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BIOL 4315/6315 Neuroscience Mon Wed - NEURO Lecture 03 Neurons and Glia I
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00:02 This is lecture three of neuroscience. the first lecture of neurons and glia
00:07 comprise about 10% of the total cell in the brain and glia comprise about
00:13 of all of the total population of cells in the brain. And I
00:18 said the ironic thing is 90% of probably up until 10 years ago was
00:25 on neurons. And 10% of neuroscience really exploring to see what we're
00:31 And glia is really coming out. very interesting types of cells. New
00:37 and glee are coming out. We've in the last 30 40 years the
00:42 of neurons in the diversity of neurons have. We have probably over 100
00:49 different subtypes of neurons in the N. S. And they have
00:52 different properties of what they do, they process information and how they convey
00:57 information to other neurons. And we seven maybe six different subtypes of glial
01:05 and some types of glial cells. at first the description is like neurons
01:10 like chips in the chocolate chip And glia in greek is glue is
01:17 dough. So you would say well know does just plays a supporting
01:21 But we're finding out that glia actually very intricately involved in communicating with neurons
01:28 allowing for neurons to find their home the early development of neuronal migration,
01:36 synoptic genesis or growth of new synopsis so on. So playing very very
01:41 role. So plus you couldn't have chocolate chip cookie without a doe it
01:47 be called chocolate or a sugar cookie guess. But I think the most
01:53 is when you have both together uh game and the brain is mainly in
01:58 stain and staining different neurons and O chemistry and immuno history chemistry is
02:06 allowed us to define a lot of subtypes of neurons based on their
02:12 But the really subtype, these different of over 100 2040 neurons that I'm
02:18 you about. There was more techniques needed to be involved. Neurons are
02:24 other cells of a few of these are basic and kind of boring maybe
02:30 that neurons have these specialized axons and eventual segment here axon hillock is where
02:38 potential gets generated. The action potential conducted down the axon which is the
02:45 ated process of the neuron that means it's insulated and so that electricity from
02:51 selma can be delivered. That same of charge can be delivered to distal
02:56 to which may be connecting. And could be a few micrometers away.
03:01 could be centimeters away. It could tens of centimeters away even though there's
03:06 very long axles. There's also very axons that come in the spinal cord
03:12 innovate the muscles and the lower For example, another thing that's different
03:18 these cells is they have dendrites and these processes And dendrites as we discuss
03:24 specialized structures, anatomical structures that we dendritic spines and dendritic spines. The
03:32 plastic structures in neurons and they lend to neuronal plasticity. So they can
03:43 their size. There's a number of spines that increase with activity. Or
03:49 number of dendritic spines can decrease with or they can be weakened when there
03:55 no activity when there is a lack activity. So neurons get contacted by
04:01 axons. Axons will reproduce the same potential that will produce the axon initial
04:08 will cause neurotransmitter release mostly on the and under. Den drives off neurons
04:14 inside neurons. You have the typical with a nucleus with the mitochondria and
04:21 apparatus polarized to some smooth into plasma particular, rough in the plasmid
04:28 Um all of the things you see other selves, this is some very
04:33 things jeans get transcript ID. you have transcription of genes into an
04:42 . And RNA gets translated into Uh you have this exon and intron
04:51 in the genes and during the transcription have a replica of that made into
04:56 R. N. A. And you have these regions that get removed
05:03 the messenger RNA which then gets basically into protein. And so this splicing
05:11 something that makes splice variants During You have slightly different variations and splicing
05:19 splice variants genetically is a normal Maybe that's what we're all slightly different
05:25 we're splice variants of one another. our gene codes. And you also
05:31 splice variants that can use the So, abnormal splicing of the message
05:37 end up in an abnormal protein or that has abnormal function, which can
05:44 to a disease of pathology. So messenger rNS are thought to be in
05:51 nucleus, but from the nucleus, lead through the nuclear pores and these
05:56 that shuttle them around and they then determined to either the free floating proteins
06:03 proteins that attach themselves on the plasma . And most of the discussion in
06:09 course will focus on the receptor proteins receptor proteins are both protein channels and
06:18 g protein coupled receptors that are membrane proteins. So we will talk a
06:24 about the receptor proteins and the second section of this course, it's a
06:32 genomic error. So we know the and there are different, as I
06:38 , levels by which you can study . There's different levels by which you
06:43 look at the function of the You can look at a single molecule
06:47 . You can look at a specific subtype, you can look at one
06:51 of the brain. You can look see what's going on in the entire
06:56 and one of the useful tools in post economic area are these micro
07:03 gene micro race. And they're really because you can have sort of a
07:10 eye view or a holistic view of of the jeans or the jeans that
07:17 have changed as a consequence of some of genetic mutation or disease. And
07:24 way that these micro rates are done that we produce synthetic DNA sequences that
07:31 know will have to bind to the sequences that will come from the actual
07:36 . And these micro rays can contain think these days up to 30,000 wells
07:43 each well will contain a piece of specific synthetic DNA coding for something very
07:49 . And so if there is a of a substance that is complementary and
07:55 buy into this sophisticated piece of velcro you've designed it will stick there.
