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BIOL 4315/6315 Neuroscience (18564/17642) - NEURO Lecture 03 History of Neuro and Neurons and Glia I - MO WED
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00:02 Welcome back, this is neuroscience. three, we're gonna finish talking about
00:07 history and move into understanding neurons and we stress last lecture how in the
00:17 three centuries the focus has been to different parts of the brain and different
00:24 of the brain that are responsible for functions, localization of different brain areas
00:30 their specific functions. In the light that we discussed expressive aphasia that is
00:38 by Broca's area receptive aphasia that is by vernon CAs area located here.
00:45 also talked about economic amnesia. global aphasia is. And so these
00:51 for with phases in the story, how broken dr Rocca has discovered Broca's
01:01 . We also talked about one of most famous patients in neuroscience and probably
01:05 psychology and psychiatry history, Phineas those science of psychology, psychiatry,
01:14 , they do have a lot of themes and so as well as neurology
01:20 neurodegenerative disorders uh and in this case because he needed to be patched up
01:27 well. The striking thing here and of the takeaways is that it wasn't
01:35 specific function that you would imagine like or sensory function like expressing something but
01:44 was more of a character, aggression being able to control yourself, changes
01:51 personality and those are the things executive that are related to the frontal lobes
01:57 the frontal lobe damage. And so then found out actually that there are
02:02 in the brain that are responsible for behavioral and personality executive trades and functions
02:13 the same time, we, like said, entering the world in the
02:18 century of cortical stimulation studies and that when uh different parts of the brain
02:24 being stimulated to discover whether responsible for motor functions or evoking a certain emotional
02:34 Charles. Darling of course, as know from your high school studies in
02:40 and also here or otherwise at the level is one of the big people
02:50 for the theory of evolution. And at the end of the 18 19th
02:57 , he has an ability to travel the Galapagos islands on expeditions and spend
03:05 amount of time in studying the local and fauna. And so he's very
03:12 in how different animal species and there subspecies and uh geography, local geography
03:22 the Galapagos islands, how they're all in the sense of how it affects
03:30 anatomy and behavior of the birds of turtles depending on the surrounding environment.
03:41 so this this this concept of this concept of adaptation, the survival
03:48 the fittest, the ability to adopt local environments. If you may,
03:54 anatomical plasticity and behavioral plasticity. In areas, you may need to have
04:01 longer beak to get to the If you're a bird. In some
04:05 , you may not need to have longer beat in some areas you may
04:10 to underwater show color to attract a and in other areas. Birds would
04:18 that also use color to attract their and turtles. He will start studying
04:24 migration as well in the islands may small changes depending on the local environments
04:30 the procreation with the generations and the entrenchment off the changes dictated by the
04:40 . So behavioral trades, some are , others are distinct of course.
04:47 what I mean by that is that animals that pay attention and whose brains
04:54 occupied with certain behaviors. So humans have very nicely developed visual system that
05:02 will learn throughout the scores the entire from the retina to the neocortex individual
05:09 . But so will have the non primates and monkeys will have very nicely
05:17 visual system and the anatomy there is certain map that actually represents a visual
05:25 of the world all the way from retina. A point by point we
05:30 it retina topic map a point by map of the outside world that is
05:36 in the exhibit a low been the visual cortex and there's a certain structure
05:42 accompanies that point by point representation of outside visual world that you're observing.
05:48 that is actually reflected in the circuitry the function of the primary visual cortex
05:55 . Now other animals may use different and for rodents and for cats and
06:05 other animal senses of smell, somatic maybe more dominant rather than vision.
06:12 vision and visual sense is not as developed and in rodents you will find
06:19 maps that we call barrel cortex or pads map and that is that each
06:28 of these dots here which we will in the Samata sense of cortex off
06:32 rodents and all of the other animals have a pad that has whiskers.
