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BIOL 4315 Neuroscience Tue Th 8.30-10am - NEURO Lecture 05 GLIA 3 and Resting Membrane Potential
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00:02 This is lecture five of neuroscience. gonna finish talking about neurons and glia
00:10 we will start talking about resting membrane new routes Now when we talked about
00:17 cells, we over viewed several different of cells right? We talked about
00:25 which are illustrated here. We talked micro glia, we talked about the
00:31 gender asides. So if you recall watch the videos of michael glia as
00:37 most mobile units in the brain. are scavengers. They are responsible for
00:44 debris, cleanup following the injury and of the tissues most mobile because they
00:50 around and michael glee also involved in of inflammation because they are involved in
00:58 of the pro inflammatory cytokine release in brain. These are micro glial
01:05 We talked about astrocytes and we discussed astrocytes play very important functions especially what
01:12 call a tripartite synapse Synapse where you two neurons connecting. And the third
01:21 in that synapse is astrocytes and astrid processes that wrap around the synapses.
01:28 actively control the birth of new synopsis after genesis regulate the strength of the
01:34 and contribute to the synaptic plasticity, synaptic plasticity and glial cells also regulate
01:42 and ions. So there can be fluctuations of free floating neurotransmitters in the
01:50 or increases in ionic species that will discussing today such as calcium such as
01:58 . And so astrocytes will siphon off basically redistribute higher concentrations of these ions
02:07 neurotransmitters throughout the astra acidic network. they serve a lot of functions.
02:13 also they control the blood brain So there and feet are part of
02:19 blood brain barrier that we discussed. is the blood brain barrier where you
02:24 them, the filial cells and the junctions. So things cannot pass through
02:29 tight junctions. Only very small molecules molecules that are soluble member insoluble lipid
02:37 molecules or molecules that have their carriers, co transporters or facilitators that
02:45 allow them to enter into the brain . And the last checkpoint in the
02:50 tissue is astro glial and food It's a very important role. So
02:58 and having this barrier as we discussed the great advantage because things from the
03:04 do not really pass into the But at the same time it's a
03:10 because if you want to treat a or brain dysfunction and most of the
03:16 in the market are ingestible meaning their or pills that go through the digestive
03:24 and through the digestive system they get the systematic circulation which is your blood
03:30 and from that systematic circulation they have enter into the brain through the blood
03:35 barrier. And that's why when you commercials. So you read warnings on
03:41 labels of prescription pharmaceutical drugs, you see that there are a lot of
03:48 side effects. You're treating a neurological being Parkinson's or epilepsy or some dysfunction
03:57 the brain. But you're delivering the systematically the injustice means that means only
04:04 fraction of that drug is getting into brain. And that drug, a
04:09 of drugs, a lot of they act on both the brain and
04:15 periphery because there are similar proteins in periphery. They're similar targets in the
04:22 or the same targets that exist in brain and the periphery. So this
04:26 where you have so many side effects could be listed on the what are
04:32 prescription drug monograms or even on the . V. Commercials when you hear
04:39 drug that is treating Alzheimer's disease. it's causing constipation and all all sorts
04:45 things. So that's the blood brain and brief illegal deandra sites are responsible
04:53 providing Myelin Nation two neurons. So look into the legal tender asides.
05:01 at the very beginning these are the subtypes of the real cells. The
05:06 cell that I haven't mentioned so far radial glial cells. We watched the
05:11 of how radial wheel cells above precursors real cells and precursors to neurons.
05:19 they're also the guides the physical guides neurons to reach their final destinations.
05:26 migration. The chain migration along these provided by the radio wheel cells during
05:32 development for neurons to find their final within the precise circuits. Okay so
05:41 my island nation, the logo down will provide Myelin sheets in the central
05:48 system. So each one of these from a legal gender aside will create
05:54 individual myelin sheet segment. So one democracy side can send many of its
06:02 processes to wrap around many different axons the vicinity. And each one of
06:08 processes will create a single myelin segment an axon. Can be multiple axons
06:15 it is insulating in the peripheral nervous . You have Schwann cells. Schwann
06:23 are different. Schwann cells is a Schwann cell with a nucleus that creates
06:29 single myelin segment. So that's in peripheral nervous system. This is the
06:34 between seeing us and P. And . Of course as we talked about
06:40 is necessary so that you have installation once the action potential gets produced in
06:46 axon initial segment in the axon That the amplitude of that action potential
06:52 the same when it reaches the external so it continues to regenerate at
06:59 What we call node of ranveer. nodes of round beers are these breaks
07:06 between the myelin sheet segments and that's action potentials will regenerate as they travel
07:13 the axon so that when they reach axonal terminal, there is still the
07:18 amplitude as when they started at the initial segment. Mhm. Mhm.
07:28 is the my eliminated optic nerve fibers have been cut in cross section.
07:36 you're basically these five or so the that have been cut if you make
07:40 we know they're not hoses with their and you can see the sheets of
07:45 wrapping around. This is the note ranveer. We will have energy,
07:51 mitochondria. You'll also have high densities potassium and sodium channels in there.
07:58 we will discuss how these action potentials about, how they propagate in the
08:05 few lectures. So up to we actually discussed some disorders already.
