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00:02 Okay, So today we're going to talking about neurons and glia and we'll

00:07 on this for the next couple of . So neurons comprise about 10% and

00:14 comprise about 90% of the total brain population, neurons are like chips.

00:23 the chocolate chip cookie. And I ask is a chocolate chip cookie possible

00:32 chocolate chips. No, but is cookie possible without the dough? Just

00:41 chips. No, it's called So in order to have the brain

00:50 glia which traditionally was referred to supporting structure network. And from greek glia

01:00 the glue kind of gluing the networks to now knowing that glee are actually

01:06 intricately involved in regulating brain function. the neurons are really responsible for the

01:14 of the fast action potentials and the and that transmission in the brain.

01:20 other thing here is the game in brain is mainly in the stain like

01:24 rain and the plane in spain is in the plane and that is as

01:32 recall from previous lectures, you really visualize sells individual neurons unless sustain

01:40 You cannot visualize networks unless sustain But we also discuss a technique and

01:46 contrast technique that does allow you to neurons at least there's so most if

01:51 their processes to a great extent without any stains. And as we talk

01:58 neurons and glia, it's a it's topic that obviously is a review and

02:05 levels because neurons are just like other and neurons will have, the cell

02:13 will have the nucleus will have the machinery and the nucleus it will have

02:19 organelles surrounding it mitochondria which is very , has a lot of energy production

02:26 neurons and in the brain we have desperados you have holly robinson complexes.

02:34 have rough and the plastic ridiculous smooth the plastic ridiculous uh where there is

02:41 of calcium inside the south and inside Solich of free calcium. And the

02:46 of plasma neuroses very tightly regulated because not just in the ion that's also

02:51 messenger inside the south. And there some unique aspects that you're observing here

02:57 the neurons such as for example this Philip and myelin sheets. These white

03:06 myelin installation like that surrounds these And this zone is where the action

03:15 is produced. So all of the is integrated from all of the different

03:22 of the sell by the selma. if the cell is excited enough or

03:28 enough input will generate an output which in the form of an action potential

03:33 gets generate an accent, initial hill , accident initial segment here and then

03:40 travels down the myelin native access once reaches its terminal down the mile undated

03:47 into another neuron. That actual potential gets generated here is the same attitude

03:53 external terminal as it was at the of its initiation near the soma.

04:01 this action potential then results in the polarization of external terminal and release of

04:05 neurotransmitter that neurotransmitter. Well done. synapses will monitor them rise and good

04:12 synaptic projections going onto the selma's and going to be a release of neurotransmitter

04:18 posson optically. These neurons will then receptors and then your expands is also

04:26 a unique feature two neurons and we'll why they are important also uh in

04:33 of developmental mental litigations especially this is that's very basic. You have

04:42 N. A. That gets transcribed RNA are in a gets transported from

04:51 and there's splicing of RNA that takes . And during the splicing you splice

05:01 the in trance. Okay. And leave only the exxons and you create

05:09 messenger RNA. And so you have variants and supplies variants can be both

05:14 and pathological slight variations. And splash is what makes us slightly different and

05:21 brain cells and processing capabilities. problem capabilities of these cells and also

05:29 variants. Could be pathological meaning if message is not sliced correctly could be

05:34 a protein that has a slightly wrong and that protein and the wrong

05:41 This project could be either contributing underlying disease because that protein could be a

05:48 channel that's in the plasma membrane Organelles and the plastic particular ribosomes and five

05:57 complexes uh messenger and a and then proteins that get translated and can either

06:04 santa's olic or free floating or membrane programs and we'll discuss a lot of

06:11 associated proteins because these are membrane receptors receptor channels and voltage gated channels that

06:18 study at the level of the It's a post genomic era. And

06:24 we can utilize these micro racer, micro race that allow us to describe

06:34 have a son of a bird's eye of all of the genes. And

06:39 can have up to 30 or 40,000 that are encoded within this microbrewery.

06:47 you will walk around the campus and will see advertisements for 20 cents per

06:55 pair or a dollar for whatever basis synthetic DNA. And because we know

07:03 code. So we can now lay code inside these wells inside this microchip

07:11 really, really microscopic wells. You to use a microscope visualize them.

07:17 the advantage of that is now you say, Okay, I have 40,000

07:22 of interest. I'm going to let's say this. 30,000 40,000

07:28 I'm gonna uninterested in these and I'm to see what this gene expression is

07:35 the development. Let's say how changes in the developed. You can ask

07:40 question, I want to see if is genetic changes in the brain that's

07:46 versus non collective brain that has alzheimer's is not an Alzheimer's disease, you

07:54 use animal models, you can use um tissue of course if it's resected

08:02 the surgery uh potentially from a human it's much harder to obtain those

08:09 And the sample size is usually very . But you can have analysis in

08:18 normal brain and would say brain that a pathology. And the idea here

08:24 that you will then take em RNA wine one and M RNA from brain

08:30 and you will apply it and jeanne reduced expression and brain to will appear

08:36 gene with reduced expression and bray juan appear green gene with equivalent expression and

08:43 in both brains will give you a signal. It's really a fluorescent yellow

08:48 . What is the signal on the slide is essentially if there is a

08:53 of that gene it will have a sequence to the synthetic piece of the

08:59 that you placed inside the well. a lot of it will buy instead

09:03 a like to exactly matching very sophisticated piece. So it matches a lot

09:10 it will bind. So you have over expression and you will compare and

09:16 of the genes will go up and of the genes will go down and

09:21 you will say okay when I look I compare normal brain versus a pathological

09:27 disease. Brain I see that there changes in 2000 genes and say it's

09:38 . Well okay so you've gotten some then you're gonna say okay some of

09:43 genes went up by five times. then I see that 20 genes went

09:51 20 times. Who said, oh must be important. That wants to

09:55 . The mouse must be somehow contributing disease. Always make this job.

