pole, so to speak, which den drives in the Southern Pole,

18:03 is Axl pseudo unit polar cells or cells Again, a retinal cells to

18:10 find them in the olfactory epithelium on someone spinal cord suit early in a

18:17 cells, you know, you polar cells are, uh, cell

18:24 cells. They have peripheral axe song projects the skin and muscle, and

18:30 has essential acts on single process. by for Kate is single acts on

18:38 external terminals that contact spinal cord cells This is our dorsal root ganglion cell

18:48 . It's pseudo unit polar because it a peripheral axum, and it has

18:53 central access. It doesn't have a north done dried south. Excellent,

18:59 instead north. Maximum inside back. subsidiary. The polar cells, those

19:05 mechanic receptors for perception and sensations of Jane pressure projections. They're going to

19:14 spinal cord, as we discussed You have a lot of multipolar salsa

19:19 the brain, three times a multipolar to show that the bottom off this

19:24 two diagrams. Uh, first one motive during a spinal cord. It's

19:30 because it has multiple poor, poor . Accent is pointing one direction,

19:36 then you have done dried, start radial E and have multiple projections in

19:42 directions. Karama Bill Salus in hippocampus Perama, tal cells of the

19:47 We actually mentioned and discussed these prom sauces or the major excited Forest house

19:53 the court. Actual criminal solace. describe a shaped sort of like a

19:58 three dimensional paramour bid on by that and has an ethical 10. Brian

20:04 in the top 10 and has Basil , sir, creating out of the

20:09 of the pyramid. And also the of the pyramid is because we have

20:13 projection off the axe on. So are around. It all sounds

20:18 Very sauce on their campus. On left, The motor neurons are motor

20:23 of the spinal cord. And on right, at the bottom riot is

20:27 of, um, many lure. either Mr many artists. Ah,

20:32 cell is a poor Kenji style of Balham that has again, that's a

20:38 self, and it has an incredibly dendritic tree. So when we talk

20:46 cells having hundreds of thousands of just look at the magnitude and the

20:55 off off this dendritic tree. And imagine the the month of computation that

21:05 cell has to dio in order. , they're in quickly calculate all of

21:13 information from all of its inputs, the more complex cease trees are,

21:19 more studied are the den drives with spines. The more complex is

21:26 computation, But that computation, even Sarah Palin, the potentially cell level

21:32 to happen on the order of milliseconds cerebellum is being some of the fine

21:41 Command Adjustment center, essentially middle name motor commands has to do very quick

21:49 . Very quick calculations or two. you have different times off sin ounces

21:57 where you have different types of polarities and different times of war. Apologies

22:02 describe this cells based on the Um, spinal motor neuron is a

22:08 has about 10,000 synapses. Um, cell can have up 250,000 synopsis or

22:17 ? Nah, just stick em Um, then drilling tree.

22:26 now there's some other classifications based on fact that some parents are very clearly

22:33 neurons that will have spines. And can see these spines and you stay

22:37 the South so you can see this protrusions using a light microscope, and

22:42 will be some several not contain any . And also you can. There's

22:48 other gasification based on spying on our . Me. Um, now what

22:53 It was straight a year is actually fact that one very important way in

23:02 we classifying neurons it's not homely by way they look so morphology. But

23:10 way they're connected. Whether their projections or their local network into the runs

23:16 on the excitability of excited Turney So inhuman, very solves. They're

23:22 different. Shapes are excited yourselves. different shapes of prohibitory yourself, one

23:27 specific markers do they have inside? that's another way in which we would

23:32 , classify them and finally would have action potentials that they produce. Whatever

23:39 sequences of action potentials that they can , we call them firing signatures.

23:45 if you look in the image on right, it's actually the first published

23:51 recording from squid. Giant Axiron is first published actual potential in 1930 I'm

23:59 Hodgkin and Huxley. Imagine how they to do it in 1939. They

24:07 squids, so the squid was not like the one you see in the

24:12 . The swell of the ships but axe on in the screen is pretty

24:17 . About one millimeter in diameter or is something that you can die sacked

24:23 see. With the naked eye and recording. They stuck these accidents with

24:31 and they projected electrical currents. Shown is a fluctuation from minus 17 millet

24:39 approximately, which is minus more like 55 million balls, which is

24:46 Memory potential is very fast situation in water for a couple of milliseconds to

24:52 40 million volts on the scale and back. Teoh, the resting member

24:58 potential So they would capture that using electrodes, and they would project the

25:05 of the actual potential onto the bacillus . And then they would take the

25:11 camera mounted over the screen of the sculpt, and they would take a

25:18 after action potential that would take a of what the bacillus cope was

25:24 So quite interesting. Way off of things again. We're not Houston.

