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00:00 this is lecture eight of neuroscience. today we will talk about the action

00:07 . So the action potential three and propagation. We're going to review some

00:12 the concepts that you learned over the couple of lectures onto this slide here

00:38 potential. So now you know a about what's happening during the action

00:43 Uh but we also reviewed some other is actually not the this is the

00:51 that we reviewed last time. So to remember is that we still talked

00:57 the membrane equivalent circuits which was basically of the properties of the biophysics of

01:03 plasma membrane. And I've asked you know the symbols for resistor conductor or

01:11 resistance conductor for battery as well as . We talked about these circuits that

01:19 essentially membrane equivalent circuits that can be by these different parliaments, the batteries

01:32 , capacitor, active pumps. Even that was one important concept that you

01:39 get a question or two on. other important concept is the resistance and

01:47 with properties of the cell. And fact that the resistance is inversely proportional

01:56 to the size of the radius of cell and capacitance, the larger to

02:02 , the larger the surface area, larger is the capacities. So that

02:07 an important concept that contributed to us about the fact that when you look

02:13 the cellular response as opposed to the that comes from instrumentation, the change

02:21 current stepwise current. A cellular response gonna have this ramp up and then

02:30 down and that's because of the resistance capacity, the properties of the

02:37 Number three important concept that we discussed lecture was the I. V.

02:44 . And we talked about the current plots and when we talked about current

02:51 plots we discussed the following concepts. said that first of all you have

03:05 nana empires, negative nana empires for . Then the voltage have milli

03:16 And let's say this is -100 -50 plus 50 plus more. So we

03:31 about the fact that some of that current voltage plots may be linear.

03:40 means that for the same change in you will have an equivalent change in

03:50 because we're talking about channels and flux ions through membrane channels that are dependent

03:59 voltage. So we talked about how is gating the channels we're talking about

04:06 for the action potential. Okay and drew a couple of other plots and

04:15 said that this is a linear on chi v plot. But I indicated

04:22 there are some responses from the south the channels that are nonlinear. That

04:31 that the same change. And the actually generates a very different change in

04:42 and that there is a preference for channel to conduct ions and the direction

04:48 conductance is inward. So by definition negative nana Appiah deflections is an inward

04:57 . Positive is an outward current. so now the other two plots that

05:10 drew on here is I said I ask you in the exam for something

05:17 this if I drew a plot and said um can you tell me if

05:25 ivy plot refers to sodium or potassium ? And I've asked you to know

05:33 uh nursed equation, global equation and potential values potassium and I said the

05:42 equilibrium potential value is gonna be And so this is would be a

05:50 of potassium because at -90 there's no between VM and the equilibrium potential and

05:59 you recall the change in current is strides, the driving force, there's

06:05 driving force here for potassium and then said I may draw another plot that

06:12 like this and ask you, does represent potassium and sodium? And there

06:18 be many ways that you can envision that potassium is going outwardly on this

06:24 . This is positive 55. And said remember this is a sodium reversal

06:29 . So this would be a representative the sodium current. Okay, and

06:41 that when we talk about the membrane value which is calculated from some of

06:51 sodium, even chloride ions from the is really important for mobility at rest

06:58 the greatest potassium from the ability during rising phase of action potential is the

07:04 sodium. So these things change and will hugely influence the overall membrane

07:12 Okay, so now we're down to four from last lecture and that is

07:18 voltage plan. So you don't need memorize the circuit but what you have

07:25 is conceptually understand what this technology allows to do. And what this technology

07:32 you to do is to control membrane to clamp membrane voltage. Or there's

07:40 desired or what we call a holding command potential. So this technique is

07:49 in order to tease out individual Is that underlie the action potentials?

07:57 originally action potentials were recorded, you reporting voltage change in voltage. Now

08:08 want to be the equals IR you the current to control the voltage.

08:13 you want to be on the other of the equation. V control the

08:19 to record the current. Okay. this technique was used by Hodgkin and

08:29 in isolating the individual conductance is for and potassium mines. So, what

08:37 did in this experiment that reviewed is stepwise deep polarization, showed an inward

08:45 that's transient, followed by an outward that sustained and persistent during the

08:52 And that the inward current reverse of 52 which I call positive 55.