10:01 your mentor tells you that this is genius study in the lab out of

10:04 20. So you're going to pursue one and that's where you kind of

10:08 to drop your research because the mentors pay for the research too. But

10:17 24 change Mean that it's most important five whole change. We don't know

10:27 , biological systems. Uh Central nervous is a nonlinear system That poll change

10:35 be extremely important as compared to 25 . We also don't know which change

10:40 place far. Maybe this five ball was there and then the 25 phone

10:47 followed in other genes. So you , you don't get answers to these

10:52 . But then you know, you you read information, let's say you

10:57 honed in on those 20 genes that up 20 times. You read the

11:02 , you read about epilepsy, you , you know, always talks about

11:05 23 genes. Now you're going to some additional studies in these 23 genes

11:11 find out maybe what part of the they're really over expressed in what sells

11:16 subtypes of cell sage emerged first. what point of pathology? There are

11:23 expressed at the beginning the end after all of these things. But this

11:28 a really good birds eye view of going on on hundreds if not thousands

11:35 genetic changes inside the brain. And is a powerful tool that can be

11:39 in studying the neuropathology as well. under plastic, ridiculous. Um

11:47 protein folding and calcium regulation old You have post translational processing and protein

11:56 . That's what is responsible for when proteins come out and they get sorted

12:00 and go to their final destinations. is very important. So is the

12:05 cycle and you'll have to memorize the cycle. Just kidding because even if

12:11 do you'll forget it and I have do it at some point. I

12:15 it. There's a certain aspects that very important to remember always about the

12:22 production inside the south. And please talk about chemistry professors that I said

12:27 about scratch cycle today. So ATP generating energy and like I said,

12:34 brain is about 3% of the total of the body but it consumes over

12:40 of the total energy. So it's consumes a lot. It's a small

12:46 that sucks a lot of energy. operating outside of the delivery. Um

12:51 operating in a non linear fashion and in stores energy sources protein and sugar

12:58 get turned into hieratic acid Through the process produced 80 p. and carbon

13:08 co. two and this https and important for different processes inside nerves.

13:15 so this is as deep as we're to go into this. But keeping

13:20 mind also reminding you that 80 And like other organ Alice is a

13:25 membrane organelles that has the inner And these very uh unique kind of

13:32 imagination snake like number niss formations that referred to Christie foster lipid Beiler is

13:43 plasma membrane fossil liquid by layer contains audience contains proteins that are channels.

13:53 means that these are the proteins that allow the passage of ion student small

14:00 . Then there are some proteins that trans membrane proteins. That means they

14:04 both extra cellular side of intracellular side are not channels but they may be

14:10 to other proteins inside the south. this is would be an example of

14:14 protein coupled receptors. So in this both of these the this this one

14:20 the middle and this one is a . They can both be receptors of

14:25 . They can both by the chemical them. One of them will conduct

14:29 through it and another one will not anything through it. But instead will

14:35 that message to the interconnected you've heard complex then you have carbohydrates that are

14:43 the south and obviously black of proteus the core of the plasma membrane is

14:49 possible lipid bi layer. We have fatty acid non polar. I drove

14:58 . They're afraid of water tales. the polar hydra filic heads that are

15:03 false statement glycerol and the possible lipid layer is interspersed with the cholesterol

15:11 And so if you were to take lipid molecules and just throw them in

15:16 equally solution that would actually aggregate themselves this Byler and typically form around shape

15:23 mycelium which is essentially the basis behind the organ Alice and even the whole

15:31 with the cell membrane and underlying here this uh rather dynamic possible lipid structure

15:43 because it actually rearranges and the molecules are embedded and even trance membrane proteins

15:50 move through that possibility by layer and very fascinating We can move micro meters

15:56 milliseconds. The receptors that are not in synopsis can move into the synopsis

16:02 the membrane. They don't have to be shuttled through the side of plasma

16:07 some way and inserted but they can travel through the membrane at very fast

16:13 and the overall structure of the cell . And if you recall the doing

16:20 that we looked at, they had the different shapes is supported by the

16:27 sadness, chemical elements. So in following slide we look into the sinus

16:32 elements. But you can rearrange the side of skeletal elements and that would

16:37 like rearranging the beams and supporting uh of the wall and moving it into

16:47 different part of the house and now have a different shape to the room

16:51 the house, you rearrange the side skeletal elements and the plasma member and

16:56 the drywall that you put around and you have a different arrangement, different