25:31 is cure codes and digital now. then the author of the article Hoskins

25:38 would send the image would send the paper with the image, and the

25:43 would produce copies of these using print copying machines. And you would get

25:49 publication and mail because there was no or you would go to the library

25:55 read the uh, journal of and you would find information about the

26:02 published interest. Sally Life Recording. the first published action potential humans.

26:08 . You've given how Look at They just recorded this. That's,

26:13 , almost 100 years ago. 80 ago, the first recording of action

26:19 published. So it tells you how when you until 1939 we didn't really

26:25 the way we knew that they produce potentials. There was no way of

26:29 capturing that information you have, which in Arctic needs, that all of

26:34 Hodgkin reflexively on some other false that mold. Now this is one of

26:39 favorite Dia graphs and and in this because it describes and it shows to

26:48 everything that we've been talking about. what you have you want to 21

26:54 subtypes of cells, in particular different of inhibitory cells or into neurons Inhibitory

27:04 in the structure that we keep talking hippocampus that codes for memory codes memory

27:11 is responsible for memory recall as well semantic memory. It's emotional information

27:20 And what you see is that if looked in the campus, hippocampus actually

27:25 , uh uh three major last stride . Adams triumph. Rommedahl Astride of

27:32 eons, there's one more striking. possible. Larry. It's a very

27:37 , but mostly it's considered an R cortex, which is surprised that

27:43 Three major, dominant leg most of south and, uh, hippocampus will

27:50 relocated and striving for middle. And because there's very high density off your

27:55 the valuable Perama tal cells that will across this wide stratum Pirmin Allen,

28:02 there would be expressed it very high . I don't see if I can

28:12 the question. Yes. Did you a question? Yes, I have

28:32 question. And so what? You're our interest, your arms, What

28:39 showing Very good question. If I correct, that showing is both the

28:45 . Cells of the projection cells and abdominal cells that are projection cells excited

28:50 ourselves have shown here and green, , sort of a bluish colors.

28:59 they're labelled C B plus and C minus. And then you have from

29:05 to ride Teoh this kind of violet one through 21 dozer the inhibitory.

29:15 does that answer your question? So that means the blue cells are

29:21 . Terry on a neurons and then orange and red and violent. No

29:27 of you to be clarifying this. that blue cells are the exciting Torrey

29:32 . Nall sells their projection cells to cells. This beram inal cells that

29:37 labeled here, Stevie Plus and C minus. They will actually project to

29:42 the arrows. The blue arrows going there will project out of the

29:47 so they will project a distant parts the hippocampus. Is these air the

29:52 cells? And these? Were they for yourselves? Now, one through

29:56 there, flanked by the inhibitory Interneuron the inhibitory Interneuron principle that have there

30:03 must located in different players. So can see 12456 1921. They have

30:09 Somis in the Rommedahl earlier, And if you look there, axe

30:15 or their synapses are shown is yellow . So 2341234 will be targeting mostly

30:25 the soem us around the somatic areas the Haram it'll cells. That means

30:31 I have a really significant impact on integrative properties because, uh,

30:37 it'll south. And so most are for integration of the signal. They

30:41 a significant control inhibitory control of These parameter all sauce we're going to

30:48 out into the adjacent networks. So you look, it sounds like five

30:53 six, their synapses distended, projecting that, uh, so much projecting

31:00 onto the applicant will done dries and done hearts. So of course it

31:07 influence the integrative properties. But the that the stronger your synaptic impulses are

31:14 to re cells. In this a stronger and more of the synaptic

31:18 emperors are around the so most of excited resells them or off the insecurities

31:24 off these sounds is going to It was close by them. And

31:28 can see that some of the South 10 11 and 12 they have their

31:34 cops or their sin absence located with very half a co down tries of

31:40 perama tal salt. So, the point of the slide is to

31:47 you that first of all, you see the orientation off. The location

31:52 the so most of the Interneuron is in different parts of the hippocampus that

31:58 synapses project into different parts of the to ourselves, which will communicate the

32:04 of these political left words. You see that there, Dan dries.