06:39 these whiskers are very important for others they feel the environment by whisking around
06:45 sniffing around and when they whisk around do it with a certain frequency and
06:50 certain frequency as it helps them find food as helps them made, gets
06:58 into their brains. And the You have this anatomy where each one
07:06 these dots, we call it a . Each one of these barrels actually
07:12 a distinct whisker on the whisker So if you have five rows of
07:19 and seven or 88 whiskers in each , you will have five rows of
07:24 barrels And seven or 8 whiskers in one of these roads. And this
07:30 at the level of the primaries amount sensory cortex. And so it's not
07:37 the beaks, it's not only yeah of some skin between the digits that
07:47 animals swim. It's not only it's not only these things that are
07:53 but also the representation of how an perceives an outside world, what senses
08:00 dominating the environment, survival appropriation of animal that's going to be reflected in
08:07 max in the cortical naps And the in the new york cortex. And
08:14 particular we're talking about the primary sensory provision and primary somatic sensory areas for
08:22 sensation which a lot of it comes whisking around. And uh indeed you
08:30 not find this map in humans because don't have whiskers and we don't have
08:39 of whiskers, we have facial which we don't really use it
08:45 find food or feel the environment around uh unless it's very intimate. But
08:55 than that you wouldn't have this map the human cortex. And that's the
09:01 point is that evolution is environmental, nature, it's the genes, it's
09:11 and what you see on the anatomical changes on the outside. You
09:15 have certain neuro anatomical maps, circuitry that is reflecting the life and the
09:25 of different species. Now we are starting to understand in the 19th century
09:35 there are different parts of the brain for different functions. But we really
09:41 of just take the brain and visualize inside of it. and that is
09:48 the brain tissue is translucent and prior 19th century microscopes are for optical
09:58 the first microscopes that are capable of , having a resolution enough to see
10:05 single cell Become available in 1820s. that means that uh soma or cell
10:18 . About 10 micrometers for neurons is 10 micrometers in diameter. He now
10:25 microscopes that have enough resolution to visualize 10 Michaelm cell. But you have
10:38 obstacle. If you just take the the brain tissue or neurons and plop
10:45 under a microscope, you really cannot very much. Especially in the 1820s
10:53 tissues rather translucent. And because most the people are looking at this translucent
11:02 , they're not understanding. And they're whether the brain, the cortex and
11:07 cns is made up of distinct individual cells or whether the brain is some
11:16 of a continuous cytoplasmic entity with millions nuclei interspersed underneath the same side of
11:26 Mick cover up. So you have camps the ridiculous theory that holds that
11:33 nervous system is a sensation. It's network multiple nuclei but has cytoplasmic continuity
11:44 one place in the network to So you would say that Green matter
11:48 just all one thing with these multiple spread around them at the same
11:55 You also have a neuron doctrine And biology it's also known as South Theory
12:02 it's happening concurrently. This debate of to understand how different organs, not
12:07 the brain, but how different organs . Look at this microscopic level.
12:16 neuron doctrine argues that neurons or brain are discrete cells, cold neurons,
12:23 with just one nucleus surrounded by its cell membrane and here come into play
12:32 of the most interesting people that were in the descriptions of neurons neuron doctrine
12:40 even synopsis of synaptic connectivity, the , cortical networks and such. And
12:48 you first start with Camelia Golgi who 1873 in Italy um discovers what is
12:59 now a Golgi stain. He essentially that in photography at the time.
13:07 you were taking pictures, the only that you were doing that you would
13:12 to have silver nitrate stains and you to develop the pictures using the silver
13:19 stains and photography. So he decides apply what is being used as as
13:26 chemicals and photography and photo development and , I'm going to apply these chemicals
13:34 the brain in a different way. that's the beauty of being a scientist
13:41 medical doctor can never do something like applied or do something in somebody's brain
13:48 several different ways to see what happens stained as human brain several times.
13:55 , postmortem, Yes, but in in living tissue. No. And
14:00 this is all done. And of in vitro, in viva is in
14:05 whole animal. In vitro is outside animal, it's an isolated brain and
14:12 slice prepared from that brain or something of that, a small network that
14:18 been isolated. Amelia Golgi then finds way that if he partially takes the
14:25 off the off the brain and immerses in the silver nitrate stain when he
14:32 the brain and develop said sort of similar techniques like in photography, he
14:41 these beautifully looking neurons with very complex . So he revealed the selma's of
14:49 neurons. He reveals all of the of these neurons, the dem rights
14:53 the accents in full, but only fraction of these neurons, one too
15:02 percent of europe's absorb the silver nitrate and developed. So what you're seeing
15:10 these pictures is just a fraction, small fraction percentage fraction of all of
15:17 neurons. Only a small fraction of get stained. Ra Monica. How
15:25 is probably the most famous stanish neuroscientist for Camelia Golgi. He's in his
15:34 studying and he's using the Golgi stain produces these beautiful images and beautiful drawings
15:41 neuronal networks. The very forward the interesting thing is that Camelia Golgi
15:52 actually despite having invented the stain that is very discreet anatomy for individual
16:01 Despite of that, Camelia Golgi is proponent of particular theory and Camelia Golgi
16:11 is a student as a proponent of neuron doctrine and even more so he
16:18 about how individual neurons connect with each and how these connections are plastic.
