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00:00 Work. Welcome. This is lecture of Neuroscience and we were discussing some

00:06 concepts and important stops along the history development of this very interdisciplinary field of

00:14 field of science. It's going to me to change the slides, having

00:22 really hard time right now. There go. We talked about ancient

00:33 we talked about Roman Empire. We how it was difficult to understand the

00:39 anatomy because it was not allowed to human dissections until renaissance times and that's

00:44 the development of the modern human. at that point, there is no

00:50 that the brain is the most important of the body. Now, the

00:55 starts about what are different parts of brain look like. What are they

01:00 for in this ventricular localization of the function comes about as suggesting that ventricles

01:08 where there's something stored in these There's some fluid, there is some

01:13 and the communication in the brain and of distal like motor control of the

01:19 and legs is due to the ventricles the specific localization of the brain function

01:25 the ventricles. It gets throughout the . But there's also a distinction between

01:31 gray matter which is softer, potentially information white matter, which is

01:36 We now know these are the myelinated that interconnect neuronal networks. It's harder

01:42 nature. Um and is responsible for that information. We have no doubt

01:49 modern day and modern neurons that the comes from the cellular networks. We

01:59 call this into question once in a , especially when it comes to near

02:05 experiences or brief lucidity before death where is no matter to support some of

02:11 functions that humans regain very briefly before pass. So, but overall,

02:18 the understand it's a complex network of with intricate connectivity in the brain,

02:26 what's responsible for your thoughts, for learning, for your mind. But

02:31 was called into question and we started about Rene de Carte who came up

02:38 a really famous phrase, I think , I am Cogito Ergo and Rene

02:44 Carte starts looking at the whole human and also control of the human body

02:50 the brain as a fluid mechanical So he is off the impression that

02:57 information from the ventricles likely located here communicated through nerves that serve sort of

03:04 pipes that pump either the fluids or from those ventricles to control the

03:11 He distinguishes between what would be cognitive, reflective behavior versus reflexes and

03:23 is illustrated here by this image where child that has never seen a fire

03:30 , experienced it and extend the hand the fire and immediately withdraw it reflexively

03:36 even thinking about it. The same if you step on a sharp object

03:40 as a glass or a nail, step off of it immediately, that's

03:45 behavior. A lot of these things handled at the level of the spinal

03:50 . Of course, you are consciously that you just step potential in a

03:53 object. And then you can execute complex conscious command which is going to

04:00 complex motor activities such as going to first aid kit, taking the triple

04:07 cream, putting it on the putting a band aid or bandaging it

04:12 going to seek medical health, maybe up the phone to call somebody.

04:20 , nerves are still viewed as pipes mind is thought to be outside of

04:26 matter. Therefore, mind is not part of this gray matter white matter

04:33 . It's somewhere out there just like soul. Where is your soul?

04:44 is it? Uh So it's sort a soft like somebody may have had

04:49 question actually over email from this section that. So, so where they

04:53 the mind was out there out And so the connection and formation of

05:02 mind is by something that's out there to Rene de card, that gets

05:09 through the eyes gets seen, gets to single nucleus pineal gland, it's

05:18 centrally within the brain. It's large its structure. And when he looks

05:23 the brain, he sees lateral left structure, right side structure, replica

05:28 that almost like mirror structures. And sees this pineal gland that is big

05:36 it's in the, in the middle , and it's one. So he

05:39 that's why I think it's important comes the eyes. Goes to plan of

05:44 . That's where you have the Now, the formation of the mind

05:49 in contact with this outside energy spirits, whatever you may want to

05:55 it and then gets communicated through fluids gasses, move the nerves really cool

06:05 . And uh we now know that are not pipes and that they do

06:14 pump gasses or pump fluids from the into the rest of the brain or

06:21 and the nerves and the periphery arms legs through gasses or fluids. In

06:28 17 eighties, Luigi Galvani works with preparations and he has a rotating static

06:38 generator. It's also called a Laden . So he generates electricity and he

06:45 a frog that he has dissected and shocks the frog's nerve. And he

06:51 that the muscle contracts and then he the frog's muscle and he sees that

06:57 muscle also contracts. And to this , we know that the two excitable

07:03 in our body from four types of is muscle and nervous tissue. And

07:11 now he understands that he replicates that many different animals, he understands now

07:19 nerves are not water pipes or channels the cart before him thought. And

07:25 nerves are actually electrical conductors. They conduct electricity and they can generate

07:33 So the electrical generators and conductors. therefore, you have this overlay image

07:42 what one would see typically in the boxes someplace running through your body.