32:08 of them are pointing horizontally, and of them were pointing vertically. So

32:14 of these air distinguishing factors and some. The most important factor is

32:20 staining staining for some of the Albelin marker. So you will see

32:24 example three. Beram It'll sells one them. Sayings for CB were just

32:30 and positive and solitude are killed. Negative. The other two are more

32:35 , and they're less densely located in tried already Adam talk and the other

32:41 stratum. Laurean's bottom flair. If look 234 actually old basket cells.

32:50 the difference between 234 obvious is like me. The difference is pretty obvious

32:56 of the solo where the stones are , which lair? But what is

33:00 difference between two and four Morphological e , they live the same. The

33:05 also located in uh uh, striding a dollar two and four. The

33:12 drives are pointing vertically their inhibitory Cielo cops are targeting the same part

33:22 the X sanitary beram. It'll cells salts. So how do you distinguish

33:27 two and four? Well, to from PV, which stands from Peru

33:33 Int and four stands from Basket Sal in big with three and CCK stands

33:42 Callisto Kinda and voltage on da the main channel big look three.

33:51 this is the final way to distinguish that. Some of these very fine

33:56 of these inhibit their Internet arrests. may not be reflected in their morphology

34:01 their sights. Architecture that you have actually cross stain these cells for some

34:10 or genetic markers are some expression Marcus they contained, such as provided

34:16 uh, hope in them Publicist, kind and the That's, um you

34:21 , pressing and so on. So is the definitive fiction morphology, synaptic

34:30 . Uh, would they stain And then this is just still the

34:37 . So finally, for you to tell the difference between the stalls,

34:42 also have to include their action potential so you can imagine two cells that

34:50 next to each other. And I that these cells were different, but

34:55 you have sell also look very but this is one way in which

34:59 performed these experiments on I was doing I post doctoral research. Ah George

35:08 University in Fairfax, Virginia uh, I was studying epilepsy, and I

35:17 interested to see one action potential parents produced by different cells in normal tissues

35:25 how these electrical action potential parents change neuro pathological conditions such as epilepsy and

35:35 models. And what is showing this in the middle is a photo Micrografx

35:42 photographed through a microscope of what we as a whole cell patch. Clamp

35:48 from the last lecture whereby you see lectures on a glass electricity targeting individual

35:55 , some the last on the Both of these neurons get a positive

36:01 . They get positive current that gets through these micro electrodes into the individual

36:08 . Cell on the left responds by a very high frequency terrain of action

36:17 . So you see these spikes and going up. Each one of these

36:21 is an action potential. The cell the right receives the exact same impotence

36:26 cell on the left, but it a much slower and different shave action

36:33 So these are what we call no action Potential firing signatures. The one

36:40 the last is very much representative off firing inhibitory Interneuron, since it was

36:48 the right, is representative off excited and slow of firing the Ramelow

36:56 So during the experiment, especially if doing interest annular also recording In this

37:04 , we're doing also recording the The environment that you have inside the

37:10 actually represents the same cytoplasmic environment. even if you touch or if you

37:16 a small window to the south through electrode, the style is viable.

37:22 can survive for a couple of And you're pretending that you're just on

37:27 of that south through this electric with side of plastic. And during the

37:34 , he in this, uh, solution you also have a guy euro

37:41 die is referring to or by a , and I So that's another dying

37:47 adult to your less try. You golgi stain. You have missile

37:59 I'm writing it down because he's a exam. Questions you have. What

38:04 stains that we talked about Anybody remembers , missile bios, iten When Euro

38:15 is another one, but we're talking now. We also talked about horseradish

38:22 days. Do you remember that H p horseradish peroxide ezam viruses used for

38:29 purposes. Okay, so these are of the great questions to know that

38:35 between these different stains and dyes or reminding Tobias Iten is used during the

38:42 recording its place to sign the electrodes it diffuses into the cells during the

38:50 recordings. When you do after the is, you recover the tissue in

38:56 exposing tissue, you expose the stain by using immuno histological techniques, you