08:15 in particular, we talked about Alzheimer's and I asked you to make a
08:22 for Alzheimer's disease. And keep your for Alzheimer's disease. And that's because
08:26 going to come back and talk about when we talk about neural transmission and
08:30 we talk about the city alkaline So you will be able to add
08:35 information and have it in one We also talked about autism spectrum
08:43 When we talked about the fragile X . So we said that if you
08:49 abnormal dendritic spine formation, you have densities of dendritic spines during early
08:57 It's associated with mental and sometimes social . Now we discussed that autism spectrum
09:07 is a developmental disorder because it usually or diagnosed or occurs in the first
09:12 years of life, but it doesn't the cases of adult autism. There
09:20 cases of adult autism and late diagnosis adult years or even the emergence of
09:26 autistic traits into the adult life. , um, fragile X syndrome is
09:35 this umbrella of autism spectrum disorders that discussed. Roger lex syndrome produces this
09:44 RP protein. And so if you missing the FMR PEA protein and fragile
09:50 . I'm just reciting what we already about. When you get abnormal formation
09:56 the dendritic spines and Children that have X. We will have these elongated
10:06 , usually very, very abnormally long large foreheads and long faces. That
10:11 not to say that a lot of developing kids wouldn't have these features like
10:17 years or uh long faces of big , you know, But this is
10:24 of one of the features and fragile that you can you can observe from
10:29 outside. So these Children would you know, an ability to socially
10:35 with others. They'll have developmental And depending on the severity, this
10:40 a genetic disorder fragile acts. So linked to genetic abnormality where you are
10:46 a gene and that gene is necessary the normal formation of dendritic spines.
10:52 you're missing that gene as a genetic and the more severe, the absence
10:57 that gene is the more severe is symptoms. So if you're just missing
11:02 little bit of that gene, the X chromosome is just a little bit
11:07 . But you're still expressing some of podium, you may still have some
11:11 the dendritic spines in certain parts that normally distributed and others are not and
11:17 symptoms may not be as severe. it could be just social uh interactions
11:24 recommendation social interactions. Or if you a more severe case and missing a
11:30 of that protein then you will have epilepsy and seizures. So the more
11:36 is the genetic dysfunction in the fragile . And this is not fragile
11:42 But the basically the more problematic is symptomatic symptomology to more severe is the
11:53 . Mhm. Any other disorders that talked about so far and remember that
12:01 . S. D. Is very from Alzheimer's and Alzheimer's. We pointed
12:04 two hallmarks of Alzheimer's disease. The thoroughly tangos inside the cells and amyloid
12:14 outside the cells. And we distinguished like autism spectrum disorders, developmental
12:21 the onset of Alzheimer's disease is and aging Population so 50 plus is more
12:31 develop Alzheimer's disease. So today we're add a couple of diseases. Ah
12:40 are the ones that we may not back really and talk that much throughout
12:44 course that may come back. But , this is disorders that now relate
12:51 myelin dysfunction and the installation of the in order for myelin to properly compact
13:03 and wrap itself around. There's a mechanism of proteins that regulate that wrapping
13:10 in a precise manner. So they myelin basic proteins and they're controlling this
13:17 and this wrapping of myelin around the . So there are seven related
13:24 Example of such protein is myelin associated E. Um and it's responsible for
13:33 of myelin ation and silence self So if there is a dysfunction in
13:38 of these seven myelin basic proteins, may have a variety of ways in
13:45 the insulation is impaired. Could be impairment and initiation of insulation, inability
13:52 properly recognize that the South. So can start insulating or other problems or
13:59 and proper folding. Okay, so there are two disorders that we will
14:09 in relation to abnormal myelin nation, sclerosis and shark look marry tooth
14:18 It's a little older slide and I need to update the yellow because it
14:22 show up very well. But an of multiple sclerosis is is shown and
14:32 here. So, first of we always started multiple floors. Is
14:35 a developmental disorder? Is this an population disorder? What do you know
14:40 multiple sclerosis? When do you When do you think it occurs?
14:49 . Mhm. So, I the pathology of the disease, that's
14:55 you're talking about. So remember that talked about the prevalence first. So
15:00 . What's the population that suffers from ? So the population is usually answered
15:05 in the 30's again, You I want you to start forming when
15:08 think about the disease. You know who immediately talking about aging population,
15:15 spectrum developing this falls right in the age, I would say that's when
15:21 most starts showing up. Uh could due to mutations on chromosome 18.
15:28 other locations, could be have So this is pathology, right.
15:37 that causes is a mutation on the pathology. What it what it does
15:44 it causes de Myelin nation. So is a normally myelin ated axon.
15:49 you can see these really dark bands this axon. This is an axon
15:55 missing model. So this is pathology have the my island nation as a
16:02 of dim Allan nation, you have . So on on the outside if
16:10 is an expressive symptomology of multiple especially at advanced stages, it may
16:18 itself as tremors. It may express as convulsions. It may express itself
16:25 spasms and rigidity. Spasms meaning your just locks up intensifies. And you
16:32 rigidity. And it's very difficult because you even type to force yourself to
16:37 it for a few minutes in one it will get painful and you'll be
16:41 . Now, imagine this four hours . Alright, so so this is
16:49 . Uh this is C. S. Disorder. So do you
16:53 the traumas and convulsions is going to the only symptomology that these people
17:00 What happens if you d myelin it accents the impulses are not traveling in
17:06 correct way. And you have demanded in the C. N.