17:00 house. Always like to show this on fluid mosaic model is pretty basic

17:09 I like it because it just reminds that it's a dynamic structure and we

17:15 should view and understand it is a structure. When we talk about neurons

17:20 the brain, neurons that are very and very dynamic at producing their electrical

17:26 chemical communication. Uh huh. Set and being in the world. It's

17:34 shells history from your team. It's pretty much Yeah. And in my

17:46 and regroup a member naturally settled in because their jails rebuild water as their

17:56 , attracted, doing some cholesterol and few carl hybrids. And you have

18:02 basic structure of the plasma membrane within lipid molecules. We also find different

18:11 which do various things for to sell instance, they receive signals from the

18:17 outside when they transport nutrients in So major proposes the membrane with a

18:25 of different limits carbohydrates approaching and these pronounced stationary. They constantly move within

18:36 structure. We were in changing your . Yeah. The survival of all

18:44 rests on this veil of material. . Suddenly we're just to politics

18:55 So it's a it's a pretty simple but it illustrates exactly the point that

19:01 trying to get at about the fluid the fluid, mosaic marble. It's

19:07 mosaic mosaic of proteins, carbohydrates, of proteins, cholesterol. And it's

19:16 changing mosaic. It's a dynamic Is mosaic, not just because it's

19:21 by fluid, but because it actually changing. When we look at the

19:26 side of skeletal elements, we have subtypes of micro tubules and your filaments

19:32 intermediary filaments of micro filaments. The tubules are the largest set of

19:40 allowing us about 20 nanometers in The neural filaments are the medium size

19:46 of skeletal elements and the micro filaments the smallest ones. And they're comprised

19:53 the acting molecules. Um and these especially active molecules, have the ability

20:03 make longer change. Prelim arised diploma were broken up into shorter change.

20:10 as they do so, they can rearrange themselves underneath the hospital, it'd

20:16 plasma membrane and give the plasma member a different shape and different dynamics for

20:22 fluid mosaic and interactions. If you on the right here. This is

20:28 electron microscope picture that's taken through an that has been sliced through lengthwise.

20:37 if you just took a cucumber instead cutting it in half, you sliced

20:42 alone flies then with you seeing here clearly on the outside edges of the

20:50 of flies and the plasma membrane is sheets of mylan that surround that acts

20:57 and inside the acts on. You , seeing these would look like kind

21:01 like spaghetti ease long, stringy spaghetti looking things. Those are the micro

21:08 . The micro tubules are very important external transport for serving as a highway

21:16 things to be delivered from the soma the peripheral vice versa from the peripheral

21:21 aspects of the cell, into the into the selma. This is an

21:28 of a fibroblast cell and what this illustrates very well is yellow is the

21:38 turbulent molecules is micro tubules. Blue acting micro filaments and purple, staying

21:49 as a nucleus. This is a glass. Al It's a beautiful stain

21:54 shows that surrounding the nucleus immediately surrounding nucleus of the core of the

22:02 If you want to call it the of the house, you have yellow

22:09 on micro tubules and as you go to the outer edges of the cell

22:16 more so outside of the selma using molecules and that just supports the idea

22:25 the smallest sinus chemical elements would be the support for the outer edges and

22:33 determining the outer shape of the plasma and their rearrangement underneath. The possibility

22:41 Beiler will also cause the change in shape of the foster the Tyler at

22:48 plasma membrane. So in this next we start talking about Alzheimer's disease and

22:56 understand why we talk about Alzheimer's disease the context of the sinus chemical

23:04 But in general I had this slide I thought in this presentation but it

23:11 and I use a different slide um I think is on your blackboard

23:19 but I'll make sure it is that want to talk about Alzheimer's disease in

23:23 case the hallmarks pathological hallmarks of Alzheimer's . And this is what I would

23:29 for you all to do this If you're a good student, you're

23:34 notes and you're taking either notes on or you're taking them digitally. During

23:43 course of the semester, we will about six, maybe seven, maybe

23:49 neurological disorders. And when we talk these disorders today, for example,

23:54 will talk about Alzheimer's disease and we certain aspects of Alzheimer's disease today.

24:03 at the same time, uh we come back to Alzheimer's disease when we're

24:11 a single cooling signaling and synaptic So what I usually recommend is that

24:18 we have a notebook, you dedicate page or in the back of the

24:24 , you basically dedicate uh you basically a page. You dedicate a page

24:45 each of these neurological disorders and you do it at the end of your

24:49 or you can dedicate a new digital for or you can just dedicate one

24:56 as you go through your notes. I recommend to set it aside because

25:01 keep coming back and talking about these throughout the semester as we learn new

25:07 in neuroscience in general. But today going to start developing some of the

25:12 or maybe some of the language that's basic, but maybe you haven't thought

25:17 before and some of the language that's clinical. I would say to that

25:23 you haven't thought about it before. . So let's start with. This

25:30 I've asked this question yesterday in class I came completely prepared. I

25:36 how prevalent this Alzheimer's disease? And is Alzheimer's disease? Alzheimer's disease is

25:41 form of dementia as a neurodegenerative That means that neurons degenerate is a

25:50 disorder? Also because it's a neurological is a disorder of the brain.