08:58 this is a reversal of the sodium because in the other values which are

09:04 more positive potentials holding potentials. This a voltage clamp holding potential positive

09:11 It shows that now sodium is flowing the opposite direction. Okay, It's

09:19 outward instead of inward and that there's sustained outward current. So, as

09:26 discuss, the action potential. Rising is dominated by many sodium channels opening

09:34 for a millisecond or so in reflected in an average of these civilian

09:41 here to multiple channels and then potassium are delayed. But once they're open

09:49 potassium channels, the currents are So we call them sustained as long

09:55 there is a sustained deep polarizing Um the next thing that we talked

10:04 is the structure of the voltage gated channel And we pointed out that it's

10:10 four subunit structure that has six trans segments where S4 is a voltaic sense

10:19 it has positively charged amino acid residues us five and a six. You

10:25 the for loop that comes together from subunits to serve as a selectivity filter

10:30 select for sodium. Uh the way the sodium channel gates open is through

10:38 confirmation all change In this three dimensional structure. And the way that confirmation

10:45 change comes about is that once you the membrane from negative 65 which is

10:52 negative charge and attracting this positive charge stay here on the side of plasma

10:58 of the membrane, you add positive here again, positive charge would be

11:03 from synaptic inputs. And if it the membrane potential, the threshold you

11:08 produce an action potential. So if reaches those close values, what happens

11:13 now the inside of the number and becoming more positive. It's not completely

11:19 but it's more positive than the build of that positive charge or less negative

11:24 starts repelling. It's not as attractive this both incentive to stay on the

11:31 of plasma side. So it shifts this protein structure and as it shifted

11:36 conformational change which opens the gates for sodium channel. And we talked about

11:42 types of gates, these arms that closed here, we call them activation

11:48 and this ball and chain like structure called inactivation gates. And if you

11:56 polarize plasma members of the south, sodium channels will open so activation the

12:02 sensor will slide up the activation gates open. But that same confirmation all

12:07 in the protein structure will encourage for ball and chain mechanism to basically plug

12:14 the channel four. And at this the channel and number three is inactivated

12:21 this channel will remain inactivated until you the D polarizing stimulus in the plasma

12:29 Repola rises to a resting membrane And as it re polarizes to resting

12:36 potential, that voltage sensor is gonna drawn to the negative car and downward

12:43 causing this ball and chain to swing which is called Dean activation and subsequently

12:51 closure of the activation gates. So have to go 1234, 1234.

12:58 this is the reason why, as spoke that sodium, one of the

13:02 why sodium doesn't reach the Librium potential sodium during the rising peak of the

13:07 potential. This reason is the kinetics the closure of the sodium channels

13:13 In other words. Okay, so is what a voltage clamp. Modern

13:21 clamp would look like. Instead of circuit with two electrodes, you have

13:27 electrode. And the reason why from electorates you can go down to one

13:33 is once the circuit became super they can do both stimulate and sample

13:40 they can do it at such fast rates 10 kHz, 16 kHz,

13:46 kHz. Which means that 10,000 samples second. So we can capture a

13:52 of information still on the data without information at such high sampling rates.

13:59 this is a typical setup that I you earlier that I said it's underneath

14:05 microscope, you guide the electors to south. And this illustrates that in

14:11 instances instead of recording activity from the south, you may want to record

14:17 just from a patch of the And what you're hoping for is that

14:21 of the membrane will contain your voltage gated channels or receptor ligand gated

14:30 that this piece of the member will that channel eventually. And this is

14:36 like a reduced way of looking at cell even more so than recording activity

14:41 the whole cell. But it's very because now you can test the flux

14:47 ions. You can change the concentration the pipette, you can change the

14:52 of this outside environment and you can testing how different substances such as in

14:59 original days of roderick Mackinnon, how toxins were affecting the flux of ions

15:04 potassium channels. As he was deriving structure of those potassium channels. You

15:09 see how different chemicals pharmacological agents affect of different channels such as sodium

15:18 And these techniques they called voltage clamp or or patch clamp techniques. They

15:27 several, they come in several so to speak. It's still that

15:32 recording pipette. That pipette if you has to have a certain solution inside

15:40 represents either the inside of the cellar of the cell, whatever experimental you

15:45 it to be. And in some you can have an attached recording.

