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BIOL 4315/6315 Neuroscience (18564/17642) - NEURO Lecture 04 Neurons and Glia MO WED
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00:01 Welcome back to this nurse on selection We're continuing talking about neurons and
00:09 We're talking about foster olympic beyeler the . And if you were to take
00:13 hydrophobic non polar tails which are fatty tales that who joined with these polar
00:20 filic head group which is codeine withdrawal the head and tails. And
00:26 you were to place these uh lipids a fluid they would actually accumulate into
00:35 by layer like structure and form the form essentially the surround like structures so
00:44 together where the heads are always exposed the acquis solution. So the membranes
00:55 not rigid and the elements that are these membranes are not rigid and it's
01:01 relevant especially too fast processing that takes in the brain. And as you
01:07 see the membranes will have proteins. of these proteins that are trans membrane
01:15 are also channels. That means that is going to be molecules or ions
01:21 may be passing through these channels. of these are receptor proteins that are
01:31 or that are linked to other structures the cell. So these could be
01:36 protein coupled receptors. It's a receptor is not a channel but instead it
01:42 tattered and connected to a complex like g protein complex intracellular early uh and
01:49 these receptors and channel receptors will be likely interacting with some of the chemical
01:56 neurotransmitters that get released the cells they contain carbohydrates and like a protein.
02:04 you can imagine the surface of the to serve like sugar coated in the
02:09 in the membrane. You will have lot of cholesterol molecules interspersed and that's
02:14 cholesterols, player and neuronal function because is contributing a lot to the mechanics
02:23 the fluidity of this foster lipid bi . Now these molecules and these proteins
02:33 are embedded in the plasma membrane, very dynamic. So even large receptor
02:42 proteins can move micro meter is over and not all of these are located
02:51 the parts of the plasma membrane that in the synapse. They could be
02:57 what you call an extra synoptic outside this announced. And these receptor channels
03:03 then travel very quickly in the fluid . Like moving through this plasma membrane
03:10 another location such as synapse and inserting of these receptor channels inside of the
03:18 . Now, the other important elements support and provide that structure, the
03:26 of the plasma membrane are the underlying of skeletal elements. So, side
03:31 skeletal elements will be like the support the beams that hold up the wolf
03:38 the house and give it a certain and that's what different side of skeletal
03:42 that we'll discuss in a little bit . Uh This is a basic
03:50 But I like showing that because mm is something that is simple but a
03:58 good explanation and a good explanation of fluid mosaic model and the position of
04:08 outside world class. Remember as crucial this barrier is is surprisingly flexible.
04:20 . Carl getting way began, acknowledges w because their jails with groundwater in
04:32 heads attractive, doing some cholesterol and and you have the basic structure of
04:40 brain way different proteins which signals from world outside transport nutrients way. So
04:59 proposes a emerging and these molecules are seizure, They constantly move with
05:14 their positions, the survival of all rests on this veil of Nigeria.
05:25 little memory just to and you can how there is this. It's a
05:41 because supplies my number and it's comprised these different elements almost like a Marseille
05:47 its fluid because it's not only the move, but as you can see
05:54 you disturbed the plasma membrane to a degree it can rearrange itself.
06:06 And that's that's what happens actually. you think about brain plasticity, we've
06:15 talking about brain plasticity as it especially to the gendered experience. Guess
06:21 needs to happen if you are growing dungeon explains, you need to bring
06:28 the whole slew of elements status, supporting molecules and your plasma membranes have
06:39 rearrange into different shapes and if you're that ended explained that it did expire
06:46 to grow in size typically becomes larger week, weeks and apps we undertake
06:54 may become smaller size and essentially disappear how that is happening is because you
07:02 have a rearrangement of the underlying side skeletal elements who have the rearrangement of
07:07 possibility by layer and of course the that you will see in the mosaic
07:13 the composition of the different elements in plasma membrane. Okay, so the
07:23 mosaic model of the plasma membrane, leads us to these underlying status chemical
07:29 which you may know from other biology . You have micro tubules, you
07:35 neural filaments or intermediary filaments and you micro filaments. So, if you
07:42 in this cartoon image here, It that these three different side of skeletal
07:51 are different in several ways, but striking one is their size to Berlin
08:00 are small that they comprise the largest of scalp diploma, which is micro
08:06 , then you have your own filaments about 10 nanometers in diameter. And
08:13 you have micro filaments that are comprised these acting molecules that are only five
08:20 and damn. And on the what you see here is an electron
08:26 image of essentially cross sectional image across ax on and the neuron. And
08:36 you look on the edges of this of all, you'll see this
08:39 I am here, but more strikingly here at the bottom, you'll see
08:44 looks like lines almost looks like. you were to take a tree and
08:50 of kind of a cross. If were to cut the tree in half
08:55 that's exactly actually what this is. is an accident split in half these
09:00 that you're seeing here different sheets and of smiling that forms around the accents
09:10 you will be seeing different organize with you see these what looked like almost
09:16 wires and these are micro tubules. a lot of times these types of
09:24 are referred to as micro tubular highways micro tubules serve essentially as a highway
09:33 different things to be delivered from the , which synthesizes most of the things
09:38 the south to the periphery. This aspects of the south or vice versa
09:44 the periphery into the some. So you were to take an example of
09:52 next cell here, which is a type of cell is a Fiber glass
10:01 it actually stands for two million active it stands for the nucleus. The
10:07 here is purple. Oh, the . Bulent molecules which would be
10:16 Two bills largest elements are in And what is very evident is that
10:24 micro tubular elements are concentrated at the of the cell and closer toward the
10:33 of the cell. While the smallest that are comprised of the acting molecules
10:42 shown here in blue and you see the outer edges specifically closer to the
10:50 membrane is where you see the highest of these acting molecules. And that's
10:56 these side of skeletal elements like active . They can co joined together.