25:57 I said, what is the Sea of Alzheimer's disease. So this

26:07 the first term prevalence of the And what is the prevalence of the

26:11 ? How common is the disease? commonly does this disease occur? Have

26:15 thought of how common the South Do you have any friends in class

26:22 have Alzheimer's disease? Do you have grandparents or their friends that have Alzheimer's

26:30 ? So now you start thinking well what age is this? A is

26:36 a disease of the young. Is a disease of the middle ages.

26:40 a aging? It's correlated with Is this part of normal aging to

26:48 losing memory and good demented and have disease. No, maybe to lose

26:54 skills, certain agility, certain aspects members. Okay. But what we're

27:00 to talk today about is something that to severe pathology in the brain.

27:04 , so far it's problems. And asked that question in class yesterday and

27:10 had a very good student and she looking it up immediately as I was

27:15 me and she said In the ages 71% of all, 70 years of

27:20 of older Think she said it's about or 15%. So here is your

27:28 of your answer. What happens at age? Are you more likely to

27:34 Alzheimer's if you live to 19? the answer is yes, That number

27:39 up very rapidly out. But I exactly know what it is. And

27:44 not asking you to to remember this the exam. And I'm asking you

27:50 think about the concept with prevalence. is the disease prevalence? The disease

27:56 starts increasing after 50 years of there's a curve that's enough for curve

28:01 the older you get, the more you are to develop Alzheimer's disease.

28:05 over 90 years of age is it very, very problem becomes in tens

28:12 the percentages. So now. Is it? Uh, only in

28:22 United States. Yeah. And why I ask that? Because there's a

28:30 of certain disease in one geographical Ethnic Cultural Location vs Another one.

28:39 could be a higher incidence of epilepsy certain countries and low incidence of

28:45 It's in other countries, nations, people that use some of the foods

28:52 that are inherently anti inflammatory. A of the political see, research has

28:59 to why there's lesser prevalence c of incidents and opulence incidents in India is

29:06 under reported. Is there something going ? It's probably both. But curcumin

29:12 is being researched as a potential dietary . It is normal for for local

29:21 that actually could be beneficial, preventative reducing a certain disease. Okay,

29:30 , uh symptoms of the disease? is a symptom And what are some

29:37 the Alzheimer's symptoms? So the difficulty hasn't put Russia and Alzheimer's

29:46 You have a progression of the distance the early symptoms of the disease could

29:51 loss of short term memory. Disorientation anxiety. Mhm. And so when

29:58 come into the doctor's office, you say I have a clock in my

30:03 . My neurons are dying. I feel it. I have a pain

30:08 my hand. That's my symptoms. know, I I can't hear anything

30:13 my right ear. That's a symptom not a cause so early Alzheimer's symptoms

30:20 mild alzheimer's symptoms is, like I , memory loss, anxiety, disorientation

30:25 them. What happens later? You the formation of a pathology and the

30:33 becomes more with progressive, becomes worse worse pathologies of that thing and that

30:42 causes the progression of the disease and understand why in one second we'll come

30:50 to more severe symptoms. But let's about what is technology. You want

30:56 get down to the underlying causes of symptoms, right? So if somebody

31:06 forgetting or somebody has anxiety or depression is also part of the Alzheimer's disease

31:15 you lose touch with the society and ability to interact with people which isolates

31:21 further On the pathology level, there two important hallmarks at the cellular

31:30 One of them is the formation of amyloid plaques. We also refer to

31:34 as beta amyloid plaques or senile plaques Alzheimer's flax isn't that aggregates proteins that

31:42 abnormal aggregates in the brain. They calcify and they start ruining the local

31:49 of the network. If the accents located close to these flags and accident

31:56 segment and acts on Philip will be and won't be able to produce action

32:03 . So on the outside of the you have the formation of the

32:09 But those plaques on the outside obviously pitching and intruding on physically. The

32:18 form in certain parts of the brain the campus, certain parts of the

32:23 . In early Alzheimer's pathology where some platform then they migrate throughout the whole

32:31 . That's another weird thing is that kind of like think they throughout the

32:34 brain and at advanced stages of the will have a massive invasion throughout the

32:41 . Uh these amyloid or senile flags the south. You have another pathological

32:50 hallmark, which is Nurofen brutally So remember I showed you the

32:57 These, I said that those are tubules. So the spaghetti is and

33:01 micro tubules are being used for delivering to and from the cells. So

33:12 . You go back to this presentation , you have molecules and you have

33:26 klasnic transport and you have those micro and other side of skeletal elements that

33:32 to be precisely arranged in order for micro tubular highways to try to transport

33:38 in the correct way At the slow , which is 1-10 mm a

33:43 Fast acts of plasma transport, which about a meter. Day. Uh

33:49 millimeters today versus a meter. There have two types of transport, interrogate

33:56 and retrograde transport interrogate transport. You have these little engine proteins like arms

34:02 the cartoon like fashion that will pass it needs to be uh protein or

34:09 from the selma interrogators from the soma the peru for And then on the

34:17 hand, down in the middle of class, I'm sorry, I'm

34:20 I can't stay here. Can you outside please? You have the same

34:27 ? Okay, sorry, no Um I leave the door opens.