08:01 it's not it will not. And now you can have this holistic view
08:07 the brain. You can take brain one and brain number two, you
08:12 put vial of messenger RNA. From brain one labeled in red and from
08:17 to labeled in green. You can the applied uh solution to the
08:23 N. A micro ray. And genes with reduced expression brain too will
08:31 red jeans with the will and the with will be yellow and jeans with
08:35 expression and brain one will be The nice thing about this is that
08:42 can look and see what genes were top and more genes went down as
08:46 consequence of let's say one of the is a normal brain and another brain
08:51 an epileptic brain. It's a great to look. But then it's also
08:58 of a macro view and what you see is 300 genes that went up
09:05 200 genes that went down. Which are important, The ones that are
09:11 uh the ones that are going you don't know because we don't
09:15 You now have to look and Okay, I'm studying epilepsy And I
09:20 that out of these 200 genes, know that out of these 300 genes
09:25 one thought for example, I know 20 of them are implicated in epilepsy
09:31 certain types of epilepsy. So let see if there's 20 are up regulated
09:37 . That's one way to approach Another way is we know about these
09:42 , what are these other 280 genes being up regulated or another 200 are
09:47 down regulated. Okay, so you do searches through literature if you're interested
09:53 studying epilepsy until you find maybe 10 genes of interest that this is I
10:00 this is what's really changing in these . This is my epilepsy model.
10:05 done research, I looked at the expressions to look at other articles and
10:09 like that and then I always say your mentor tells you we're going to
10:14 these two genes and you say, , unless you're ramon and said
10:19 I'm also going to study this third . But you have to convince the
10:23 you can do that. It's a these two and I'll say but I'm
10:26 interested in the third one but it you know 500 bucks to do um
10:30 know history chemistry and the third So it costs money to do resource
10:33 say well if I do these can I look at this third
10:37 I was like okay so so this a bird's eye view of maybe what's
10:44 with groups of genes that may be with the disease of conditions that are
10:51 up groups of genes that are going uh and it's possible through these micro
10:59 . I have a pretty good understanding what's going on. But then you
11:02 to hone in and study specific Study actions and things like that of
11:08 genes and proteins and everything downstream. creating uh proteins and organelles you have
11:18 and the plasma particularly we have protein but you also have calcium regulation.
11:23 it's a huge store calcium intracellular calcium apparatus responsible for or post translational processing
11:31 protein sorting side applies. And with membrane bound mitochondria, ian mitochondria in
11:39 goes through the Krebs cycle produces energy the form of A. T.
11:45 . And the brain consumes over 20% the total body energy. So it's
11:53 about 3-5% of the total body But it consumes over 20% of all
12:00 the metabolic energy. Everything we're eating producing is feeding the brain. So
12:10 often say that the brain is actually nonlinear system that's operating outside of the
12:16 of the equilibrium. Especially when you about equilibrium for you know metabolism,
12:23 size versus how much it needs. brain needs way more for its size
12:28 than than a lot of other And so you have obviously dietary and
12:34 energy sources, protein sugars, fat into piru vic acid. You have
12:41 , process production of a. P. And C. 02.
12:45 you'll see a lot of mitochondria and soma. And that's nothing surprising all
12:49 the Selma's cells and will have a of energy in our selma's. But
12:55 pointed out last lecture that you will mitochondria and dendritic spines also. And
13:01 why I said that in dendritic spines will have certain elements to do post
13:07 all work like smooth and the plasma . Um And you have some sources
13:11 energy like a teepee through mitochondria. why it makes these dendritic spanned some
13:17 biochemical independent units functioning slightly independent from rest of the dendritic shaft and the
13:25 of the Selma. Uh membranes in , plasma membranes are fluid. Isse
13:33 dynamic. So the cell membranes are rigid and they don't stand there like
13:39 concrete building. There's a lot of that's happening in the plasma membranes and
13:45 will learn that in the brain. a lot of movement within the plasma
13:49 . So you have the plasma membrane is comprised of the phosphor lifted Beiler
13:56 has the polar hydro filic head group glycerol that's the head and the hydrophobic
14:04 that turn into each other. And if you would apply for possible lipids
14:10 any fluid, they would essentially form uh my seals around like structures where
14:17 have the hydrophobic uh tails coming together the hydro filic heads facing either the
14:27 environment of the cell or the extra environment you have here receptor proteins,
14:36 proteins, Gallico proteins, sugars cholesterol you also have the side of skeletal
14:46 that are very important. And beside skeletal elements are also not rigid.