16:26 he's very, very forward thinking and doesn't exactly know how they connect.
16:31 Sir Charles Carrington is credited with going deeper and coining the term and describing
16:39 term called the synapse. And that's location where essentially communication between two neurons
16:46 place a very specialist location. So their rounds visible. You have Golgi
16:57 . Emilio Golgi publishes a method and really really advanced microscopes that can actually
17:08 the actual sin assets. I'm not until 1950s. So although those microscopes
17:16 had enough of the resolution to resolve cells to show you the hundreds,
17:22 processes axons, even external terminals. could not have enough resolution to visualize
17:28 actual synapse. You needed to have more powerful microscopes. Almost 100 and
17:33 years later, 100 and 30 years here are some of the drawings by
17:40 Kahala and you can see that his are still being published to this
17:46 His beautiful prom. It'll cells in cortex that have dem drives done
17:52 so depicted and brown and toxins are in black and think look at how
18:00 cool it is. So he postulates the signal somehow goes into the so
18:09 and then the signal comes out of Selma's. So he's postulating that most
18:14 the input is shown by these black coming in from the adjacent cell
18:21 You can see these black arrows are done rides and Selma's and then the
18:30 accents which are the outputs are carrying information to yet other cells with these
18:36 black Arabs there is a directionality in . There is a hypothesis that gun
18:46 and some absorb the information input received input and that the axons carry the
18:55 . It's actually true to this very detailed descriptions. He talks about
19:04 as well, 19 oh six Nobel given to both of them familiar Golgi
19:13 harmonica hall but they remain rivals to end and community Goldie still believes in
19:20 ridiculous theory. So I use this an example of how you actually,
19:28 you're doing research first of all, and research gives them an unprecedented ability
19:36 muck around and see what this team going to do to the brain and
19:43 discover something huge that is to this being used in the labs to describe
19:48 anatomy of neurons in the brains. science allows you to do that of
19:56 have a hypothesis and then that an lesson year to be learned is that
20:01 you're working with somebody you're respecting, say you're working with your mentor,
20:07 may have differences in how you understand science of how you understand the end
20:15 and that's okay too, especially if can win the Nobel prize for that
20:21 . So uh huh At that we still don't know that neurons generate
20:27 potentials. So although we know that have electricity by electricity, we now
20:35 these discrete units that seem to be with each other in a specific
20:41 We don't know what that action potential because we don't have a sensitive enough
20:47 until But middle of the 20th century detect that information, electro physiological.
20:56 nestle stain is another stand commonly used the brain. Uh yeah, discovered
21:03 France. And so and it's very for describing what we call the sites
21:11 architecture off the brain. And in case this you can see each one
21:18 these little blue dots, these tiny little blue dots is an individual
21:25 So why Golgi stain? Missile stain stay in all of the cell phone
21:32 , all of the knows all of glia. And when you see these
21:37 bands look like, that means that density of the south of these dark
21:42 is very high dancing and where you less of the darkness, that means
21:47 dead, there's less density and the the cells are stacked in that
21:56 And so this allows for another great . Barbadian Brotman to use missile stain
22:09 to describe the brain based on the of architecture and the site architect tonic
22:17 is that different functional areas are determined observing variations in the structure density,
22:27 architecture off the cells. So he's that if you come to a place
22:34 the brain that looks like good, has a different like one house That
22:42 three stories and six rooms in each . And then you come to a
22:49 in the brain that looks like it maybe six stories and it has 100
22:55 in each story. Then you would suggested those parts of the brain must
23:02 serve different functions. So when you your 1st 1st discovered it on a
23:08 scale by observing blunt trauma and injury missing pieces of the brain like in
23:15 area. Yeah or vernon cas area with Phineas gage massive trauma to the
23:24 . Now, instead of that, going on a microscopic level. And
23:28 saying, let me look on a level how these cells are arranged
23:34 Because that means a lot house with stories and 15 hallways and 15 rooms
23:42 one thing a house with three stories two Hallways and 15 rooms is a
23:48 different way that you navigate through the . It's a completely different way how
23:54 people may walk through that house in certain amount of time? It's
24:01 The rooms are two separated, maybe there is too many hallways and so
24:05 and so forth. And so you to think about that as an analogy
24:09 different networks in the brain and because have different structure packing densities,
24:18 they also have different wiring and connectivity they sub serve different functions in certain
24:25 of the areas of the brain described dr Brotman is still very widely used
24:31 every day, neuroscience and science and languages. So what we talked about
24:40 that standard light microscope later. go ahead. Well, your
24:49 What is the gold you staying actually ? Yeah. The Golgi stain.
