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00:00 starting to record this lecture. So is ours. Third Neuroscience Biology 43

00:08 Biology 63 15 Lecture There are some items that we have to discuss from

00:15 syllabus in particular that we are now the confirmation for all of the Casa

00:28 exam Dave's. So those days that Conrad are no longer draft dates.

00:35 first midterm will be on September Monday. Your second mid term will

00:43 on October 28th Wednesday. And your exam, which is your final

00:53 Uh, equivalent in mid term exam be in December 14th on Monday.

01:00 falls to be the regular David for particular exam schedule when I know that

01:09 is quite a bit of time between 7th Monday in December 14th. So

01:17 December 7th, I will hold a session before the exam, where you

01:24 ask me any questions that are related that section, that exam, and

01:30 you will have a week. So have to time yourself and pace yourself

01:35 you still have material fresh and you it, uh, so that you

01:42 be essentially, um, well prepared the exam. Okay, now.

01:50 the exam dates a set in Casa virtual. I have spoken with Casa

01:56 they have, uh, said that will have a sample test for

02:05 Teoh register with costed to log in take the sample test. I think

02:11 the sample test aspires. Understand? along the lines of a very general

02:18 of information that you will be asked you log in to make sure that

02:22 are navigating the virtual space successfully. Once that virtual examines set up,

02:29 just received the confirmations for the days the weekend on the news that they

02:34 have the virtual test sample. for you set up. I will

02:41 you know once that sample was set , the test sample set up so

02:45 we can all go through it. the meantime, if you go Teoh

02:50 cost A website. Ah, you be able to see information that,

02:57 , basically explains to you everything about virtual examination. Now again, the

03:06 EC stand is not cumulative. It over the last section. But as

03:11 explained earlier, second exam will build the material that you learned on the

03:17 section and third example build on the from the previous two sections as

03:25 All right, so this is a a bust again on Wednesday after the

03:31 will have a review, um, the material. And also later this

03:38 , I will send a message to of the graduate students and 63 15

03:44 a time for us all together and on Zoom. I think maybe that

03:49 be, if the course for everyone class next Monday. But we can

03:56 the additional assignment for the graduate students this course. Okay, so please

04:05 . Teoh cost a website. I establish a folder in black board over

04:11 next day that will have the links cost a website. And if there

04:16 any additional information, I will put post it there in that folder.

04:21 once we have a sample that you log on and virtually taken and

04:27 make sure all the systems are a , I will again notify everyone in

04:35 . Okay, so I am recording lecture. Thank you for reminding

04:40 Please continue reminding me, um, you, for some reason. See

04:44 I don't I'm gonna pause the recording , just to switch the screen are

04:51 . Third lecture material were sort of , um, going through some of

04:58 slides that are listed in lecture, , lectured to. But in

05:03 we have already started talking about neurons glia and is a reminder the three

05:10 important cathedrals with their unique accomplishments communion with the Golgi stain, sir.

05:19 Ramon Alcohol with the the drawings and descriptions of neural networks and brain

05:29 uh, Sir Charles Sherington, who has spent time in coining the term

05:35 and forecasting and describing some of the and some of the interesting,

05:43 biological descriptions off this synaptic cleft in synapse. So if you're in cold

05:51 , Goldie was, ah, proponent since the shell or a theory that

05:59 called the ridiculous theory and particular theory for single side of plasma continuity between

06:07 nuclei and Ramon. Alcohol was a off the during doctrine or the South

06:14 , arguing that the South Dorantes, individual discreet units and this drawing in

06:20 middle of the slide in yellow illustrates what Ramon alcohol do sows their

06:28 The accents that carry the signal has and black, and they have arrows

06:33 indicate that there is a flow of signal, and through these processes,

06:37 particular, other cells will be The other synopsis so quite remarkable that

06:45 had such a four side more than years ago. Another very important

06:52 And it's different from the Golgi Golgi Stain isn't shown, and as

06:57 adventure, that class picks up only 3 to 5% of all of the

07:02 . But Durrance it pick up the silver, uh, Golgi. Stain

07:08 stain extensively. So not just So most, but all of their

07:13 that down drives these air, usually upwards and the shown on brown.

07:18 these drawings here in the middle of page and ASEAN's Andi accents and all

07:25 the processes of all of the ramifications these processes and contacts with other neurons

07:33 that works on that is staying there very important was missile stained missile stain

07:39 all of the neurons and glial cells essentially does not stain. The process

07:45 so you cannot see the process is you can see here some of the

07:49 coming of the cell body. It's used to describe the anatomy of the

07:54 , but try that that architecture of neural networks, where these styles neuron

08:00 are like building blocks and building a architecture. So what we're looking at

08:07 , for example, is a and the brain is a cross section

08:14 the brain and the top blue. ah, structure that we mentioned

08:21 It's called the hippocampus of the hippocampus this very sharp blue lime and one

08:28 the loot desire sharp blue line is all of the neuronal soma cell bodies

08:35 concentrated. And so, if you at the Jason structure nearby, you

08:40 see that this structure you can actually six layers In that structure, they

08:45 like sort of, Ah, don't, uh, layers one over

08:51 one over another. And this is sixth layer lateral Jinich alert nucleus of

08:57 follows. So as I mentioned to , that is no signs of Senator

09:02 . We high certain landmarks that indicate us the location of specific brain not

09:08 infrastructures, the layers or maybe even subtypes of cells. And this sort

09:15 description is called site Architecture and Corbyn Brockman, Doctor Brockman used this missile