14:51 change their shape and their arrangement and changing the side of skeletal structure underneath
14:56 plasma membrane, plasma membrane is capable changing its shape and maintaining its
15:04 So let me pause this for a between the living machinery of the inner
15:12 and the harsh conditions of the outside stands the cell's plasma membrane as crucial
15:19 this barrier is. It's surprisingly push it and watch it move poke
15:26 enough and it might break and begin regroup. The lipid molecules of the
15:32 naturally assemble in a double layer because tails repel water as their heads attracted
15:39 in some cholesterol and a few carbohydrates you have the basic structure of a
15:46 membrane within these lipid molecules. We find different proteins which do various things
15:54 the cell. For instance, they signals from the world outside or they
16:01 nutrients and waste. So nature composes membrane with a combination or mosaic of
16:08 lipids, carbohydrates and proteins and these are not stationary. They constantly move
16:17 the structure, fluidly changing their The survival of all life rests on
16:26 veil of material, A supple membrane two molecules thick. So this reorganization
16:38 you're seeing here with with a stronger movement. It's something that can
16:46 Not necessarily because the cell gets mechanically or the can have that because you
16:54 mechanical uh receptors. But because there be a rearrangement of side of skeletal
17:01 and there could be a rearrangement of phosphor lipid bi layer. There could
17:07 movement of these molecules fairly fast movement the plasma membrane. So you have
17:15 that are trans membrane proteins there on sides of the membrane. They will
17:21 through this membrane and they will move really fast. They will move micro
17:26 in milliseconds. So they're like zooming of them are like zooming across the
17:32 . That's why you should visualize plasma as a dynamic fluid dynamic model.
17:39 should visualize and exp eines is something fluid dynamic plastic and change their number
17:45 change their shape and therefore you can their functional properties as well.
17:54 may I ask a question? Regarding the mitochondria. You had mentioned
18:01 there's concentrations of them in the soma dendritic spines. Are they also in
18:07 pre synaptic terminals or anywhere else? . Yeah. You will find.
18:12 you are correct. You will find and pre synaptic terminals. And so
18:16 is another area. And the cell requires energy and in this case it
18:21 energy is you're asking correctly for neurotransmitter and recycling of neurotransmitter vesicles and refilling
18:29 the neurotransmitters. And part of it done through acidification and part of it
18:34 requiring energy in the form of a . So let's talk about the side
18:40 skeletal elements. You have micro neural filaments or intermediary filaments and micro
18:46 . Micro filaments are comprised of active and they're the smallest side of skeletal
18:54 and they're the most dynamic side of elements. So you can prelim arise
18:59 molecules and make these long chains. you can depolymerization. You can cut
19:04 chains into shorter change and as you these active molecules you essentially can be
19:11 the very outer edges of the side skeletal lattice that is holding up the
19:17 membrane and giving the plasma membrane a shape. You have your affiliate mints
19:22 are approximately 10 nanometers and you have tubules the largest uh center skeletal
19:29 20 nanometers across. This is a through a Myelin ated axon. So
19:36 , what you're seeing is this is . And these lines here is a
19:43 of the Myelin that gets wrapped around sheets around the axon. That's what
19:48 seeing these lines. This part here the inside of the axon and inside
19:56 axon. You see these other lines here and we refer to these as
20:02 tubular highlands. And so these side skeletal elements are not only for obviously
20:09 the structure of the cell and the boundaries, the shape of the plasma
20:13 , but also very key for cellular . And if you have abnormalities inside
20:21 skeletal elements, if you have tangling of skeletal elements, you could have
20:28 transport. And transport is very important think of the soma as sort of
20:35 city utilities that distributes the gas, , your wifi and things like
20:44 And it needs to deliver that wifi your neighborhood and gas to your neighborhood
20:49 so on. So it's really important that you have these delivery highways that
20:55 properly functioning for all of these In this case, it's energy
21:02 proteins that get transported back and forth the ectoplasmic transport. This is a
21:10 that is looking at the fiber blast . So it's not a neuron,
21:15 a fiber blast. But it shows purple the nucleus of the fiber
21:21 And then yellow. It shows the lint stain. Right? So we're
21:27 at the micro tubules here and in , it's showing the acting. So
21:35 acting, we're looking at micro filaments it is very clear that these larger
21:41 of skeletal elements are really playing major role around the core of the selma
21:48 around the nucleus. And the smaller the acting elements that can quickly prelim
21:55 and d prelim arise. I'm located more distal parts of the cell where
22:02 would be really shaping the fine structure the plasma membrane. Now for Alzheimer's
22:10 or hallmarks of Alzheimer's disease, I a better slide that I will include
22:16 you uh that I want to And it's and it's this particular slide
22:23 I don't know. It's not showing full screen. Okay. What?