11:02 get prelim arise together into longer change can deploy, memorize and get broken
11:07 into shorter chains. And these arrangements changes in the sight of skeletal
11:13 especially in the acting arrangements is what the outer shape of the neuron or
11:19 number and not just out of shape it, but obviously will impact the
11:25 mosaic behavior of that specific patch of plasma membrane. And uh I have
11:36 image of Alzheimer's disease, but I don't like it. So I use
11:42 image and I don't know why the and save on the presentation. But
11:47 me talk about this in another Let me pause this for a
11:53 Mm I do not believe like I'm the course of the semester, I'm
12:00 to introduce it to several neurological Today we're going to talk a little
12:05 about Alzheimer's disease. I want to it to that disorder. We may
12:09 back to that disorder a month later something may happen in this world and
12:15 may want to talk about that Okay. Or something may transpire where
12:23 learning additional material and it is related through that same disorder and you understand
12:29 now differently. So you may come to that disorder and add additional notes
12:36 it throughout the semester. So I that if you're doing the paper notebooks
12:42 you dedicate. Maybe a few pages the back of the announced neurological disorders
12:49 after page to each one of these . Uh and we'll start developing the
12:55 also not just a scientific but also of the clinical language by which you
13:03 be talking about some of these neurological . So I don't remember how
13:11 maybe six or seven or eight that will we will talk about when we
13:16 mention but we will bring up here Alzheimer's disease today. And Alzheimer's disease
13:27 a dementia. Okay. Uh It's neuro degenerative disorder. It means that
13:38 degenerate and die. And as we previously already in this class C.
13:44 . S. And neurons do not . So once you kill the sensory
13:52 and other cells in the cns they not re grow and regenerate and the
13:59 do not regrow. It's a neurodegenerative . Then you will hear in clinical
14:08 the prevalence see of this disorder for time of the onset. That means
14:13 common is this disorder? How common Alzheimer's disease? So this is a
14:19 for you. You can look it but it's a question for you,
14:24 many people just think about it? think would have Alzheimer's or see now
14:34 what percentage of people ends up having percentage changes. But then you'll say
14:42 what at what age, right? will say at what age, I
14:46 know many people. And my classes have Alzheimer's disease, You look it
14:53 . Okay awesome. So some of claws just looked it up and says
15:06 71 and over 14% and I don't your source. So I'm not I'm
15:12 really this person, is there University Michigan? So it's an academic
15:18 So it's not that, you but it's 14%. That's what you're
15:23 in 71 and over. And that's that's the point because it doesn't say
15:28 general population Alzheimer's is probably zero 1% . But the older you get,
15:36 higher chances you have of developing dementia Alzheimer's disease. And it actually that
15:42 he goes up after 50 years of as an upward curve trying uh developing
15:51 disease. Yeah. 30 How 37% of 90 years and older.
16:04 you can see that this firm, I was saying, it starts with
16:07 50 and it's pretty steeply rising curve the end of life. And a
16:13 of people will say, well, , you know, just forgetting
16:17 Well, that's one thing, forgetting , dementia and Alzheimer's disease. That's
16:22 just forgetting things. It's a It's not normal part of aging.
16:29 this disease has a cellular network Uh and these are the pathological hallmarks
16:39 this disease and in the brain there two major pathological hallmarks of Alzheimer's
16:48 There is information of what you may heard of a senile plaques or sometimes
16:55 will say dementia plaques or alzheimer's plaques the brain? They are data amyloid
17:03 there. Aggregations of abnormally formed. huh Prudence that essentially intertwined themselves in
17:13 tissue and get harder, get somewhat . And there is a whole process
17:21 that surround the formation of these inflammation and also neuro degeneration. And
17:32 is what's happening on the outside of south. Yes. Mhm. For
17:39 , Yeah. Uh They also are to as amyloid plaques as in the
17:45 or senile plaques. Alzheimer's black sometimes on the inside. Remember I was
17:53 to you and I was telling you the uh how important it is to
18:00 a precise side of skeletal arrangement because have the micro tubular highways. You
18:07 the uh Euro filaments and you have side of skeletal elements. And besides
18:15 this side of skeletal elements supporting the structure of the plasma membrane in the
18:19 and giving the shape of the experience we talked about earlier, I told
18:25 they're also very important for transporting the , the goods, especially the digital
18:31 of the self from Arizona. And Alzheimer's disease, you have formation of
18:36 february tangles. That means that the growth and the site of skeletal elements
18:43 tangled up. And so what happens if during rush hour you close two
18:50 instead of four lanes going between here Galleria, it's a nightmare. It's
18:54 45 minute drive. So you cannot the Galleria, you have this 45
18:59 and that's so now you can imagine level of sight of skeletal elements to
19:04 the lanes are tangled up. Micro highways are tangled up. What's going
19:11 with the delivery of nutrients from one of the south and the other.