15:51 this attached recording is basically the end that elector just attaches to the plasma

15:59 . And then now you have access records from a small patch of the

16:05 just through the channels that are open . So that's one way of doing

16:10 . Very common way of doing these physiological recordings of neuronal activity. Is

16:18 whole cell recording in that situation when guide that micro electorate to the

16:24 it's not only attached to the amplifiers it's also attached to a little tube

16:30 that little tube is attached to another tube? And that another little tube

16:34 attached to syringe. And the experimenter a syringe so the experimenter can approach

16:41 cell with the lecture and suction So it attaches to the neuronal membrane

16:49 then produce even stronger fast suction through syringe to bust open that plasma membrane

16:56 separate it to gain access to the cell and record all of the car

17:02 . That would be flexing through the cell and the side of plaza in

17:07 situation becomes continuous with the pipette So that means that whatever you have

17:12 the pipe at what we call the pipette solution or inter cellular solution should

17:19 what the cytoplasm of the neuron would in some other instances, instead of

17:28 the membrane to gain wholesale access, electrode actually withdraws itself a little

17:37 Well, you know, it takes skill to do that. It's a

17:41 , not a robot that does that it breaks off a piece of the

17:47 from the rest of the south. this is an interesting configuration because now

17:53 inside of this channel say sodium the inside of this channel is exposed

18:01 the outside. Okay, that's why called inside out recording. Now,

18:09 you put certain substances for example that not cross the channel and do not

18:13 the membrane, especially in pharmacology, may have a question, which part

18:19 the channel does it bind, bind side of plas mix side of the

18:23 . Does it bind the extra cellular of the channel? If it binds

18:28 cytoplasmic side of the channel, you'd to do the inside out recordings because

18:33 would expose the inside of the channel whatever would be binding to that channel

18:39 you see what effect it has on current flux through the channel there.

18:45 it's an inside out recording. Uh in some other instances you actually withdraw

18:54 piece of the number rain and you it as you're retracting it. And

19:01 happens is that if you're lucky, membrane will Rien il. But instead

19:07 exposing the cytoplasmic side, it actually the extra cellular side of that

19:16 So once again, if you have that do not cross through the channels

19:20 not cross through the membranes or not soluble and you're interested to know how

19:26 given substance with the fact that flux sodium channels through potassium channels.

19:32 you have a lot of tools at , you can use chemicals for pharmacological

19:38 , you can clamp the voltage. you can just look at sodium current

19:44 of these patches of membranes will contain potassium and calcium channels. And so

19:50 can isolate them based on their equilibrium and based on their kinetic properties of

19:57 and closing to identify different currents and different substances would affect. Either the

20:04 inside out or outside, which is out recordings or outside out activity.

20:11 would be exerted on these channels by substances. So there is this uh

20:22 interesting story and I'm gonna maybe pause recording for a second. Yeah

20:32 Fan tastic. Beautiful language isn't God's . Don't eat another bite. Couldn't

20:52 mr Simpson, I shall be We have reason to believe you have

20:57 poison poison. What should I What should I do? Tell me

21:02 . No need to panic. There's map to the hospital on the back

21:05 the menu. Try something new What will it hurt you homer?

21:12 never heard of a poison pork Your wife agreed that I should break

21:16 to you know need I can read like a book. Oh it's good

21:23 isn't it? No. Mr If in fact you've consumed the venom

21:28 the blowfish and from what the chef told me it's quite probable you have

21:33 hours to live 24 hours. Well I'm sorry I kept you waiting so

21:39 . Oh Mark, I'm gonna I'm gonna die. Well if there's

21:44 consolation is that you will feel no at all until sometime tomorrow evening when

21:49 heart suddenly explodes Now. A little anxiety is normal. You can expect

21:54 go through five stages. The first denial. No way because I'm not

21:58 . Second is anger you. Little that comes fear, Fear what's

22:04 Fear bargaining doc. You gotta get out of this. I'll make it

22:07 your while. Finally, acceptance. , we all gotta go sometime.

22:11 Simpson your progress Astounds me. I leave you two alone. Perhaps this

22:16 will be helpful. So you're going die. Mm. Faith tenses on

23:13 success battle has been great. I supposed to be the last lecture.

23:24 . That's truly not at his best . Let's see, I was trying

23:39 find the Fish, which there are 100 species worldwide. You need a

23:48 to sell puffer fish in japan, as a buyer you need one too

23:58 Okamoto has a fuego restaurant and of a license. He's not here to

24:04 the increasingly popular nontoxic farmed food which be recognized by its shorter fins.