22:39 sir. Okay so throughout this course will discuss several neurological disorders and I
22:49 that if you have a notebook or you have some notes, if you
22:55 a page to Alzheimer's disease and that dedicate a page two, we're going
23:01 talk about epilepsy and there's gonna be whole half of lecturing epilepsy. We
23:06 talk about autism spectrum disorders. We touch on several disorders and as we
23:12 talking about neurological disorders. We also to start introducing a little bit of
23:17 clinical language that people would use. talking about neurological disorders. A major
23:25 disorders you have migraines show epilepsy, have a list of major neurological disorders
23:35 we're not going to be able to them all? Uh and today we
23:40 start talking about Alzheimer's disease. But is not the last time we talked
23:43 Alzheimer's disease. Today, we're gonna about certain aspects of Alzheimer's disease.
23:49 when we talk about neural transmission and , we will talk about other aspects
23:56 Alzheimer's disease. So when you talk disease in general, the first question
24:02 comes to mind, at least to , like what, what is
24:06 So now we know it's a disease the brain. Just neurological disorder.
24:10 not a disease of the living. does it occur? When does multiple
24:17 occur? Versus Alzheimer's disease. When the onset of epilepsy, autism versus
24:24 disease? Parkinson's disease? Huntington's So, Alzheimer's disease. When you
24:32 of Alzheimer's, you think of elderly And the part of the language and
24:38 diseases the onset or the prevalence. , when is the onset of the
24:42 ? Typically in Alzheimer's is 50 and , the prevalence. See increases the
24:48 you get. That means there's more with Alzheimer's disease percentage wise as they
24:54 older, what comes to mind when think about Alzheimer's disease? And when
25:01 envision a person with Alzheimer's disease? it a person that cannot walk?
25:07 it a person that cannot here, it a person? What is the
25:11 you're thinking it's something to do with . And quite often people think memory
25:19 not being able to remember. And you talk about dementia, memory
25:25 there's many other aspects of Alzheimer's Depression, anxiety. What what are
25:32 are these things like memory loss? don't remember. It's a symptom it's
25:40 a mechanism of action. Memory loss not a mechanism of action. There's
25:44 mechanism behind the formation of memory and of memory on the on the cellular
25:48 the circuit level. But when you and you complain of something to your
25:53 , I have a headache. It's symptom. All right. And you
25:58 headaches and you have migraines, which very different people. Confuse headaches with
26:04 . Migraine is actually disability. It's neurological disorder versus headaches. Migraines is
26:10 debilitating neurological disorder. Can put a out of commission for days versus headaches
26:17 can be treated with Advil and and painkillers. So, so Alzheimer's disease
26:24 is an older people? It's more the older you are the higher prevalence
26:29 Alzheimer's disease. Is it a part normal aging. Does that mean that
26:33 you're gonna lift 100 2040 you're gonna up with Alzheimer's disease? No,
26:39 a disease. It's not a part normal aging. What causes this
26:46 If you knew what causes diseases you start stopping them, Right? I
26:51 a gene for Alzheimer's? And by this coconut husk? And that's the
26:59 . No. Then you stop eating husk or you do something like
27:03 A lot of times we don't know causes of the disease. There are
27:07 aspects of Alzheimer's disease that are It means that there are certain genetically
27:15 component that makes you more susceptible. mean you will have Alzheimer's disease,
27:20 you're more likely. And then there sporadic onset of disease. We don't
27:28 why the person becomes ill. We know why a child starts having
27:36 And when you see the symptoms, you try to understand what is happening
27:43 the pathology or the impairments that are on the cellular level. Maybe if
27:51 in a clinic, you can do pet scan of the brain, you
27:55 do a cat scan of the you can localize the area, you
28:00 do other things. But with Alzheimer's , you have this symptomology and the
28:07 of cellular hallmarks of Alzheimer's disease actually big part related to side of skeletal
28:15 . And that's why I'm introducing Alzheimer's here. There's a normal neuro and
28:22 disease. You have to pathological One of them is formation of neuro
28:29 tangles, neural fibrosis to skeletal elements tangled up and we talked about how
28:36 it is to have these clear highways side of skeletal elements moving freely.
28:42 prelim arising. Prelim arising for plasticity transportation. So if you have the
28:48 , you have impairment of impairment and transport, that means you may not
28:52 able to deliver the heat? The to your dendritic antennas and that's gonna
28:58 bad news for that. Then drive of the south. And this is
29:05 you typically hear about. When you about Alzheimer's disease. Pathology is amyloid
29:12 and amyloid beta plaques a lot of they would be referred to senile plaques
29:18 this is really aggregation of normal aggregation proteins called peptides and then calcification in
29:26 local area. And this is not that plaque here that gets calcified.
29:33 starts impending physically on neurons and the sensitive parts of neurons to these senile
29:41 or or amyloid beta plaques. Is axon initial segment. An axon
29:48 As I mentioned, an axon initial is responsible for producing action potentials.