19:15 could take a very long time. could deliver less nutrients than the cell
19:20 just all aspects of the sound So on the outside you have the
19:25 of the flags. On the you have the formation of the
19:30 When the plaques form on the outside the south, they actually start impinges
19:34 the anatomy. And in particular, found out in the last decade that
19:42 axons are most sensitive to the formation these amyloid plaques. That means that
19:49 these plaques form in the vicinity of ax on that accident gets impacted first
19:56 . So must make it impacted because these flags grow and they occupy larger
20:01 in the brain and there's sort of multiply and they migrate, they
20:07 they don't form all over the cortex the advanced stages. So, you
20:12 say, initial stages of Alzheimer's How would you know if somebody has
20:18 disease, you go to to search symptoms for somebody complaining about something,
20:25 . I have pain in my right . That's a symptom pain or itching
20:31 or I don't feel anything. This a symptom or my arm is just
20:38 anything and it matches the symptoms. with alzheimer's, some of the early
20:43 is confusion, memory loss and typically term memory loss and later long term
20:50 loss. And typically actually we have lot of short term memory storage and
20:58 keep erasing it and refilling it with short term memories of erasing it and
21:02 them. And then we package some things into long term memory storage.
21:07 typically those are more at the core what we are, whether it's at
21:12 core of all development, emotional emotional interactions, motor skills, whatever
21:19 is, just long term memories are and they are distributed widely. And
21:27 in early stages, short term memory symptom. Long term memory is the
21:35 showing a progression of the disease. , can you visualize these plaques non
21:45 . You can only do so if , if the pathology is so advanced
21:52 that it is almost hopeless to do non invasively at that time. So
22:00 diagnosis of somebody having Alzheimer's disease and are early stages and then later stages
22:06 anxiety. There is uh just loss uh you can say a person is
22:14 not conscious. They're not lucid, can be lucid for a period of
22:20 during the day and then they dressed and then what happens is not just
22:26 . Brain controls so many different And so when these flax form,
22:31 don't form all over the brain, actually form in certain parts of the
22:35 , hippocampus is one part of the is very susceptible. And then from
22:38 they migrate throughout and migrate throughout the into the other parts of the
22:45 Then what happens is the brain stops care of the body. So it's
22:50 just forgetting things, losing memory being , driving off. You see these
22:57 blue alerts, right? It's usually older person that's left old people's home
23:04 they haven't come back, but they the groceries at two p.m. and then
23:07 like 11 p.m. At night. And don't know where they are a lot
23:11 times that person loses spatial memory, kind of locate themselves and find
23:17 they lose a space of time, sense of time. So they make
23:22 out on the street at six a.m. think that at six PM and wonder
23:28 everybody is. Uh so and then your brain stops taking care of your
23:37 , then you stop eating and then stop breathing basically. So this this
23:45 of the disease is horrible. There that many medications that control it and
23:51 diagnosis of Alzheimer's is still the most diagnosis of Alzheimer's disease. And so
23:59 want to look at the gross structure what's happening in the healthy brain as
24:04 to a person that has severe advanced disease is you have massive shrinkage of
24:12 brain tissue and you have especially the of the, of the, of
24:17 brain matter and the loss of south general. So you have massive neuro
24:24 that's in the cortex, it's in parts of the brain, like
24:29 And again, this is the severe advanced stages that you would see.
24:35 kind of a gross anatomical pathology. is that? There are?
24:44 it's a good question proportionately why? maybe because it's more sensitive. The
24:51 are more sensitive than some of the that are my eliminated. They're just
24:55 there so they remain there. It mean that they're active but uh,
25:01 takes longer time. They're harder also for them to degenerate complete mint.