39:04 that no biting and that allows you also label the entire process is an

39:12 morphology off the South from which you recorded. So this looks very

39:18 These drawings of the sounds that were by me in this case using a

39:24 version of camera lucid up microscope still a glance mirror system, uh,

39:33 a system called Neural lucida and I the cells after the experiment and in

39:43 you see the down drives of the and and yellow. You see the

39:48 on the South's and following that this the end of the experiment, that

39:54 tissue with more exposed to neural biden I also cross stained it with markers

40:01 some at a Staten and provide algae and neuro via Tim. So that

40:08 me, for example, this salad shown here at the bottom and purple

40:12 has a narrow says some. It for somatic standing, and the East

40:17 your abiding. That means this was and I recorded, and it hasn't

40:23 marker for some at a Staten. my cell. Then I recorded from

40:28 , has a fluorescent marker for some of Staten. This cell turned out

40:33 be number seven cell allow allow themselves these horizontal like, Dent writes,

40:41 it has an ax on that goes the very topical regions of the genetic

40:47 . So I was just a big of B so a themselves, and

40:51 kept bashing and recording from them and whether there were some Sonata Staten positive

40:58 reconstructing the anatomy. So this type experiment, if you record any biological

41:06 or euro uh, neurological activity, a seizure activity from individual south and

41:13 know they're firing signatures. You know exact location of their exact morphology of

41:19 styles that you recorded from and, know, the internal markets. Then

41:24 can definitively say that this Waas Elam which stands for Koreans local awesome,

41:31 local area because it projects it's accents strangle orients s O to ask the

41:38 , distract him like an awesome malakal at the very apex off. What

41:44 be the A packs off the down off the parameters cells excited to

41:49 And there would be a sin ass on through the optical den dries of

41:53 parameter all cells modulating the distal activity the distant inputs onto these parameters cells

42:00 it hasn't done drives alarms style at bottom into neuron that projects Ah,

42:06 , projects a result. Lino Parietal on the right has the axe on

42:10 comes toward you and exits out of tissue is going out on its

42:15 projecting out of the fields of Okay, so I think that maybe

42:22 some questions. Okay, great. this is a good way for

42:28 Teoh National information or abaya attempt or your side 10 is, uh is

42:37 stain in the electrodes? No TV for car valve, you men.

42:47 is a calcium binding protein. see, what else are I also

42:58 a question. OK, Did you to raise a hand and I can

43:04 . Okay. So here, um going back to the the layout

43:09 like, the neurons and bug slide this one. So the cusp stands

43:18 the and turnarounds. Not like inhibitory . Okay? Yeah, the

43:27 the yellow god triangle. Like I them cups the you know, kind

43:32 ah, triangular. There are the synapses and visitor, perhaps drive.

43:41 for the fact is that most of excited Terry cells living there and have

43:48 so most in this struggle Permodalan the so later that basically shows you what's

43:56 these different into numerous where along the dried or so more axel wearily would

44:03 targeting and projecting inhibitory synapses onto BCE care themselves. That has to do

44:11 with with a lot of what the integrates and decides to send onto the

44:17 networks. And it has to do a lot of input. Some of

44:21 empezar coming in distantly, some of implicit coming in approximately so distantly with

44:28 fire away in first there would be into the distilled and rights and proximal

44:34 we call the ones that are close the solar. Keeping in mind that

44:39 will make that decision. So most the fast and strongest integration and the

44:48 some of the most influential decision makers the synapses that are located around the

44:54 approximately around the soma. But we call this Paris somatic regions. Does

45:00 answer your question? Um, but okay, So the top did

45:07 say it was called apple? And the bottom called Near the stratum orients

45:12 , Those of basil down rights. also you will have the arrows pointing

45:19 those air, the accents coming So they depicted. And in the

45:24 of the criminal sauces, just showing they're projecting their not showing the synapses

45:29 cups yellow cups for the excited to because they are not there in the

45:35 there Another network project on the are they so? And also the

45:40 arrows are sorry. I have a of questions for on this example,

45:46 arrows are showing that some of these are connecting onto other nearby regions off

45:55 hippocampus. But you will not be for that detail of the information.

46:01 let me clarify what you will have take away from the slide is that

46:06 have, ah, incredible diversity Ah, new rods that diversity.