09:24 in order to very carefully, describe different functional areas. So he

09:31 there different functional areas as he determined by different system structure, positioning and

09:41 connectivity between the cells. So these still Rodman areas that are being referred

09:48 and used to. And, I have ah, homework question for

09:54 that I'm really road right, right and maybe even almost answered immediately because

10:00 have all of the digital tools in of you. But the question

10:05 what is Bronfman's area for Broca's What is the number one number of

10:13 areas for brokers Area What number is learning guests area. Okay, so

10:21 remember when we looked at that Soon we looked at the damage to

10:25 area, which is in the frontal . But we said that it is

10:30 Teoh expressive aphasia. So find out broad months area number corresponds to Broca's

10:39 and which one corresponds to Vernon kiss if you call recall Vernick, it's

10:43 , which is located on the border sort of Ah, temporal parietal and

10:48 loves was related. Teoh. Receptive . Okay, so this is your

10:54 task, Thio Thio Investigate now is important is a modern understanding of neurons

11:02 line Eurostar different. We're gonna go some of the basics, lies and

11:08 blunt, uh, and you will that mirrors and many instances are just

11:13 other cells. Blood neurons have very specific features to themselves, and

11:20 could really distinguish these features in Once we had the electron microscopes.

11:27 we could visualize the synapses between the and started a standard line microscope results

11:33 0.1 micro meter. So we said the diameter of the neuron is about

11:39 micro meters, so standard, like will show a self but synapse.

11:46 spaces between neurons is only 20 nana , which is very, very small

11:53 . And it would not be resolved 200.1 micro Vera resolution. This 0.1

11:59 meter resolution is 100 nanometers, so wouldn't be able to resolve a single

12:09 electron microscopes they resolve after 0.1 nana spaces. So that means that you

12:17 have in this 29 a meter you could have 29 m divided by

12:24 one. You could have essentially 200 resolving images in the space that is

12:37 the two neurons. So with this shows is the image off dead

12:46 And that's why in euros a different they have these down drives and these

12:52 rise have these tiny protrusions that come of them and these air dendritic spines

12:57 indeed expires. The terminal I, the end of these dendritic spines will

13:02 contacting other accents on the agenda, said. That's almost informing the

13:08 and there is a different varieties of shapes of the 100 expire. Some

13:13 them are described as a study. is shown in green, where it

13:20 P S. D stands for the topic density than the some very interesting

13:25 There. There's new transmitter, receptors that are found here on the

13:31 nonstick density, and you can see read on the opposite side. You

13:35 see these small little, uh, red vesicles, red little balloons and

13:45 will contain neurotransmitters. So on the , you see the pre synaptic neuron

13:52 has neurotransmitters and the vesicles. On last, you see the pasta traffic

13:57 and used to the pasta ethic Neuron the Boston Athletic. Noon contains the

14:02 , but these neurotransmitter chemicals also the space in between and lose almost fused

14:08 is the actual soon after to And so the shape of the dendritic

14:14 changes. The number of the dendritic changes with Is that mean that needs

14:20 the grid expires? Or the most segment anatomical segment off the neuron,

14:27 by forming new gendered experience, you be forming new memories. New experiences

14:35 be registered. If you persistently experiencing , you will form new synapses when

14:42 learning you're registering certain pathways in your , and then you can recall the

14:48 places because you're reactivating certain synapses that active when you were learning. A

14:55 synapses informed is a part of that process equally so you can also lose

15:00 some of these dendritic spines and lose synapse. This is the normal process

15:05 plasticity, and some gaining synopsis and its called, uh, Clinton she

15:13 of the synapses, strengthening the efficacy the synapses is potentially aiding the synapses

15:19 weakening or eliminating. These include ex and abscesses, repurchase depression or depressing

15:27 in these synapses. That these dendritic and potentially driving the synapses away altogether

15:34 that happens is a part of normal and forgetting. Process is a part

15:39 normal experiences and emotional development process, and also abnormal loss of the synapses

15:49 with neurological disorders, imbalances in the . So most of our brains are

15:57 . They don't have neurological disorders in in the sense of normalcy. And

16:01 have very dynamic struck cious Lee synapse system. One neuron could have up

16:08 100,000 off these dendritic spines and so the amount of the computation the

16:17 on does is by gathering information from of the active. And all of

16:21 have been it's an absence. Some these different experience will be contacted by

16:27 turn their transmitters and other these spines be, ah, uh, targeted

16:33 the inhibitory neurotransmitters. So by balancing and inhibition but balancing activity and having

16:41 plasticity, the ability to reshape the , this is very key to normal

16:47 function a very key dysfunction that can in the case of neurological disorders.

16:57 . So this is some of the from my laboratory and the microscope that

17:05 use here is light microscope. But we have is we have ah,

17:13 infrared contrast microscope built in here, infrared camera that, speaking of the

17:21 So the eyepieces in the front is you would see the specimens yourself.

