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00:00 great. So this is lecture for neuroscience and we're still talking about neuron

00:07 glia and in particular, we discussed , very specific on morphological,

00:17 features of neurons in particular, done and dendritic spines. And what we

00:22 about This is a beast under EC are actually the most distal elements.

00:30 the most, uh, plastic these 100 explains are where the synapses

00:39 located. So you can see that the right. Here is the photo

00:45 image showing the spine and at the time, that's showing that within that

00:52 you have synaptic bottle Upali Rivasseau mo , which indicates that these fines these

01:01 spines have their own little by a machinery. Therefore, certain things like

01:09 can be translated at the level of synapses that or drink spines. The

01:16 receptors could be inserted within the Uh, and the other elements off

01:23 synapses could be supported by this polarized complex. And on the left side

01:30 see a picture of external probable. we talked about is that there are

01:34 shapes of these 100 x spines and specific anatomy of peace 100 exponents density

01:41 peace, dendritic spines, arrangement of dendritic spines and their shapes. They

01:47 in different shapes, is very important normal functioning. So you would have

01:53 of isn't really explains on Dunn drives one neuron, and they would be

01:59 by both excited, very other excited and other inhibitory neurons. And most

02:05 these sponsor true seeing here like this would be on the excited Terry projection

02:11 is a reminder. We talked about if you have impairment in the spine

02:21 and the number of spires or in densities off the spines along down

02:28 then it can be causing very severe in the brain. Um, we

02:36 about ah ah, one neurological disorder that neurological disorder that we discussed was

02:45 the context of the side of skeletal . If you remember, um,

02:50 me just remind you quickly from the that we discussed three times of side

02:57 scalable governments, the microfilm mints in filaments than the market tubules. We

03:03 that the micro filaments that are made of the act and molecules are the

03:08 dynamic. Cyrus Skeletal, our these air the side of skeletal elements

03:13 you will find the here labeled and in the most distant parts of the

03:19 , supporting the outer edges of the membrane. Essentially shaping that are edges

03:25 the plasma membrane. Neural filaments also referred to his intermediary filaments and micro

03:35 . I'm laid up off the tubular that basically produced the surround the on

03:42 round two bills of these micro tubules pictured here on the right and the

03:47 are traversing through accents and the very for a subtle transport to the image

03:53 the righteous. A cross section through axle on violin ated accent where the

04:00 edges you have mile and sheets surrounding this just remembering. And inside you

04:07 these lines that are micro tubules, we talked about the fact that

04:14 uh, acting molecules and blue of most distant molecules, that they're very

04:22 than the rearrangement. And so they be problem arising deep, all

04:28 These active molecules care red and as change their structure as they change their

04:37 , the supporting they're supporting membrane and they change their structure, the shape

04:43 the membrane changes. So you can that some of these plastic changes at

04:48 level of enduring explains and rearrangement of shape of the spine or a number

04:53 the spine or loss off the number the spine has been discussed.

04:58 we said of the synapse in dendritic , a school potentially ation, voluntary

05:03 ation and creation of new sin Uh, birth of new synapses is

05:10 genesis and depression of activity, a of activity in the synapses off long

05:19 . It's called long term depression, we talked about the fact that he's

05:24 be four terminal, so long term . But these are essentially equivalent celulas

05:31 stuff straits to learning and memory. as we learn and memorize things,

05:36 electrical activity and chemical activity inside the changes the side of skeletal elements.

05:43 , we arranged themselves and the change lot about the structure that they hold

05:49 member of structure that they hold We also discussed on our neurological disorders

05:57 discussed this disorder who particular Alzheimer's Um, and we talked about the

06:04 Lawrence of Alzheimer's disease. We talked the symptoms. If you recall such

06:10 number you long starting with with short memory loss, um, anxiety,

06:18 , lost sense of time, maybe anger issues depending of different stages.

06:25 the early stages of Alzheimer's that typically by short remember, lost where the

06:31 keeps re asking the same question or . It has been discussed already.

06:38 , we discussed the pathology of Alzheimer's , and I said, You should

06:42 noses. You will be asked questions that on the exam and also because

06:47 will be learning some very interesting things these different diseases, like Alzheimer's disease

06:52 the course. And if you look the overall image of the brain on

06:58 left with the shell is that in , stages of Alzheimer's disease postmortem,

07:03 after death, the show shrunken brain , especially the gray matter, than

07:08 shrunken that's been imperative with the brain would be in healthy individuals. FGM

07:15 have Alzheimer's disease. Um, Alzheimer's on a LePore for cellular level has

07:26 hallmarks of expressing extra cellular senile plaques data amyloid plaques and these plaques these

07:36 off abnormally, uh folded complex. essentially calcify, and these calcified lesions

07:46 form within the brain and the closer are in space. Teoh Neuron,

07:52 Neuronal axons The more they started bingeing the activity and essentially, um,

08:03 the activity of normally functioning cells with the cells. You will have our

08:10 top road entangles of those tangles with up elements inside the cells. And

08:20 are the elements that were discussing these the site of scalable governments. So

08:25 micro tubules and we talked about micro highways. What happens with these tangles

08:31 the highways of micro tubules would actually physically wrapped around and tangled up,

08:39 the normal transport off external transported, transport, overall insurance and again causing

08:46 generation. So Alzheimer's disease is a disease, which means that there is

08:53 significant loss and death of neurons, at that advanced stages of the

09:01 This is, um, Quincy. trying. Corn isn't on. And

09:14 the way, did you see me the slide for the Alzheimer's disease

09:22 Or was that not shared? I that when I switched the screens,

09:29 was sure in a very great just showing what I have been talking

09:36 was this Alzheimer's disease slide that we reviewed. Let's see. Yes.

09:46 now I'm gonna go back and shared for our electoral material. Still 23

09:59 we kept talking about neurons and how have some of the typical features of

10:09 cells from the organ. All's would the sin abscesses and out the

10:14 some so long and will, talk about it and greater detail as

10:19 talk about synaptic transmission. We talked example, transporting the giraffe finesse in

10:25 is responsible for interrogatory transport and which is responsible for retrograde transport.