25:01 don't know what exactly stains. Yeah a very good question. You know
25:08 answer. Let's look it up. so great question. I have to
25:17 back to him this one. Oh I want to say that it's non
25:27 picks up. It gets picked up neurons. Not certain if it finds
25:32 anything in particular. But I'll have get back to you because it doesn't
25:37 to one subtype of this neuron. just kind of a scattered throughout difference
25:44 that's the nerves. So. Uh . In other words it's not a
25:54 receptor that is finding to that would specific to one subset of subclass of
26:00 . But I have to get back you if somebody is looking it up
26:03 we speak about it you can you try him in Like Microscope has a
26:13 in advance times of about 0.1 micro . So originally you could see 10
26:19 and later you have 100.1. My increase the resolution by a lot with
26:24 space between neurons and the space and sin absence between the synapses. Because
26:32 actual physical space between one neurons. terminal and another neurons done dr for
26:41 This physical space and that physical spaces nanometers and you cannot visualize that using
26:50 light microscope. So instead of that go to like microscope. And that
26:57 get developed until Late in the 20th . Almost middle of the 20th century
27:04 electron microscope now allows you to visualize sin absence. And so what you're
27:12 here is you're seeing this that is dan which stands for dendrite and this
27:20 that you're seeing here right here, little bit in green. It's called
27:25 dendritic spine. In each one of spines is depicted here, it's like
27:30 little outgrowth that you see from the name dendritic shaft. And on these
27:38 spines you with C. PTSD which for possum attic densities which are synaptic
27:47 posson optically that will contain higher densities receptors. And these receptors are chemical
27:57 well educated receptors. They are juxtaposed the pre synaptic side shown here on
28:04 right and in red which is the terminal. And those red dots that
28:10 seen. This red dots are vesicles they contain neurotransmitters which are chemicals.
28:19 so you can see that the acts an excellent terminal comes to the past
28:23 density. That's where the neurotransmitters and vesicles will fuse preseason optically here on
28:31 right. The neurotransmitter will be released the synaptic cleft which is this 20
28:38 space between wonder on and another and the chemical will bind to the receptors
28:45 the bar synaptic density on the boston side on the down dried. And
28:51 as you can see this damn And dendritic spines come in many different
28:56 and forms some of them are Some of them are more mushroom
29:03 And so they're called a stubby a thin spine. The mushroom shaped
29:10 . The arrangement of these spines and synaptic connectivity in normal arrangement of these
29:17 is very important for normal brain Okay this is a view of uh
29:29 advanced microscopes. You have come focal . Now you have a way to
29:36 neurons without using the stain. But and still in many ways you need
29:41 different stains. Not to visualize the of neurons but to visualize where specific
29:47 specific neurotransmitters are located. And this a three dimensional representation of these dangerous
29:56 . And these days we can visualize using another technique that's called differential infrared
30:03 microscopy. Okay. Or I. . D. I. C.