17:11 What do you know about the N. S. You know that
17:13 is comprised of many different organs. to the nephrologist or parts of the
17:19 that have different functions. Uh So depending on where there is a
17:29 significant the Myelin Nation, you may a problem with sleeping. You may
17:34 problems with understanding things. If it's nation and the speech areas you'll have
17:39 with speech and so it can be different parts of the brain and ultimately
17:48 to more severe pathologies. Maybe even in the brain because you have inflammation
17:55 going on that's associated with the Myelin . This disease is recessive. So
18:02 need to bad aliens from the genetics there are models of mice. So
18:12 is what we call a shiver of . And if you have a genetic
18:17 in chromosome 18 you can read basically the pathology which is the Mollen
18:27 And when you're doing animal models such rodents you want to have and overt
18:37 that you can recognize that is likened what you would see in humans within
18:43 . So if the symptom is tremors convulsions, that's why these rodents are
18:49 shearer mice. Okay, they shiver they have demolished nation and they produce
18:56 of the symptomology is that you would able to see in human cases.
19:03 this case there is a transected normal . So in experimental models you can
19:11 effect the jeans and essentially you're reintroducing gene that is missing and you're hoping
19:18 since you reintroduce that gene into the that maybe it will function or at
19:23 it will show a part of the or maybe it will rescue.
19:28 This is what you call you have pathology or you have a loss of
19:33 , the myelin Nation and ability to produce action potentials to conduct them.
19:38 want to rescue the loss of function you rescue in this case, hoping
19:45 that gene that you transfer acted back the animal will produce. We'll fix
19:51 Smiling Nation issue and indeed you can part of the smilin. As you
19:56 see in the bottom picture, this normal. This is shiver in the
20:03 and this is transfer acted transgenic so called transgenic mouse transgenic uh,
20:12 models that have genetic mutations in them genetic mutations. So this is multiple
20:23 . Uh, and uh, there's to treat multiple sclerosis. Most of
20:31 disorders that we talk about, there's no cures. There's an improvement
20:39 we talk about epilepsy, there's some of epilepsy that people actually get cured
20:44 or they no longer have epilepsy after exit out of certain stages and in
20:49 life or the environment. Okay, , and so flight is by the
20:59 and and there is a thing called and the reason why I'm mentioning
21:03 Do you remember when we talked about infections and we said it's caused encephalitis
21:09 the brain and that's inflammation on the , basically infection of the brain
21:15 So you can have and so from lightest, so encephalitis is so much
21:22 the inflammation that causes de myelin Of the accidents through this inflammatory processes
21:30 something to mention. Let's talk about attack, marat ood disease, which
21:37 again falls under the developmental disorders but as early as the first two years
21:43 age, because it's sometimes difficult to that In this case one of those
21:49 , smiling proteins that we talked about called PPP 22. And in short
21:57 narrative diseases, too much of PMP it doesn't mean that because there's too
22:04 it's too much of Myelin never correlate things. Biology is rarely a linear
22:11 . Huh. Too much protein can bad things. Less of something
22:15 Okay. Or less of protein can more of something else. So it's
22:19 or less of protein can mean less something else. It's just As four
22:25 really there. So you have a accidents and these accidents are peripheral peripheral
22:34 Myelin nation. It happens during the . And if you have too much
22:40 this protein, first of all this a label under the microscope, this
22:46 normal protein levels and you have a of this protein. The genetic duplication
22:54 in the chromosome that produces too much that PMP 22 chromosome 17. So
23:05 the symptoms of the disease is impaired and bodily deformities. Um, the
23:15 why is because you have no myelin the peripheral nerves. And what do
23:21 know about peripheral nerves? They sound to the muscles and they move
23:26 And as the muscles move, the as you're growing, are soft because
23:32 bones are stretching. And if you're something, you can reshape your bones
23:36 now, everybody is reshaping their bones what is called a cellphone posture.
23:44 this, yes, I'm gonna see about another 30 years, people that
23:50 like this actually don't walk like this they're going to reshape their bodies.
23:56 reshape our bodies. There's actually a posture that people talk about and there's
24:01 against the screen time posture. So bones are soft and not only during
24:08 development, you can reshape the bones adulthood. You know, do one
24:12 with one hand over and over and and over and over and over.
24:15 it's going to be stronger and it's to be powerful. It's gonna reshape
24:18 bones. It's gonna reshape your reshape your joints. So the bones
24:23 soft, they're developing because the muscles not contracting and they're not moving.
24:28 have deformities in the bones. And only way that you can really treat
24:32 deformities is trying to, uh, this disease as early as possible.
24:37 most of the town is diagnosed pretty and young kids typically placed in the
24:45 . so you would place them in leg braces or hip braces and that
24:51 basically with the gate and how absolutely the symmetry of the development of the
24:59 . Okay. So that's the only treatment that you have for charlotte narrative
25:09 to try to diagnose as early as . And most of the developed urban
25:15 and cities, environments. It's But it's in more of a distant
25:23 areas where you would see later diagnosis shark at meritage, um, just
25:31 because of lack of access or education . So, Okay, so two
25:37 diseases that we added and they really related to Glion specifically to my
25:44 And again, one that you would forming during the development this abnormality,
25:51 narratives and the added that would start itself multiple sclerosis C. N.