10:31 interrogate passport direction is shown years from Selma, along with the wife of

10:37 Exxon's. That Sunil Terminal and inestimable , sort of like a protean

10:43 arms carrying vesicles of different goods along axe on two distal parts of the

10:50 , Retrograde transport would be in the directions, things that would be coming

10:55 the axe on from the still parts into the so most of their

11:01 We talked about the stains, and general it wouldn't be that abandoned

11:06 I will review all of the but just remind yourself all of the

11:11 will be so far talked about. have talked about Golgi Stain, which

11:16 a fraction of neurons but stands their anatomy, all of the processes and

11:22 songs. We talked about the missile , which stands all of the

11:27 and it's really great tool Teoh describe architectural, cellular architecture and the layering

11:34 densities of the sounds. But not is not necessarily individual morphology of the

11:40 . I believe we discussed the fact H, R P, and also

11:45 can be used not necessarily stains, a stray service that you could inject

11:52 dies together with with or strategy days as a dime or with the

11:58 is, um some of them will this retrograde driven transport with the distal

12:04 . Off neurons will pick up the or pick up the virus some together

12:09 virus conjugated with a dialect of for and down another type of guy.

12:14 it will light are all of the , most to which this particular patch

12:18 the neural network of this particular patch the skin was communicating from periphery to

12:27 neuronal cell bodies. Um, we talk about one more stained later

12:34 Now, when we talk about do it expires. What we said

12:37 that if he's dendritic, spines are and you can see that if you

12:42 , uh, side of skeletal Allen rearrangement like after rearrangement, then you

12:49 have a changes in the shapes of 100 experience. And so here you

12:54 have another disorder on your list. , this cold, uh, fragile

13:03 so and it's ah, part All it says are syndrome disorders.

13:13 is a developmental disorder, And one the features and one of the models

13:19 fragile X syndrome is this abnormal structure dendritic spines. So this is the

13:27 ology off rajel X syndrome and fragile syndrome is a pretty severe neurological developmental

13:38 that is quite often associated with seizures epilepsy in a swell as mental recommendation

13:47 significant of the issues and problems, interaction, problems and such. So

13:55 , jeans, nature, uh oh nurture, and it's a combination of

14:03 , so we know that these structures the brain very fine structure,

14:08 100 expiring, said the sin absence abs. Formacion is very much dependent

14:15 the environment very much dependent on this and the social interactions that the developing

14:23 this case is receiving. So autism disorders in general are are very,

14:34 , pretty high prominence. It's, , close to one in about 100

14:40 that get diagnosed with autism spectrum Fragile X syndrome is more rare,

14:47 this goes to the point of the home that such about fragile axes,

14:51 the impairment indigent drink spines once you imperative and expires to have impaired

14:58 expressions and shapes of these parents have Paris. Synaptic transmission have impaired synaptic

15:04 . It's apparent neural level of It could be affecting different parts of

15:08 brain. Um, uh, Once , the image on the right shows

15:14 neurons will be receiving excited to read inputs, so there are excited during

15:19 him with themselves so we can contact other excited, very suspect. Contact

15:23 other, and here the thirst contact each other, and here be

15:26 Saskin. Contact. Excited yourself. yourself. Skin contact in the

15:30 Peirsol's So, in any case, response of the Boston Attic neuron will

15:36 depend on how it integrates All of information from these orange inhibit their synopsis

15:43 are driven by GABA gamma you butyric acid and Governor Chris Emphasis Kappa

15:48 with these green synapses that are driven the excited, very blue made

15:55 And the group dramaturgical suffers shown here green. And so the job of

15:59 there on against, uh, to thousands of infants on the water millisecond

16:06 and decide whether dad neuron is excited with the levels of activity. Excited

16:12 . Ah, strong enough for it produce an action potential. When I

16:24 started telling me about different types of in the brain, I said that

16:27 can, roughly some divide them too to inhibitor. And then we

16:31 There's 100 50 different, sometimes of neurons. If we look at these

16:37 subtypes of nervous, they could be inputs that could be talking. We

16:42 be receiving imports from different parts that be talking to different um,

16:49 And, uh, even so, nerves have four functional regions that is

16:55 in the slide. So you have input components. This is an implication

16:59 and coming in from another model You have an integrative component which integration

17:06 all of the information. So typically would be thousands of model neuron starting

17:12 there. I'm talking to one neuron soma and this region close to the

17:17 , uh, sheet, uh, Meilin. First note of islands felt

17:23 on initial segment or excellent. That's where there are some actual potential

17:29 produced Teoh a cell on this, , closest region to the SoMa and

17:36 Faxon is really deciding when the style going to produce an action potential.

17:42 actual potential is produced, it gets down the axe on. So this

17:47 a conduct I'll unit thing is Mayer unit and there's a release. There's

17:53 bud off your transmitter and it could out, but it off like you're

17:58 green system to be out for that . More power, crime like

18:02 Or it could be secreted out onto things aside, Targets like like a

18:08 of the right. So if you at the second there on this,

18:12 censoring their own. So, for , censoring their own friend that receives

18:16 from the skin from the muscle cell has a comeback tile union, which

18:22 for for relax some of the which then integrative unit is the

18:27 And then it has a central from all unit, but goes and contacts

18:31 the, uh, neurons in this , motor neurons in the spinal board

18:35 neuron shown years. A third one then contact other motor neurons as

18:41 And as that information gets integrated with hacks on passes on actual potential and

18:50 the contraction of the muscles. That's target, local, Interneuron said,

18:55 in him and 30 cells. So typically expressed inhibitory uh, Gabba,

19:03 transmitter and the release Gavin transmitter and of the diversity and the brain and

19:10 cortex and other areas like hippocampus coming the diversity of the inhibitory Interneuron,

19:19 , projection into murals. A quite , but they also exist. And

19:26 , you can see local inhibitory It's on the conduct. I'll

19:31 They don't really have my allegations, there are some cells that are

19:37 I eliminated in the brain and this into neurons, which are rare.

19:43 could be Interneuron stab. Typically, said that internals are you determines inertia

19:50 networks locally. Other cells are projecting of these, not warrants. But

19:56 are some projection into neurons that will inhibitor into the information some longer that

20:03 along between on and interconnected in your . On that corpse you're and the

20:10 sounds is very interesting, because when shown is that you can active in

20:14 under cream style and missing your 100 , our actually can control.