17:26 will, we have year is we a microscope. And where you see

17:32 green line is where you have a it In this case, the specimens

17:36 a piece of the brain. And you zoom in even Mawr, you

17:40 see that there is a number off electrodes that are targeting and are actually

17:48 of the electricity placed underneath this lancer the neural Titian or inside the 1000

17:56 tissue. So why this is important because using this technique and this,

18:05 , microscope, we no longer need stain cells. These the slices that

18:10 made from Brad brains and we can visualize neurons and visualize the processes on

18:19 you're seeing here is to cells that two different cells, and they're being

18:25 by the micro electrodes. Sir Michael cell diameters 10 micro meters The diameter

18:33 the micro electrode is about one micro , and this is the way in

18:39 we can perform whole cell patch clamp or interest cellular recordings. This is

18:46 way in which we can visualize individual . Some target individual near us with

18:51 tiny micro electrodes. It's a quite difficult feat to accomplish, especially if

18:58 recording from multiple sauce at the same . At some point in my

19:03 I think I was mad enough to able to record from three and four

19:07 at the same time. Um, do need sliced brain slice preparations in

19:13 to do that, because you would be able to visualize individual neurons using

19:19 veal imaging techniques that you have in to recordings that happen in hospitals that

19:25 from the brain tissue. Most of are extra SABMiller recordings. That means

19:30 the electrodes air located outside of this versus these recordings that I'm showing you

19:36 , where individual south and electrons are the inside of the cell, forming

19:42 pash clown or interest Saleh type recordings will discuss us actually later in and

19:49 the course as well. Now some the important ideas and concepts that led

19:57 to this understanding off neurons and we'll about glee um, with Leo cells

20:03 is really a multidisciplinary historical development of size, with some of the key

20:10 along the way that we have mentioned you can review in the recorded

20:17 Um and, uh, now we that there's functional specificity. We know

20:24 certain parts of the brain and certain are responsible for specific functions. We

20:32 know is that simple tasks and some the basic mental functions associated with simple

20:38 within their simple motor control task is . Mental. Uh, performance tasks

20:45 localized to small areas of the cortex could be singular areas of the

20:51 But the more complex a task the more modalities that involves the more

20:57 of tries. Teoh blends together such smell, taste and vision, the

21:03 off the brain becomes involved in more between different several functional size, unnecessary

21:13 what we have in the brain. have both times of processing. We

21:17 serial and parallel distributed processing. So have cereal processors in the brain,

21:23 that means that we have redundant tactless certain information processing. For example,

21:29 the unusual on system in the we have three types of color

21:36 We can have one, but we three times, and there's three times

21:39 one is dysfunctional. That means you lose all of the colors. You

21:43 some of the colors, but you need tame. That's serial processing in

21:49 way they're also pathways, visual pathways other auditory, exactly. Said have

21:55 processing. And most of the systems will discuss ha streams. Neural streams

22:01 neural never wear extremes that are in and in parallel. So when they're

22:09 cereal, it's increasing in complexity. I say parallel, that means it

22:17 redundancy just like it with the example I used with the right now,

22:24 I meant is you have in parallel uh, color cones that are processing

22:31 , but that visual information, redundant that's processed in parallel by three cones

22:37 the level of the writing lists quite . You don't have the image off

22:42 visual information of the visual gestalt. visual image at the retina. That

22:48 that the complexity of that processing happens serious than at the higher brain

22:54 which is the thalamus. You will a more complex processing of the visual

22:59 , and the whole full picture of usual image will be formed on Lee

23:04 the occipital cortex is activated. And was the third major station along the

23:11 of the visual information processing. So processing and parallel color information through three

23:18 processors, while the serial processing is by increasingly having more complex interpretation

23:28 uh, sensory processing and blending off modalities in in the brain. So

23:38 put the sling tackle. Do you a dumpy? Do you feel like

23:43 ? Look, there's some pretty cool that I but I sometimes look at

23:51 . So the Clarins view is, know, we have imaging techniques that

23:57 actually show us activity inside the brain having to open the skull. So

24:06 have pad, uh, which is and emission tomography. We have Emma

24:12 , which is magnetic resonance imaging and Marai, which actually shows the activity

24:22 the brain. So these air the techniques, the patent and AM arrive

24:26 in the course will discuss them in little greater detail, then will allow

24:31 to visualize the activity of the brain intact brains. Um, and what

24:39 have here is an image that was the museum here in Houston. That's

24:44 interesting, and the study was based this image Where you can actually detect

24:49 difference is what you see here in last in the black box are to

24:56 and in one case, is the individual that is looking at the environment

25:02 has no virtual reality. And on right is the same individual that's looking

25:07 the environment that has virtual reality and these are those yellow and red dogs

25:14 the brain, on the active neurons the active networks that light up and

25:19 this experiment in the cases of the actually reacts differently, not just looking

25:26 the same image. But if this is all of a sudden Marcin virtual

25:32 or in additional dimensions, three or dimensions, then the map of the

25:37 perceiving the same imagery changes. It like it becomes more specific when it

25:43 experiencing war for real environment. But point is to say that there is

25:50 changes that were killed, recognize, these is pretty subtle changes, special

25:56 and versus no virtual reality, as Teoh epilepsy and no apple,

26:01 So some of the severe neurological conditions activities can also be picked out by

26:07 a Marai. But if you really to record electrical activity of the brain

26:12 the clinical setting, you're still on surface of the brainier reduced Teoh E

26:17 G, which is electroencephalogram. And severe cases, if you're undergoing a

26:23 surgery after trauma or um is related Cem oncological problems, then you will

26:31 intracranial recordings and actual placed in the the actual skull. And so,

26:38 off that, uh, I would Teoh mention something pretty pretty interesting,

26:47 me see if I can, pause the recording. But it's a

26:57 interesting device that he is, commercializing and this really an implanted electrode

27:08 . And it's really interesting because it's chip that gets implanted that is recording