34:35 guess it invites some guests to try use the computer because if they see

34:41 there's a hallway student and having seen anyways interrogate transport, I just got

34:50 tangled up and retrograde transport, retrograde . You'll have the dining and molecules

34:58 will go the opposite direction from the into the sun. So now going

35:06 to the Alzheimer's technology when you have side of skeletal elements and the tangle

35:13 that ruins the transport of goodies inside south of communication within the stuff.

35:20 you can say the tangles are affecting inter cellular early and then to cellular

35:28 and transportation. And the plaques are extra cellular and intracellular communication and connectivity

35:39 the networks and the plain wool Uh and unfortunately, you cannot really

35:47 the early pathology of Alzheimer's disease and cannot really visualize the plaques or some

35:53 markers that are associated that you can up and the person is either susceptible

35:59 is developed. The flax and the diagnosis for Alzheimer's disease comes postmortem.

36:07 a pathologist can look at the brain in severe advanced stages of the

36:16 the brain would be written by the and tangles. The cells will be

36:23 neurons and accents will stop communicating and the signals and at the gross anatomical

36:31 you will see a shrinkage and loss gray matter in particular but also white

36:38 gray matter is the loss of them bodies And then some of the white

36:44 fibers that still remain. There is there are more original and the violence

36:50 remains around them so you can still it. But this is the advanced

36:56 Alzheimer's disease. Brain on the right to normal brain structure here as the

37:04 uh So this is severe pathology. happens when you have these flags and

37:14 all over your brain? It's not that you're disoriented. Then you get

37:21 blue alert saying an elderly personal after and they haven't been seen for a

37:26 . It's usually they went to grocery the spatial disorientation, the campaign in

37:30 home. It's time disorientation. So it's you know, if it's a

37:36 somebody thinks at six a.m. And six And wondering why everything is closed and

37:41 all the people are, It happens and then it gets worse. Brain

37:48 communicate things don't register short term memory going first, then it starts affecting

37:54 term memory. Then you start losing ability to be lucid in this

38:00 You're almost like stuck in your own that cannot interpret things from the outside

38:06 and then it starts shutting down vital , eating, swallowing, drinking,

38:16 , breathing and you're done. So is this is the real real nasty

38:25 . And then you will say okay that was the therapy so everybody you

38:30 anxious enough can you stop all There's no cure for Alzheimer's disease.

38:34 only therapies that will slow down the of Alzheimer's disease. But there is

38:41 character. So what does that That means that you can only hope

38:49 the person lives longer and when somebody Alzheimer's disease, they may also have

38:55 comorbidities. That's another thing in the capital. What's the co morbidity?

39:01 you have Alzheimer's in your 70 some old you're 50 more times likely to

39:07 epilepsy. That's a co morbidity. not always get affected the main

39:13 Alzheimer's disease or comorbidities epilepsy. Can person die from epilepsy? Yes it's

39:19 morbidity because co morbidity is usually uh the progression of not only disease but

39:28 shortened the lifestyle. Uh huh. inability to move your motor function because

39:36 impacted your motor centers, the plaques you fall and you break your

39:41 So now you have all sorts of breakage problems and uh bone problems.

39:49 the central is also co morbidity, of social interactions. You can do

39:54 as co ability to try not to to anybody for two months. I

39:58 understand who you talking to or every seeing a person and thinking that that

40:04 is a new person but it's actually same person we've been seeing. So

40:11 stops the progression of the disease and of the therapy right now targets a

40:16 Colin system for the energetic system and a single clothing inside the synopsis.

40:26 you will say ah so there is there. Yes. So these flags

40:31 kill a single Cobain producing neurons in brain. And that seems to be

40:36 of the major targets in early to onset of Alzheimer's disease is the death

40:42 these neurons in the brain that produced single goal and not all the neurons

40:47 the brain produced a set of You understand which ones? And that's

40:52 I asked you to leave some space we will talk about Alzheimer's medications when

40:57 in the second section, when we about a set of Comey neural transmission

41:01 you'll be able to add on to . And it's really for you because

41:06 not just to answer the exam it's for you at the end of

41:10 semester to look at that page that start at the beginning of the semester

41:14 say, okay, God, I this, this, this,

41:17 And we even reviewed this and then added more things to. All

41:23 And yesterday also had a very interesting in the classroom where one of the

41:31 have worked with dementia and Alzheimer's patients shared some of his personal experiences and

41:40 mental stimulation, mental agility, social , social interactions are incredibly important for

41:48 people and I tell you that because very difficult right now with covid where

41:54 of the older people or you could they were shut off from their families

42:00 a really strong impact, you know ? Because it had a really strong

42:05 on the past if you have a or if you have somebody a dog

42:11 the family, that dog was with owner for a whole year. All

42:15 a sudden that owners started going back the restaurants again, going back to

42:19 job, dogs are freaking out to a lot of anxiety. So when

42:23 talk about dogs, so think think about, you know,

42:28 think about lack of social interaction, sensations, all of these things that

42:35 really very important. So stimulate your in your families. That's how I

42:42 , you know, with, with everything that you can social interactions

42:48 mental agility things. And there's some interesting study of nuns that were somewhat

42:58 from the outside world. They didn't their own social circle small circle and

43:04 were very interactive and they were reading journals every day and they had book

43:11 not stop and they had all of discussions and prayer groups and stuff like

43:16 , had a very, very little instead of Alzheimer's disease. So it

43:22 to show you that the continuing mental , not only after you get your

43:29 , but also when you're getting old important, just as important in making

43:33 go to the gym. It's just important an elderly age to pick up

43:39 tried to do a sudoku because it be really good for your brain.