25:57 . Instead of preference And 30s or . Mm hmm. 30 years of
26:05 . Okay. This concludes, I talking about neurons and glia. But
26:12 again, we're never going to talk , We're never going to stop talking
26:16 neurons and Glia. And of course going to continue. It's just that
26:19 lectures conclusion. Mm hmm. So , if you look in your
26:29 you have this neurons and glia, is what we're talking about. And
26:33 you have this four or 5 billion and resting member and potential.
26:39 so this is the, for a , this is the material that I'm
26:55 . Okay, because if you go five, Which is today, some
27:03 4-5, I'm going to finish But if you go to five,
27:07 first slide will already have an overview what we're talking about today, which
27:11 hope to do the next next So today we're going to start talking
27:18 neuronal number and address right. And actual potential. What is resting membrane
27:34 ? Resting membrane potential is illustrated with example here you can see that the
27:40 which is ions that are charged, positively or negatively charged, accumulated,
27:46 charged on on the outside of the , negatively charged ions from the inside
27:51 the membrane. And if you have volt meter And you named the outside
27:59 zero Millwall's meaning it's the ground. then you pluck your electrode into the
28:05 membrane of this neuron. You will a change with respect to the ground
28:10 -65 million volts. So, as to the outside environment of the
28:16 the inner part of the plasma membrane the cell is negatively charged and it
28:23 a charge of minus 65 million barrels are excitable neurons are excitable membranes.
28:35 have only two types of excitable muscle and nerve mhm And when they're
28:48 , they're resting at -65 million And it does not mean just like
28:55 I still showing those When neurons are at -65 million volts. It doesn't
29:11 that the number in potential Will be flat at -65 million balls. Nothing
29:24 biology is flat. When you see flat line in the hospital, it
29:28 one thing. Mhm Thank you. Wrestling member and potential is at -65
29:40 volts for A millisecond, maybe maybe 20, maybe a second.
29:47 reality this resting membrane potential will call, it will do a random
30:01 . It will fluctuate into more positive , let's say -55 million volts.
30:07 into not more negative potentials, let's -70 million volts. And it can
30:14 this random walk and fluctuate. So it's going to more positive potentials,
30:19 because it's receiving excitatory inputs and it's becoming more negative. It's because
30:25 receiving inhibitory inputs. Goblin. So resting membrane potential never think about it
30:31 a one flat line at 65 is and biology have a lot of fluctuations
30:37 the lines. Anything temperature, the , it's never stuck at one.
30:43 you go down to decimal points, always changes that are happening and air
30:49 and temperature is alone. Okay, , if this neuron reaches a potential
31:01 about -45 million bowls, this neuron then produce an action potential. So
31:13 action potentials are incredibly fast. They're the order of a few milliseconds and
31:19 will understand everything about these action And so this value here -45 is
31:25 the threshold value for generating the action , the action potential and the action
31:34 neurons, the person of the plasma , all of the action that you're
31:39 neurons and these excitable number uh neural are across the plasma membrane here.
31:47 there's a reason why neurons produce these fast action potentials. Because you are
31:54 fast. Think about how many things can do at the same time.
31:59 multi task within seconds. And sometimes even forget like you're driving a
32:06 where was I the last five Does that happen to you? So
32:10 back on the road but I never . Really. So where was your
32:15 ? You all of a sudden almost yourself consciously from the road. Some
32:24 in your body subconsciously was still staying lane right while you were doing
32:31 listening to somebody talking music playing and text messages at the same time.
32:38 know. And but but we do things and we multitasking it's very,
32:42 fast and different things require different speeds . Some of them slow and some
32:47 them much faster speeds. So you a question for but like said absolutely
32:55 there are like when you are dreams when you sleep and you dream when
33:01 see dreams. Yeah, it's Tell me about it. Don't tell
33:08 about your dreams but we'll talk about lowest dream. We changed neuroscience
33:13 Well dreams are its we won't have time to talk about sleep and
33:19 but your brain is very active. just that your body is disconnected.
33:23 maybe that's what you're talking about. that some some sometimes your body the
33:28 is active in the dream state, your mechanics and your motor activities is
33:32 . That's where you're lying still. in your dream you're running and doing
33:36 lot of things but you're maybe laying . Sometimes you may be moving a
33:40 bit, you know, so maybe somewhat similar the ability for the brain
33:44 still do things and and have somehow motor function ongoing with driving and steering
33:50 wheel don't do it by trying to the beat for five minutes. It's
33:55 . So uh it's very interesting dreams , I don't know what dreams
34:02 There's a big debate of dreams what are typically there are like unusual combinations
34:07 things that have been seen, what be predicted from things that you have
34:12 . But sometimes it's reality and sometimes not and sometimes it's very vivid and
34:19 they're very distant. So there's a world of what's going on dreams in
34:24 way is also brain plasticity, you things if the big beer attacked you
34:30 day, you're going to have a . Very likely. You're gonna be
34:34 and you're gonna be thinking is that coming in and I'm going to
34:37 Your brain is going to be occupied it. You know, I had
34:40 bad dream and maybe that is necessary that you can get over it because
34:45 you see, there's different forms of . Some forms of plasticity help you
34:50 things. Other forms of plasticity. necessary that you forget things if you
34:55 forget things. If you don't forget things. Especially that would be
35:03 very difficult. So, it's a deep question. And that's a separate
35:07 I think. But we're gonna go to some very basic things and that's
35:11 reflex art and this is how you produce these fast action potentials. And
35:16 of the reasons you would produce action for reflexes to very quickly reflexively react
35:23 the changing outside environment. And we're to talk about knee jerk stretch or
35:29 tendon, reflex, and the reflex , which is the simplest kind of
35:34 pathway that you find between the knee the spinal cord. And this is
35:41 thing that I would like for you do, because I would like for
35:44 today to make a table on different subtypes. And because we already discussed
35:52 different cell subtypes that it would be for you to keep track of
35:57 Okay, so I will mention the subtypes that we have talked about so
36:04 . Mhm. We talked about pyramidal . We talked about inter neurons in
36:20 hippocampus con and I'm talking about neurons . So we also talked about glial
36:32 but when we talk about resting membrane or action potential we're gonna talk about
36:38 survives of neurons of these cells. . So what type of cell is
36:45 parameter herself? Is it excitatory This is an excitatory self was
36:53 And excited to herself because it releases . There's a neurotransmitter. Whoa.