29:55 whatever reason, these plaques and then proximity of axon initial segment that accident
30:00 segment starts failing whether they're using some outside whether it's physical damage, inflammation
30:09 makes the axons very sensitive and affects action potential production. This is on
30:16 cellular level. So one pathologies inside south other pathologies outside the south on
30:24 gross level. And the final diagnosis Alzheimer's disease often comes postmortem. If
30:34 actually could visualize the formation of these early on? That's what the modern
30:40 is working on. Are there any markers. Is there anything we can
30:45 up from fluids that would indicate that person with onset of memory loss and
30:51 symptomology of dementia actually has Alzheimer's disease is it something else? Because some
30:58 these symptoms can be shared, meaning you have memory loss in traumatic brain
31:06 , but it's not Alzheimer's disease. , so some of the symptoms may
31:10 overlapping between different neurological disorders. You can have tremors in Parkinson's
31:18 you can have tremors that look like pill. Epic jerks and tremors could
31:23 confused depending on the actual expression with . On the gross scale. Advanced
31:31 disease causes massive shrinkage, neuronal It's neurodegenerative disorder, neurons start
31:39 The brain shrinks gray matter especially And that means that your cells and
31:47 cells are dying in the white You recall that the violated accent.
31:51 there's some connections there. Deep rooted are remaining advanced stages of Alzheimer's
31:59 Is the diseased brain fails to take of the body when the brain is
32:06 impacted with so many plaques and death shrinkage, you start impacting parts of
32:14 brain that are responsible for vital body , which is eating swallowing breathing
32:28 trade okay, so these these initial that that that people experience with ALzheimer's
32:36 that can eventually kill a person because brains are are shrinking and dying and
32:42 significant generation. So I'll make sure include the slide for you guys,
32:48 have it and you know, it's proper one Instead of this one and
33:00 little bit more about the spine. you have these dendritic spines have the
33:06 axon hillock initial segment where the action that gets generated, it usually will
33:12 its digital terminal. But on the it can send one called axon collaterals
33:18 communicate that information into multiple different cells it tries to reach the final destination
33:26 the axon. As uh somebody already there's mitochondria as you can see energy
33:34 and synaptic vesicles. The synaptic vesicles contain neurotransmitters called active zones. And
33:42 optical, you have the receptors that the buzz and the possum attic side
33:47 usually have the prostatic densities. That that there's aggregation of these receptor proteins
33:52 optically and they're placing themselves in a strategic position to very quickly be bound
33:59 the neurotransmitters. And this synaptic 20 nanometers is synaptic cleft is 20
34:07 and this is the part that Sir Sherington was involved in in describing uh
34:14 coining the term of of the synapse transport can be slugs of plasmid
34:23 You can have fast ectoplasmic transport. early experiments, you used the dice
34:32 in the axon and the tie with thread or fishing line uh and watching
34:42 fast this dye is going to travel the axon. So measuring the distance
34:47 the time by which that blue dye and you have radioactively labeled nucleic acids
34:55 more sophisticated ways later to look at . And we've also discovered there's fast
35:01 and terra great transport. Something from soma into the distal regions is mediated
35:07 Kennison. Like if you think about , they're a little kind of a
35:12 like arms that past these different elements the micro tubular highways. Retrograde lee
35:22 it's vesicles or elements of different organelles pertains, they get transferred transported back
35:30 dining. So there's like 22 services girls that way and lift goes the
35:37 way to trace. Where connections can found. We use uh labeling and
35:47 use what we call tracers. And are viruses that can act as tracers
35:55 viruses will climb along the cells. modern science can label these viruses um
36:01 to the advantage of labeling things or peroxide days like a died in this
36:07 you have an injection of horseradish So let's say you want to know
36:13 part of the brain, what what are connected to this part of the
36:17 . So you'll inject us di di taken them by the external terminals.
36:22 dyes are uh capable of retrograde transport they will from the periphery will be
36:30 retro greatly into the solos and that okay this patch of the brain is
36:36 to this nose. This patch of skin is connected to these nerds and
36:41 on and so forth. It's a useful technique. Some viruses are capable
36:47 . Some molecules dyes are capable of and terra grade and retrograde movement depending
36:54 the conditions and some dyes and molecules capable of transit haptic. So you
37:03 trace potentially from here all the way the next synapse, to the third
37:08 uh where these neurons could be And this is how we started discovering
37:15 the side of architect tonic methods. described all of the cells. Then
37:19 started using these tracers to see the between these cells to start describing the
37:27 of the highway map of the The dreaded spines, as we
37:34 will contain post synaptic densities by the Drian smooth and the plasmid particular um
37:41 to the pre synaptic terminals here. spine can have one synapse, a
37:48 spine can have three synapses and these are plastic and strength of these
37:58 their shape and their efficiency will very depend on the activity. Right,
38:10 this is another disease that we're going introduce today. So you'll have to
38:21 it down yourselves. We're gonna briefly about a disease called fragile X
38:30 fragile like in fragile on the cardboard . When you should think somebody had
38:36 fragile X syndrome and it falls under spectrum disorders and it said we're not
38:49 to talk much and as far as symptomology of fragile X syndrome, You
38:55 look it up yourselves but it's a reputation, it's early developmental mental
39:06 It has not only the problems that would see in autism like social
39:14 isolation and things like that. But also has more severe problems fragile
39:20 Kids often have epilepsy and often has . One of the hallmarks fragile X
39:29 and one of the models to study like syndrome is this impairment and will
39:36 in anatomy and there is a there a certain gene that is implicated.