30:09 IR microscopy. And in this case is depicted here is you place a
30:17 of the brain underneath the microscope and are the eyepieces through which you could
30:22 observing the tissue underneath. And if went directly into your eye pieces you
30:29 see much. It would be So you'd have to use a
30:33 And instead the signal through the mirror gets sent to the infrared camera and
30:41 infrared camera using differential infrared contrast and series of mirrors here and filters produces
30:52 where you can visualize individual neurons without any state. And so what you
30:58 here this is a setup that is in my lab another building. And
31:05 we used to do the slices and them underneath the brain, you're not
31:09 visualize the slices. But then you then use the micro electrodes, these
31:14 micro electrodes using which you could approach cells and record electrical activity or stimulate
31:22 cells and stimulate the networks of the with electrical activity. And so a
31:28 of times this is we're talking about technique which is infrared imaging of the
31:34 issue. But in general this type technique of recording from the south while
31:39 them or recording in vivo recording electrical is referred to as electrophysiology or
31:49 So the current view is of course have uh view that is trying to
31:57 all encompassing by that. I mean have a macro view and this macro
32:06 allows us to understand what different lobes responsible for. And we also have
32:13 micro view microscopic view in the molecular and even the genetic view and the
32:22 view is that inside different cells and different synapses. And then did experience
32:29 will have different molecules, you will different subsets of receptors, different subsets
32:36 neurotransmitters that different neurons use in different of the brain. The ultimate holy
32:45 of neuroscience used to non invasively understand on a single cell level while also
32:56 it at a whole brain or a level. We're not quite there
33:01 We can non invasively observe activity in brain using FmRI, which is functional
33:08 resonance imaging. We can also observe activity using what is shown here using
33:16 and emission tomography or pet scanning pet images. But those techniques do not
33:25 us a resolution of a single Those techniques do not give us a
33:32 of a single synapse and that's where you have to rely on basic
33:38 If you want to study activity of single molecule single sent out for single
33:46 non invasively, it is very impossible do in humans, especially when you're
33:53 about C. N. S. experimenting. So obviously this is the
33:58 science part in a in the What you want to do is in
34:03 clinic, you want to diagnose the cause of the disease because when a
34:12 comes in with symptoms, whatever the are, that's that's not the
34:17 This is an expression whatever causing these , whether it's genetic, chemical traumatic
34:28 the first thing that doctors will do of course, after they inspect you
34:35 at you superficially, they look in blood and if you're complaining of certain
34:40 in your head, are you having problems with pain and migraines or something
34:47 that. They may do one of cans and this is non invasive technique
34:52 look at what your brain is And of course to look if there
34:57 any damage in the brain grows damage not at the level of the single
35:01 . And so if you look at and a person is looking at words
35:06 the exhibit a low where the visual from the ice is going through the
35:11 of Logan, the primary visual cortex going to be most active when the
35:16 is listening to words, you will more of the temporal lobe and also
35:21 aphasia area, vernon cas area which be located right here. If you're
35:27 words, which area would you then expressive Aphasia would engage Broca's area,
35:32 also engage the motor cortex which is more, you know the front
35:38 And if you're thinking of words that can see the completely different areas of
35:42 brain get engaged. It's not allowing the primary sensory areas of looking or
35:50 , looking, listening, okay, speaking but it's actually different areas of
35:56 brain that we got engaged And quite get a question here. So does
36:02 mean that we can only use 10% our brain? And the answer is
36:08 can use only 10% of your friends you want to. You can use
36:15 of your brain. You can use of your brain and some really bad
36:20 , you can use 100% of the but that would mean epileptic seizure.
36:27 there is no such thing that we use 10% of our brain as its
36:32 90%. You just tap into that neuroscience and all the rest of the
36:39 and the reality is a different tasks all different areas of the brain and
36:47 we multi task, when you when you're listening to something, you're
36:51 and like your emotional and all of going on whatever efficient all of these
36:58 parts of the brain get engaged and They interact with each other and at
37:03 point it could be 10% over it's active almost. So yeah,
37:11 ultimate is to be able to walk the clinic and to get your Fmri
37:19 your pet scan done and to visualize noninvasive rent at a network level with
37:30 gross mouths while at the same time and computing with every salad, every
37:37 story, we're not there. But is I think the task that is
37:44 to get solved this century, we understand activity in the single synapse by
37:50 end of the century and we'll have tools to understand it at the level
37:54 the network noninvasive able to that's a . Mhm Okay, mm. The
38:10 year is Each function is observed by than one neural pathway. Okay,
38:34 so that means that there is redundancy the cns and that's for protected reasons
38:42 one pathways damaged others may compensate. in the beginning when you didn't have
38:48 sensitive tools that would make the localization brain function quite a challenge because you
38:55 several pathways that can lead to the result. And even several anatomical pathways
39:00 responsible for processing same or similar sensor , emotions also have localization. And
39:10 you have temporal lobe epilepsy or you micro stimulation of temporal lobe and certain
39:16 areas in the brain, you can vote the same emotions that you would
39:21 and you're experiencing joy or fear or sadness and the brains are smart and
39:32 mass that you're seeing this map is virtual reality and then the map gets
39:38 in virtual reality and it doesn't mean the map gets bigger but the activity
39:43 gets a little bit different and you see more right here on the ride
39:47 more orangey and more of a spread activity. So even even immersing one
39:55 virtual reality has an effect on the function on the brain maps that are
40:02 by these external stimulus. Okay. functions consist of multiple processes that occur
40:11 specific areas of the brain. We imaging studies that reveal different processes.