37:06 type of cell besides excitatory? Yes a multipolar self. We're a prominent
37:18 located black. We talked about the . What we talked about cortex.
37:32 you. This is your parameter all and you know a lot more about
37:37 it'll cells actually. What else do know about? Private all cells they
37:42 like pyramids. They have apex and . Done rights now the base and
37:55 Dill. Right. Have an axon that axon travels long distances. Okay
38:06 their projection cells, wow and we'll more about parameter cells actually in this
38:17 . But this is a good introduction what you know so far about
38:22 It'll cells Next we talked about inter . We looked in particular in the
38:33 in the hippocampus and we said that neuronal diversity and diversity and neuronal function
38:41 the ethnicity which rhythms means computation, means behavior rhythms. Mean thoughts,
38:48 . Mean memories, motor tasks, of that. Okay so we talked
38:54 inter neurons of the hippocampus. What of cell are they their inhibitory.
39:02 are they in inventory? Because that's . They release Gaba. Okay.
39:12 kind of polarity? Inter neurons have . What? Multipolar? That's just
39:19 symbol. You can put the words a different symbol for it. Where
39:24 they located? Well I just have hippocampus. But in reality the hippocampus
39:34 . T. X. Plus Thanks. And what did we learn
39:46 inter neurons in hippocampus? That they're ? Which means that the projections of
39:57 inter neurons our local their axons projected parameter cells locally. They don't come
40:07 of the typical. There's also in science and especially in Neurosciences. Exception
40:13 every rule there's inhibitory projections. Cell in a while and they're excited to
40:20 into neurons once in awhile. Don't anyone. Don't talk about it
40:24 Don't confuse yourself. Don't take take notes. Alright so now we
40:35 the endurance of the hippocampus. Today we're going to introduce three more
40:41 . You already heard about them. , we talked about that. All
40:45 the sensory information from the peripheral below neck comes from dorsal root ganglion
40:51 These are the cells right here that have their peripheral axons in the muscles
40:59 the joints and they will have their sensory neuron soma is form right outside
41:07 spinal cord and called this dorsal root ? It's a collection of neuronal
41:14 And their central axons of the geology will project into the spinal cord?
41:25 no. Yes I call them DRG of dorsal root ganglion cells. What
41:33 of cell is it? Is it inhibitory? And I was excited to
41:42 . What type of neurotransmitter does it ? Yeah. When I wrote it
41:52 here I will ask you on the . Yes. There is both.
42:01 is a way to tao, there a way to see. There's a
42:04 to draw if I drew the sell you and I said is this a
42:11 solar into neurons? What would you ? Okay so there's many different
42:17 You can draw it. There's you can look at the action potential
42:22 of parameter self versus the inter neural many different ways. So but you
42:30 to keep the information that I'm telling here because this is all a part
42:35 understanding and building neuronal circuits in your . And once you know the neuronal
42:42 plus minus is you can do a of things with it. You can
42:45 math with it, you can do with it, you can do what
42:49 with it. So DRG neurons are excitatory neurotransmitter. Uh huh. And
43:01 are also what type of cell they're sudo Unipol herself. That's my symbol
43:09 pseudo Unipol herself. This is also talked about this in your previous notes
43:15 . Where's dorsal root ganglion cells Well we just talked about it.
43:21 spinal cord but they're selma's are located outside the spinal cord. More so
43:34 ganglion south, we'll pick up the of the stimulus. So when you
43:40 to doctor's office and he does a checkup on europe, you go to
43:44 neurologist office. You will be sitting the table. All right. And
43:49 the doctor will take a your leg be hanging and the doctor will take
43:55 little knowledge and hit your head Uh So it's uh me and see
44:06 happening with your leg. How you jerks. Right? This is the
44:11 that we're talking about the patella So, you have to have a
44:15 . And the stimulus is this mallet that's hitting right here onto the,
44:23 the joint. Okay, this is right here. The information dorsal regaining
44:28 picks up from muscle spindle carries that and the central action carries that information
44:34 the spinal cord. It answers the cord on the dorsal side and then
44:39 spinal cord, it can synapse immediately the motor neuron. So this is
44:43 motor neuron. Once it's synapses onto motor neuron, this motor neuron can
44:48 onto the cell. The quadriceps cell causes contraction of this muscle causes contraction
44:55 this muscle will kick your leg Okay, so that sells that it
45:03 his motor narrows, murdering your Are excitatory motor neurons are multi polar
45:16 neurons live in spinal cord moment neurons , student Colin mm hmm.