27:16 brain activity, and there is some say ethical backlash that he is

27:26 But I would also suggest that in cases where you have complete loss of

27:33 Oster their paralysis Yeah, but you have brain activity. I'm looking at

27:39 from or of ah, neuro degenerative healing perspective to actually see if,

27:47 , this device it's not billings to is not going to be used something

27:53 enhances, um, our performance. try that maybe helps people that have

28:00 severe brain injuries. But the, , the startup is already testing distin

28:10 humans. So I just wanted to that out that every day we're advancing

28:17 we as humans are not only recording Nick Kennedy in this case with

28:23 but also how are we going to that information that we record for what

28:28 ? And in my view, we help neurological patients that are severe near

28:35 generation that can reactivate awakened retrain brain to improve their function is really a

28:45 tool. Okay, with me imported your gown Now we know that each

28:52 is subsumed by more than one neural . That's why I said that there's

28:56 processing when one thought ways damaged. have others that may compensate, you

29:01 , other parts of the brain that take over the damaged part of the

29:07 . Emotions, things like emotions, also localized memories, the localize and

29:12 distributed through the brakes. While there structures that are responsible for encoding the

29:17 or recall of the memory storage of memory and is widely distributed emotional tac

29:24 and emotional stark, it's also pretty distributed within the limbic system. We

29:30 balls very key structures such as frontal , hippocampus and make the loans

29:37 So once we have the cell elementary and things that we dio that even

29:45 , you know, we're had writing down as we're talking and we're looking

29:51 the wash at the same time. pretty seamless for us, but if

29:55 can imagine with those brain maps, inside the brain as we change our

30:00 functions in our thinking tyrants that these mass also changing because these brain maps

30:07 really representation of the activity. A of these into the EC, spines

30:11 critics in absence. We know that spines and synapses change therefore These maps

30:19 change these maps Learn to become something you using them a lot to learn

30:25 become something else. If you're using parts of the off their off your

30:29 , different parts of the body. , if you look at some of

30:34 image ing like positron uh, emission image ing, which is really what

30:41 have to realize when your image ing of the brain year image ing the

30:46 , consumption of oxygen consumption of Lucas these techniques are really just,

30:52 telling you how much, uh, activity is happening in these particular

30:58 But it's very clear that when you're at the words, your occipital lobe

31:02 the left top is eliminated in A B when you're listening towards, you

31:08 see the on auditory area, and temporal lobe is illuminated. When,

31:15 Steve's speaking words, guess what it's motor cortex and very close to the

31:20 area or it assistant get illuminated. what happens in D when you're thinking

31:26 large these different areas, So it's a different area from when you were

31:32 to words, or that when you looking at horses get activated because the

31:39 involves other parts of the brain that not primarily concerned with sensor information

31:44 But as much as with Com Uh, intellectual information processing?

31:53 these spines. You know, these are now being described This mushroom shaped

32:00 Stan or shortened stubby. And there's about this anatomy, different types of

32:06 and the length of the spice. is very important. So in cases

32:10 neurological disorders, you may have and Spicer will review conditions and which

32:17 have, uh, dysfunctional dendritic We can also this age visualize even

32:25 molecule so we can trace single molecules just single synapse activity in a single

32:32 as but activity of a single How that molecule it's traversing through through

32:38 south. Okay, so with I'm gonna, uh, switch into

32:50 following lecture on, uh, can see now the screen of neurons and

32:59 ? Can somebody confirm that they're seeing nerds Ingredients came? Yes. Thank

33:05 . Great. So, again, stain and unearned doctrine were very important

33:10 order for us toe. Understand that have these cells called neurons,

33:17 uh, now we understand we have and we understand a lot about neurons

33:23 we understand a lot about genetics and genetics and things like that and some

33:30 the basic things that happened. Endurance . All of the styles you have

33:34 transcription, uh, into the are a you have already and processing.

33:41 , you have slicing that happens between and I are in a and so

33:48 you refer to splice variants during the variance one pieces off, the genetic

33:54 in transfer being thrown out and the are being kept from us a journey

34:00 code into pro dance according to channel put into, uh, something else

34:07 Jewel. So what you have is have different Spice Arians, and it's

34:14 in a way. We're sort of splice variants off of our own of

34:20 own genetic material, and it's a thing, but you can also have

34:26 pathological spice parents of during this transcription process, you missing part of the

34:35 , slice it in the wrong kind way. You can have a pathological

34:40 from these gene genetics plaice variations. Russell half regular organ. Now I'll

34:47 the plasmid particular rival Sum's and Paul sums, uh, driver sums covering

34:54 roof of the plasma. Critical, uh, messenger name will exit out

34:59 the nuclear pores, and some of will be destined to become a freely

35:05 protean, and others will be destined become a membrane associated protein from this

35:13 code. Um, so what's important is we're reviewing some of the basic

35:21 . I think that will be interesting your own to review how viruses,

35:27 , work also. Now the debate we raised at the beginning of this

35:33 is that we're still not certain if 19 of Corona virus enters into the

35:42 . Right? We discussed a A study by the Boston grew that

35:51 that they did not find much of viral load or inflammation in the

35:57 but they found degeneration. So their is that the virus is not entering

36:03 the brain. That's probably not crossing blood brain barrier cold in 19.