40:18 called an elementary operations such as looking words we have processing both in serious
40:24 in parallel. That means in It means that it's hierarchically more
40:32 Your retina doesn't understand the outside world way your primary visual cortex does.
40:39 there's a hierarchy and each synaptic junction is a complexity and the processing that
40:47 all the way to the neocortex and the association areas of the cortex and
40:53 parallel means that there are several There are two eyes there two
40:59 those basic examples of parallel processing. you make a right and left and
41:05 don't lose the entire half of the field visual that let me field,
41:09 you lose one, I In fact lose periphery on one side, peripheral
41:16 vision. Even simplest mental activity requires of processes and multiple areas of the
41:23 . Such processes appear introspectively seamless to . We don't often think about multitasking
41:31 how many parts of our brains are . And sometimes we just get tired
41:36 fall asleep and now our brains go a different rhythm and they're still
41:42 So if you measure brain activity and you look at the brain maps,
41:46 just the brain maps are still the motive function is disconnected. So
41:52 you're dreaming that you're flying, you're there in bed and fluttering yourself up
41:57 down. You're just dreaming. You're , the motors cut off the motor
42:03 . But all of the kid in brain and imagines of dreaming and replace
42:08 , you will see that we will it. So it's not like when
42:11 go to sleep. That's from nothing in the brain. Uh There's
42:19 specialists of the nervous system, There a couple of questions and I often
42:24 about that neurologist as an MD. interested in diseases of the nervous
42:29 It's a person that will for example you have a family member that has
42:36 that has Alzheimer's disease. Parkinson's disease neurologist is a person that is going
42:43 help you with a diagnosis of that . And treatment of that disease was
42:50 medications difficult psychiatrists is also an Is a mood personality disorder. Person
43:04 is the surgeon of the brain and cord. So anything to do with
43:10 cord surgery and these are by the 10 Year residencies to be a
43:17 Um you have to really train yourself quite often you don't get to do
43:25 surgeries in the hippocampus and you know and then in the spinal record and
43:31 typically specialist on spinal cord surgeries or stem surgeries for cancer surgeries like we
43:41 eliminating cancer tumor formations from the Um You're a pathologist can be an
43:52 or PhD and I know a couple very successful ph D. S that
43:59 departments at the hospital's pathology department because are now looking at the tissue taking
44:07 samples of the tissue to rely. say you suspect that there's a glioma
44:14 real blast um a tumor life information the brain and and uh and uh
44:24 the surgery, see that too much eliminated. You're going to take a
44:29 of that tissue and you're going to it under a microscope to understand that
44:36 better. Oh, so there's also of course that you would be studying
44:46 neuropathologist, not just the anatomy and in the anatomy and histology of the
44:53 , but also markers. And as said, the levels of analysis and
45:00 goes from molecular all the way to for molecular similar molecules cells, networks
45:10 systems that are made up of many behavior which is coordinated typically by several
45:19 and cognition, which involves many different of the brain. An experimental
45:26 you have many different areas to indulge and explore depending on what really interests
45:34 , whether it's a chemistry or whether electric, electricity, electronics and physics
45:41 whether it's psychology. So my primary originally as neurophysiologist, no pharmacologists.
45:51 you're anonymous. And that's how I trained as a classical nure anonymous and
45:59 poking brain cells, applying different understanding trying to understand brain function,
46:07 and chemical about brain function. Also quite a bit experience with molecular and
46:14 neuroscience in the past, but mostly collaborative projects. So I just put
46:20 there for you because neuroscience actually can applied in many different fields and it
46:28 not be listed here, but it be for example neuro rehabilitation. And
46:35 list is maybe a little bit longer you to see that even for
46:40 a nursing school. If you become nurse, you could have a specialty
46:44 neurology or specialty in neuroscience or nurse which will allow you to specialize in
46:51 specific area. So, uh there's careers that benefit from Neurosciences, occupational
47:01 , speech pathology drug re have artificial . There's a lot of neuro people
47:08 went into artificial intelligence because it's kind a lengthen away and trying to understand
47:14 way the networks and the brain work the way the networks and the computers
47:19 the way the brain learns, the the computers learn. Can we make
47:24 computers learn? And these computer networks and be plastic. The ultimate is
47:28 make them as plastic and as advanced the brain tissues that are so
47:34 But of course it's a rigid issue it doesn't really delete uh something by
47:42 unless I press the button. Not true. You should say that last
47:50 other stuff without pressing the Button. , so this concludes our view of
47:56 of the history of neuroscience. And we'll continue here. We can start
48:05 about neurons and glia neurons are like in a chocolate chip cookie. Mongolia
48:12 like the dough glia and greek stands glue. And I think that can
48:20 have a cookie without chocolate chips? can but it's just you know,
48:27 just a sweet dough is boring. But can you have a cookie without