46:13 this structure that we're looking at hippocampus in fact, even in the corn

46:17 of diversity stems from the diversity in human very Selves. The function of

46:23 local and heavens air into your answer control these excited to resells local,

46:30 , the diversity of these inhibitor In order for us to some classify

46:36 , we need to know their We need to know their 100 external

46:42 that we need to know the firing and the internal staining markets. Then

46:48 can identify individual sub process of these that these individuals, some classes of

46:54 South by projecting on to different parts the criminal sauce, will influence with

47:00 prominent all cell network. With this hippocampus network, well, community to

47:07 distant leopards. Because thes perama, cells are not as diverse. They're

47:12 to resells, but they're important because will project information that they will contact

47:18 just on that works outside of the so that starting with the take on

47:23 , it don't have to memorized 21 sometimes of cells. You don't have

47:29 memorize all of the markers You asked TV and I think I responded.

47:37 is around human. Uh, I responded twice. Uh, if

47:44 want to know, CB stands for cold end in, um and,

47:53 , when you wouldn't I wouldn't ask that detail. I think the take

47:56 message here is a diversity of the , how you sub classify them and

48:02 these inhibit the endurance of fact. projection. Vermont's. Okay, So

48:11 we have these signatures and this is interesting slide that I like. And

48:16 the slide depicts is depict a patch the new quacks and it shows

48:24 lot of cells in this network in new cortical network and is just attach

48:30 Palestine micro meters. So maybe it's cells across its ah 100 times 10

48:37 meters, maybe only once than to a patch of the cortex, and

48:42 has shown here is the diversity off cortical neurons. The diversity off there

48:52 behaviors in this case that the patterns the signatures of the action potential

48:59 So you can be in the small and you can imbed electro nor patch

49:05 to the any number off these And these cells can be excited to

49:12 , or they can be inhibitory But these cells will have a different

49:19 to the same stimulus. So the on the laughter called the D

49:26 which stands for delayed stuttering ignorance, legs stuttering. There is the so

49:32 because when they receive a positive influx car for stimulation, they respond by

49:41 , I'm dropped an intermittent trains of potentials. So if Franken Illustrated would

49:48 like, oh, the polarization signal well on. And so they're called

50:00 if you give them more current, positive and put that delay decreases as

50:05 can see here, and the delay be decreasing. But there would still

50:10 stuttering. Then there are cells, example, at the bottom laughed that

50:18 our BST, but these ah bursting type of cells. And what it

50:25 is that when it receives the same as the cell in the top

50:29 instead of having a delayed response in flat electrical line, been with trains

50:36 actual potential started stuttering mug, it produced a Sinus sword like waves in

50:43 member and potential in the changes in member of potential and produces bursts of

50:49 potentials that a pretty uniform and repetitive of infertility. Then there are cells

50:56 produce, uh, just continuous This would be the sound that

51:02 uh, shown on the top arrived N a. C stance broke classico

51:08 accommodating self. And that means that a little current and produces low frequency

51:13 action potentials with more, Kern produces high frequencies of action. But that

51:18 not the case with all of the in general. The number of action

51:24 of the frequency of these action potentials the amplitude of the stimulus, the

51:30 of the him. So this is way in which neurons encode information and

51:36 information. Important information, strong lots of action potentials, I frequency

51:43 firing of action potentials. Not important . Weak, impotent, out,

51:48 few action for 10 songs. And let the rest until I get input

51:53 in Austin abscess. And it's strong for me to get the polarizing to

51:57 a that strain of actual potential. just illustrates it behind an incredible electrical

52:05 off these neurons and neocortex in If a campus was just sentenced as

52:11 example, but you will find an diversity off Salles neuron all across cortical

52:20 , Needham Quarter call and CNN s how you can really start thinking about

52:27 action potential trains to be snow and to each other is that these subtypes

52:33 cells is different. 150 different sometimes sows is Interneuron so that we looked

52:39 21 different subtypes of Interneuron. what they do is they have their

52:46 dialect is the same language that they the same, the same language off

52:51 action potential also off the deep But it's 100 50 different dialects.