20:19 that's a violation of massive construction of Aries. So there's a control of

20:24 a violation of that's in construction so can see that the input components are

20:30 different. Weaken becoming from the muscle spindle, southern neurons, integrative

20:36 . Pretty much as always, the Conduct AL unit is the accidents and

20:43 Carpathian. It is external terminals. can see that the outputs can be

20:48 other Sallis of muscles, cap Hillary's uM or on account of a secretion

20:54 fashion. The other way and very way of classifying neurons is based on

21:02 morphology. Um, what we have descriptions off cells based on morphology and

21:12 , So most neurons have polarity. you look in a you have unit

21:18 cell and it's a typical invertebrate neuron you have at the bottom cell body

21:23 ax on the dendrite of both axle the dendrite ER, pointing to one

21:29 saying North Pole, this is unit herself and be you have by Bowler

21:35 , such as bipolar selloff, the bipolar cell you have done drives

21:41 appointing North and one poll. You cell body and then you have ax

21:46 . That is on the opposite Let's say south South Pole. So

21:51 is bipolar or so pseudo you. cell is a cell that we already

21:56 this a gangrene and south off dorsal or dorsal root ganglion cell DRG

22:02 These are the cells that are located the door sold side of the spinal

22:07 . These are the cells that have peripheral axum. They've just the skin

22:11 muscles and picks up the information. same kind of receptor information. Touch

22:18 pressure and carry son information through peripheral into the cell body, which is

22:25 that ganglion outside the spinal cord and from the cell body. That information

22:31 conducted through a central axle, so the hide as you know I was

22:38 axe on this by Frick ated into peripheral side and into the central side

22:45 through the central axe. On on external terminals, the pseudo unit bowler

22:51 cells Dear G stands for dorsal root Cells will be contacting other motor neurons

22:58 exciting other motor Daryn's, So is unit bowler because it doesn't really have

23:05 of like clear holes because it is bifurcated process. On doesn't really have

23:12 dendritic, uh, trees for receiving , but rather it's both excellent sort

23:20 communicating that information. Conducting the information , have three times of multipolar

23:29 You have a motor neuron, a cord, which would be located and

23:35 side of the spinal cord. And said, there is enough excitement from

23:41 unit polo. Dorsal root ganglion the Sensory south, the Mona Endurance

23:48 get excited, and motor neurons will send that information through the axe on

23:56 the muscle or to the skin. if it says information to the muscle

24:02 contract the muscle friends. But these multi pull ourselves because they have radio

24:09 oriented Dan drives around the SoMa, it's not clear that damn rise air

24:15 into one direction of another one, another, rather than spread out

24:20 And Exxon's also RAM if I mostly one direction, obviously out of the

24:25 cord, into the, uh, into the muscles. But there's

24:32 uh, crosstalk between, um into and motor neuron was just a little

24:38 . What we discussed a full started the spinal cord later in this course

24:43 the little indeed have, a barometer sell of hippocampus. This is a

24:48 excited to re projection cell. It , ah, again, this multi

24:54 . It has a pickle, Then that I studied with Riddick spines.

24:59 the apex of the pyramid, and the base of the German you have

25:03 , then drives that are coming out accidents will run long distance just

25:10 Just still sounds, um, this that works. We've been foreign tanks

25:14 hippocampus or between people, campus and parts of the court tax. On

25:19 ride, you have one of the favorite anonymous. They're not on the

25:26 is of Kenji style of star showing its incredible complexity of the dendritic

25:33 most ing of 250,000 synapses onto a south. So my cell bodies still

25:41 the integration computation happens and the actual is produced. Ah, between the

25:49 , the initial segment of the axe and that information is being communicated.

25:53 the calculations that this town needs to from hundreds of thousands of synapses is

25:59 the order of milliseconds. Cerebellum, , in particular, would be responsible

26:06 adjusting fine motor commands and motor commands already initiated by the corn tax,

26:13 , at the level of the cerebellum into the spinal cords. It's very

26:18 for contraction of muscles, a movement very, very fast processing of

26:24 So the neurons are spiny and others spiny. So some of the neurons

26:28 you seeing here, for example, be very clearly containing spines and

26:34 Uh, may not have these Um, nonetheless, we have all

26:40 these beautiful anatomy and so 1939. we're classifying neurons based on connectivity so

26:48 can see the weather than projection Where there locally located into neurons,

26:54 classifying them with excited for an So whether they're expressing looting, mate

27:00 job. We also is not enough to know one of those 150 sometimes

27:08 stars by having that information. So need information about a specific cell,

27:13 markers that are found in cells just Europe. Appetizer nerve in Europe.

27:18 transmitters that are expressed by these sounds Gava I would have made. But

27:24 importantly is also the output off the , And the album of any neuron

27:31 measured in the sense off the action referring to this aspiring signatures of the

27:39 . So what you're seeing is the recording of the action potential that was

27:44 in 1939 by Hodgkins. Harshly, were recording these action potential. Strong's

27:51 Giant Ax on Again. This is the giant squid that comes out of

27:58 water and swallows the ships, but the squint that has a prudent,

28:04 axe on that's one millimeter in diameter can be dissected out and seen with

28:10 naked eye. And you can perform off you could sticking electrodes inside these

28:16 , and as such, you could electrical potential, so asking women are

28:22 on 1939 on the whole, this throughout who still didn't see an action

28:28 . So how was this done? 1939 and electric was stalking the

28:34 the electrical potential was amplified through some projected onto this telescope and you

28:41 this very fast fluctuation from about minus millet balls, Teoh plus four Djamila

28:48 that happens within a matter of a of milliseconds and returned back Teoh the

28:55 after the action potential. So this was projected onto the basilisk.

29:02 and the Polaroid camera was placed on window of the Silla scope and the

29:08 was taken and the Polaroid picture was sent to the journal. There was

29:13 emails that was mailed to the uh, together with graphs that were

29:20 by hand, uh, such as grass and son and then the publisher

29:27 May Friends, copies of this, , copier machines. And so the

29:36 and the articles would be bound and the journal would be printed and

29:41 on most of the library's. And could not go online and find that

29:48 You have to go to the Teoh actually find that physical journal physical

29:55 and open and read that article or that article at a cost. And

30:01 the time when I was in graduate , you could copy articles from the

30:06 before you had the off the information , and it was costing and sometimes

30:16 5 to 10 cents a piece. girl star like 20 pages. So

30:22 would, you know, a one $2 just to get an article coffee

30:27 you could take it home and read , mark it up and do some

30:32 on it. So it's said it's different times now. Course everything is

30:37 and we have digital amplifiers and computer Really cool. And we also have

30:45 very interesting understanding off neurons not only on anatomy but also on electrophysiology.