48:34 dog. Yeah. Not at Right. You just have melted chocolate
48:43 . So You want to have Glia is 90% of what the brain
48:50 actually neurons is 10% of what the is comprised of, 90% of the
48:57 until probably last decades studied 10 Of brain. Maybe that's where the 10%
49:04 the brain comes from. Because 10% the neurons is, you know,
49:08 Smith of using 10% of the And then what we know about the
49:13 of how we visualize it now non in viva. And of course in
49:18 experimentally again and the brain is mainly the state. And we talked about
49:27 just like the the rain in spain family in the plane neurons. You
49:43 everything about them because you know everything cells. But there are certain things
49:48 are different in neurons, certain things you don't know about. Maybe it's
49:54 things that you're gonna learn about in course. Basic things that has a
50:00 soma as a nucleus, wow, in the main source of energy and
50:10 , wow. And that is That is very important. As I
50:16 to you, the brain, There's about 3% of your total body
50:22 It consumes about 20% of your total coverage. Yes, it sucks a
50:29 of a lot of goodies get sucked the brain to sustain the activity of
50:34 control center. Course you have other such as the golgi apparatus, smoothie
50:45 and expires. Make ridiculous pull the . Great. What is different about
50:51 cells is that these cells have accidents accidents in most of neurons are my
50:58 . So because neurons produce action potentials they produce electrical activity and that activity
51:04 generated at the acts on initial segment located very close to the selma.
51:11 accent is insulated just like any other . I mean the reason for it
51:17 you want information from this mouse to the information on your computer. And
51:26 I were to strip all of the off of it and expose the wires
51:32 touch the wires, I may get . But also part of that information
51:38 not reach the computer. It would unstable. And so just like with
51:45 wires, accidents are insulated and they're by mile and sheets that are flown
51:51 glial cells. And you learn their specifically by glial cells called ligo dangerous
51:58 . The other thing that's different about is that they have these dendritic spines
52:05 you can say well okay so hair while hair cells are sensory neurons but
52:10 have cilia, you'll say well there's other cells in the gut that will
52:15 micro cilia and that sort of it's of a different then that expands our
52:22 to neurons and dendritic spines. They plastic so you grow spines. You
52:29 them during the development. You strengthen make them larger. You we can
52:34 them smaller and get rid of them just during the development but also in
52:39 adulthood. There's one thing for sure that we have finite storage in our
52:46 . We cannot store all of the that would alarm in our lives.
52:51 a lot of that information to very . Very important information gets segmented into
52:55 we call a long term memory and term memory storage and a lot of
53:01 is intertwined with other senses. And may not have that long term memory
53:06 a long time until you smell something you hear the music and you're
53:10 oh my God, somewhere off You know like I remember this and
53:17 you have that event that happened that's to that song. You know?
53:22 uh but other things you'll forget forget the names of the people that were
53:27 . But the feeling maybe there and key people that maybe are still your
53:32 from 2016 you'll remember. But it's finite and and that's why you have
53:40 synopsis that are growing certain synapses that going away, The ones that are
53:45 for being strengthened and they're becoming more and the ones that are not,
53:50 going to win. So you have lot of plasticity at the level of
53:54 synapse system, You have these specialist terminals that will contact not only the
54:00 something that expires but also the soul of these neurons and that's where you
54:05 have the electrical output. The first here and then when it reaches the
54:12 panel terminal from a different accent that here it will cause the release of
54:17 neurotransmitter. So its electrochemical communication. This is just very basic review.
54:27 genes transcription, you have RNA you have export of RNA shuttles from
54:36 nucleus. You have a gene from transcribed into RNA that gets spliced into
54:43 journey. And then this is the or burdens for chemical lists all the
54:53 stuff. You know. Spice variances be an important or interesting subject to
54:59 up here because splice variants is what us sort of a variant of each
55:06 . There are plenty of normal splice . These areas that get uh excised
55:15 N tron areas and the Exxon areas placed into messenger RNA. So during
55:23 slicing process you have variants which are . We think differently slightly slightly different
55:36 but there's also pathological values. So you during the slicing process did not
55:42 the message correctly, it can become source or cause of certain pathology in
55:48 case neuropathology and neurological disorder. organize files, rough and the plasmid
55:57 polar ribosomes ribosomes and you have messenger that encodes proteins and some of these
56:06 audience become freely floating and other proteins numbering associated. So we're gonna talk
56:14 lot about the membrane associated proteins because will be our channels membrane channels and
56:21 receptors, G protein coupled receptors as as receptor channels. Yeah, it's
56:35 post genomic era. So we can profile differences in gene expression at this
56:42 scale. We can again take what called a micro array. And now
56:49 we know the code, we can a synthetic D. N.