52:58 100 50 different ways off, integrating information as a neuro and producing 100

53:07 different patterns, signature patterns, and this is what we know so far

53:14 the brain and the overall activity. off the individual activity off. Uh

53:23 . Off these networks. So off individual activity off the cells, that

53:29 really a collected and combined activity. , far many different subtypes of the

53:36 speaking the same language, different In order for the language to be

53:42 , they have to synchronize. They to start talking in unison to be

53:48 . My distant left works and they to produce a symphony. The harmony

53:54 is, uh these oscillations of people on hyper polarization, Czar excitation in

54:03 tradition. So we have. incredibly complex networks have one language,

54:10 different dialects. In a way, can also perceive it as a Morse

54:15 . The cell on the top left , did it that is, and

54:24 cell in the bottom rice be It's like more skulled, right?

54:33 can decide for it. This is digital of action potentials. Is the

54:38 code anything that happens underneath action These deep polarization is that don't generate

54:44 potential changes of the number and potential do not generate action potentials. You

54:51 view it as an analog. Two neurons in the way have two

54:55 of operation. An alarm, other mode that decides whether two fine,

55:00 potential or not, and the actual which is all or non event.

55:06 , in a way it's kind of a digital note 0 to 15 the

55:10 potential. That means the release of at the synapse and either fluctuations that

55:18 not produce action potentials do not resolve deep polarisation of release of the

55:25 Okay, so this is Ah, . When I was doing the postdoctoral

55:34 that I was telling you and Julia George Mason University and you can see

55:42 I am sin angled for electrodes underneath dishes are actually was the doing of

55:50 quadruple recording from from brain tissue here these arms year shown in black,

56:00 , one of them on the Burly. There's a micro electrodes

56:06 so we have a very, very way, digitally and manually, also

56:12 to manipulate using these electrodes and move in precise position onto individual cells.

56:19 very sophisticated holders were sophisticated equipment, when you run out of very sophisticated

56:27 . Some far, right? You see I had Teoh adopt a

56:32 It was loosened. The laboratory loner , hold one of my electricity was

56:37 . Thio more distantly located amplifier. this is the way that we in

56:43 you can record concurrent activity interest Alya from the sauces. Is it?

56:48 in? Was you Jim monitor? the electrical activity? Or in a

56:53 , you can say this is a in which you can, uh,

56:59 is the way in which you um, listen, Dune Teoh dialect

57:06 these different cells. Ah, some them are, uh, really,

57:13 interesting experiments that revolve around these. very technically complex experiments. But there

57:19 a lot of fun to do as was a graduate student KOSDAQ and Little

57:23 some graduate students here at the University Houston as well. But when push

57:30 to shove and you're really determined, need to do staff, you

57:33 look for expensive pieces of equipment. look for last steady solutions. Teoh

57:39 the most data that you can. the game and the brain is also

57:44 data on glia. Now that we you know about the morphology of

57:51 So I understand that they produce these , different electrical recordings. They have

57:59 languages dialect. Now let's talk about glioma functions of prettiest mast. And

58:08 their name originally means glue or glia means glue. For a long

58:16 , it was thought that glee I served the supportive and insulated function to

58:21 and that sort of about it. that is not the case. You

58:27 very different sub dives off my of that are responsible for different things.

58:35 responsible for cleanup for damage repair and of the grill sauce Michael glial

58:41 actus scavenger cells of the cleanup local . Now they're also Astor sized are

58:50 for nurturance, mirror and I on and housekeeping chores. So they really

58:58 housekeeping choices really regulating synaptic transmission, , radio glial cells. They guide

59:05 migration and process out girls on Real stars can also service neuronal real

59:17 . So the actually real cells that precursors to what is going to become

59:23 final subtype of glial cells or in , Leo sauce release growth factors,

59:31 those are very important for maintaining and the slow growth off the brains to

59:37 the support of the brain. Synapses plasticity, Astra size real sauce are

59:44 part of the world brain barrier, they're part of the filter essentially,

59:49 decides what crosses between the blood into brain. Most importantly, they're not

59:57 their act if they actively control soon Genesis synapse numbers synapse function, Synapse

60:06 , which is snapped. The Genesis synaptic plasticity. So a lot of

60:11 growth the factors control synaptic plasticity. Glee also are responsible for release off

60:21 inflammatory sytem kinds, doing year about side to kind storms or inflammatory

60:29 Information. In the brain. It usually abnormal control off site, a

60:35 release and inflammation that stems from that the brain. But glia. Unlike

60:43 , Deunan produce action potentials. They on produce action potentials, and instead

60:50 communicate with these slow or calcium right? Somehow, no. So

61:00 talk about different real sense. Let's about first that insulation and protection In

61:05 peripheral nervous system. You have Schwann again. We have central nervous

61:11 Emperor forever system. So we have cells that Miley and accidents in the

61:17 nervous system. The Schwann so is single segment of the Mylar axle.