43:44 keeping up this activity is keeping up technology which is important. You know

43:51 that didn't learn how to use they didn't just not learn how to

43:55 email, that kind of a lost connection that everybody else younger and the

44:01 has and it goes to the, know to the heart of not just

44:08 connection and email but an actual interaction is lost too. Have a

44:14 So even when we know about Alzheimer's it? Yeah, History of

44:23 Okay, I agree anywhere. so more susceptible parts of the

44:29 it's not that it's occurring only in prefrontal cortex is plaques at the bond

44:34 will be scattered throughout your diplomatic but cortex in certain parts of the prefrontal

44:41 will contain those problematic there as And this seems to be a susceptible

44:46 of the brain that is more susceptible the pathology that goes earlier on as

44:54 to other other parts of the Hippocampus for example is very susceptible than

45:00 short term memory loss. So you argue that that is also part of

45:03 brain that shows early Alzheimer's pathology. platform ation is their prevalence in campus

45:12 well. And in fact there are that show that from hippocampus through interregional

45:17 and other types of vortexes and near temple of with this migration to displace

45:22 these plaques. So it's a very question because there are deaf. Oh

45:27 parts of the brain that are more . These pathologies and kind of a

45:32 out earlier as opposed to right. you'll you'll see when we talk about

45:38 little cooling and cold energy projections and see where they're located. Maybe it

45:42 make more sensitive to the prefrontal Yeah, you're welcome. So damned

45:50 . And dendritic spines. It's something unique. We have axons accidents can

45:54 collaterals. That means that they can . And then axon will also have

46:00 terminal or Bhutan Bhutan and present means a kind of a fancy language and

46:07 and french bhutan's button synapse in passing that an accent can leave a synapse

46:14 then continue on with the main Uh So little shop and then terminate

46:19 else with more synopsis at the external . Yeah, mitochondria which is also

46:26 important there for vesicular release on The axon initial segment generates the action

46:35 gets regenerated the axa donnell nodes of gear and then there's a deep polarization

46:43 this pre synaptic terminal. This influx calcium and fusion of the synaptic vesicles

46:49 release of the neurotransmitter into the synaptic boston ap typically will have densities when

46:56 refer to earliest prostatic densities of the that are chemical or wagon gated channels

47:03 lot of times that will be juxtaposed sitting on the fast synaptic membrane And

47:08 this distance between the pre synaptic and map it is called the synaptic cleft

47:13 the whole process of demobilisation message neurotransmitter release binding of that. They're

47:20 receptor and subsequent response, electrical and response. And the problematic cell is

47:27 to as synaptic transmission. We will synaptic transmission in great detail in the

47:35 section of this course. Now some the stains and this transport that we

47:42 interrogate and retrograde transport can also be advantage by the stains and for us

47:48 study and to understand the connectivity of projections from the periphery into the central

47:54 or from the central parts into the . So you want to know with

48:00 piece of the brain of this patch the muscle or skin is connected to

48:05 salads and so you would use something horse riders. Barack's days and you

48:10 inject it into this patch right here neurons that have their accidents will absorb

48:17 peroxide days and it is being transported . So from the periphery from these

48:24 terminals it will deliver to die into soma into these neurons here. So

48:32 will know that this patch, like said at the brain of this pack

48:35 the skin is connected to this network neurons here. It's a useful tool

48:41 use and staining uh science modern day and neuroscience takes advantage of the viruses

48:49 well. We had a herpes virus rabies virus that also get to the

48:58 or to the central parts and to selma's through retrograde transport. We will

49:04 about shingles later in the course when talk about Samantha sensory system which essentially

49:09 a herpes zoster virus which has the to do both. It has the

49:14 to go until era grade from the into the periphery in and retrograde.

49:21 gets into the body from retrograde and dormant. And then it reappears again

49:29 terra great from the centre into the . So now then drives are very

49:36 and good experience are very important. you saw. They have different shapes

49:41 they described in different shapes. They their own Paula ribosomes conflict system.