24:10 is he interested in the small species in the wild from japanese waters.

24:16 true connoisseur is only looking for one toxic wild as fresh as possible and

24:23 means tora fugu tiger puffer fish. Kobe beef of fugu cuisine.

24:43 A single specimen of this species which only found in the sea of japan

24:48 well cost €100 one of Tokyo's historic is located around Asakusa temple. Most

25:04 fugu restaurants are to be found There are about 3000 restaurants specializing in

25:10 in Tokyo today From the outside, usually easy to recognize and they're always

25:16 specialized. One of them is Ricky's restaurant where sometimes even Prime Ministers drop

25:28 war says its name, the pure place. You also need a license

25:34 prepare fuku. The poison in Fugu tetrodotoxin. It's 1000 times more potent

25:41 cyanide and there is no antidote. poison paralyzes its victims but leaves them

25:48 conscious. Proper preparation is critical. skin and entrails of the fish are

25:55 and they must not contaminate the non meat on the muscles. High concentrations

26:10 highly poisonous tetrodotoxin are found in the , especially the liver and ovaries.

26:17 disposal is necessary. So I want pause it for a second. So

26:22 gonna talk about tetrodotoxin ttx and I'll you what it does. But I

26:28 want to tell you that tetrodotoxin is the fish in these organs but it's

26:35 not synthesized by this fish. It there because of the bacteria in the

26:44 and in certain organs. And so is sort of gonna be a little

26:48 of a theme to is we're gonna at some toxins that are produced by

26:54 by clamps by shellfish and it's again not that the animal is synthesizing this

27:03 but it's coming from bacteria that are in these animals. And so these

27:11 of meat are obviously very highly prized they're prepared. They're definitely I guess

27:20 the poison of the fish triggers numbness the mouth and is intoxicating. So

27:27 has certain intoxicating value. The reason people pay a lot of money and

27:33 have to have a seven year license the chef to prepare your food.

27:37 people pay a lot of money because the tingling sensation and maybe some other

27:45 or whatever sensations that people may feel the reason why you have to have

27:51 license is because if you don't separate organs and you don't cut the fish

27:59 you can basically cause the sushi and sashimi pieces to be poisoned. And

28:10 there used to be quite a few from consuming raw fugu and it's become

28:19 better now obviously just maybe one or or two or a few but there's

28:25 whole ritual behind it the way it's , the way it's served and it's

28:31 obviously for special occasions and people enjoy this. So this is a popular

28:40 to do in Tokyo and I would to go to that restaurant to try

28:46 food and fish some someday. Now that didn't work out as well for

28:55 Simpson because the chef was busy but what we're talking about is what I

29:05 mouthwatering tales of toxins because it looks delicious to try you know that sushi

29:14 but it's it can be containing So Tetrodotoxin. Tetrodotoxin not not not

29:23 miss accidentally is a is a traditional to consume. And so it's it's

29:32 in Japan and the scientists that plays key role in demonstrating the cellular mechanisms

29:41 action for mechanisms of action channel mechanisms action of tetrodotoxin is Toshio Narahashi.

29:50 a very interesting story that he basically about late fifties, early sixties in

29:57 story. That's one of the other of discoveries that are encouraged to to

30:02 at just like we talked about roderick and the structure of potassium channels.

30:08 this is his story, so he a toxin and he's very interested in

30:13 channels and so he goes to biochemistry and there's even a description if I'm

30:19 mistaken here or someplace else that after biochemists like after the big talk and

30:25 meeting, he starts talking about these and people are like what are you

30:30 about? What channels? So that late fifties sixties people were just catching

30:35 that there are channels that they're conducting . And biochemists were not as interested

30:41 that until they became really interested in , you know, so he has

30:46 10th or the toxin but he doesn't what it does exactly, He has

30:52 to record action potentials and he sees there's a paralysis, there's a blockade

30:57 action potentials. So he can test and the models where he can record

31:03 but to definitively prove what it he needs to get to voltage

31:08 So in the early 60s he has to travel the United States from Japan

31:14 a year worth of research and And during that year he carries a

31:19 of TTX in his jacket pocket. then he within that year he has

31:25 opportunity to go and work with the clamp set up. They were rare

31:29 that age still and what he does he demonstrates that when he applies

31:39 So this is our stimulation here and have this very strong inward current followed

31:44 an outward current. Just like we about with Hodgkin and Huxley and this

31:50 in the presence of tetrodotoxin. So you add that to the toxin,

31:55 selectively blocks sodium. Both educated sodium without affecting the outward potassium conductance

32:04 And so now he understood definitively by voltage clamp that T. T.