39:42 don't have it on a slide so won't keep naming things that are not
39:45 the slide because it's hard to write down. But if you have an
39:50 in that gene this is a them from a normal in fund. And
39:56 is the good spine anatomy in a in front, it has a certain
40:02 , has a certain distribution as a shape. And this is from a
40:09 retarded brain or fragile X. And you can see that there's nothing
40:18 between the spine and animal. Dendrite hasn't changed itself that much. That
40:24 would be able to obviously say this very different from this. But dendritic
40:29 are very different. Their distribution and along the dendrite has changed the shape
40:37 changed and they seem to have these much elongated processes that are coming off
40:44 genetically and activity dependent processes in this it's a genetic impairment that can lead
40:52 mental degradation that can lead to these dendritic spines. But the way these
40:59 are shaped during early development very much on the different levels of activity sensory
41:06 , the psycho physiological stimuli that a is getting. A very important for
41:16 development of the spines. And and about that a single cell. This
41:23 a single neuron will contain thousands of , thousands of dendritic spines. Some
41:31 these dendritic spines are green, innovative glutamate axons. Glutamate is the major
41:39 turn neurotransmitter in the brain. Uh and everywhere you're seeing green is where
41:50 would have excited the synopsis and shown in orange is the major inhibitory
41:58 gamma and you know butyric acid or . And everywhere you see orange that
42:04 be inhibitory. Synopsis. Glutamate tries raise excitability neurons and de polarize these
42:16 ordering these neurons. You're excited, should fire an action potential, communicate
42:21 good news to the connected neuron and ergic. So these are glue,
42:28 from ultimate. These are Gaba ergic from Gaba. Gaba ergic synopsis are
42:35 . They're down opening activity in this the hyper polarizing this neuron and saying
42:41 , you sit still, you sit , don't fire in action for
42:47 This neuron receives potentially hundreds of inputs the same time excited to an
42:55 Maybe not all exactly at the same with a fraction of milliseconds apart from
43:00 another. This neuron has to make decision very fast decision integrates. So
43:07 is the integrated unit integrates information pluses minuses positive and negative inputs and
43:15 am I going to find action potential communicate that to Melanie. So you
43:21 imagine how important it is to have precise anatomy, distribution and structure of
43:27 good expands because structure also means function structures impaired function impaired building. That
43:36 the building structure is impaired. It's gonna crumble and fall down.
43:41 so it's very important that once you the number the strength the distribution of
43:50 dendritic spines, you now can integrate information and the processing capabilities of that
43:58 are impaired and communication to the other is also impaired. That's why that
44:12 in general. It's a it's a question that's uh epilepsy has different receptor
44:19 associated with it. The two major , the two major neurotransmitters excited to
44:27 inhibitory Gaba. You can view uh can view epilepsy as an imbalance between
44:36 and inhibition. And yes, it be because there's an impaired gaba but
44:41 also could be because there's too much and gaba is in the normal functioning
44:46 . And when we talk about epilepsy realize that there's other um protein channels
44:53 are also very important, especially for forms of epilepsy. But in
44:58 one of the things with epilepsy is there is a lack of inhibition.
45:03 of the anticonvulsant drugs will boost the of inhibition. Uh huh. And
45:15 way that you hope would contain Too much excitation will lead to
45:21 So that's kind of what the thinking it. So it's a very good
45:25 . It's a little bit more complicated maybe you hope to hear. But
45:29 general yeah, epilepsy can be viewed lack of inhibition or imbalance and excitation
45:35 the condition. Very good. Okay you have the four major regions,
45:46 regions for neurons. You have the region. You have the integrative region
45:52 is the selma that we discussed. have the conduct I'll region which is
45:57 axons and the Myelin nation insulation and axons and the output region which is
46:03 external terminals. You can have some almost secretion mode. When you're talking
46:11 neuro endocrine system you can have neurons a sensor neuron that has a axon
46:20 the periphery, on the skin, into dorsal root, ganglion and contacts
46:26 neuron in the spinal cord, another motor neuron that comes out the ventral
46:34 of the spinal cord. You guys all this motor, the ventral side
46:39 will target muscles. You have neurons project long distances and neurons that are
46:47 local and more local neurons they're referred as inter neurons. And inter neurons
46:55 the most part overwhelmingly are inhibitory gaba sounds. So longer range projection.