07:48 these are the nerves that would be of the nerves running through the body

07:53 controlling the muscles and controlling your motor your motor outputs that come from your

08:00 cortex. All right. Now, move into the 19th century. In

08:09 19th century, we already understand major of the CNS. We're looking at

08:15 central nervous system as comprised of the or cerebral cortex, cerebellum, which

08:24 on the back of the brain, brain stem, which essentially holds the

08:29 , the stem of the brain, is in your neck area going down

08:33 the neck region. And then of , from the cervical here, you

08:38 your spinal cord that goes all the as one continuous structure to lumbar two

08:46 three and then spreads into the nerves penetrate the lower limbs, have control

08:52 the lower limbs, nerves are studied wires. And so there is a

08:58 of studies that stimulate the nerves and beautiful system to work with is the

09:04 cord, spinal cord has the dorsal of the spinal cord where all of

09:12 sensor information is going to come So any information from touching the

09:17 anywhere below the neck is going to processed by the spinal fluid. Everything

09:24 the neck is gonna get processed by stem and other structures. The nerves

09:28 are found there that we call the nerves that we'll study in this course

09:32 well. So, but you have dorsal component that forms what is called

09:38 root ganglion. There's collections of the soma in this clump right here and

09:46 are projections. So they will have peripheral axon in the skin, any

09:51 temperature pain, it communicates into the part of the spinal cord which is

09:58 is on your back and then the command comes out from the ventral side

10:04 the spinal cord, ventral is in front. So this will form the

10:11 nerve which will have the dorsal sensory running into the spinal cord. We

10:17 the a a sensory inputs. And the ventral side, it will have

10:24 neurons that will send their axons through same enveloped nerve bundle to stimulate the

10:32 . And we will study the neuromuscular at the beginning. Uh the section

10:37 we talk about the s naive transmission well. Now, you have a

10:42 where you can stimulate sensory, stimulate , you can ablate it or cut

10:48 ventral side or the dorsal side and what repercussions it has. Of

10:52 these are animal experiments and they already that there's sensory dorsal carrying information aha

11:02 there is ether coming out of the cord into the periphery, motor neuron

11:08 that is for muscle control. So we're here at the 19th century,

11:13 picking apart, not just looking at nerves, but looking at the structure

11:18 the spinal nerves, distinguishing between sensory motor components. And then there is

11:26 really interesting science that's huge and it's dominating a lot of brain or neuroscientists

11:34 that day. A lot of them relating more to psychology. At the

11:38 . We have uh roots of psych uh uh uh uh psychology and

11:43 And so, so you have the that is an intersection between biology and

11:49 . It's called phrenology. And it about from this Viennese physician Franz Joseph

11:56 , from his theories. It's different Galen that we discussed. We discussed

12:01 as the person that was using animal dissections to describe human anatomy. And

12:07 said it was flawed in part because that. But yo, Joseph Gao

12:13 the system of phonology. Uh what after here is specific localization of the

12:19 function. Now, an argument ensues all of the brain is responsible for

12:26 of the functions. Therefore, if have a piece of the brain on

12:29 right side here of the parietal lobe gonna process all of the same functions

12:34 that uh piece in the temporal lobe the other side and the piece on

12:39 left side in the occipital lobe, all responsible for all the functions.

12:43 if you damage a little bit of brain, you lose all of the

12:46 to a small degree but to preserve functions to the larger. Well,

12:52 is another idea that maybe that's not case that maybe specific areas, specific

12:59 in the brain, specific parts of cortex or the lobes are responsible for

13:04 function. So, uh or probably lack of any imaging techniques that are

13:12 at the time to visualize the bones x-rays have come later or the tissues

13:19 come also later with CT scans and scans and pet scans and things like

13:26 in the activity. So you cannot any of that. So Franz Joseph

13:32 comes up with a system of these tenants that says the brain is the

13:37 of the mind. There's no dispute the mind is composed of multiple distinct

13:42 faculties while you can be basically very . And they think that that's an

13:47 faculty or generosity, for example, they're distinct, these faculties, you

13:54 , like uh aggression or generosity or or other things, traits that you

14:02 think of an individual because they're He believes that each faculty must have

14:09 separate seat or organ in the brain then he says the size of an

14:16 , other things being equal is a of its power. So if you

14:22 a small muscle, you can lift dumbbell, big muscle, you can

14:28 £200 dumbbell size, right? And things being equal is a measure of

14:36 power. What does he imply with ? He implies that two things.

14:43 of all, that we will have size organs. So if you're generous

14:50 that's an innate faculty, your organ generosity is gonna be bigger than other

14:57 that may be having other traits. right. So the shape of the

15:05 is determined by the development of the organs. As the skull takes its

15:11 from the brain, the surface of skull can be read as an accurate

15:16 of psychological aptitudes and tendencies. Organs responsible for different intellectual aptitudes and character

15:31 . So you're very interested in certain you in features or you know,

15:36 mother is so generous, she just everything away. Well, she gave

15:40 the house, she gave away the . You know, she's just so

15:44 . I don't know, it just everything away. I'm gonna take her

15:47 Joseph Gao. Walk in the Joseph office, knock, knock,

15:53 You were here for phrenology consultation. , I am sit it. The

15:59 sits down and the phrenologist takes out tool. It's not invasive or no

16:08 takes out the stool and the stool the size, the circumference, the

16:14 , it measures the angles and he the stool all around the skull of

16:20 person. And what is he doing those tools? His theory is that

16:26 you have that large area for generosity your skull develops, your skull is

16:34 . So in any infant and any , it's pretty scary. Actually,

16:38 even have these soft spots. One in, in the front because the

16:42 plays, have not even fused and about the size of the skull in

16:46 infant, the size of a fist and the size of your skulls now

16:53 adults. So the bones grow and bones shape themselves, the bones are

17:00 and the bones shape themselves around the , neuronal tissue that's underneath it.