61:24 in between the smile and Jackson's, have knows of ranveer. They're separating

61:31 now the bottom you have Central Nervous , or CNS and and C N

61:38 . You have a little Denver sites down. Besides, unlike Schwann sauce

61:44 the PNS in the CIA, NASA dander sides have multiple arms that come

61:50 these 1000. Each one of these of processes becomes a separate segment,

61:57 a separate segment violence sheets segment and one only go down beside produces many

62:06 , and it can produce many segments many accidents of different neuron. And

62:14 one of the distinct wind, just distinct issues between the mile a nation

62:20 the PMS versus the CNN. So the, uh, last, what

62:29 have is a picture of the top them. Exercise or exercise fill most

62:36 the space in the brain that is occupied. My neurosis of blood vessels

62:41 Astra size will have most space, they will have very complex asked acidic

62:46 and there will be sending a lot the Kallstrom signal Studi streets of siphoning

62:53 neurotransmitters. And I asked you in of these trees are very much actively

62:59 in control. What? Bring Barry control off synaptic transmission. So,

63:07 , neurotransmitter level so as well as in the brain in the centre

63:12 Now, if we're talking about my nation off, you take him from

63:16 bottom last. Do you have an off a very different cell, of

63:20 , which is illegal. Dunder side it Underside again is wraps around and

63:27 d smile and she's that air separated knows of run, veer, note

63:32 run There is a side where the potential is gonna get regenerated so that

63:37 same action potential, the same amplitude action potential that was produced with the

63:42 of the soma is also regenerated. each note of are here so that

63:48 amplitude of the actual patricians preserved all way to the synaptic terminal to the

63:55 terminal to where the action potential will neurotransmitter classical fusion and neurotransmitter leads.

64:04 , if you have violent nation there is several, uh, Prodi

64:13 that are involved in violent compaction because can imagine. It's a pretty sophisticated

64:20 of one cell's membrane of processes wrapping around that, the one growing and

64:27 around that'll. So you have Ah, seven more related Prodi Insee

64:35 , basic prone audience of control. live action and examples of these are

64:42 an associative black, a protean mag is responsible for salads, sell recognition

64:49 initiation of my elimination. So these Brody is will serve a different function

64:55 the case of mag is really initiating myelin ation process living not a style

65:02 recognising another cell Uh, you can problems. And in my island nation

65:11 , and, uh, of inflammation and De Milo nation will cause

65:17 significant problems. We're not really gonna about, um, injections. And

65:23 for my life is But we will PMP two is another perform island

65:29 which is apparent. Charcot Marie tooth . Sorry, this isn't yellow,

65:33 you can see very clearly. But the name of the disease. Charcot

65:38 Tooth disease and on the right with shown is a fact that deem island

65:48 is one of the features of another disorder that you should add to your

65:53 . And that is multiples. Um de Milo, Nation of accents

66:00 multiple sclerosis happens. And the It happens to the central nervous system

66:07 the central nervous system. In the of the mass, in the central

66:13 system, you have the mile a off different axles. And therefore,

66:20 you think of multiple sclerosis depending on region of the brain that is most

66:25 by deem island nation, you will a stronger impact on that particular

66:31 So if it is the, loan corn tax, where you have

66:36 Milo nation you may experienced significant motor may experience, uh, treacherous.

66:45 it is in certain parts of the that controls emotions or memory, you

66:52 experience memory loss. You may experience bows and emotional mood swings. Show

67:00 sclerosis does not just affect the and this is one of the features

67:05 multiple sclerosis is tremors. So what know about the masses that you can

67:13 or mass, but causing a mutation chromosome 18 was one of the

67:18 And when you cause a mutation and um, 18 you vote tremors and

67:26 sometimes convulsions, muscular convulsions, in the these animals and wish you

67:33 a genetic you saving mutation, which need to have to paddle wheels.