36:10 other studies that were done previously, were indications that the virus actually interest

36:17 the brain and causes what we described as a full athletic lesions or encephalitis

36:23 condition where you have very prominent inflammatory and inflammation of the brain as well

36:31 nearly generation. So if virus does into the cells, remind yourselves how

36:40 work. So this is your second . What is oneness? Virus do

36:45 restricts the cells and to generating zone . It's takes over the host genetic

36:56 and in fact, a portion about . We keep talking about evolutionary

37:02 We we have a lot of genes . A portion of our genetic code

37:08 to be changed influence. And they together with the nation. Together with

37:14 viruses, um, viral infections have down production of certain chemicals and plans

37:24 potentially turned on evolution of certain systems immune responses that to date we have

37:31 our bodies and our still evolving. talked about my current race, and

37:38 month's try showed you Brain Atlas, is really Ah Alan brain half.

37:44 , there is a Lincoln, our materials toe, Alan brain outlets that

37:48 can review, and one of the . There was my crew race and

37:54 studies of the brain, and this very simple terms trying Teoh explain what

38:00 micro arrays are. What if you're familiar with these techniques Where you really

38:05 simple terms? What do you really starving? We have a micro

38:10 Where you tracking Here. So what have in the last years, you

38:13 a plate to call micro plates, plates, and they will have these

38:18 well, something have can have, 80,000 of these mind. It's called

38:24 car a Jean Marc Cory and inside walls because we know two genetic A

38:29 genomic Aris. So we know one of the delay is coding for for

38:35 watts. And we have synthetic DNAs represent genes of interest or than each

38:41 of these. Well, now we take two brains. Brain Juan.

38:45 say that is normal Brain to that even in fact, that are maybe

38:50 to that is a pill epic, ? And we essentially have ah,

38:55 , are in a that we extract brain long and brain, too.

38:59 we implying onto the DNA on my right, and so jeans that have

39:06 expression and bring to will have a signal genes that have reduced expression.

39:15 Bray Juan, we'll have a green . Genes that high equivalent expression or

39:23 changes in an expression of that gene glow has yellow. So you have

39:31 microscopic slide you have. These style are starting the day with specific gene

39:37 in these little whiles and the way you can visualize that this is a

39:43 specific and very sophisticated piece of dull , where a specific sequence has to

39:52 to your synthetic DNA sequence of Emory, in a sequence isolated from

39:57 brain, has to stick to your sequence in the more of it

40:01 Or in this case, the lesson , the more gradual how half the

40:08 of the brain one jean sticking the of the green you'll have lower.

40:16 you have on the left is a map, and this heat map will

40:20 , if you have 30,000 gene wells there, this heat mom, or

40:26 you a bird's eye view what is in this brain. Let's see brain

40:31 and pull out there, and this a brilliant technique to have an overall

40:38 and try to understand what genes and expression Misch a changing as a consequence

40:44 disease. Now, when you are likely based with this Migra ray,

40:52 out split is you may have 200 and reduced on brain Teoh 500 different

41:00 reduced on brain one. Uh, , so then you look for the

41:08 and have the biggest differences. You're that the genes that have the biggest

41:14 in expression or some of the most to this disease probably that is the

41:21 , right? But we know that nations, sometimes little things not the

41:26 expression changes actual addicting. The bigger changes very likely than you use other

41:34 . You use that, uh, library searches and trying to understand what

41:41 you're looking at. If you're looking Apple s TV and your song Jian

41:45 on 400 genes. But you know only 20 of them are really,

41:50 highly relevant to ample of senior. you can narrow down two twenties Now

41:56 can maybe narrow down from this 25 then maybe your boss will tell you

42:03 I'm studying this gene in the so make sure you pick this one

42:06 of five that we study because, know, this is something the person

42:11 passionate about. Um, but like said, it's not always the big

42:18 addicted other things changes sometimes minor The a story changes and can can also

42:26 in pretty significant changes. So let's through some of the organelles, the

42:33 particular more they have the protein You have Kallstrom regulations self. A

42:38 of calcium is being stored on this your intracellular calcium stores in news suk

42:43 lot of energy and they consume a off Ah, um uh,

42:54 And they need a lot of calcium transportation in a lot of counseling for

43:00 release. So this is a very organ. L energy, of

43:06 is generated by modern Conry. In can remind yourself of the Krebs

43:12 but essentially you have dietary and stored sources at the bottom, and a

43:19 as protean should in fact, it on fire Olek Asset and goes through

43:25 oxygenation process and conversion into the e . P on carbon dioxide. And

43:33 have these crist a galley, this membranes on our remember and softer

43:41 Bilal Khan DRI and in mitochondria and be located very much so around the

43:46 , but also very much so within sin access and the genetic spines,

43:53 look at the possible live it by uh, model. And it's

43:59 It's also the fact that the plasma are the fossil lipid by Lares a

44:05 dynamic structure that you have, channels with some trip Rodin's,

44:14 channel Proteas. They're embedded inside this lipid by lair. It is actually

44:21 just sitting there in space, but is constantly moving. It's constantly moving

44:29 fluid. This environment underneath it is by side of skeletal elements inside of

44:36 elements that are at the distal parts the synapses are also the most

44:42 our man says So the composition of hospital it violated the plasma membrane gets

44:50 , uh, and, uh, renewed by activity and by different environments

44:59 the outside of the salad, the of the cell. So trying,

45:03 , find this. Uh um, very cool movie. Give me one

45:12 , please. Okay. This is very quick kind of a basic movie

45:18 describes where I just talked about is fluid mosaic model off the off the

45:25 membrane on the other cell at the the living machinery of beginner cell.