17:07 that is true. You don't have uh skull plates fused. You'll have

17:11 soft spot here and another one in back up until about one years of

17:16 . It's pretty scary because you put finger and it's, and it's soft

17:20 . It's almost like, can I like poke through it and my finger

17:24 gonna go into somebody's brain, you . But no, because we have

17:28 meninges covering and protecting the surface. skull does shape itself around the developing

17:35 nervous system, nervous tissue. You have heard of a condition hydrocephalus and

17:41 feature of that condition are these very , what is typically depicted like alien

17:47 . Although we don't know what kind pets aliens had and what kind of

17:50 they come in. But let's say large heads. And that's because in

17:54 , there's an accumulation of a lot fluid. If it doesn't get drained

17:58 early development, that fluid in the starts pushing on the tissue, that

18:03 starts pushing on the skull and the starts expanding. So they knew

18:09 And so he's taken it too far he would measure people's skulls. And

18:14 had all of these areas that they on the skull by measuring sizes and

18:21 and ridges on their skull. They that ah ha indeed area, whatever

18:26 B is can be noticeably seen here the generosity area. You are

18:33 Can't do anything about it, an trait. Your mother will keep giving

18:36 all the cows. All right. he drafts up a report. So

18:42 a lot of, there's a lot cool things that are going on

18:45 There's a lot of cool details that going on here. It's we're really

18:50 to understand what part of the brain responsible for what trade or function as

18:55 may. And if you go into library in 1848 and 1877 chronological Journal

19:05 , Science of Health and it talks the, the, the chronology,

19:13 , this magnetism. So there's a bit of uh you know, quackery

19:18 on in there. And obviously what has thought of is correct is that

19:23 parts of the brain are responsible for functions. However, you cannot read

19:27 book by its cover. You cannot a, apart from hydrocephalus condition,

19:33 is severe neurological disorder. From looking somebody's skull. You cannot tell their

19:39 traits or abilities. You just the size of an organ doesn't really

19:45 that you're going to be more power the brain and smarter, I'm a

19:49 head and I'm teaching you elephants have heads and much bigger brains than

19:56 So that means that they should be the world at the top of the

20:00 chain. Maybe we should go back that old image of elephants carrying the

20:05 on their shoulders. Uh But that not the case, the size actually

20:11 important, but only to a certain , what is more important is the

20:18 of that tissue and the complexity of connectivity and interconnectivity and processing ability of

20:24 tissue. And so size is This is important. We're pushing the

20:30 forward and trying to localize specific functions the brain, but it fails because

20:36 looks at the cover, it looks the skull, it doesn't really look

20:39 the brain, doesn't look at the tissue. And what we understood early

20:46 uh about localization of specific brain functions emerges in the 19th century from the

20:53 of doctor Paul Broer, he has patient and that patient expresses or has

21:01 aphasia, expressive aphasia is difficulty and inability to convey thoughts through speech or

21:10 . You have very difficult time saying , you have difficult time stringing words

21:15 into sentence. You have difficult time things down. So it's inevitably linked

21:22 a motor function because this is expression your speech. It's not understanding of

21:27 speech, it's not listening to the , it's producing the speech or

21:30 The speech expresses the patient. And looks in the brain of this patient

21:35 mortem art to death and finds a in the left side in the left

21:42 in this area right here. And is very puzzled. So he writes

21:48 his other colleagues, there's no there's no email, he writes to

21:52 other colleagues letters and he says, you have at that point, there

21:58 brain banks that scientists could refer Do you have any of you scientists

22:06 Europe everywhere we can send the Do you have these cases of expressive

22:12 ? Can I have the brain if in the bank? And so soon

22:16 , he collects uh examples of several that have all damage to this area

22:24 . This area is now called Broca . And all of these patients exhibit

22:31 eas so now what he proclaims is we speak with the left hemisphere,

22:38 where the speech is located there's no in the right hemisphere, but it's

22:43 to damage this area to cause expressive . Now, sometime later, there's

22:52 discovery of another area vicus area where damage to Verus area. And the

22:58 theme in these studies is what we loss of function studies and the loss

23:03 function, inability to express yourself and aphasia, loss of function in receptive

23:10 is difficult and inability to understand or read the language, but the patient

23:21 hear and see the print but cannot sense. So that's a receptive inability

23:27 receive the information. It's not about it, it's about receiving it.