47:07 neurons do exist. But most of inter neurons and especially the inhibit their
47:13 neurons are in with the local neuronal and then finally you also have projection
47:23 cells that are not shown here and under queen cell. Again that can
47:29 the fact that as a constriction and a violation on the micro capillaries too
47:35 different targets. And how did we up with these classifications of 120 130
47:44 set of neurons. In the original we looked at the morphology of the
47:52 . So this is the morphological specification self types based on their anatomy,
47:59 on their shape. You have uni south, it's a soma here.
48:03 nobody axon and one north pole. know bipolar cell. You have soma
48:11 north pole, south pole. You sudo uni polar cell. This is
48:17 dorsal root ganglion cell, dorsal root cells will have peripheral axon to skin
48:23 muscle dorsal root ganglion selma that projects the central axon external terminals into the
48:33 cord pseudo uni polar cell because it two poles but it's really like flowing
48:42 one direction. The signal most of neurons in the brain. On multipolar
48:47 very complex. This is a motor of the spinal cord which is multipolar
48:53 . It'll sell in the hippocampus parameter of the neocortex is one of the
48:59 studied cells. Excitatory cell in the and you also have the sophisticated looking
49:08 tingey sells of cerebellum and the first to draw these cells was none other
49:13 ramon alcohol. Um Wow, imagine , something like that from a
49:21 These cells with energy cells are up synapses on these complex. And tennis
49:33 . So think about the speed and complexity of computation. One unit has
49:37 perform this bombarded hundreds, thousands of within 12 milliseconds that says I'm going
49:44 do something good or you know state , another millisecond or two or
49:52 There are some neurons that are spiny some neurons that are a spiny.
49:57 the spines there are some neurons that not have it expands and that's not
50:02 . That's just another variation in neurons neurons or projection cells or into
50:10 We already started that discussing the concepts what you may have is you may
50:14 a local circuit and inter neurons are activity in this local circuit, projection
50:20 are typically excited parameter cells that will that information from local circuits to the
50:28 circuits that are further away. And of the projection neurons are excited and
50:34 of the local into neurons are So that's another way that you distinguish
50:39 on excitability. You also have self markers or certain genes, podiums,
50:49 that get expressed in certain types of and not in other types of knowns
50:56 in 1939 I believe Hodgkin and These two scientists published the first inter
51:06 recording of the action potential 1939. lot of the fast electrophysiology circuits came
51:18 because of the wars actually. And still in the electrophysiology labs, we
51:24 our equipment with B and C. stands for british navy cable, british
51:30 cables were the same as you, navy cables. And those were the
51:34 oscilloscopes and radar detectives that were being by the navy and submarines. And
51:40 were then brought into the lab electrophysiology . So we had the fastest silla
51:46 . We had the micro electrodes, could stick some big axons and 1939
51:54 is no computer, there's no cell . So you capture this action potential
52:03 the oscilloscope screen. What do you with that? Just place yourself in
52:14 ? What do I, what tools I have at hand? You have
52:18 Polaroid camera? You do. So are you gonna tell somebody you saw
52:25 ? You're gonna draw it, you're to take a picture of the Polaroid
52:30 on the screen of the oscilloscope. you have one Polaroid. What do
52:37 do with that? There's no no facts, No cell phone.
52:42 black and white copy machines as you . So you make 10 copies and
52:49 it to the journal 10 black and copies. And there's no computers.
52:54 how do you write an article about ? It's called the typewriter type.
53:02 no control Z button. So if mistyped something MS write something white
53:12 If it's too big, take the page out and start over. You
53:19 you're lucky if it's line five and messed up really bad. But in
53:23 middle of the page you're like oh I submit this or do I spend
53:27 hour retyping all of its. So that's that's what it took and that's
53:33 it took somebody to show this and they shared was the first high potential
53:38 order 1 to 2 milliseconds, assure fluctuation from about minus 60 mila
53:43 About positive 40 million bowls. And was the first action prevention and that
53:48 very important. So let's see where are today. I'm gonna introduce the
53:54 and I'm gonna come back and talk the slide again because quite a few
53:59 have questions about these slides but what know today, for example, if
54:05 look at a very famous and one the best studied structures in the brain
54:11 the hippocampus and I mentioned see that campus is a part of the limbic
54:17 . The campus is involved in memory , emotional processing and memory recall and
54:23 particular what we call semantic memory which your storytelling memory events, spaces.