30:55 this is one of my favorites lies this course, and this is one

30:58 the slides that may be shocked students they first have a look at it

31:03 they think they have to memorize and everything on this line. Let me

31:07 you what you really have to know the slide number one is if you

31:11 here you have these blue greenish sounds a label CD Plus or C B

31:17 CD stands for cold bingen. It's Bingen Be. It's a specific marker

31:29 is found in certain excited, very , but they get the campus and

31:35 excited tourists. Also, the hippocampus have that marker and others will

31:40 So this is the only really distinguishing between the excited terror cells in the

31:49 . Now this is important because there not that much of the diversity of

31:56 for peripheral self. But these excited parameter. All cells are going to

32:01 the information out of the campus. mostly three layers in the hippocampus.

32:07 bottom layer stratum orients the middle there houses the highest density of West

32:12 but most of brown all cells. striking through the dollar. That's what's

32:16 from the delivers of a prominent sauce be living there. Then you have

32:21 . Ready. Adam was the third , and the very tips of the

32:24 dries would be contacting the layer that's Strider Left almost a more Larry.

32:29 do not have to memorize the but when you have to understand is

32:33 following thing. If you look in strong just like hippocampus of the

32:38 80% 80% of the South's 80 to even of the South will be

32:45 Very Selves will be these excited to . Their onset of Sean were

32:50 But as I said, despite the that there's 80 to 90% of excited

32:55 , Austin view snap works. There's one distinction between these cells, and

33:01 not morphological distinction. It's slightly with So most are located CB minus saucer

33:07 , slightly throwing Orian stratum, Orien and structure of the atom, where

33:12 Plast house, a very clearly located for our there isn't that much

33:18 Morphological was speaking, and the electric is speaking to these in. The

33:26 also will project out information and contact parts of the brain and other

33:32 These cells of flying by cells from Teoh, Reg, Teoh, violet

33:39 basically labeled one through 21. Would be cells these 1000 different types of

33:48 neurons. They would comprise only about to 20% of the total neurons in

33:55 hippocampus across, but they are the Diverse sat of the South, These

34:04 in dinners they're all expressing gather as to the prom. It'll south.

34:10 all expressing bloomy. So they projected made and communicated the information about

34:17 not work started just open networks. these in a very diverse subset of

34:23 hit of the Internet and they distinguished by very diverse morphology and

34:29 First of all, they're located across different layers. Second of all,

34:36 yellow cops that are yellow triangles that that are coming out of each one

34:41 the sounds represent the location of the where the subtype 13 21 will be

34:48 most of the inhibitor synopsis. So you look at the cells 1234 there

34:54 be targeting the so much especially 23 four will be targeting the so most

35:00 the Haram it'll cells located referring Then he moved two missiles that control

35:06 project their synapses onto the soldiers, , off the around the summons.

35:13 they excited her projection sauce actually have tight control of what information gets projected

35:20 off this now for because as we about the integration of the signal happens

35:26 the level of the SoMa and the initial segment where the action potential is

35:32 . Now you can see the some the Cielo cops, like from the

35:35 number 71 of my favorites else's alarm for so orients look more similar calorie

35:43 it said it says it's accident all way from the audience level lot layer

35:49 the bottom, all the way to very ethical den dries of the parameter

35:53 cells. So you see those yellow from cell number seven. But the

35:58 a packs of the parameter old and tree at the local awesome look around

36:05 Ira. That's what it's referred to allow himself, Uh, and you

36:09 see that these synapses will be targeting parts of the prom. It'll sounds

36:15 be targeting the inputs that air coming distantly so they will be modulating a

36:20 of the infants that air coming into , uh down drives distantly, but

36:26 will not. Number seven will not a significant the fact of the integrative

36:31 off the sober, But number number three and number four the yellow

36:36 and project onto the Soma is here will have a very significant defense on

36:41 integrative properties in action potential firing off cells and what information gets projected.

36:48 , finally, we can see that of these south like, for

36:52 two and flora. Very similar. have the same location of the so

36:58 the Denver rise to shown even orange red. So they have these down

37:02 center projecting birdie. Fully two and almost look identical. Their synapses are

37:09 identical. So what is the Both of these number to remember for

37:14 called basket South's. But number two positively for par. Vile demon.

37:24 , which is, uh, it , a calcium binding protein involved

37:31 Let me infer that in the chest human. Okay, well, this

37:50 the kind of Okay, so just few. Just a few chats

38:03 Uh, so now again, you to remember that number forest problem,

38:11 positive A two is problem and Number four CCK. It was just

38:17 kind of positive. Now there's not exam questions again. The Jaco

38:22 from this is that four years of we defined which some type of the

38:27 you are looking at. You need know the precise Ma'afala juvie cells.

38:31 you also need to know the intracellular for these cells and the other tinkle

38:37 that the complexity of information processing and off. What is happening on the

38:42 sanitary projection cells comes from the very population of being human. Third

38:48 The not such a diverse population of jury cells, which are projection sauce

38:53 excited to information to other networks. is a recording from my live

39:00 and there's a showed you differential infrared month. CrossFit The last time these

39:06 to sounds that a Rashed physical wholesale clamp recordings there to electorates essentially recording

39:13 activity from the cells. The cell the last in the Sala on the

39:17 received identical input, identical amplitude and duration. We're both stimulated to the

39:24 degree, but you can see the on the last responded by producing very

39:29 and slightly lower amplitude action potentials very frequency off the action potentials, whereas

39:38 sell him the ride receiving the exact man foods actually responded by producing a

39:44 slower train of action potentials. Each of these upwards sticks eyes an action

39:52 and it was larger amplitude action but long as high frequency. So

40:03 listening to know what Adi cells I don't know that they have different

40:08 signatures during the experiment Life experiment in brain tissue inside these electorates which are

40:16 trying to mimic the interest cellular the cytoplasmic environment of these 1000 signed

40:22 Electra's I had another by die and die is called a neuro bio.