23:32 patients that have receptive aphasia, they damage to nicu area. So damage

23:38 broker area or loss of function equates expressive aphasia, damage to nicu

23:45 loss of function equates to receptive There are a lot of uh significant

23:54 of fibers uh that are interconnecting. Aus and Vernis aus. And there

24:01 also two more types of aphasia. of them is anomic or amnesia,

24:06 . It's the least severe form of where you have difficulty in using the

24:10 names for particular objects, people and , nouns and verbs. I think

24:15 all have transient, uh anomic uh uh amnesia or amnesia, aphasia at

24:22 point. You cannot remember. And like you have that phenomenal the tip

24:27 my tongue, like it's some buzzing a neural circuit and you just cannot

24:31 that connection to that what we call gram of the neural circuit that processes

24:38 is at the tip of your the name of the person or the

24:41 or the year or something like And then there is the most severe

24:45 of aphasia, that's global aphasia where have damage to multiple language areas and

24:53 lose almost all language function. Those both comprehension, ex expression, they

24:58 read or write. What we have from this work of the loss of

25:03 is there are multiple areas, many that process and produce language. There

25:10 areas that are receiving language information, are areas that are expressing that language

25:15 between everything else that we're capable of with language and even the thoughts and

25:20 new things and the poetry uh that produced by many different parts that are

25:28 for language, the same as in occipital lobe, you have the primary

25:34 cortex, then we'll study the whole system all the way through the primary

25:39 cortex. But we'll also understand that there, there's over 20 different areas

25:44 process visual information and they're all slightly for slightly different function of that visual

25:51 processing. So this is very revealing it's not necessarily very exact in the

25:59 that this has been called somewhat into Barnica Broca area of the location.

26:06 much of the speech do you lose course, Broca area is located very

26:10 to the primary motor cortex, which in your frontal lobe, which be

26:15 be this massive area right here. therefore, it's more tied to

26:21 right? But uh there's still a of things that are being investigated and

26:26 . But we now understand it's very , many different structures for even one

26:32 . And then we come to this here still talking about localization of specific

26:38 function at the epicenter of the slide F Gauge, whose story is

26:47 really interesting and it's very important for and psychology. Gauge is working as

26:56 explosives master. Uh when in the of the 19th century, you have

27:04 England railroads that are being laid through mountain ranges there. And what you

27:09 to do is you have to flatten ground for the train to pass through

27:14 mountains and the crevices in between the . So there's a lot of explosions

27:19 the rocks going on. And the who's pictured here is using this

27:25 which is really like a metal spare packing the explosives into the rocks and

27:33 a controlled explosion to clear the area the railroads. And what happens is

27:38 that gets uncontrolled is that accidentally as packing the explosives and explosion happens.

27:47 metal bar projects like a bullet out his hands, enters underneath his cheek

27:56 here and exits through the top of skull in the frontal lobe here.

28:05 This is for gauge, holding that bar that penetrated through his brain.

28:12 you would imagine that such a severe brain injury, such a severe trauma

28:17 result from the person being dead in person losing many functions, maybe not

28:22 able to walk or talk or, of course, he has a loss

28:27 function. He cannot see in this because that's been damaged has been

28:31 nerves have been cut completely. But months later, he comes back to

28:37 for his job again. He's he's talking, he's doing a lot

28:43 things that he was doing before this except he cannot control his aggression.

28:51 very aggressive. But we now understand you can lose large chunks of the

28:59 such as in this case and really an impact on executive function, which

29:05 the frontal and prefrontal lobes. They're for having an impact on control of

29:11 aggression or behavior. But you are functional member of the society, maybe

29:16 little bit dangerous. And so there counseling him traveling from United States to

29:21 , killing some people taking the boat to the Gulf of Mexico to Texas

29:25 something like that or Florida coming But then there are other counts of

29:29 like he wasn't that bad. This exaggerated. So uh a lot of

29:34 story isn't known what happens after this , but he is really used as

29:40 example for two reasons because there's a of function, huge damage to the

29:46 tissue, loss of function is like said, this executive function and control

29:50 aggression and behavior. But he also epilepsy. And that's another thing that

29:59 now know and we learned that one and we'll talk about epilepsy briefly in

30:04 course is one of the major neurological . What we still know to date

30:09 traumatic brain injury can cause epilepsy. can lead to severe damage,

30:19 loss of neurons, what we call . It can be a continuous chronic

30:26 following an injury that eventually causes his in 1860. So an individual that

30:37 epilepsy following traumatic brain injury doesn't always it right away. There is what

30:44 call a latent period and that latent following the trauma following the data minute

30:51 the injury can be a couple of or it can be as long as

30:56 decade before an individual develops epilepsy. don't know exactly when he developed

31:01 But what we learned is that he 12 years following his accident and he

31:08 from a condition that that's called status and status epilepticus is a generalized form

31:15 seizure that if it cannot be it will essentially burn the circuits in

31:21 uh in the brain and will cause of an individual. So he,

31:26 , he, he, he has condition but that condition also doesn't um

31:33 his passing 12 years from the date injury. Yes, right now that

31:43 like a week. Uh I had great injury. No, this is

31:48 great one. So sometimes you can a seizure immediately following a trauma.