45:32 the harsh conditions of the outside it stands the cells plasma membrane.

45:38 crucial as this barrier is, it's flexible. It wasn't card enough,

45:46 it might break and begin to Lipid molecules of the membrane, naturally

45:53 in a double layer because their tails water, is their heads attractive,

45:59 some cholesterol and a few couple and you have the basic structure of

46:05 plasma membrane. Within these lipid we also find different proteins, which

46:12 various things for the cell. For , they receive signals from the world

46:20 or the transport nutrients it waste. denture composes the membrane with a combination

46:26 mosaic of different lipids, carbohydrates and . And these molecules are not

46:35 They constantly within the structure, fluidly their positions. The survival of our

46:44 life rest on this veil of A simple membrane, just two molecules

46:54 that's dictionary and when. When, it's when they're non station, where

47:01 actually not stationary and when you think they're just bobbing around a little bit

47:06 a very slow fashion. Some of receptor, uh, protean channels can

47:17 the length of the entire cell within , the length of the entire synapse

47:24 microseconds. So some of this movement insertion of the new Proteus into the

47:31 because remember, the synapses ended very are possible. It that bile Aris's

47:37 a very fast process. Okay, not according um, Now, if

47:47 look at the side of skeletal elements narrows, you have micro tubules,

47:52 filaments which are also Lomas intermediary fill and microfilm months. Um,

48:00 the microfilm linens this has shown are smallest diameter side of skeletal elements are

48:06 of the acting Bala kills. And you have a constant Poland memorization information

48:13 these acting chains into microfilm nous and organization of break up a piece,

48:18 filling this intra foreign chains that the chance or individual acting molecules altogether.

48:25 new of elements are about 10 and meters in diameter, and they really

48:29 ball like filaments of micro tubules are of like tubules that are organized from

48:37 billion molecules arranging them in the tube spear like structures. If you look

48:43 the right at the cross section, is a cross section through the axe

48:48 The first thing to notice is that the outside of the axe onwards,

48:53 Meilin axe on, you see these ? This is actual sheets of Meiling

48:59 are raft up around axe on Honest cut in high. So you're

49:04 through, sort of. Ah, , halfway through the accident, you

49:08 the carrot in half care of this and you can see on the

49:13 Here you see these sheets of my . Inside, you see these tubular

49:19 highway, so you we would for as market tubular highways. And these

49:25 micro tubules of micro tubular highways that be carrying the nutrients and the necessary

49:33 molecules from the periphery and also from central locations in the soma into the

49:39 peripheral parts of didn't rise and accents most of the biochemical machinery. The

49:47 of the things that no, these still located around the soma. It

49:50 to be transported a gust through the tubular dress board. But There is

49:56 metabolic and independent metabolic and synthesizing machinery located at this and nationals as

50:04 If we look at this stay in year, it's a three colors in

50:10 . The yellow color, which is villain again, the yellow color as

50:14 two billion, which stands for micro . The blue is active so

50:20 Yes, for micro filaments. Acting of purple is this stain for the

50:27 , and this is taken from a cell. But the reason why I'm

50:31 you this is because it very clearly that the acting molecule, the smallest

50:38 blocks of the side of skeletal are located in the most distal peripheral

50:44 of the South, most closely associated a member Impossible it bit by layer

50:50 the cell and the yellow tribulation, tubular, high oyster market tubules.

50:56 very much concentrated around the SoMa unveiled certain processes, said radiate out of

51:02 spinal blast sounds, whether in the of neurons would be gone. The

51:07 , so when that tells you, the most dynamic element acting microfilm,

51:13 looking at the very distant parts off membrane. Therefore, you will find

51:20 polarization. Deep organization of these active , which would influence the shape of

51:25 plasma membrane, which would influence the of its UNIX science, which would

51:31 that function or efficacy of the doing or may breakdown of these active molecules

51:40 something good experience may be contributing to process of depression. And,

51:46 the driving away off the necessary to it explains. I have the slide

51:54 year, but I actually should have , much better sliced to share with

52:01 recording. Uh, no. We about Alzheimer's disease, and when we

52:12 about loss of memory, for and we talked about certain symptoms of

52:18 disease in our case, we're gonna talking more about neuropathology or false

52:25 And, uh ah, now the most important, um, features of

52:35 disease. No, psychologically of the off plaques they're referred to see now

52:43 . They're also referred to as bait plaques. Um, and you have

52:49 normal tangle formation and entanglement off, , information of these plaques, typically

52:59 of the cells and the closer toward so most of the south. They

53:05 the more been impact that will have the city of the South of depending

53:10 where the plaques are located in what of the brain is gonna have the

53:14 serious affect and damage in that part the brain. And the second your

53:22 feature is tangles. And, it says, dying neurons with tangles

53:29 tall Prodi entangles performed so data amyloid and towel, Prodi and tangles,

53:38 Prodi and tangos. The reason why talking about that, uh, going

53:43 tangle op in the tangle lob the tubules, the tangle of the side

53:49 skeletal elements. And when the micro gets tangled micro tubules like you

53:56 they're like micro tubular highway, so tubular highways traversing through the processes.