40:32 Oh, or bio cited interchangeably. this diet is different. So

40:43 we've talked about stains and dyes that kind of inject into the tissue on

40:50 see what it would with parts of brain or what cells take up the

40:55 . In this case, that die located inside the the solution inside the

41:02 solution and during the experiment that dying into the cells and after the

41:09 what you do is you recover this from which you recorded and then you

41:16 in you noticed a chemistry. In case, the dye gets exposed and

41:21 can see two types of cells that reconstructed from a similar recording. The

41:27 hung the last is actually allow It says It's axe on and live

41:32 stratum orients Best region to SLM region the very golf. And it has

41:39 dries that are projecting horizontally. So based on the firing properties and on

41:45 anatomy, I was pretty sure this a LA himself. The cell on

41:49 Ryan isn't a projection excited to resell projection Excited. Very solid, of

41:55 , Has this. Ah, beautiful out of adultery go Basil Dan drives

42:01 out of the base of the pyramid well a Zacks on projecting out in

42:08 . And it's actually coming out to the visual field and disappear. So

42:13 projection acts on that was exiting I couldn't see the ramifications on the

42:19 side like I could see on the . Self shown here on the

42:24 No, Uh, like I for us to know the anatomy and

42:29 signatures is almost enough to determine if is one of the 21 different sub

42:34 cells. But the final definitive answer come from these interests. Al.

42:39 markers so it for Ah, alarm a positive for Sonata statin, which

42:47 song. This is another style that provide women positive, which isn't

42:52 But I did not record from So a recording from this Samantha Staten

42:57 that also staying for N b and b stands for their abide. So

43:04 me write to you with Samata Statment former Oh, in a second.

43:16 two stat eso it is being there buy it. Okay. Okay.

43:34 . So now I was absolutely sure I had that whole I'm cell that

43:39 some out of staten positive that had new Arbeitman die and then it using

43:44 different technique. This is a fluorescent . The ride with using the modern

43:50 camera lucida that Ramon Inca how originally They used a modern day neural lucida

43:57 and actually drew and reconstructed the cells our self inspired by Ramona alcohol in

44:04 work. So I could tell for that this was an excited, very

44:09 Perama normal cell. And this was alarm cell which would respond Teoh cell

44:15 seven in this diagram here. This how specific you need to get.

44:22 is one of the recordings that would like. I think I already showed

44:27 to you before. And you have sophisticated pieces of equipment. You have

44:34 very powerful pre amplifiers on the left , girly. This is ah,

44:40 manipulator. So these would be PS . Very sensitive or mechanical. Micro

44:48 center. Very sensitive holders. set up like this, uh,

44:56 when graduate students are the students. , we're learning from me how to

45:01 this kind of a sad up. have to explain to them that

45:05 this particular startup you're looking at you not think of looks very in

45:10 but it's about $100,000 car. uh, just just how how would

45:18 drive $100,000 car if you if you where you were sitting behind the

45:23 of course, everybody has a different driving. But how would you drive

45:28 ? So you have to drive it carefully. You have Teoh.

45:31 it's very sensitive pieces of equipment. very expensive pieces of equipment. But

45:36 you have to work with the situation . This is an example of such

45:41 situation where in the back here on ride. The room is,

45:46 in onto the sat up here. of my holders broke and I had

45:52 attach my electrodes onto a pen here white. So I had to very

45:59 glue during the experiment because I didn't to lose the recording and reinstall

46:04 Very careful. Uh, in the using this, uh, 10 electrode

46:11 that was number sophisticated, not very , and it got the job done

46:15 the moment. So problem solving is half of it, actually, in

46:21 and especially when you're working with set like electrophysiology neurophysiology sat us. You're

46:29 about probably 50 different variables. You to keep track in your head.

46:36 50 different variables. You have to sure that your tissue is doing

46:40 The tissue that is sitting here under microscope is actually being supplied by exit

46:46 ated official cerebrospinal fluid pretending for pretending this piece of sliced petition brain tissue

46:55 it's still actually inside the cerebrospinal fluid the brain. Do you have to

47:00 about the tissue? Have to worry the microscopes You have to worry about

47:03 lenses. You have to worry if have lasers in the microscopes or very

47:09 themes of light, you can burn tissue. This is just this is

47:14 , you know, making sure that is happy sitting in this wall and

47:17 can observe it and visualize the Using the friend and Franchot McCroskey p

47:23 get to that point is about three of work Now. The after passed

47:29 cells and your tissues alive for about to 12 hours, and this is

47:38 of like a surgery like a real where, you know, when the

47:43 walks in an operating room, he's . There's no texting, there's a

47:48 messages and, you know, social posts and take talks. You wearing

47:55 Pampers? You need Teoh. Because may last about 12 hours in the

48:03 room, you cannot leave. You even sometimes take a simple for

48:09 and you have to build that stamina like training. It's like training for

48:13 marathon. You start running or one two K five K. You're making

48:19 1 marathon Find doing that. This what this is was with this it

48:25 . So what? Actually, I use the restroom. But a lot

48:28 these experiments would you grab us for and preparing them. And this is

48:34 future experiments and preparing the tissue doing for 68 hours to the poor.

48:41 , your knack, your muscles, hands are hurting your name and then

48:49 clean up absolutely everything sticking stand because residue chemical residue can be left no

48:56 residue. Pinto left your operating and sterile environment when you're doing these electric

49:03 experiments like that. So it's very . You're talking about 12 14 hour

49:11 . I could dio three of these maximum four of these days a

49:19 and the other days would be dedicated writing to analyzing data to fixing equipment

49:26 problem solving the noises and the This is this Israel dedication. This

49:31 this is real science and hearts and that you have to put in in

49:38 to to work with with pieces of like this and drive them successful.