25:07 the accident, initial segments which are my eliminated, they get effective in
25:12 plan. And that's why the accidents really sensitive, I said. But
25:17 the longer range fibers of white matter age, 5% just a little bit
25:22 prominent than remain no longer. So , what are some of the things
25:30 terms that you've learned today that there symptoms, right. Somebody has
25:38 I have a lot of anxiety. can't remember anything. I can't count
25:43 What's after 47, you know, is a concern. So we're going
25:48 test that may be given after two . Memory task to try to tease
25:55 whether this is maybe an early stage dementia or alzheimer's and the symptoms can
26:01 worse. This is an expression of disease symptoms is an expression of the
26:08 . Pathology is what we see under or pathology is what you see and
26:17 growth structure, anatomical structural level. underlying causes are some of this pathological
26:29 . The death of the neurons, formation of the plaques that you're a
26:33 tangles when you come to the question authority, right. And the reason
26:44 I'm walking you through this, this just very basic parents and you may
26:47 already thought about them are or learned them, but some of you may
26:51 and may not have thought about these aspects. So now, yes,
26:56 . And what is therapy in Alzheimer's ? Well, I guess in early
27:03 you can slow the progression of the by mental exercises, physical exercises,
27:12 and potentially medications too. And then it comes down to the medications,
27:18 medications and most instances target acetylcholine So you're like, oh wait a
27:29 . But you didn't tell us that tells pathology this and then you'll say
27:33 what cells are dead. So in Alzheimer's and the progression of Alzheimer's disease
27:39 the acetylcholine neurons in the brain that until most of the alzheimer's medications and
27:48 will learn that the whole coal energy Colin signaling in the brain of
27:52 allergic synopsis and receptors synthesis and degradation a single Colin. But it's Colin
28:01 neurons that are dead. And so medications, most medications tried to boost
28:08 you call the city locally in tone Colin urgent tone in the synopsis.
28:14 try to boost that tone. And there's another medication that I don't really
28:20 to talk about, but it concerns excited to a neurotransmitter, an
28:25 D. A receptor in particular that of you may have heard about.
28:30 in any case the most important point that there are neurotransmitter and chemical systems
28:36 are associated that go kind of off early in the disease. And also
28:46 second point is that Alzheimer's medications only down the progression of the disease.
28:53 no cure for all the time in cities. So um did you have
29:02 question now help? Like, you , it's like technology to be used
29:10 be helpful in like keeping people and it. And you know, I
29:15 because a special lots of special uh that sometimes from. Yeah, so
29:28 has a comment about technology being a area. I agree with you.
29:32 also to a point I think that know, early detection and mental agility
29:38 keeping out with mental agility is very . There was a study a while
29:44 of nuns. That group is a old age and they somewhat have a
29:51 up environment except you know, their amount of themselves but they're somewhat isolated
29:56 self isolating themselves from the rest of world. And they were added writers
30:02 readers, they were all writing their and they were just reading and have
30:07 book clubs and discussions. And that of nuns had very very very low
30:16 of Alzheimer's disease. So there was big argument made that mental conditioning,
30:23 agility, mental tasking into the old . I think that the point that
30:30 bring up the technology is not only and could be used to help Alzheimer's
30:36 and other dementia patients and other neurological . But that also I think that
30:44 noticed that older people that have not up with everyday technology like computers,
30:52 and cell phones have further isolated themselves from certain means of communication from the
31:00 , maybe from their loved ones in way. And that is I think
31:07 we're going to be seeing some correlation too in the sense of Mhm.
31:14 people don't want all of the stimulation all of the technology, but I
31:20 , if you don't learn how to it, it doesn't mean you have
31:23 use it, You know, your time 12 hours a day, you
31:27 use it one hour day but learn to do it. You know,
31:31 an important part and older people that take up that challenge to learn the
31:36 technological developments, I think may be to losing touch a little bit with
31:43 with reality of things happening and that's I would imagine that's also part of
31:49 , you know, if you are or developing alzheimer's disease, that probably
31:53 not a good time. Yes, think the purpose of education, I
32:03 didn't nail on the head of my isolation and how that contributes to accessing
32:11 injury or accessible insult. Has somebody a bunch of process? So earlier
32:17 the mask is a phenomenon of dementia is so friendly because a dementia patient
32:24 uh we'll try everything they can to the symptoms that they're experiencing in order
32:30 avoid social real fuel and loss of or loss of status within a family
32:35 social structure. And that continues to chances. Financial stresses, increased chances
32:43 family, concrete uh loss of socialization loss of future skills, which later
32:50 into further isolation that can contribute physical and which results in hospitalization and
32:57 which results in the instagram anesthesia which affected which uh the older population,
33:05 dementia patients in general and very, studio. And you see in my
33:11 , you've seen this this form um people has to that social isolation
33:18 That's why in uh different races of , so much on developing social
33:28 developing independence and facilitating independence of people are going through dementia processes can still
33:36 exactly as much for themselves as they . And then right at that
33:40 everything else gets broken by days or or a facility or whatever. And
33:46 long as you like doctors, he , as long as you stimulate keep
33:52 simulation as maximum as possible uh and don't throw somebody into a situation where
33:59 is doing everything, making as much themselves. Yeah, I think it
34:05 slows down. Especially thank you so for that insight and I hope that
34:15 on zoom could pick up someone with of the students was commenting on.