54:01 so most of the euros are providing nutrients of transporting goods through the

54:07 Now what do you do with these ? Prodi? Entangles is you tangle

54:12 the highways and what happens if you one over Passover that its major accidents

54:18 good scandal be delivered. And so start impairing the transportation off the goods

54:27 the sauce is well, eventually leading neuro degeneration leading to death off

54:34 dying murals with tangles and shrunken So what has shown here is the

54:40 of the healthy brain and then the divine stages of Alzheimer's disease. That

54:46 matter, especially the gray matter, known to be shrunken because of the

54:51 neurodegenerative processes. So these are pretty , dangerous of Alzheimer's disease and symptomatically

54:59 in early initial stages off Alzheimer's This is pathology fail, and we're

55:06 about symptoms is what is happening to person. Short term memory loss,

55:11 remembering, asking things the same Several cons a day. So start

55:19 that an elderly individual you just had conversation with them about Suzanne. And

55:26 minutes later or 10 minutes later, person will ask. So do you

55:31 Suzanne and you'll say, Well, just had a conversation about Suzanne and

55:37 person, Uh, there's experiencing Well, look a little bit

55:43 Uh, so confusion, which now on anxiety. Not not being able

55:51 here everything correctly, maybe understand everything they and remember not remembering the

55:59 not remembering what you just discussed on short term, um, makes people

56:07 , make people depressed and makes them withdrawing themselves from social interactions.

56:18 there is, um, also often confusion about the time of the

56:25 to when looking at the clock, could be seven o'clock and personal

56:34 They may forget that they just woke , and they may think that they

56:40 to go to that because it's in evening time some of the clocks or

56:44 of our time. So these are of the symptoms, and there some

56:48 that can be done to detect on symptoms of Offerman's this season. This

56:54 advanced stages. Now, when you in the brain and you see the

56:59 in the brain and see, maybe some questions, but this will go

57:04 your all time was Disease section, we will actually expand on. The

57:09 will look at some interesting things through course of the semester, so save

57:14 space under this, uh ah, , uh, disease section. Question

57:21 on the tangles between the same neurons different ones, so the tangles are

57:26 within neurons. The tangles are actually the neurons, but what they do

57:31 they wrap around and tangle of the . Tubular highways. The plaques that

57:37 data amyloid plaques are on the outside extra cellular. The protean aggregates that

57:45 together let me become calcified to sort like calcified lesions on the outside of

57:51 cell. But if those calcified lesions near Axiron, accidental function and accidental

57:58 and signalling is impaired. If it impinge ing and is located on the

58:03 and maybe some of the bias synthesis metabolic machinery is impaired. So the

58:09 of these blacks and I actually have very interesting article. I will post

58:12 I publish with colleagues for Baylor College Medicine, where few years ago I

58:19 a theory that the closer the plaques two neurons, the more impaired

58:27 uh, external firing going to And it wasn't sentient, unusual

58:32 except that I came up with a . I came up with a song

58:36 how we can measure the proximity that no methodology by which we could measure

58:41 proximity of the flax to certain And my colleague Matthew Raz Bond and

58:47 got together Baylor College of Medicine and talented student. It is. Laborde

58:52 took upon this project, and indeed used an old way off, sort

58:58 a circular distance measurement that was used anatomical descriptions that we applied to look

59:05 the proximity and the correlation between the of the plaques to the accents in

59:11 to the level of the impairment by south of these toxins. So very

59:16 question. Okay, Okay, So you can share. Resource is

59:25 neurons that south? Yes. And more details that will discuss, for

59:30 , where we talk about hippocampus will back and talk about the semantic

59:36 So some of these, uh, about Alzheimer's disease are going to be

59:41 going through the semester. And it's interesting for me, because go that

59:47 seems to be causing pretty significant recovery is, like into traumatic brain

59:53 Some of it is like in almost like dementia like syndrome that seems

59:59 be transient. But in some patients lasts up to six months, which

60:05 really, really ah, significant, that the virus may not enter the

60:11 based on the articles that we looked . Okay, so let's go.

60:18 gonna partners, um, recording and moving on to Den Dries and you

60:23 to do. It expires that we . We have accidents coming out so

60:27 of the Denver rise would be sort apex. At the apex of the

60:32 bodies, the cell body here is is an exciting story, their own

60:37 Perama Nall cells that serve a shaped a three dimensional pyramid, with the

60:41 extra live containing the done drives from air called optical done dries. Of

60:45 down drives that are coming at the of the spare men are called basil

60:49 drives at the very bottom of the pyramid. You have the axe on

60:54 acts on ratifies into collateral, so presence outfit as distilled terminal parts.

61:02 it also get contact cells along the . If you look at the pre

61:08 terminal where you had excellent terminal, I mentioned, you will see a

61:12 of mitochondria there, too. Not a Selma's, but in the external

61:17 . The reason for it is because need a lot of energy. Diffuse

61:21 bicycle for exercise doses and back for psychosis. So once the nutrients that

61:29 the actual potential rise in the sudden pre synaptic terminal. Yeah, influx

61:34 Councilman Deep polarisation on fusion off Best possible number and release of newer transmitters

61:41 the synaptic class. And then they through the synaptic last 29 a meter

61:47 and Boston an ethically and these pasta densities binding to the respective receptor.

61:54 the state that is excited to re to make neurotransmitter glutamate is a major

61:59 for a neurotransmitter. The brain, pasta not preclude, um, interests

62:03 . That limit will bind to the , and the receptors will initiate cost

62:09 to the response of the cell of posson optic nerve and really depends on

62:13 type of there stab Chris that it with it. He's very specialized area

62:18 of sin options. Now extra synaptic outside of the synapses. You can

62:22 have receptors located there not as active don't contribute that much to levels of

62:29 , although they do contributes and levels activity that can also be actively recruited

62:34 the extra synaptic spaces. Mosey on you're the foster live with Beyeler through

62:40 fluid, most A into the synaptic based on demand, is the receptors

62:46 can also be internalized or they could inserted in the membranes of that process

62:51 dynamic to not only the movement through plasma membrane, but insertion of the

62:56 membrane or removal from the plasma membrane recycle on in the south machinery.