54:33 think stories that happen. There are types of memories such as procedural memory
54:40 physical memory and it's mediated by other of your brain. But hippocampus is
54:46 well studied, it's very easy to it and animals. It's easy to
54:53 it it's easy to find this strategy amidala which is a parameter cell layer
55:02 and it's inhabited by these projection excited parameter cells. And this is a
55:08 example that I'm gonna use to show one circuit and how complex it is
55:15 it's cellular diversity. And also we'll looking a little bit at the functional
55:22 here too. So if you look the hippocampus is dominated by three of
55:28 three layers already out on top strategy a model which will contain the parameter
55:35 and they're called parameter cells because they are shaped like pyramids. There's almost
55:40 shaped like pyramids. The strata of below. It's not neocortex it's not
55:47 six layer structure hippocampus is referred to our key cortex. It's archaic
55:54 It's dominated by three layers are key wants to be a neocortex. It's
56:02 very very slowly evolutionarily into something else it is but everything else in the
56:08 and body. But if you look the at the campus one thing that
56:13 see is that this parameter is dominated Karam it'll self is excited to our
56:18 and you'll say well is it just subtype of excitatory cells and if you
56:24 in these excitatory cells morphological E. that are C. D. Plus
56:30 cd anonymous they will look the same if you record activity from them They're
56:35 really. They release glutamate and they in about a similar play. So
56:41 the one some type of anxiety resells turns out is a two seconds inside
56:45 your cells. And the difference between is one expresses called which is an
56:53 marker. This is a calcium binding from Calvin then. And the other
56:59 of the excitatory projection cell that is her that looks the same and fires
57:05 same action potentials. The same frequency action potentials. The same pattern of
57:10 potentials but it doesn't have covid. so these excitatory cells from mostly strategy
57:18 a dollar layer they're going to receive onto the gun rights. They're going
57:24 process the information and they're going to that information out of the Canada.
57:34 much diversity and as far as the theirselves go just said they look the
57:40 . They behave functionally the same. means they produce the same frequency and
57:47 of action potentials. Each one of sticks is an action potential. So
57:53 look the same. They talk the . The only difference is they project
57:58 the same regions far off the excitatory some have called them then and others
58:06 . However when we staying for Gaba the inhibitory cells we discover is at
58:16 21 subtypes and this is from So I should probably re upload one
58:22 2020 will probably show 25 different sub these 21 different subtypes are all inhibit
58:31 self sustained for Gaba. It means they release Gaba inhibitory neurons and when
58:39 stand for them they some of them similar anatomy and are located 1 to
58:48 with very similar anatomically. This is Soma, this is the den drive
58:55 these yellow cups are the axons and yellow cops are targeting these excitatory
59:03 So if the yellow cups are targeting soma is they're targeting the soma as
59:08 yellow cups are axons are targeting gen some yellow cups targeting axles of the
59:20 so that tells you that these inhibitory first of all they're all local and
59:27 will be also contacting this parameter So parameter sauce is gonna get an
59:33 positive input coming in from another part the brain. And this parameter cells
59:38 gonna say good, we got positive . These inhibitor engineers are also going
59:43 receive input from another part of the and they're gonna start playing very differently
59:49 they will start affecting the activity of exciting current cells inhibiting these excited cells
59:56 finally be excited to ourselves will have decide if they project that information,
60:01 an action potential and project that information distances or no. So once again
60:08 are complexity in this structure here in hippocampus, that sub cellular sub diversity
60:17 complexity comes from the inhibitory cells And inhibitory cells can fire action potentials in
60:25 different patterns from the excitatory cells And one of these inhibitory cells. It
60:33 its own anatomy. It also has markers Why is one and two different
60:41 two and four different? Because two a basket cell. It's called the
60:45 cell that expresses privileged women and It looks exactly the same as to
60:53 it expresses. C. C. . Which stands for colossus token in
60:58 be glued. Three. Ultimately, distinguish between cellular subtypes based on the
61:07 or morphology, their location within the which layer their axonal projections but ultimately
61:17 inter cellular markers and their functional How do they produce action potentials?
61:24 they produce very fast frequencies of action ? The slow frequencies of action
61:28 Are they the same patterns? But are different patterns. And then you
61:32 start forming this view of the local that are being controlled and trained and
61:39 made a lot more complex by the ourselves. And the excitatory cells is
61:44 that receives them. Listens to everybody says okay, we're gonna communicate or
61:50 right, I'll be quiet. But inhibitory cells very much control this output
61:55 is going to be going out of campus which is communicating that information long
62:01 when we come back on Wednesday? will pick up with the slide and
62:05 will continue talking about the different functional . So these anatomical properties that you're
62:14 and inter cellular markets that you're seeing gonna end up in different way.
62:19 neurons top and the languages, the potentials, the frequency and the patterns
62:25 these action potentials. So I will some of this for you on
62:31 not to be missed. Have a evening,
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