34:21 . Uh it's very helpful. It's insightful and encouraged very much comments like
34:28 , especially if you have experiences. what you have mentioned is I was
34:34 to speak about this later and of , but what you have mentioned is
34:37 like physical injuries that may happen to that is confused and isolated and awkward
34:45 because they're confused and they're forgetting the and so on. So a lot
34:50 these things are referred to as comorbidities it's not just the physical injury of
34:58 or getting lost and not finding home three days from getting robbed by somebody
35:02 so on. But if you look the alzheimer's patients and prevalence sea of
35:11 and epileptic seizures That curve of Alzheimer's in 50s going up and if the
35:18 has Alzheimer's in their 70s, there about 50 times more likely to have
35:25 . Yeah, 50 times more So there's also other neurodegenerative neurological disorders
35:34 come about from these massive gross abnormalities eventually form. You know, they
35:41 from these small little warming things forming the cells and and and inside and
35:49 and then they caused this massive And uh you will see other problems
35:56 like seizures. You will see other disorders associated or other what are called
36:03 . That comorbidities because they uh make a life the patient's life that has
36:11 disease shorter because it has an associated or comorbidities. So thank you so
36:19 for that comment. Um So use slide. Don't use this slide for
36:27 disease. Um And uh use some this knowledge and some of the information
36:33 you wrote down. And a perfect is we're gonna come back and talk
36:39 Alzheimer's disease medications when we talk about city of coding pathways. And well
36:46 that point, you'll also understand why only slows down to the progression of
36:50 disease. Because once the neuron is , you can only so much stimulate
36:55 neuron that cannot produce much. So any case, what are some of
37:02 very other unique things that we're discussing neurons that dendritic spines that you find
37:09 the damn drives. You see these action potential will be generated attacks on
37:14 segment here, right? Very close the soma. And then that signal
37:19 going to get sent down to And this acts on May ram if
37:25 so it may split into several what call collaterals. At the end of
37:30 acts on you will have a Mcdonnell like Sana terminal or button or Bhutan
37:38 Bhutan's and innocent. That means that acts on a form of synapse and
37:43 the larger part of the accident may traveling on to another part of the
37:48 . Once in the external terminal you a lot of mitochondria because you need
37:54 supply and that energy supply is needed the vesicles that are found in the
38:00 to refuse to the plasma membrane to to release their content into the synaptic
38:08 and then to be recycled back and the President optic part of the synapse
38:15 boston optically. The boston optic done and then drink spine. You will
38:20 these past synaptic density is that we saw previously an electron microscope picture.
38:26 are the densities of the receptors that sitting juxtaposed to the neurotransmitter vesicles on
38:33 pre synaptic side. And so collectively is synaptic transmission when you have an
38:41 potential that generates a voltage changed. both exchange get transmitted all the way
38:49 D. Polarizes acts on terminal and deep polarization and subsequent influx of calcium
38:55 in the release of the neurotransmitter. neurotransmitter binding to the post synaptic receptors
39:02 evoke the past synaptic responses. So is a full kind of a cycle
39:07 synaptic transmission. We will spend a of time talking about synaptic transmission in
39:13 second part of the course. So go a lot into these details.
39:18 so in axons you have ectoplasmic you have slow ectoplasmic transport and fast
39:25 plasma transport. You have interrogated transport retrograde transport and terror grade is from
39:31 soma into the periphery. And we shown here these little motor like molecules
39:40 proteins that carry vesicles and carry other right along the micro tubules. So
39:47 is cartoon like representation of these knesset like little arms, little engine motors
39:54 and passing down the goodies down the tubules traveling in one direction and to
40:00 the goodies back. You have dynamic is retrograde from the periphery. Using
40:05 micro tubular highways will bring the goodies forward the soma where they need to
40:10 reprocessed and recent facist and potentially re back on the connection to be delivered
40:17 to the 1st 1. This is simple cartoon like representation but it's easy
40:24 imagine that you if you were just take and tangle up these micro
40:29 These guys actions and dynamics will not able to do their job and travel
40:34 and they would clog up things and will have abnormal communication and then there
40:41 in the south. Yeah the game the brain is mostly in the stain
40:49 a lot of times you have good that this transport contributes to. And
40:56 particular we're gonna look at some of dyes and viruses that can travel retrograde
41:04 . So retrograde really means from the . Like from the patch of the
41:10 or another network in the brain and periphery. Let's say in a sensor
41:16 that will get absorbed by the accidents retrograde really transported into the summers.
41:22 if you inject the horseradish Barack see which is a chemical stay in a
41:27 dive that H. R. Specifically horse riders proxies will get picked
41:33 by the axons and we'll get transported then you'll see okay I injected a
41:40 of H. R. P. but this patch of whatever you want
41:44 say, its skin is connected to neurons here. These specific heroes,
41:51 kind of a retrograde transports are great staining for realizing where from the periphery
41:56 from the example terminals is the way the neurons of interest. If you're
42:02 that particular area, herpes virus bring virus also be capable of retrograde
42:10 And we'll talk about shingles later. of course when we talk about Samantha
42:16 system and as a result the virus is capable of both interrogated and retrograde
42:24 then interrogate travel after being dormant for time. So you can take advantage
42:32 this transport. We can take advantage this transport for studying their anatomy.