31:55 in order for you to be as you learn later in the course

31:59 epilepsy, one seizure is not In fact, uh a lot of

32:05 will have what we call febrile heat induced seizures when their temperature goes

32:10 the roof due to infection or flu inflammation. And you know, you're

32:15 to take kids, like if they over 104 just rush on, call

32:20 nurse and rush on to er, you can't get to er, the

32:24 will tell you put them in the bath because you cannot have that temperature

32:30 so long. But very likely uh that have the temperature go up,

32:35 are also temperature dependent, trauma chemical dependent. So they will have

32:40 seizure. It's called febrile seizure. never have a seizure again and they'll

32:44 develop epilepsy. So in order for to qualify as epilepsy, you have

32:49 have multiple seizures, but you are that following a trauma or an impact

32:55 a severe concussion as it happens in sports, you can have a seizure

33:00 the spot. It doesn't mean you epilepsy and it's very relevant because you

33:07 been hearing all of the discussion, know, now the football playoffs going

33:11 , it's really exciting games. But saw last year, you know,

33:15 being knocked out in the middle of field had a cardiac uh failure was

33:21 to the hospital. There is a tight controls around concussions that happen in

33:27 . Now, earlier, it was about get back to fight, you

33:33 , get over, get over get back. Now there's a whole

33:37 , especially at a more professional especially in football, other contact

33:42 rugby, where they will monitor that will take, the vitals will monitor

33:47 individual, monitor their ice and say . And sometimes you see people uh

33:53 one of the players, uh last , the season was asked to sit

33:58 for for many games because he had concussions. And that's another factor.

34:03 Another factor is if you have repeated , you're likely to develop a condition

34:09 is called chronic traumatic encephalopathy or which has a lot of uh pathology

34:17 is similar to Alzheimer's disease. So , you can look at the football

34:22 brains that had multiple concussions developed CTE at 30 years of age, their

34:27 look like Alzheimer's patients at 90 years age. So, so all good

34:34 and some of the things like the clinical stuff we actually introduce and

34:38 a little bit about not just on cellular level, but even on the

34:42 and even treatments in this course. . Uh Charles Darwin is important to

34:49 as one of the people that contributed to the theory of evolution and his

34:54 was spectacular, right? He was all around Galapagos Islands, at least

34:58 we know what he did is observations animals and their natural environments. And

35:04 was studying turtles, he was studying , finches, he was studying um

35:10 in the water and he was looking their morphological features such as the beaks

35:15 example. And he would say, , it's interesting in Galapagos, you

35:20 these islands or the lago of islands is dis in distance. They're located

35:24 close to each other but is an very, very diverse and could be

35:30 different and, and some islands would all volcanic soil and others. It's

35:35 and, and, and so on so forth. So he observes these

35:39 on the outside the fins of the , the shapes and the sizes of

35:44 beaks, the formation and the movement the turtles on one island versus that

35:51 . And the spirit of evolution basically that you have to adapt in order

35:56 survive. But what happens is it's only your external organs or external shapes

36:05 the beaks or uh fins on the that are being altered is also the

36:11 structures that are responsible for having a structure in the brain and function in

36:16 brain in order to adapt to that ecosystem on that island. And if

36:23 look across species in the in the closest relatives to, to

36:31 you have very precisely developed visual cortex it doesn't show much to you

36:37 it will show a lot more when study the visual system. But in

36:42 , what rodents do is they whisk . And if you look in the

36:46 cortex, you will find the structure is referred to as the car

36:52 Each one of these barrels corresponds to single wher same number of rows,

37:00 , number of whiskers in the same number of barrel rows, a

37:04 of barrels in the and we don't this anatomy because guess what? This

37:13 survival and procreation depends on whisking around . Doesn't we have facial hair?

37:21 we don't do it to touch things feel things around. It's a different

37:30 and we don't have that same So this is anatomical map. You

37:36 have this whisper mouth in our We don't have a whisper map and

37:42 map is a structure on top of structural map. There's going to be

37:48 , neuronal activity in neuronal networks. structure and function of the structure and

37:55 structure are intertwined. OK. we're getting to the point where a

38:04 of very interesting things happen. We seeing individual cells using microscopes. Uh

38:12 I told you that if you take brain and you make a slice of

38:15 brain and you just look at it looks translucent. You will see

38:19 little bit of gray matter, a bit of white matter, but you

38:21 see individual neurons. No, for reasons because it's translucent. And the

38:27 reason is at that time or until uh 18 twenties and really about middle

38:34 the 19th century, there's no microscopes have high enough resolution to see individual

38:42 . And even when those microscopes are , they're looking and they're really not

38:48 individual neurons and the game in the is mainly in the stain. So

38:56 Golgi pictured here, Clio Golgi is very inquisitive scientist and professor and his

39:05 Santiago Ramon Cajal, probably the most neuroscientist definitely in Spain uh Institute of

39:14 Monica in Spain, Golgi, Emilio Italian, very inquisitive scientist. What

39:22 have is you have photography, how photography done in the 19th century?

39:31 know how pictures were taken iphone 13 exist. So you have to have

39:43 film, have to expose the you have to go in the dark

39:50 , the red light have to develop film. So it exposes the contrast

39:57 it was all black and white, gray scale. Basically use a number

40:02 chemicals in this process. And you use a number of codes,

40:08 preserve it so that when you take photograph, you scratch, it doesn't

40:12 come on, it's code. So observes this process, Camellia Gulian and

40:17 process is silver nitrates are being used as part of the exposure and the

40:24 process of photographs. And he ha let me take it to the

40:32 , why not? Let me apply on some brains and see what

40:38 And this is what you can do a basic scientist. That's a huge

40:43 . You can have a brain you can see something somewhere else to

40:46 , I'm gonna order it. So long as you know, it's legal

40:49 , whatever allowed you have it in lab, you can try it.