45:34 In addition to contacting motor neurons essentially you if you want to have a
45:40 synaptic a single synapse reflex. This an example of mono synaptic reflex.
45:46 excited the spindle with a stimulus and one synapse dorsal root ganglion south of
45:54 motor neuron air. You can cause contraction of the muscle. But guess
46:00 for every muscle? When you contract an opposing muscle right? When you
46:05 the biceps, what happens to the it's relaxed when you contract the
46:11 what's happening to the biceps? It's or extended? Okay so in order
46:18 this reflex to be appropriate you need relax or inhibit the activity of the
46:28 flexor muscles. And so the same neuron dorsal root ganglion cell will also
46:37 information to the inhibit their inter So, mm hmm. Inter neurons
46:52 try inhibitory. Mhm. Our malta We live in spinal cord and they
47:06 glycerine. So wait a second you that inter neurons release Gaba and an
47:18 releases license. And I also told there's exceptions to everything in science.
47:24 in the spinal cord those into neurons slicing in the C. N.
47:30 . In the cortex and the hippocampus release Gaba. So it's basically two
47:36 in our transmitters. And when we about N. M. D.
47:39 glue dramaturgical neural transmission. You will another role. That glass in place
47:43 C. N. S. Which excited to actually the effect of this
47:49 depends on what receptor it binds You understand that when we talk about
47:56 transmission. So are these interneuron projection A motor neurons projections house. Yes
48:06 they project out of the spinal cord the periphery. But you wouldn't call
48:11 like typical cns projection cells but they their axons out into neurons again our
48:19 . So you can see that control the inhibition is happening here locally in
48:23 spinal cord and the output comes out the central horn of the spinal cord
48:30 order for for the different stimulus signal is incoming information into C.
48:37 S. To cause a proper contraction this muscle. You have to excite
48:42 motor neuron to the contraction of this and you have to inhibit and quick
48:47 the motor nerve and relaxing quiet for opposing muscles. And so you have
48:54 reflexes which are mona's synaptic in reality for the knee jerk reflex to be
49:00 operational intact. Its policy synaptic because need to involve the opposing muscle and
49:05 need to involve other synapses such as inter neurons that we talked about,
49:11 activation of motor which is different. coming from the C. N.
49:15 . To execute the function in the . There's a lot of complex reflexes
49:21 and complex reflexes are not just involving synopsis complex reflexes can involve several brain
49:28 , several nuclear in the brain an of a complex reflex at the level
49:34 brain stem is a gag reflex when get nauseous or you get gag,
49:40 not something that you control consciously. it involves many different centers and that
49:45 doesn't have to do with somebody touching but with other things such as
49:50 snails or mental anxiety, um mentally laws here. He was a fast
50:00 . Okay, so these are the that I took and maybe I'm gonna
50:06 a picture of these notes so that can be nice to all of the
50:13 that are on Zuma. Maybe you see my scribble. Mhm. So
50:24 may want to have a separate page a table for for the cells you
50:32 want to create your own symbols or it out for the cells. But
50:36 are all very good exam questions, know, those are ganglion cells that
50:41 local into neuron or is it an sensory cell, yep, control And
50:52 say that again, sorry, show that complex. Well, the
51:02 basically, if I'm understanding correctly, have to know the circuit for the
51:07 reflexes were not discussing. I mean not discussing the cells right now,
51:13 if you understand this sequence of advance in the circuit, it's important because
51:18 very basic circuit and also the major subtypes and what they are so that
51:23 can start building this language uh so we can understand what's happening in the
51:30 better and better and more and Okay. The cast of chemicals that
51:35 important for the wrestling member in Some very basic things. It's a
51:41 solution. It's a quiz environment inside house and outside of the cells our
51:46 are comprised of flood 70% of aqueous . Oxygen attracts extra electrons and has
51:53 charge hydrogen has that positive charge hydrogen held by equivalent bonds, other
52:02 molecules dissolved in the water molecules. ions atoms or molecules that have net
52:09 charge. The form ionic bonds such sodium plus as a positive cat ion
52:16 chloride mindless and negative. An ion . The number of protons and electrons
52:23 would determine this valances. So you have plus or two plus like counseling
52:27 pluses dive Alan katana and then Moana versus Duyvil and cast iron versus an
52:35 . So you have these ions sodium and they're surrounded floating around the
52:43 The most important ions for understanding the member and potential are the sodium,
52:50 chloride and calcium. Most of the across plasma membrane that is of interest
52:57 us. And the flocks of ions plasma membrane is sodium and potassium for
53:03 potential production. Um, there is disparity in the concentration of these ions
53:11 plasma number disparity meaning that these ions not freely pass through the foster lipid
53:18 layer for these ions to pass. have to pass through ion channels there
53:23 protein channels and these channels are regulated they're not open always. They can
53:32 given certain conditions. They can be by many things. The next few
53:37 we'll talk about voltage gated channels which that these channels are opened by a
53:43 in the voltage. There's ligand gated which means the chemical has to bind
53:49 that channel in order for it to . Okay, there's maracana receptors from
53:55 gated channels. That means there has be a physical pressure such as on
54:00 hair cells in order for the channels open so many different ways. But
54:05 channels are dependent in this case on membrane potential, whether they're open or
54:12 . They're dependent on the voltage. is a lot of sodium on the
54:19 and there's little sodium on the inside on the inside of the cell it's
54:24 potassium ion that is the most concentrated the most dominant again chloride. There's
54:32 chloride on the outside of the And little chloride on the inside and
54:37 biggest discrepancy and concentration gradient exists for . There is very very little calcium
54:49 the inside of the south as compared the outside of the cell. Will
54:53 this in the second. In addition these ion channels that are important for
55:00 and keeping this resting number and You also have N. A.