42:38 the connectivity between different networks or from periphery to the neurons of interest that
42:44 studying. And as we discussed the great spines come in different
42:50 Concise is they're dispersed in certain densities them really shafts and they're juxtaposed to
42:57 external terminals. It contains synaptic pilot complexes and they also contain a lot
43:06 mitochondria, which means that dendritic spines somewhat biochemical independent units away from the
43:17 of the south. What do you by that? That means that by
43:23 polio rob Osama complex, you can do things locally at the level of
43:28 synapse. You can translate messengers into . And there's a good experience without
43:37 to go all the way to the , all the way to the nucleus
43:41 say I need a memory, need make something for me. And I'm
43:47 the way over there on that branch the dendrite, the little we've hanging
43:51 . So this is interesting. They a lot of energy and they have
43:57 ability to synthesize therefore somewhat biochemical independent the damn right. And from the
44:05 , they are very much dependent on and environment. The plasticity of dendritic
44:13 . The arrangement densities are very much on the levels of activity and
44:21 Or a lot of fans is called dependent plasticity. Because these elements are
44:26 most plastic elements in the brain is good experience. Wait. Mhm.
44:37 . And this is second disease of day. We're going to talk about
44:43 retardation. And on the left you a dem drive from a normal and
44:50 on the ride. You haven't done from the mentally retarded and immediately.
44:57 should see a striking difference in what expands. Dendritic spines are very sparsely
45:08 distributed here densely packed in certain They are very elongated. They have
45:16 much different anatomy from the deck spines are from the normal And so the
45:23 disease that we introduced today for mental is developmental relegation in the case of
45:32 spectrum disorders. And we're going to a condition known as fragile X
45:44 autism spectrum disorders. There's multiple disorders fall under what usually people call autism
45:55 And fragile X. Is under that of the disorders and fragile X
46:05 You will have the underlying pathology of abnormal, then you expand formation fragile
46:14 . Kids that Children would have uh will also have other severe problems.
46:22 may have other comorbidities. They may apoplectic and they have seizures as
46:29 The point is that dendritic spines are important and different things go array in
46:39 pathologies underlying different neurological conditions. Alzheimer's is the tangles and plaques and neuro
46:48 of neurons and the elderly population abnormal have been good experience. You're talking
46:55 the Della developmental developmental disorder developmental There could be severe, it could
47:04 not so severe. And you have that have autism spectrum disorders that are
47:10 brilliant actually but we'll actually never know they're gonna get expires look like but
47:18 will always know that under certain models in the lab and also in humans
47:25 you will see this abnormal and responsibility connectivity. You will see some different
47:33 also in some cases than most of would have. Okay, that's very
47:41 because the good experiences where the communication styles take place and the good
47:49 You can see that this neuron shown in blue actually has two types of
47:56 dominant synopsis. Glue, dermatologic synopsis here is blue are these are excitatory
48:04 from the neuron and Gabba synopsis or . Allergic Synopsis and Gabbana are
48:11 R stands for glutamate receptor and this receptor is stained and green here.
48:17 anywhere around the cell we're seeing, is glutamate receptors there and Gaba
48:24 Our and rad and Gabba Synopsis and receptors are inhibitory onto this now.
48:33 as I mentioned to you anyone of given neurons could be having thousands to
48:38 of thousands to hundreds of thousands of synopsis and the synapses are not just
48:44 , go, go, go go is excitation plus plus plus plus plus
48:49 also inhibition which is stop, stop, stop, stop or minus
48:53 minus minus. The synapses are localized different aspects of the cells. Some
49:00 them are very close to the soma others are located quite a pistol and
49:07 neuron would then process information from excited inhibitor synopsis and the processing of information
49:17 very important. And the neuron will a decision whether it's excited about to
49:23 pass on the information by generating an potential. So if you have abnormal
49:29 , if you have abnormal densities of good explains you may be specifically
49:35 you have excited to inhibit Terrace you may be miscommunicated the information from
49:41 excited to inhibit. There is analysis means you're processing ability goes down for
49:47 cells and interpretation of information whether it's inputs coming in or internal thoughts coming
49:56 then become become different. Okay So that's very important to keep in
50:04 . Is 100 experiences not just excited , they also synopsis and spines.
50:09 can receive inhibitory inputs. Not just imports but the integrative and computational power
50:16 a single neuron is very powerful. very fast and it is computing thousands
50:23 different variables within milliseconds. But the part all neurons have four functional parts
50:31 is the input integration, conduct out and the output part. So this
50:39 a model neuron. This is an , you can have a sensor neuron
50:43 an input and have a motor neuron an input. Local interneuron projection.