40:54 is really gonna punish you unless you all of your time and money on

40:57 for many, many years. But when he does that, he applies

41:02 silver nitrate stain. He sees this fraction of neurons pick up the

41:12 a fraction 1 to 3% or so all of the neurons. So a

41:17 small fraction of all of the neurons the brain will pick up the golden

41:22 . And when they get exposed, reveal the entire anatomy with the

41:27 with the dendrites and with the accents Ramon Cajal, his student is the

41:34 that is sitting and doing these drawings the day and at night and has

41:40 very interesting life doing that. And describes here, what we'll study is

41:46 retinal projections from the retina some of that become contralateral and cross over into

41:52 optic chiasm. Here, others that a lateral from the temporal retina and

41:58 to the same side of the Don't worry, you'll know all of

42:02 hippocampus which has different types of This is a structure called the

42:08 It looks a little bit like a horse look shaped like a sea

42:12 This is a massive cell called Kinji that has over 100,000 inputs on this

42:19 tweet. So, Ramonica Hal uses stain and exposes these neurons. And

42:25 that same time, there's a raging about reticular theory versus neuron chain,

42:32 do chain. If you've taken biology , it's also self theory. What

42:38 the debate? The debate is that reticular theory proponents primarily because the brain

42:43 translucent, it looks like it was kind of one interconnected, especially before

42:48 bul stain. The proponents of reticular say that it's all one sensum with

42:55 cytoplasmic envelope and having many many they know millions of nid. It's one

43:04 structure enveloped by one cytoplasmic membrane, ? And having cytoplasmic continuity in this

43:15 massive network surrounded by one membrane, all a sensation. And of

43:23 Ramon Kahal and Camello Golgi, despite fact that he invented the Golgi

43:28 And despite the fact that Golgi stain individual neurons with their processes such as

43:35 . And Axons Golgi argues in favor the reticular theory. And his student

43:43 Hall argues in favor of the neuron . He says, no, you're

43:50 . These are discrete individual units that even puts these arrows. And he

43:55 , you know what these are He says these dendrites probably receive information

44:02 this dendritic tree. And then something here which is in the song of

44:06 information gets processed. And then he arrows saying, you know what from

44:12 SOMA that information, these are axons information travels through the axons onto the

44:19 cells and adjacent networks. He also that these connections, we don't know

44:27 they are yet. We don't have name for them yet. Charles Sherrington

44:32 up with a name synapse points, storm and starts studying the synaptic transmission

44:41 understanding the synapse and wins a Nobel in Physiology and Medicine in 1932.

44:46 that, there's a synopsis and he to a Ramonica ha 2030 years before

44:56 , these synopsis are not rigid that neurons connect to each other and then

45:01 disconnect and maybe they form other So he without knowing introduces this concept

45:09 neuronal plasticity or synaptic plasticity that is important in early development and learning and

45:17 uh ending in and forgetting things as . So OK, what happens?

45:27 disagrees with his boss, but in , together with his boss, they

45:34 Nobel Prize in Physiology in medicine. is an important example of progress and

45:46 in science, dogmatism and rigidity in that remains, despite looking in the

45:53 and seeing these individual units, it remains. There should be an important

45:59 for you. Let's use A I generation, older people. What is

46:03 thing? A I, I don't to use it. I don't believe

46:06 . You're cheating. Everything should just directly from you. New generation.

46:11 use A I, we are not . We're just helping. It's helping

46:15 to move ahead. It's two different of thought. Oh, so afraid

46:19 A I, no, I'm gonna advantage and use it, you

46:22 the same in science and the same may encounter with your mentors or with

46:28 bosses in the future, you may studying some molecule, some pathway,

46:32 disease and there's going to be an way of dogmatic, maybe not as

46:38 as it used to be 100 years or more. But there's an established

46:44 of doing something and you as a scientist or medical professional or engineer.

46:52 , you know, there's a better and uh it's not like this.

46:56 like this. Actually there's a better can encounter a lot of resistance.

47:01 lot of times when there's a new in science, any science, a

47:07 tries to publish his or her work that work gets peer reviewed. It

47:14 you send it into the journal so cannot just publish work. I have

47:19 experiments. These are my results. are my figures published. No,

47:23 submit it to the journal, journal then contact maybe 10 different scientists

47:31 hey, can you review this The person that submitted the paper doesn't

47:36 who's going to review. It does know even after review sometimes now they

47:40 saying we reviewed it after the especially for the accepted papers. The

47:46 who get rejected still don't say who it, but they review it and

47:50 say no, we get this work 10 years. It's like what you're

47:55 here and it says no, don't believe so that it may take

47:58 years, it may take five years a person just to publish their work

48:02 convince somebody, especially if they're seeing new, something exciting. And uh

48:08 , it, it, it can , it can be difficult. But

48:13 , you know, at that uh Ramona Cajal resists his mentor and

48:20 a Nobel Prize. So you can in disagreement with your mentor. So

48:23 scientific disagreement, not personal, personal work. Usually you have to leave

48:28 line. But uh scientific, you , if it is, if it

48:33 based on peer reviewed, on discoveries your own intelligent thought processing and um

48:43 guessing that you have or intuition or something that you saw that could relate

48:48 it, you know, it's, , it's very important. You can

48:52 be successful and both of them are . Um And Ramonica hal draws these

49:01 , he does not know that neurons generate action potential. So we know

49:05 nerves running into the muscles can generate potentials. But we don't know whether

49:09 individual units can generate action potentials. electricity and he cannot visualize synapses.