49:44 right, so now we're gonna talk glia. Leah for a long time

49:50 start. Teoh have the passive support insulation function for insurance. But that

49:58 not the case. We are Uh, they're responsible for housekeeping

50:08 The guide neuronal migration, the release factors Some of these air slow growth

50:16 the comprised one brain barrier and filter gets from the blood into the

50:22 They actively control Sonata Genesis system after , information of new synapses, synapse

50:29 in as function and sending a strength asked plasticity. But what glia do

50:35 do is they do non produce ison or calcium weights if you do

50:43 Yeah, I was sorry. They know produce counter action potentials, but

50:49 , instead they communicate through these deep polarization is through callous string

50:55 and so Bria does not produce fast potentials again. Fast action potentials is

51:02 unique feature of euros, but also glia comprise about 90% of the total

51:10 bio NASA to speak sangria responsible for installation and violin nation in peripheral nervous

51:19 . If we look at the peripheral of performers that are contracting the

51:24 you will have Schwann south, where Schwann Saul will form an individual mile

51:29 sheet to unit each one of the is an individual mile and union 100

51:36 nerve. Okay, So in this axle, which you see essentially is

51:42 nation in periphery by Schwann cells In central nervous system, you have a

51:48 deandra science illegal down there, size a soma and that soma has many

51:54 processes that are radiating out. Each of these processes can become a separate

52:00 segment on a one many different surrounding and accents that are surrounding this illegal

52:11 side. So what we have is we have, uh, Schwann

52:16 . Once I was one uh, segment and a legal danger signs.

52:24 living under side It's processes produces many and segments on many accents that are

52:31 in the area. If you have mile a nation by the South,

52:37 is one function that it serves ostracised has shown here Hoster size actually filled

52:43 of the space in the brain. asir size do not participate in this

52:48 nation processes Astra Sizable will discuss but obeyed. In synods control, master

52:55 participate in a clearance of neurotransmitters in brain barrier, but they do not

53:02 the smile and so a little Denver . This was something that is very

53:07 Sow for my elimination, if you . For example, through the violin

53:12 optic nerve, you will see the of my island. So when it

53:16 , this is one of these illegal underside processes, grows around and wraps

53:22 warming in, um, individual, , violent segment. And in between

53:30 violent segments, you will have notes run beer. This is where the

53:34 potential will get regenerated. It will produced close to the SoMa. But

53:40 it travels down the went of the of the very terminal of Accel,

53:44 amplitude of that actual potential was not to change because we'll get regenerated each

53:50 beer mile and dysfunction, smiling nation of my island problem of action of

53:58 island. Proper expression off milon Basic which control island compassion, can result

54:05 some severe disorders. So we're gonna on, for example, mag mile

54:15 , glycoprotein and as an example, mile and basic Prodi Um, so

54:20 seven related pro dance and Matt would responsible for South a cell recognition.

54:27 this brought in will recognize and Deron recognize acts on that will be responsible

54:34 initiating the violin nations that these different prudence are responsible for different functions.

54:41 this smile, a nation of the unfolding. Uh, she's, uh

54:47 you have information, do you have of the brain that can also cause

54:54 Mile the nation? It is referred his insofar answer Follow. My line

54:59 it's a yellow so you can read very well. But I think you

55:04 may be able to answer far lower life this, uh, but we're

55:10 discuss to disorders in particular when we're focus into disorders to take away for

55:15 exam, the strikeout marriage with disease multiple sclerosis. All right, so

55:21 have your sanction on neurological disorders on a new sectional. Multiple sclerosis,

55:29 sclerosis. There's an autoimmune disorder is non immune disorder, which means that

55:38 body itself is reacting to violin. is treating Meilin. It is recognizing

55:44 . Meilin is a foreign invader, it starts basically just strolling its own

55:54 . It's autoimmune disorder. Multiple Ah, typical expression off symptoms of

56:00 sclerosis would be in the thirties and inclined divers. From the motor

56:05 you can have tremors and spasms. associated with multiple sclerosis. And if

56:13 is because there could be an effect the central deem island nation where the

56:17 commands air coming out properly from the holder. Or it could be

56:24 uh, related to the conduction information the periphery. So if we were

56:31 about germs and convulsions is one of symptoms of multiple sclerosis. Now you

56:36 imagine that if the mile a nation happening in the regions of the brain

56:40 are not responsible for motor commands such the frontal cortex, what do you

56:47 will be affected in these individuals? could be emotional center center, in

56:53 , that it could be the highland of expression, aggression, high levels

56:58 fear, maybe anxiety, emotion. could be affected because when you d

57:05 ate the access to basically are producing proper information transmission between South and if

57:11 the level off the motor commands, on. The level of tremors were

57:17 of spasms, lockups, Bennet, level of the cognitive dysfunctions, our

57:24 dysfunctions that could be it could be many different things, including censor information

57:30 . Uh, this model here for multiple sclerosis. One of them almost

57:37 a mutation, which is a recess mutation. You need to battle eagles

57:42 chromosome 18. And if you have normal mosque in on the ride in

57:48 If you cut through that there, you will see beautiful and my eliminated

57:53 in the miles it is a transgenic that has a mutation. The

58:00 In chromosome 18 you will have a , a mouse. So the female

58:05 of the shiver amounts. This is , which is essentially replicating and modeling

58:11 tremors and the convulsions that you would multiple sclerosis. Uh, so this

58:18 mice will have deem island nation will a significant shivering you Kenbrell sq,

58:24 of this Meilin Nation live trance faction jeans. So if you transfer,

58:28 a normal gene on this transgenic you can partially rebuild the smile.

58:33 nation and you can obviously partially rescue the behavioral or the definitive expression off

58:41 disease. He's a multiple sclerosis, we make them by during the course

58:46 talk more about multiple sclerosis. the disorder you were discussing in relation to

58:54 Meilin Nation is Shark Out Mary where you have to march off peripheral

59:01 and Prodi m 22 p. P. 22. So what is

59:06 on the right here is that you have over expression or duplication of this

59:11 on chromosome 17 that codes for too. And then the bottom Ryan

59:17 an actual stain fluorescent stain that is too much of the genetic expression.