50:50 neuro endocrine cells can also contact neurons most of the time is the sort
50:56 the thinking or the final decision which made by the summers of the status
51:03 . I'll units most of the There's one conduct I'll unit which is
51:07 axon. But in some of the cells like dorsal root ganglion cell for
51:13 that carries the sensor information to the cord, you will have the peripheral
51:19 on which is innovating or say the cells or muscle cells in the periphery
51:27 and the central axis on. So really are not having a dendrite in
51:32 case most of the inputs that come the cells will come into the dendrite
51:37 Selma's. But in the case of studio unit polar cells you will have
51:42 peripheral axe on that will receive the and you will have the central acts
51:47 it will put the output, that gets processed at this cellular uh Selma
51:54 here. Yes. Mhm. The blue uh patches or bars around
52:03 accident represents my nomination. So and an important part of this conduct.
52:08 process that action potential and gets generated to the south comas. The amplitude
52:14 the size of that action potential is the same as the size of that
52:19 potential and it arrives at its outfit attacks on all terminal. That's because
52:24 action potential gets regenerated. Each node the smile and sheets here. These
52:31 are called nodes of ranveer and they're with the sodium or potassium channels that
52:37 the action potentials and the output them the sex on all terminals can again
52:43 on to other neurons into muscles on capillary. So you can have a
52:48 constriction of days of dilation aspect of control and more or less in the
52:54 endocrine system. You can imagine you have more of a para crime like
52:59 that can affect larger chemical functioning of body. Yeah, so these are
53:09 of the principles of the wet wet wear that we have the bioware that
53:15 have the networks that we have The of these networks and how they communicate
53:21 each other. And now in order understand the networks, you really have
53:26 understand individual units and neurons in that . And it turns out that we
53:32 close to 150 different subtypes of And thus there is a need to
53:38 these neurons and you can classify these based on that anatomy polarity as is
53:45 here, you can classify these neurons on genetic markers and molecules that they
53:52 . You can classify these neurons in different ways. But if you look
53:56 just morphological or a structural polarity classification these neurons and you'll have these unit
54:04 cells that are common to invertebrates South of right now that has done
54:11 and has an axon has two very pulse the north pole and the south
54:16 studio unit polar cell because it's sort a not not just Suda has like
54:23 poll because it's just one ax on one is a peripheral side and that
54:27 central side. And then most of neurons that you find in the brain
54:32 going to be multipolar cells. That that they will have polarities that are
54:37 out from the cell. Such as example of a motor neurons in the
54:43 cord or an excited to prom. sell of the cortex and the hippocampus
54:49 one of the most famous most beautiful Salvador Monica. Hall also driven first
54:56 cell of the cerebellum that has this extensive tree and now you can say
55:02 so unit solar cells and vertebrates, cells are mostly sensory cells. Retinal
55:09 , Brazilian spinal cord pseudo unit polar and the counter receptors actually mostly touch
55:16 information of pressure information. So as matter of sensory uh dorsal root ganglion
55:23 , multipolar cells, how many poles how many synopsis It's a predominant time
55:29 it's spinal motor neuron. You have . So analysis And for Kinji Salad
55:34 have up was 150,000. Some actions seven and that's what I was talking
55:40 . Not all of them are just go go start on do something but
55:46 come in at different times. The . The synapses get activated different times
55:51 it has to be processed in a fast manner. And so imagine the
55:56 that this cell has to go through capturing all of the information. This
56:01 branch like antenna. Yes, number . Uh So can the dendrites interact
56:12 the soma of another neuron? Most his son absence. R accidents to
56:17 . But then you have accent, driving accidents, accidents and then drives
56:22 dress. Uh And every rule that learn in neuroscience and probably in every
56:29 has an exception or a few. . Very good question. But that's
56:35 very is just kind of a simple . One poll, two poles and
56:41 polls. And most of the cells that we have in the in the
56:45 and polish house. Some of them spying. Some of them are spine
56:49 and drink spines present on some neurons they're not present. So now all
56:56 the insurance will have these prominent and expanse. Um What else? How
57:04 can we classify neurons, connectivity, the projection cells or with the infant
57:10 some of the cells and most of time we're talking about excitatory neurons.
57:19 of these projection cells are the cells will project the one area of the
57:24 to another area of the brain. means that we'll have a long
57:28 It will project from one part of hippocampus, another part of the hippocampus
57:34 from hippocampus to cortex. So projection into neurons usually will have shorter accents
57:40 they will be controlling activity locally in networks. You can classify ourselves based
57:46 excitability, excited to reverses inhibitory. find out very shortly that inhibitory world
57:54 a lot more interesting than the excitatory and that there's a lot more interesting
58:00 . And the inhibitors cell populations as to the excited terry cell population,
58:06 load cells, south specific markers, you have two cells that look alike
58:12 in the same region, they project same distance. We're both excited to
58:18 or they're both inhibit ourselves. What do you have in your toolbox?