49:18 the reason why is because synapses are small. The the the distance physical

49:23 between two neurons is about 20 nanometers space. So at that time,

49:27 don't have enough of the resolution with microscopes to see that spatial resolution that

49:34 of a detail. There is another that has been developed by uh Nel

49:47 Nissel and Niel stain is different from stain. Nile stain will in fact

49:53 all of neurons and all of the missile stain will get picked up by

50:00 A and poly ribosomes which live mostly . So therefore, as you use

50:09 stain, all of those elements, and glia will pick up the Nissel

50:13 will expose their SOMA really well, it will not reveal the precise morphology

50:21 the processes such as dendrites and axons a Golgi stain would. Uh So

50:29 is really good for looking at the of the location of the packing densities

50:36 you see these darker bands. That that the cells are clamp up here

50:41 located closer to each other in It's really good method to see layers

50:47 these cells. And Trian Broman, Brodman is using missile stain and it's

50:55 it, cutting the brain into little and pieces and is using this stain

51:01 this outlining structure. The orientation uh hacking densities of neurons in the brain

51:13 said that we have to look at brain here. What we now call

51:17 broad areas because as I said, and function are interdependent on each

51:24 So, so this is the only we can really understand if we can

51:27 understanding the packing deads and these orientation later connectivity of these neuronal networks.

51:35 they are called cy architectonic methods. different functional areas would be determined by

51:42 underlying structure or the anatomy and packing of these cells and their orientations throughout

51:48 brain. So we cannot see synopsis modern day ST standard life microscope can

51:59 0.1 micrometer. Does that mean anything you? How big are neurons anybody

52:17 10 micrometers? They can be as smaller, it can be much,

52:21 larger but average about 10 micros of . So processes can be way way

52:29 of your processes. Some can be others can travel very far distances.

52:37 is one millimeter? How many micrometers in one millimeter patrick? Where's the

53:03 ? Right? 1000 micrometers? So you have 10 micrometers in diameter

53:09 these neurons and the space between two that have the synapsis talking to each

53:21 . These are my two neurons with so much this space here it's 29

53:30 . So even today, 200 years , we still using light standard light

53:38 are short of having that spatial resolution see 20 nanometer space because we're processing

53:44 1 to 1 micrometers. OK. right. Now, what do we

53:55 in order to see the spaces? need an electron microscope. It's a

54:00 different. Most of you are familiar the standard light microscope, but an

54:06 microscope, you have to go in separate room. It's a big piece

54:10 equipment and has a resolution of 0.1 boom. Now, we can see

54:15 synopsis. Now, Ramonica Hall can to everybody but that comes about uh

54:21 the middle of the 20th century. it's a little too late for him

54:25 visualize it. Another important technique that introduced for visualizing neu neurons and neuroscience

54:34 infrared imaging using infrared cameras. So was a setup that I was running

54:41 actively for many years at the University Houston here where you have a brain

54:46 that gets placed right here underneath the lenses. This is your eye

54:52 And so if you looked in you wouldn't see anything but with a

54:57 light and a set of filters and that information from the slide over here

55:07 there's a little green light just for illustration purposes that information travels through the

55:12 of mirrors into the back camera here is an infrared camera. And that

55:19 camera is connected to a monitor. when you look in the monitor without

55:26 stain, you can visualize individual And this is a very common

55:32 infrared visualization and doing neurophysiological studies or studies where you have a microelectrode and

55:40 study the action potential some resting number potential. Later in this course,

55:45 have a micro electrode and that microelectrode typically the tip of that micro electrode

55:52 typically on the order of one a to one micrometer where we can target

56:00 neurons. So we don't have to in the brain. We can visualize

56:05 neurons. You have to have infrared , we can visualize their selma and

56:11 pretty well but not to the same . And to the same great detail

56:16 Gogi stain would reveal it still. it's not used to describe the morphology

56:21 the cell, but rather to visualize the cells in specific brain structures

56:27 um target them with the micro Since we have more powerful tools to

56:37 neurons and to visualize synapses in these , we understand that dendrites contain these

56:45 specialized protrusions that we call dendritic And this is where most of the

56:52 between neurons from one neuron to the happens is by contacting these dendritic spines

56:58 this dendritic shaft and it can be of spines in some instances, tens

57:04 thousands of spines and tens of thousands synapses formed on a single neuron.