59:22 much of the GMP 22 if you not necessarily lack of podium, but

59:30 too much of the pro Dan or of that podium during the wrong time

59:34 the development or a lot of the with aging. All of these things

59:39 be contributing now. Teoh Different and . Mylar nation process means what happens

59:48 , uh, sharks Got married We're now talking more specifically about peripheral

59:54 , and so it will be a toe mess affecting Sienna central nervous

60:00 where this is affecting peripheral parents and nerves. What you have is during

60:06 development when you have deem island the bone structure is soft and the

60:11 are shaping. Unfortunately, if your and pretty significant deformity, it's bodily

60:18 is especially of lower extremities. Individuals Charcot married to disease will often have

60:27 to control impaired, gave by often from side to side and throwing legs

60:35 and right to move forward. And is because there isn't enough stimulation going

60:41 the muscles during the development. In earlier, you can detect that there

60:47 an impairment in violation of the Earlier, you can diagnose sharp but

60:52 to disease early. You can place individuals and braces, which would help

60:57 essentially preserve, uh, normal or normal bone instruction. Hopefully help with

61:05 impaired gait and movement. So in different disorders multiple sclerosis, auto

61:15 Uh, this is a developmental disorder to pro damn Shark got married to

61:25 . So overall, this slide actually a great fly to talk about different

61:32 of different real South alone. Slide it has Liggett undersized, and it

61:38 you that it has different processes wrapping , informing mile and sheaths around the

61:45 . It has Astra sides on the , and you can see the exercise

61:50 these blaring, complex Astra acidic trees very responsible for clearing Um,

61:58 neurotransmitters around the synapses so you can a lot of their processes wrapped around

62:02 synopsis. A lot of times it's to stripe our ties to naps.

62:08 , neuron contacting another neuron. And Astra side of Leah is there,

62:13 them out of neural transmission and also hop have normal fluxus in the

62:20 So once these local synapses gets very , that could be a significant flocks

62:26 potassium, significant flocks of sodium and ions. And with Astra sisal

62:32 they will slurp up this, abnormally high concentration of ions, and

62:39 will siphon it, often distributed through massive network. And what that does

62:46 that basically controls, uh, hot , a piece of normal high levels

62:52 Ionic and the transmitter concentrations by siphoning off. And because ostracised are connected

63:00 other Astor science gabbed junctures, do learn about gap junctions later? Of

63:05 , these air the receptors that will the South physically one to another will

63:11 the silence and information through a very on specific network that is interconnected.

63:18 specific. Astra size. On the hand, you see ostracised that have

63:23 end feet or their processes. We them and feet placed on the capital

63:29 , microcap Hillary's and they're forming the brain barrier. They're also interacting at

63:36 top with dependable cells, and the cells that separating out the street respond

63:43 fluid. Basically, the curricula space the interest initial space interstitial space surrounding

63:50 actual neurons era, dependable cells. are also stem like cells todo

63:58 A bendable cells can become other types RIA, potentially even neurons. For

64:06 long time, we thought that there that many stem cells from the adult

64:11 . And now there are two Is that first of all, there

64:14 still stem cells with certain parts of in Asian brains. Second theories that

64:21 might be justus many of the stem , but the go dormant. So

64:26 a whole new science that is not to believe. It is related to

64:32 cells and regenerative medicine and regenerative compounds can prevent, uh, first of

64:39 the degradation of telomeres that happened with and second of all, a

64:44 Some of these stem cells that might doorman, including some of the potentially

64:49 Penda Mall South's, uh, a part of the brain that will

64:54 some of the highest members of stand and their dog brains. This cell

65:00 here on the right is a micro cells from microbial seller. This is

65:06 , the most mobile al a month the tissue. And it is very

65:11 reacting to the injury when the injury in the tissue. And so I'm

65:18 , uh, stop the sheriff for a second and their records in their

65:26 . And this is an example off glial. Ciao. Okay, so

65:32 this this string that you have seen across and you see the timeline I'm

65:39 experiment from 1989 Ancient experiment. It even rial. What was that?

65:50 there we are, isn't Iran, that neuron is migrating along the radio

65:58 . Also, radio glial cells, service servers. A lattice is a

66:04 where neurons newly forming, migrating their will latch onto the slider. There

66:11 form side of plasma continuity with radio South's. It will actually form side

66:17 plasma continuity of the remember this continuity , well, crawl along these radio

66:25 cells to find its final destination. just which is just, uh,

66:33 remarkable. Um and, uh, show you one more movie that actually

66:48 shows. Ah, smorgasbord off neuronal going on. There we are.

66:57 should be able to see this. you can see that again. You

67:05 tens of neurons ear migrating along this climbing along the lattices of the

67:12 Real south. The white is not because when you're on suborned or not

67:18 within their final destination within, let's cortical layer for and they're not born

67:24 be one of those 21 stuff faster , but rather they actually has to

67:30 their destination. So the use radio cells as a lattice is a ladder

67:36 migrate from certain parts of the brain the ventricular zones where most of the

67:41 air born to quite distant parts of brain, to find their exact brain

67:49 , which you can say exact Then you have to find the exact

67:55 in that brain structure like layer and then you have to find exact

68:02 in the house in that neighborhood, would be that particular cells soothing another

68:07 location where fire. And then you Teoh form connections with about thousands of

68:14 and a living in the neighborhood to which ones you're gonna talk to you

68:19 strengthen your synapses. Which ones? meaningful which ones you want to

68:24 And I talked to. It's the , but but Easterner finds its final

68:31 , and radio glia is an intricate of of this process. Now,

68:38 final moving that I would like to you is microglia. Micro glia are

68:46 dynamic elements. And in this would you have is you have first

68:57 the movie and I will explain it in greater detail. This is the

69:03 . But start is the injured that of this movement is microbe. Leah

69:13 Glee is a lattice microbe. Are the scavengers the most mobile elements

69:20 the brain tissue? Okay, here is an injury. This is this

69:25 wide blonde there's an injury and then what happens with micro glia surrounding this

69:31 . First of all, they start their processes toward the side of the

69:38 . Boo OK, second, they start moving physically. The sal on

69:46 last, for example, jump from location to another and other sauce air

69:51 into the fuel. The view more that were not there. So you

69:57 these micro glial elements and in the of injury in the case, off

70:03 get activated the micro glial cells to sides of kinds, and they control

70:09 release of scientific arts, actually Santa of these pro inflammatory side to

70:15 You should pay attention to them because is a debate Offsides of kind storms

70:21 cold in 19 in the body. there's a new hypothesis all turned you

70:27 next week. Brendan Kind and Okay, review that bread and kind

70:33 ace inhibitor hypothesis of code in 19 it's nonstop. A is supposed to

70:40 a combination off the sides of kind branding kind and storms that seem to

70:44 a lot of, uh, evoke lot of symptomology that you will be

70:50 in in closed in 19. my 13 year old daughter was fascinated

70:56 hear that there is hyaluronic acid in loans because she's putting highly ironic acid

71:01 there on her face. It's it's a new thing in the systematics

71:07 hyaluronic acid absorbs a lot of more , a great for moisturizing purposes.