58:23 tease out the difference in these Sometimes genetic markers you have chemical neurotransmitters
58:31 these cells may express. You're peptides they may be carrying. So you'll
58:37 out that two adjacent cells that look the same that have excitatory or inhibitory
58:45 . They actually have different chemical that express and therefore they are different.
58:49 types of cells, we have the genetic code in every cell, but
58:54 a portion of that code gets expressed the cell in order to make that
58:59 different different subjects, neurons are not . They produce action potentials and action
59:06 have their firing signatures, which means In neuron and this is the first
59:13 intracellular recording of an action potential that done from the squid giant acts on
59:21 Buy house can and Hartford. These fast fluctuations of about 100 million balls
59:28 size that are produced by cells. have different patterns and each subtype of
59:36 cell will produce a different pattern of pattern of the action potentials.
59:46 okay. And so here I'll introduce you the hit hippocampal network and you
59:54 look at this and you will say is going on here and I will
60:00 tell you that hippocampus is probably the famous and the most studied structure and
60:08 . It has three very prominent layers um Mohammed ali here in the middle
60:13 is densely populated by prominent south. is flanked by two other Lestrade already
60:19 stratum orients. And then of course a kind of 1/4 last stratum like
60:24 Asamoah Gloria but in general hippocampus is a three layer dominant structure. So
60:33 , so what? So this green cells that are shown here the excitatory
60:40 up types And where you have 1234 the way to 21. These are
60:47 inhibitors cell subtypes if you will find the hippocampal. Not for So where
60:55 you see more diversity? You see lot more diversity? And the inhibitors
61:00 networks is compared to the excitatory soul the parameter excited to ourselves. If
61:06 excited enough if they get strong enough from another region of the hippocampus or
61:12 outside of the hippocampus. They are cells and they will send out their
61:18 into other regions. These 21 subtypes into neurons, inhibitory cells there are
61:27 to be controlling the activity of the locally and they're not projecting that activity
61:32 of these networks. What makes them ? Wow 1 to live in stratum
61:42 Madeline layer there is so much a for middle layer but three is located
61:49 the way over here. That's so so the selma location. Some soma
61:53 located in look an awesome layer. are located. And orients layer,
61:59 are located the ready autumn layer. else is different? The dendritic projections
62:09 and two. They have projections going way. So they have projections going
62:15 . 1516 17. They live in different layer and have their projections going
62:22 . Uh huh. So the polarity important here. What is different between
62:28 and 4? They have the soma the same layer. They have their
62:35 rides going the same directions. These cops that represents synapses or external
62:43 External synapses that shows you where those neurons will be synapses onto the excitatory
62:52 and two and 4. They have synapses located in the same area.
62:59 what's the difference between two and There's obviously no morphological difference. But
63:05 you look here there's basket PV and CCK The glued three for #
63:17 So this is what I was telling then if you want to tease out
63:21 difference, they're both inhibit their cells both live in the same way they
63:26 look exactly the same there. Axonal are going through the same location in
63:30 parietal cells. The difference is that guys expressed per volume in T.
63:37 . Stands for pro volume which is calcium binding protein. And these guys
63:42 are also basket cells that express another CCK colossus token. Um And they
63:50 stained positively for the glue three which details of this are not important.
63:55 take home message that is important is the two cells live next to each
64:00 identical morphological functionally. Also they inhibit but they will have a different marker
64:08 LaMarca. Different chemical expression inside the which makes them different. And so
64:15 hippocampus you have 21 subtypes of this inhibit their inter neurons locally controlling activity
64:22 the parameter cells in the inhibitory While these parameter cells are receiving long
64:30 inputs from someplace else and deciding whether will send out or be excited enough
64:36 control them not by this network or they're going to be excited enough and
64:42 controlled enough by the inhibition and send an output to another region of the
64:46 until another adjacent region of so the and neuronal patterns and neuronal processing and
64:58 comes from the diversity of the inhibitor subtypes and excited to re cellular.
65:06 they're really not much different except they're a little bit away from the pyramidal
65:12 paranzino seller and the either half B. Which stands for Kolb indian
65:17 they don't have called India. And is the only really difference the excitatory
65:23 of projection cells but the pattern of outputs of these excited for prom it'll
65:31 will be entrained and dictated by the of the inhibitor activity that is produced
65:38 these different subtypes of inhibitory sauce and campus. Yeah. Okay so I
65:48 this could be a good moment to . I'm gonna show you next some
65:52 the experiments that I did in my in recording activity from neurons and describing
65:59 specific subtypes of the south and the . And my quest was to find
66:05 what different sometimes of cells are doing the formation of epileptic seizure events and
66:13 I will play you some of the that we did in my lab as
66:17 . And that is going to be week from now. So you're gonna
66:21 to patiently wait for some really cool and some more cool information on neurons
66:28 glia in the meantime have a good of the week. Happy over the
66:33 day and I will see you on next week and I will see you
66:42 zoom on Wednesday next week. That goes for those on zoom. There
66:47 no monday lecture for labor day. enjoy be safe. Use sunscreen and
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