57:09 is just a fragment of a dendrite a single neuron with its dendritic

57:17 If you look here at the electron , dem is dendrite, not

57:24 it's dendrite. This is mitochondria This is postsynaptic density. So these

57:30 will contain postsynaptic densities of postsynaptic receptors they're directly physically juxtaposed to these red

57:40 that are axons. And as you see inside the red axons, you

57:45 these red round organelle sort of vesicles are filled with neurotransmitter. So they

57:52 be fused with a plasma membrane here the Axion of one neuron releasing that

57:59 in that tiny 20 nanometer space. on the other side, on the

58:05 spin a posy nap density receptors that bind that chemical causing a posy response

58:11 the cell. And these dendritic spines in many different shapes. There are

58:18 that I described here study then spine the mushroom shaped spine. This one

58:25 here. So there are some certain shapes in these spines and they're

58:30 very important in the early development especially throughout the adult life and for normal

58:39 function as a whole. And we'll what can happen if you have a

58:44 in the anatomy or loss of dendritic , it can lead to pretty severe

58:49 conditions, developmental conditions, what we in modern day neuroscience. So today

58:57 the levels that we can study are vast, we can study individual

59:04 we can study individual molecules, we image individual molecules of individual cells,

59:11 can sequence RNAs from individual cells. A seek and sort them and tag

59:17 with different tags. We understand pretty the anatomy of neurons and their

59:23 although it's still ongoing war probably And we also have a view of

59:32 brain activity noninvasively at the clinical So what do you have here is

59:41 of human brain as a person is at words, listening to words,

59:47 , words or thinking of words. are positron and mission tomography or pet

59:54 . Pet scans can show indirect activity neurons but we are imaging neuronal activity

60:02 . So no longer have to open skull. The person just like with

60:06 MRI, the pet scan goes into circular tube in the hospital or clinic

60:14 their brain or their bodies get You can ask people to do different

60:19 , think of words, speak words image their brain activity. So we

60:23 not have the resolution of single We cannot image single neurons, we

60:28 image neuronal networks being active. And can see that very distinct areas of

60:35 brain are activated for distinct functions. as it concerns the speech,

60:41 speaking and thinking of the words we these brain maps. A brain activity

60:48 or brain maps sometimes also referred to brain waves because they travel through the

60:54 networks can virtual reality change the We have of course, imaging

61:02 pet scans F MRI that we study in the course. A great way

61:07 confirm noninvasively specific localizations of brain functions as looking at the words versus writing

61:15 . Each function is subserve by more one neural pathway. We know that

61:19 is a redundancy in process and we two eyes, two years, there's

61:22 lot of redundancy where our sensors are . And even the processing of that

61:27 information is further diverged into different lines processing that information. For speech.

61:34 talked about 20 different areas. So have to take out big, big

61:38 of left hemisphere. In order to lose speech, you have redundancy when

61:43 pathway is damaged, there's plasticity that that neurons can reconnect in different

61:50 And when they reconnect, they are uh compensating for the loss of

61:59 And a very broad sense of somebody's one sense, they can't hear

62:04 their senses of smell, their senses touch or vision might be heightened.

62:13 reconfiguration of the brain that happened to certain extent. Although there's no regeneration

62:20 lost neurons in the CNS, there a regeneration of peripheral nerves and that's

62:26 because they're in different environment. So grain processing is both cereal and

62:35 in parallel redundancy repetition. In hierarchically more complex. What your eye

62:43 is not the picture of the south wall that you form in the

62:48 That information from retinol network, it processed to a certain extent gets sent

62:53 a higher order centers and the thalamus processed there gets sent to the higher

62:58 centers hierarchically making that information more more complex and also more holistic to

63:06 you form the final image of the world, such processing appears introspectively seamless

63:13 us. And also know that A is based on neural networks, virtual

63:19 can definitely affect our brains can affect brain maps. Here is an image

63:25 with virtual reality or no virtual So you sit in front of two

63:29 screen and you do the snowballs at , at the snowman here and they

63:35 and this is the image without no reality. And then you place an

63:39 within the virtual reality where they have actually sort of clicking the mouse being

63:43 this three dimensional world and it changes brain map for the same function.

63:51 yes, this immersion of artificial enhanced reality or augmented reality virtual reality

64:00 A I are very, very interesting there are some interesting thoughts that are

64:05 in the field that we refer to meta. And that's not because of

64:10 , it's because of meta as a in general. Meta pseudo says patients

64:15 have inflammation, they have pain and lot of heat. You can place

64:21 in virtual reality in the snow and and they actually measurable decrease in the

64:28 and inflammation and in their body or areas. So there's definitely interaction

64:35 Uh And it's all, it's all us. Now. I was just

64:39 to a program about the new uh . I guess iphone doesn't want to

64:45 them headsets, but new headsets that bringing some of these elements into everyday

64:51 , not affordable right now for most the people, but soon will be

64:56 . Well, there's a few more about the kind of a where you

65:00 go with Neuroscience. I'm gonna leave here today and we'll come back,

65:04 discuss a couple of these slides before plunge into the neurons and glia

65:10 So again, thank you for being . Appreciate it. I'll see everyone

65:14

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