55:05 . A. T. P. . S. Or sodium potassium
55:09 And as you'll see once these channels based on voltage, the ionic concentrations
55:16 redistribute based on the chemical concentration But when it comes down to N
55:23 K T P A. S, always works in the same direction and
55:27 always works against the concentration gradient for and against the concentration gradient for
55:35 It does so by using a eating up a lot of energy.
55:44 as you know these channels and these have built very basic things. You
55:51 amino assets, the building blocks or that you put together. You create
55:58 of this amino acid with peptide bonds power top types. Okay. And
56:04 have if you review there are certain assets that are essential and non essential
56:12 assets and that means that there are amino assets that the basic biology that
56:17 learned probably in high school that you in your own bodies. And there's
56:21 stuff that you have to go and them in the field and put it
56:24 your mouth and eat it. So will have it of course in the
56:29 that is in the grocery stores. think about what hunter gatherers had to
56:34 in order to understand that their diet to be supplemented with amino acids and
56:40 like omega. I mean assets as , oils and fats, proteins then
56:47 strong. These individual lucy and Syrian , amino acid molecules get strung together
56:54 a chain. This primary structure of acid, the secondary structure would be
57:00 here. This chains can then be sort of like in a corkscrew or
57:05 can be sheeted like sheets and called sheets. And this is a secondary
57:13 . Then in C you will have example amino assets that will form a
57:19 trans membrane segment. Alright, that for a trans membrane segment, A
57:25 of the protein that trans membrane that piece of the protein that trans
57:29 segment can get joined with other trans segments. In this case it's for
57:35 membrane segments can be five trans membrane can be six trans membrane segments within
57:40 channel. There are four trans member segments that will now comprise a subunit
57:48 the protein. In this case of protein channel and this is now a
57:54 structure and multiple sub units will get together to create the co ordinary
58:02 So multiple subunits will come together the variations of subunits. One channel can
58:09 different variations of sub units, let's it has Pasadena's alpha alpha, beta
58:15 Yama. They will also have alpha , beta, beta beta. All
58:21 . And it could be the same but it could be slightly different functions
58:26 that channel depending on the subunit composition that protein channel. Yes, now
58:32 have this polyp peptide units that come get embedded in the trans membrane essentially
58:38 trans memory segments, trans membrane subunits the whole channel I am channels are
58:47 ion channels will not just open and of the size that will let in
58:51 of the islands that fit through that . Instead, you can look at
58:55 channels as molecular seeds. They're seeding which ions are going to go through
59:02 not just based on the size, also there are much so on the
59:07 interactions that that specific ion will happen its own specific channel. So these
59:15 that you can see in this example is a sodium channel. You can
59:18 that the sodium is surrounded by water lot of times we'll call them waters
59:24 hydration, of clouds of hydration because on the size of an eye on
59:30 cloud will have a different size. . And the sodium ion which is
59:37 on the outside, there's a lot sodium and now this channel is open
59:42 was open, sodium ion will come the channel will reach the innermost lumen
59:50 that channel. There's actually a filtration acid proteins that are sitting there will
59:57 stripped off the waters and will also briefly interact with an exposed amino acid
60:07 on this inner lumen of the sodium that's specific for sodium ion and it
60:14 be a negatively charged amino acid revenue and that negatively charged amino acid residue
60:21 briefly will attract the positive charge, minor actually will propel it. So
60:27 stripping attraction will cause us the propeller of the sodium through the channels.
60:34 it goes now in the wider part the cytoplasmic side of the channel.
60:39 , it gets immediately bathes surrounded by waters of hydration. Okay, so
60:46 muscular junction and this is the junction we talked about. This is neuro
60:52 junction and this reflex because neuro muscular neuron contacts a muscle cell, neuro
61:00 junction. So we're talking about this muscular junction, you have a release
61:08 acetylcholine on motor neurons and is excited neurotransmitter and you'll see that acetylcholine and
61:14 cns again has a different function. not about contracting the muscles of the
61:21 . Single acetylcholine receptor channel can conduct million ions a second. So this
61:29 conductance of current which is, I review alms law in a little
61:36 N A K. T. P can deliver on the 100 ions on
61:40 . So it tells you that the channels voltage gated ion channels. They're
61:46 . They can conduct a lot of . The pumps are slow. Mhm
61:53 are selective island filters sodium, the of waters by amino acid residue centers
61:59 with larger diameter potassium is trapped inside out. So in this case potassium
62:05 would be larger and wouldn't fit. then you'll say well then that means
62:08 potassium channel is larger and therefore sodium should fit through it. But that's
62:14 that simple because the waters of the size is going to be
62:19 Brown sodium versus potassium island. And residue interaction sodium channel is going to
62:27 slightly different from interaction with potassium channel essentially either sodium or sodium channel or
62:34 from a potassium channel. At some , the selectivity rules can be broken
62:39 if the brain is functioning abnormally or there is abnormal activity like epileptic
62:47 there's gonna be leaking of ions in out of all of the channels in
62:52 different ways that we don't really understand well within normal controlled fashions, it's
62:57 selective and you have sodium selective channel selective channel chloride, calcium and so
63:04 . Yeah. So for the is 100? 100 or is it?