49:50 and mitochondria. And these dendritic spines suggests that the critic spines are can

49:58 biochemically independent from the dendritic shaft and the selma they can actually then translate

50:06 elements and certain proteins at the level the dendritic spine independently or turning on

50:13 off the genetic machinery at the level the selma. And obviously the spine

50:19 juxtaposed to the sex onal terminal. a second disease that we introduced

50:30 And this disease is autism spectrum disorders in particular fragile tax so fragile like

50:40 fragile glass X. X. So autism spectrum disorders underneath. Autumn

50:50 disorders is an umbrella of many different . And we're not going to discuss

50:57 likes to the same great extent that talked about Alzheimer's and we'll talk some

51:03 multiple sclerosis and we'll talk some more multiple sclerosis. But it's very important

51:08 understand that the precise formation I've been expired. The precise sub cellular arrangement

51:20 densities along the dendritic shop and precise of these funds equals normal function and

51:30 fragile acts and in developmental mental This is an image of a mentally

51:38 and in funds and it's done And one very obvious striking difference immediately

51:45 not in the dendritic shaft but in structure and densities of the genuine expanse

51:52 see that some of them are very expressed here and there's a whole so

51:57 is no continuity and there's a scattered expression of these super alligators,

52:08 And what is the this is the , the inability to learn. So

52:18 retardation comorbidities such as epilepsy and seizures also be present and fragile X.

52:24 Children. So having these invent experience very important. The good expanses where

52:32 synapses are formed. We have synaptic if you have this abnormal organization that

52:42 that you're not processing information properly. inputs that are coming in cannot be

52:49 properly. Therefore the information either the of the internal information from intellectual or

52:58 capabilities inside the brain are quite just like this image of the dendritic

53:05 is distorted. Image of a normal X. Pine shaft. In addition

53:13 as I mentioned will receive excitatory Glutamate which is excited to a neurotransmitter

53:20 the brain. Blue R stands for receptors. And anywhere you see Green

53:26 is sustained for glutamate receptors. And means that anywhere you see a dot

53:32 a pump tape there is a synapse an excited terry senator. And in

53:40 these spines are not only targeted by tourists. Synopsis neurons have both excitatory

53:48 inhibitory inputs. And Gava synopsis and receptor shows an orange. Are they

53:57 their receptors? Yeah. So you see everywhere that's in green is excited

54:04 synopsis and everywhere you see Orange here inhibitors announces and they have to make

54:14 inputs and communications with wisdom. Good . And we cannot do it when

54:20 have abnormal anatomy after the good experience you have lack of dendritic spines or

54:28 densities of those spines. So neuron to integrate information from hundreds of thousands

54:36 excited third hundreds of thousands of the synopsis. It does. That process

54:43 is very fast. It's a fast and single neuron can make a decision

54:50 milliseconds networks and make decisions within milliseconds this is when I mentioned last lecture

54:59 artificial intelligence, Why artificial networks are in how the brain networks learn.

55:06 is our brain that works are really at certain things processing each one of

55:12 neurons is like a mini computer. process is thousands of inputs within

55:20 What our brains not very good The electronic networks are good at.

55:25 it's we're good because we can start stop whatever we want to do and

55:30 can switch into a different mode. can switch into different processing ballot.

55:36 that takes time. The computers cannot start and stop themselves unless you program

55:43 to start and stop. But what you do when you close one software

55:48 you open another one. It opens right up right now for humans you

55:54 to be an equivalent. You have finish taking no stand up and play

56:01 . You have to do it with click and you did not really.

56:07 it's a lot of wetware that we that's involved in switching that went way

56:14 takes time. It takes emotional takes motivational component to switch it. There's

56:22 sympathetic system that yes, the big is coming at you you react and

56:27 going to take time to stand there think about it. So there's certain

56:32 you know that our conscious certain aspects are reflective but a fast in this

56:38 that we're talking about in the processing properties of the networks and then other

56:43 that disadvantage to the digital world that have. The networks that can turn

56:49 and turn on and off. But networks are very sophisticated. You've been

56:55 audiophiles house that has an audiophile equipment up, has to be amplifiers

57:02 It's usually the process of turning on 67 buttons waiting for things to warm

57:07 until finally the music comes out of speakers and it's not that simple.

57:13 just things to think about and things start taking notes on. Uh most

57:20 the neurons uh not just about this but about neurological disorders. We may

57:26 return to talk about fragile X syndrome we may talk about autism spectrum disorders

57:31 sometimes we bring up things and sometimes talk about things that something happens like

57:38 happens in this world. Uh and know, we have to watch the

57:45 joe Rogan, he's taking some taliban anti warming solution of the two

57:53 you know, should look into his , see what happens to him,

57:57 know, and if something happens and talk about, is there something going

58:02 there? Yeah, that's okay. making sure you guys the lab,

58:09 other distractions apart from me. So continue a little bit. We'll discuss

58:15 fact that most neurons have four functional . You can have a model neuron

58:22 an input here and put can come sensory neuron from the skin, leather

58:28 neuron, local interneuron projection into neuroendocrine sauce and you understand what we

58:34 , what we mean by all of and the subsequent slides uh the input

58:40 . This is where that input The integrated region is usually the

58:46 the conduct. I'll region is the that are my pollinated and the output

58:51 is where the excellent terminals are with release synoptic neurotransmitter. And you can

58:58 an output in the form of secretion genetic neuron into muscles. You can

59:03 a Vassar dilating bastard constricting aspects from onto the capillary as well. And

59:08 this case more of a para crime neuro endocrine secretion that could affect the

59:14 signaling throughout the body as well. so the brain turns out has over

59:21 different subtypes of neurons. And once understood what different parts of the brain