71:13 during Cove in there's accumulation of hyaluronic in the lungs. There's activation of

71:19 fascists. Macro factors will be activated , then, to try to clean

71:25 repair, also generating inflammatory responses. you can think of these micro Publius

71:32 like resembling of the Migra fathers that would have in other parts of the

71:37 like once. But then you know happens with hyaluronic acid in the

71:41 recovered 19 and actually absorbs and forms liquid like gel like thing. And

71:49 why they say that breathing is like through Joel over your mouth.

71:55 And that's where ventilators. I'm not great and helping because you're your lungs

72:00 plugged up with John like substances caused Heil around the castle. How would

72:04 know that you would learn that inner course with my daughter, 13 year

72:09 know about it. Actually, she fascinated to hear about coaches of highly

72:14 acid because she's following Eva Longoria and prismatic standoffish with high were only

72:23 Okay, so interesting discussion all related my really, in some way.

72:30 , uh, tickle messages the micro in the most mobile. How amounts

72:36 are responsible for the clean up the that are reactive. Teoh the environment

72:46 that are involved in the on inflammatory . Uh, in the brain.

72:56 . So each real cells, in way he'd sell have their own

73:01 Teoh, serve so to speak, ? Okay, great. And final

73:11 we also we're discussing is involved in brain barrier and this is Astra glial

73:18 . So blood brain barrier, you Astra glial processes. This is our

73:22 sides. You have the parasites that surrounding and diffie liel cells, which

73:31 you're basically forming your blood vessels and have the blood inside those blood

73:38 You have tied junctions between then the L cells. And you have these

73:44 membranes. And so things that are from the blood into the brain have

73:49 go through this check points off the of the barrier. That asked a

73:55 the Thai junctions, Paris eyes across , The real processes. Also,

74:01 are specific transporters that will transport and certain elements to go into the

74:06 Tissue are this will be transported. will be defused at this will be

74:12 . But a lot of it is code transporting of goods on the blood

74:16 the brain. Blood brain barrier is in a lot of things from the

74:22 entering into the brain again. Let's back to our date of code in

74:28 right? The essentially the hotbox. you see me? A hypothesis which

74:34 that virus does not enter into the . Bruce is Ah, uh,

74:40 hypothesis with virus answers into the brain significant information because a significant neural

74:48 Because of that information who controls the of that virus? Welby's aliveness will

74:55 controlling natural spires of blood. Brain , in this case, is a

74:59 guy that's preventing a lot of stop from the blood going to the

75:03 Also, we consume a lot of like through the digestive system, sometimes

75:09 concentrations off but different columnist high OnStar , Uh uh, vitamin like illness

75:16 all of this being controlled but goes the one and with guest into the

75:22 so not everything gets passed very Now the blood brain barrier is also

75:29 obstacle. Teoh Neural drug development run . Barry is an obstacle toe neurological

75:38 development because most of the drugs that take our pills that you swallow that

75:43 that what you swallow against absorbed maybe absorbed in view of swallowtail gets digested

75:51 the stomach, gets absorbed through the system into the blood stream. And

75:58 from that blast stream will say you in a year consuming antidepressant drug for

76:04 . But any drug that is targeting anti epileptic drugs you swallowed until so

76:11 , whatever. Guess from that pill the digestive system into the blood

76:17 Now, what fraction of that pill actually going to get transferred inactivated into

76:23 brain if it crosses the blood brain ? So a lot of times,

76:27 you're designing a neuro drug, you to make sure that they're very freely

76:32 the blood brain barrier. If it cross up to the blood brain barrier

76:37 with your you're targeting a condition like . This is, uh, you

76:44 , this is where you hear Uh, they will say, You

76:51 you can take this pill for but what is it going to

76:57 It may make it Narcisse. It make you vomit in Meghalaya and

77:03 It may give you constipation, but the opposite and may give you massive

77:10 . It may start bleeding, and on the normal pains in the

77:16 Why is that you're taking a neuro really shouldn't do anything there. And

77:21 part of the challenge is that for narrow drunk to cross into the

77:27 you have to take it. Does cause a significant side effects? And

77:31 is systematically throughout the whole system with digestive system, with its a vasculature

77:37 so long, it's a smart drug . Of course, no drug is

77:42 passing into the brain concentrations that alot do not generated significant side effects.

77:51 know that you know we have a of very commonly used drugs such as

77:56 , for example from pain that are this pain, Killer said aren't quite

78:03 because it's quite dangerous to overdose with . It's quite dangerous to activate the

78:09 . Enough of the receptors in your centers for the opium is to shut

78:13 your breathing, and that is because have to have concentrations to alleviate the

78:20 in the neuropathic pain or other types pain. But it's now interfering

78:25 either with a whole body or interfering with other parts of the brain.

78:31 may be targeting one part of the , but if you're affecting brainstem that's

78:35 for the vital breathing functions, then and impression for forget some pain and

78:42 will stop dreaming on, and that the end of it all. And

78:47 we have a lot of problems. in pharmaceutical, drug development and neurological

78:53 development, plan based drug development, deals with specifically Grand blood brain

79:00 There's a great thing. It's a thing, but it's also a challenge

79:04 that perspective. Okay, so I'm stop lecturing on the material for

79:13 and I'm gonna open up the chats go through some of the questions that

79:21 may have. And by the if you have any questions in the

79:24 from the last three lack truce are lecture of this lecture. Okay,

79:32 have a question. Sounds good, he is wrong. We're office

79:42 Yes. Would you like the email and schedule a different time? Give

79:49 and like, 23 time options. we can do that. Yes.

79:55 . Thank you for asking. So will have your sample example Friday And

80:00 don't have your class on Tuesday, teaching another section of their science and

80:06 offer Labor Day on Monday. And thought it would be unfair if you

80:10 working on, uh, that extra . So we do not have a

80:15 on Tuesday. Uh, I will ah linked to the graduate students Teoh

80:23 on Tuesday about that, Simon, we will not call the regular costs

80:28 Tuesday. Yes, this still Uh, can you raise your

80:33 So I continue to you. I'm very, uh All right. Let's

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