63:13 an exchange three for 200 islands per . That's a good point. Is
63:18 34 to exchange the total of I'll have to look it up.
63:22 . Because in the following slides you see, well this is arms law
63:27 you will see maybe in this line that for it's in the following slides
63:33 for each. Okay. But for three molecules that brings out and brings
63:44 two. So I will have to up the total number of 100 and
63:48 it is made. We'll finish today briefly reminding ourselves of arms law.
63:54 that when we come back on we can finish talking about the diffusion
64:00 electro motive forces and start talking about equilibrium potential and learns equation and Goldman
64:06 cats equation so that we understand what the equilibrium potential for each ion and
64:11 how we calculate the rustic number and . So we'll spend about half an
64:16 on thursday finishing the resting membrane Election, remind yourselves on law.
64:22 long V equals ir you started learning this in high school physics. These
64:29 for voltage is measured in volts in . The most relevant scales are million
64:36 . So the action potential and the minus 65 million volts, wrestling number
64:41 potential, 100 million ball amplitude of potential, we're using the lingo of
64:47 current because I is measured in amperes neurons, the relevant scales or anything
64:56 million compares to No, no in . Resistance is measured in arms and
65:06 are very small, about 10 micrometers diameter. So they have high resistance
65:12 the smaller the sell the higher the resistance depends on the surface area and
65:20 resistance in neurons is measured in mega conductors which is an inverse of resistance
65:30 simmons and the relevant scales from neurons PICO and nana's emails. So when
65:38 talk about the conductance of single channels overall conductance of a neuron or a
65:43 you're jumping between PICO and and Siemens. These are the relevant scales
65:49 that are important for us. So equals IR G is the inverse of
65:57 one over R and therefore current is . Times of change in voltage can
66:06 calculated here. Uh Most of the that will happen. Chemical diffusion.
66:14 you just have the rule that it's plain chemical diffusion, you have a
66:21 of sodium chloride on one side of membrane and nothing on the other,
66:24 water and then you open these channels sodium and chloride. What's going to
66:29 is that sodium and chloride are gonna into the opposite direction until there is
66:36 equivalent concentration or equal molar concentration on sides of this plasma membrane for sodium
66:44 and chloride ions. So then you'll so what's the problem then?
66:49 Why isn't it just all even on sides? So that's not interesting.
66:53 have to charge up the plasma member you have to create that negative 65
66:58 volts of charge. And the reality that the ions and each ion also
67:06 an electrical driving force an electrical battery ions are charged. So as you
67:13 , you have a negative and this toad and positively charged and ions will
67:18 cat ions, I'm sorry, attracted cat out and and Niles attracted to
67:25 ode on the battery. And it's only the chemical force that drives the
67:32 concentration of these ions, but it's the electrical force of the battery,
67:37 voltage drives ions through channels to so have separation of charge across the membrane
67:44 it gives rise to the difference in potential. There's a difference in voltage
67:50 the inside versus the outside. And you have the number of potential which
67:55 VM. And addressing that number in is negative $65 million. Kind of
68:03 you have reduction in charge separation, membrane is getting more positive. It's
68:08 deep polarization. If you're adding more charge on the inside of the plasma
68:12 , it's called hyper polarization polarization is to excitability an action potential firing and
68:20 polarization equals to co essence or repression the firing and activity in the cell
68:30 general for the current flow, the are, is the direction of net
68:34 of positive charge. So by that , the ann ions move opposite to
68:41 direction and cat tiles move the same current direction. So, an example
68:52 a diffusion of forces that are equal electrical forces when they become equal to
68:59 other. This point is called equilibrium . So, I will very briefly
69:06 this to you that if you had potassium ion and you open that potassium
69:11 you have an an eye on here negatively charged protein that kind of exit
69:16 of the cell and you will expect potassium to reach the same concentration on
69:22 opposite side down this concentration gradient. what happens is that once the potassium
69:27 starts leaving the left side, I'm into the right side and there is
69:31 build up of positive charge on the of the plasma membrane that charge the
69:37 force becomes repellent. The positive charge repellent to the positively charged ions At
69:44 point, the chemical force which is chemical concentration driving potassium from left to
69:50 . The chemical force okay, is equal to electrical force, pushing that
69:57 ion the positive charge, pushing the ion back onto the same side and
70:03 where you reach the equilibrium potential for individual iron and each ion sodium
70:11 potassium chloride calcium will have their own potentials. So when we come back
70:17 thursday will walk through the equations that you calculated equilibrium potentials, will understand
70:24 reversal potential values and we'll start drawing major diagram for the action potentials,
70:30 I'll also have a slide in the notes. But if you draw it
70:33 me together and save a page for , it's a great studying tool for
70:37 and for the future. Okay, we'll end here today. I want
70:41 mobilize and save the lecture. If is some questions on chat thursday
70:49 thursday class will be in person. , so I will be here on
70:54 in person but I will have a link today we had 42 people to
71:05 mm hmm. No, 42 people . About 35 in person. So
71:13 appreciate everyone being here and keeping up attendance. I'll share the lectures.
71:18 them. By the end of this you'll have all of the lectures uploaded
71:24 I will see you all on but if you want to use zoom
71:27 thursday, uh you're welcome to do . Uh
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