59:27 doing we now started to wanting to what are the different subtypes of cells

59:32 doing. And first of all how we classify these different 100 50 cent

59:37 of cells based on what the first comes to mind is appearance more

59:42 They love different and polarity and morphology polarity. You have unit polar South

59:49 one poll, one poll just from North Pole. That's all. So

59:55 polar. South characteristic characteristic invertebrates. branches service acts on and receptive sides

60:05 cell two polls North pole and south and there's a sensory cells. We'll

60:11 about bipolar cells in the retina. we study retinol anatomy you'll find a

60:17 epithelium in the spinal cord. This a pseudo uniform yourself, pseudo uni

60:24 because it has the north and the pole. This is the same matters

60:30 sensor dorsal root ganglion cell. It one peripheral accident that goes into the

60:37 and one central acts on that goes the spinal cord. That's what pseudo

60:44 know, Poland because it kind it just has one poll Done right

60:48 be the 2nd fall. Most of south and most of the neurons in

60:54 brain are multipolar. And here's an of a motor neuron of spinal

61:01 the parameter cell of the neocortex or hippocampus or this beautiful Preqin gee cell

61:08 was originally drawn by ramon alcohol using mirror system camera lucida. So this

61:16 an extensive Three of the cerebellum for cell and it shows you the difference

61:22 the synapses, spinal motor neuron can upwards to 10,000. Synopsis And broke

61:28 the cells can have almost 150,000. a very complex puzzle. This this

61:37 ship microchip has to solve quite quickly that to other interconnected units of the

61:46 . There's other ways of classifying Not all of the neurons will have

61:51 spines, some of them will be spiny. That's another kind of a

61:56 classification projections and connectivity. Some of south will project long distances, a

62:04 range in there called projection. Their projection cells, others in control activity

62:09 the local network and they're called excitability. They can be glutamate releasing

62:18 . So the excitatory cells, they raise the activity in the brain activity

62:23 . Or they can be inhibitory. will be releasing gaba which is gamma

62:28 butyric acid and there will be dampening inhibiting the activity in the brain and

62:34 down the neuronal activity. But ultimately have to look also with the cell

62:44 . Each cell is different because it a slightly different. Each subtype of

62:48 is different because it expresses a slightly subtypes subset of the genes that code

62:55 the same in each cell we sell express slightly different part of that

63:01 And because it does so it may producing specific cell markers such as neurotransmitters

63:07 neuropathy as it expresses. And that help us distinguish, sell some that

63:12 dopamine, others have produced several others that produced in europe Captain Y

63:18 so on. Action potentials. This the first photograph of the first published

63:25 for cellular recording action potential reporting about and Huxley And the first action potential

63:34 reported in 1939. And this is picture from the silla scope showing this

63:41 about 100 million balls and size the taking place over just a few milliseconds

63:48 time. And that's important because different subtypes out of those different looking

63:57 they're not only gonna look different, not only going to express different substantive

64:02 and proteins and neurotransmitters and chemicals but also going to speak their own

64:09 So you have the same language which an action potential Continak but there's 150

64:17 , 150 languages And 150 subtypes of express themselves, electrical it through this

64:27 of actual potential firing in different Wow this tried. I'm just gonna

64:36 you briefly and I'm gonna end with today because I realized that I started

64:41 and I actually gone through quite a of material today. This is a

64:46 that will come back to the following but I will briefly introduce to you

64:51 this is a part of the hippocampal . Hippocampus is a part of the

64:56 that is famed the most studied in and it has three dominant layers ready

65:03 , tour amidala and orients layer and region of the brain is very important

65:10 memory formation, recall of memory for orientation and special member and also involved

65:17 emotional aspects of the brain process. what's very interesting and a striking example

65:26 this very well studied circuit in the is that these cells and green are

65:33 . It'll excited to ourselves that released and the only difference between them really

65:40 not in morphology but that some of produced Calvin's NCB and honest are negative

65:46 Calvin, you don't have sleeping but diversity and we'll get to the diversity

65:53 how the diverse set of inhibitor cells is responsible for diverse rhythmic activity in

66:00 brain. The diversity and local processing from the inhibitory interference inhibitor there into

66:09 because their accents are going to stay control activity in these local networks.

66:16 there's 21 different subtypes. 21 different genetic expressions and dialects that are being

66:25 to these excitatory cells and these excited of projection cells. That means that

66:32 these inhibitory cells and other excited yourselves communicate information to this excitatory network,

66:38 . once they train that once they all of these languages added the output

66:43 going to come from the projection cells forming another interconnected part of the hippocampus

66:49 not interconnected region of the brain. something of importance is going around.

66:53 putting that signal out and projecting that . So we'll stop here reminder that

67:03 you don't have a class on I'm equalizing you with the monday and

67:09 class sections. So have a long doesn't mean you don't have to come

67:16 either classes but you don't have this on Tuesday, enjoy your weekend be

67:23 . Uh and texas has tremendous Uh So I will urge you just

67:31 listening from some personal stories on delta of how quickly it spreads. And

67:38 of my friends that were vaccinated I'm very cautious after those stories and

67:44 what I said enjoy the great texas

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