63:05 transport. You have supplies like transport a slow 1 to 10 millimeters today

63:11 fast except Kliment Ectoplasmic transport. that is 1 m today. Then

63:21 a great transport. Is all of molecules that are being used in terror

63:26 . That means from Soma through a . Retrograde is from the periphery and

63:33 into the soma. So you have micro tubular highways and you actually have

63:38 engine like motor like Prodi Incirlik And they will pass this this molecule

63:45 their own will pass it, pass from one arm to the next arm

63:49 the next time to the next time the next time. Carry it through

63:53 Marco tubular highways. So contestant is do it in the entire great transport

63:59 and dining him is another molecule that's for transporting goods in the retrograde life

64:12 we can use different guys for horseradish peroxide days. Also, viruses

64:18 so much about viruses. But viruses also great tracers because a lot of

64:24 that say they, in fact the they may gets taken up by that

64:30 endings in the periphery, such as the skin or in certain parts of

64:35 brain map work. And then they retrograde. Lee transported retro Greenlee transported

64:42 the so so this retrograde transport is great way to use for staining to

64:51 where are the distal hands of these that are embedded in this piece of

64:56 network or in this piece of the ? Where are the endurance of process

65:03 from this particular part? Off the the structure We will wish you injected

65:08 die so horse riders peroxide days much herpes and Rabies virus is we'll travel

65:15 the retrograde like fashion and some Herbie Simplex virus, which caused the

65:24 , can actually first cause chicken pox the per free and then travel into

65:31 Selma's and into the spinal cord and . Dorman's of travel Retrograde Lyn ST

65:38 months until fifties or sixties, when can reappear in a single spinal nerve

65:48 shingles, causing shingles and reappear and and er greatly from the spinal

65:57 Wrong. The dorsal root ganglion. roots house If you remember the dorsal

66:02 of the spinal cord of travel back the periphery in the case of

66:08 causing rashes and causing really painful, rashes and certain bands across the body

66:16 associated with just that one single spinal one side that thus the body.

66:22 viruses can also be used a When I said that damn tries in

66:29 spines are acting sort of like independent and synthesis by. So this is

66:37 , but this illustrates on the ride that end? That it did expire

66:40 your Paul arrival SOMO complexes. So have my to Congress, and you

66:45 a Paul Arrival Sobel complex system does necessary or the local bio synthesis so

66:52 can think of these units, although connected to the big body. The

66:56 that the whole damn drive the whole , these individual spines a someone of

67:02 biochemical bias synthetic units. That means decisions can be made by the spine

67:10 tracking with the rest of the But once again, just keep in

67:15 that this is a complex process. Intel's usually activation of thousands of decent

67:23 both an excited or anything inhibitory And the plasticity processes we discussed is

67:29 activity dependent process. That means, say, if you are memorizing

67:33 if you're developing that pathway, the between those neurons of those pathways done

67:40 , and it expires. May increase number may increase insides. This is

67:46 kid independent process. If you don't that title anymore, you're not exercising

67:52 anymore. Those synapses may weekend. synapses may go away. It always

67:58 , even for motor tasks. Cognitive , some plastic longer with motor tasks

68:04 but even motor taxes for you forgot to play tennis after hold the racket

68:08 . It may take a few Once you learn, it's because your

68:12 that learn how to hold the racket play the times are now weekend because

68:17 haven't exercised for a while. talents you're coming back to Tennison.

68:21 re build these pathways, you re the Salar sisters dendritic spines and

68:29 and the dream expires. This is final slide of the day the dude

68:35 here from the normal infant shown on left and from a mentally retarded infant

68:42 on the way. So, it is suspected in an autism spectrum

68:49 . And there is ah syndrome called X Syndrome, where one of the

68:55 marks off these neurodevelopmental and neurodegenerative disorders then are abnormal shapes. Abnormal numbers

69:07 structures of the different expired structure equals , function, equal structure. Both

69:15 inseparable. And so you can see by changing the morphology and the number

69:20 spines, the processing along this complex down dried and you're on is going

69:27 be very different on their four, in conditions such as autism spectrum like

69:38 . I think he think to keep mind is that the image on the

69:41 you have redstone access that are GABA , and these inhibit there is an

69:49 and green synapses on the same cell are glued a mattress actress and those

69:54 excited tourists. An absolute so when see is that these dendritic spines that

69:59 see on the last that are expressed the dendritic trees of endurance there,

70:07 by thousands off gabber allergic. The of looting, lethargic, excited tourists

70:14 absence. So the job of this is to compute very quickly to

70:20 to pay intention to strong synapses, compute to way out that excitation once

70:27 an invention or innovation wins over depending on the type of task for

70:33 level of activity that is happening in brain. Okay, so when we

70:40 back, we're gonna, uh, talking and finish talking about narrows,

70:46 then we're gonna talk about glial So we still going to continue talking

70:53 neurons and glia. And if we're a little bit behind in our schedule

70:57 the syllabus and will get adjusted and we will catch up on the following

71:03 couple of electricity. So for I am

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