56:52 You can see these advertisements. Hey want the sequence designed for you.
56:57 like some sense 11 cents for base will design the sequence for you.
57:02 you have this synthetic D. A. And you can take this
57:05 array that will have Little while. imagine that this tiny little while.
57:09 we'll have 30,000 of them. Each of them represents a specific synthetic DNA
57:15 . And it's like a sophisticated in way you can think of sophisticated piece
57:21 velcro, it means that if you something that is complimentary in sequence.
57:30 , this is specific sequence. And you put something onto that specific sequence
57:36 will stick to it. That means you have that gene expressed by that
57:41 of tissue by that brain. And will also tell you whether you can
57:47 you compare one brain versus another brain maybe one brain will have a lot
57:52 of that uh specific gene of And so you can use these micro
57:59 to get a bird's eye view on is happening. For example, you
58:04 to compare normal brain process of disease and you will apply samples from normal
58:11 brain one versus disease brain brain to you're gonna look and study this micro
58:18 And what is going to reveal to . Let's say you have 30,000 genes
58:22 interest in the as wealth. It say that 5000 genes changed.
58:30 that's a lot. 2001. Top . Okay, I want to look
58:37 the ones at one time. 10 them on top 30 times maybe.
58:45 interesting because one of them, my studies. Okay, I have to
58:50 at that one. So, And you will say, Okay, so
58:57 do you know that if you have change in 200 genes for 2000 genes
59:02 that changes, twentyfold. that that really important. In other words,
59:09 talking about a nonlinear system. The is nonlinear system. The diseases are
59:15 necessarily linear in any way that you think of. And and here you
59:21 this this this this this problem because gene that may be changed on the
59:26 bulb maybe is the most important one you're chasing the ones that change 30
59:34 because it's nature and things sometimes when change don't necessarily again represent linear
59:44 But overall, if you have a feeling, let's say that the gene
59:48 got exploded 20,000. It's also the has been shown in that disease to
59:53 involved and it's also this and God you're on to something. You can
59:58 it down let's say two Instead of genes now to five candidate genes to
60:04 candidate genes and maybe really get to to the heart of the problem or
60:09 of the main problems and they will again. Yeah that's very basic.
60:15 have smooth er protein folding calcium You have a lot of calcium that
60:20 released from smooth and the plasma in . So we'll talk about how you
60:25 calcium induced calcium release inside the South the calcium inside the South neurons is
60:32 only an ion is also a secondary , it is very tightly regulated how
60:38 of the sata solid or free floating . The South actually have Golgi apparatus
60:44 be responsible for post translational processing, sorting to his final destinations mitochondria and
60:51 Krebs cycle that you have learned about forgot. Yeah. It's important.
60:56 have to memorize Krebs cycle. Can imagine if you have to memorize Krebs
61:00 now for biochemistry? Uh That would difficult to be a real challenge.
61:06 at some point you have to do uh And you get in the end
61:11 T. P. Of all of goodies. Dietary and stored energy sources
61:16 and sugar fat gets transformed to peru acid oxidation produces A. T.
61:22 . And CO. Two and has specific structure of this christa inside on
61:28 double membrane has a very negative charge the membranes. But that doesn't contribute
61:36 to the plasma number in charge of neurons. But nonetheless mitochondria is extremely
61:42 because of what I was telling you . The amount of energy that gets
61:47 by the brain that gets used by brain in relation to its proportion overall
61:55 to the body size, its size proportion to the body size. Okay
62:04 I want to talk to you about lipid bi layer but I think that
62:10 this could be a good stopping point . Like to show you a short
62:15 and start talking about the fluid mosaic and in general how different aspects of
62:22 plasma membrane proteins and even large receptor in the plasma membrane a very
62:32 And we moved through neuronal membranes and move on demand and they can move
62:38 lightning speeds and changing the strength and and function of the synopsis.
62:45 so that's it for today and I see everyone on Wednesday either here or
62:54 zoom. Have a good evening.
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