67:38 it's really a chromosome. Any It's a recessive a mutation,

67:45 recess of fina top that is necessary order. Teoh Evoke was called a

67:51 ver tomorrow shiver miles model off multiple . So in Schumer, muting of

68:00 riding with the shown is a normal with cross sections of accents showing these

68:06 think black rains throw blast rings and of my ligation around the accents.

68:14 in the middle thought of Micrografx, see shiver, immune, mint and

68:20 meat that has this chromosome 18 mutation than have very scant, very abnormal

68:27 island nation of the accidents. You partially rescue the FINA time, and

68:35 can partially of rescue a shiver. these minds will literally be shivering and

68:43 sometimes convulsing to Now if you transplant animal not normal, gene, it

68:51 actually improve. My nomination wants to . So again. Sorry. So

68:56 partially rebuild the myelin nation. If do essentially a genetic manipulation here,

69:06 genetic trance faction. Uh, these transgenic mice, of course, that

69:11 probably familiar with them, So in case, it's, ah, it's

69:15 mutation of That's a knocking about ob that causes the stretch mechanic miles that

69:20 the sugar amounts and then partially be with trance factor Gene. So,

69:28 , as a multiple sclerosis, by way, is very important. You

69:33 adding that information is an auto immune , so multiple sclerosis is upon immune

69:41 . That means that your own body recognizing for some reason starts recognising its

69:48 milon. This is a foreign invader stars destroying its own mile, so

69:55 an auto immune disorder. Um, other common disorder that you see with

70:02 dysfunctions is shark off marry tooth. this case, you were talking about

70:08 protean PMP, which is perfect. my eliminating pretty and PMP 22 and

70:16 have too much. There's too much the genetic expression of that. P

70:22 . V 22 eyes actually duplication Geum Promise own 17 on, and

70:31 can measure that on the writer have test tubes basically that the charges of

70:37 charts showing that PMP too as being , and that there is a much

70:44 expression of promise on the team that associated with the PMP to there's a

70:51 than high expression of that protein replication the gene and high expression of that

70:57 due to duplication of Eugene. And a developmental condition that causes impaired gait

71:04 bodily deformities. So, uh, is no cure for sure cannot marry

71:11 . What happens because this abnormal Meilin off the peripheral baby with normal this

71:21 talking about peripheral Milon program and, opposed Teoh and Mass, which is

71:27 in this in the CNS. In case, this is in the

71:30 So we're talking about Schlamme cells that's starts apparent mile the nation when it

71:37 to his abnormal stimulation of muscles. if you have a normal stimulation of

71:43 , bones develop and grow. There deformities in the bone structure that caused

71:49 bodily deformities very commonly in the lower in the legs and causes impaired gait

71:58 the solution really, as if you about the genes application and you detect

72:03 on the Charlotte married to disease than can place the developing individual into the

72:11 to perfect printed T essentially prevent the information to prevent the boned information.

72:19 Teoh hopefully help with the gate because lot of the individual civil have

72:25 um in problem gains, swinging from side to the other side and carrying

72:32 legs and a very, very uncomfortable . Eso The more we can figure

72:37 about early interventions and recovered from this . Obviously there's now medications, but

72:44 braces and with rehabilitation and physical Uh, this is this is really

72:52 . This is ah, good summary that I'm gonna leave with today's

72:58 Actually, we're gonna offline. All this sausage were discussing. So we've

73:04 about illegal down her sides on illegal . Besides, our Meilin aging cells

73:09 the central nervous system, where you see different legs or processes of these

73:15 under size will be responsible in forming individual violence segment on multiple girls you

73:23 ostracised or ostracised on the right here shown in contacting the synapses of endurance

73:30 well as the Camp Hillary's Teoh. indicates that ostracised are involved in

73:36 brain barrier and regulation. What comes the blood as well as in regulation

73:41 synaptic transmission. My googly also said smallest south in the network and they're

73:48 most mobile cells in the network. Michael Glial cells get activated during

73:54 They get activated during a physical injury doing information, and they actually can

74:02 across brain tissue. So if, , I manage, what I'll do

74:09 I'll try Teoh find a movie about with real cells for years. Just

74:16 me one

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