32:10 . And he postulated in blocks voltage sodium channels because he already knew that

32:16 potential from the literature from Hodgkin and in the forties and fifties that action

32:22 had sodium and potassium but he has seen this experimental so it took like

32:29 years with some toxin to travel the States to some set up to actually

32:34 show experimentally what it does. It affect outward potassium card. But there

32:40 other blockers. Some of these are in nature derived toxins. But some

32:46 them are just chemicals to that are blockers or they can even open channels

32:53 their blockers they called antagonists that needs close or block the channel if it's

32:59 that opens the channel or encourages downstream from that channel, it's called an

33:05 . Okay, so you have a biological and chemical antagonists or blockers of

33:12 channels. TtX for sodium potassium is little ammonium, abbreviated as T.

33:21 . And these toxins are around So saxony toxin would be present and

33:27 , mussels and during red tide and temperature when there's certain algae and blooms

33:34 the water, you're suggested to stay from certain foods. We don't have

33:40 much of the clams and mussels here texas and I guess the south coast

33:48 the United States, but in the like north east where there is a

33:55 of culture for muscles, your advice to eat, not to consume

34:00 And especially not to consume them raw those certain periods of time in nature

34:06 in texas. You know the same for uh crawfish that you're supposed to

34:15 crawfish only. This is what I taught when I went to school in

34:20 . You're only supposed to consume crawfish the months that have are in

34:25 It's easy to remember. So june August don't have ours in all 11

34:34 have the letter R. So this when you know that you can eat

34:39 is because the hottest months, it's recommended to eat crawfish. So for

34:48 a number of reasons but we have regulations and there's another bad tract code

34:54 and Colombian frog. Now when you like what what does it affect?

34:59 does it block the channel? Remember talked about it has activation gate,

35:03 has an activation gate. So these toxins will affect different parts of the

35:08 . They may have specific and unique on this three dimensional channel structure where

35:14 bind and if they bind here the is blocked and it cannot open.

35:20 they bind here, the channel can but then it gets inactivated much

35:27 Or maybe the opposite if it bounds , the channel is open and it

35:31 inactivate for a long time since sodium keeps coming in also could be a

35:37 condition. And these different binding sites different molecules help us reduce three dimensional

35:46 structure. That's what helped roderick Mackinnon that structure in three dimensions in the

35:52 . It allows you to study effects channel blockade. So you can see

35:58 it affects if it's a membrane and molecule, you can use the techniques

36:05 inside out recordings outside out recordings to where it binds on the channel different

36:13 , how it affects flux through sodium potassium, you can isolate sodium and

36:19 currents using voltage plan. Now, of these tools, basically the chemistry

36:27 , electrophysiology and the voltage clamp. these advanced IQ meets with wholesale recordings

36:34 do a lot of experimental discovery with tools. Nature is potent. It's

36:41 message to there's some very potent spider that can kill us. Um If

36:47 consume too much cetera the toxin it actually kill you by suffocating you.

36:52 it will bind to sodium channels. talking about action potentials in the brain

36:56 there's sodium channels in the periphery. need deep polarization through sodium channels for

37:02 muscles to start contracting. And so levels of TTX can start impacting the

37:08 trying muscles and basically causing you to to lose breath and suffocate. That's

37:15 of the known uh effects that causes stoppage of the horrid tomb tetrodotoxin.

37:23 when we talk about these toxins, puffer fish, newts, frogs,

37:28 don't produce them. They don't synthesize animals don't synthesize these toxins. They

37:34 them bacteria. You know that you microbiome in your guts and you have

37:41 more and way more complex genetic composition this bacterial enclaves than in your own

37:51 . So what you carry in your is actually really really complex in

37:56 And even the facts of how you things and how you can synthesize even

38:02 internally. But obviously this is coming these bacteria that we're talking about.

38:11 Now these are the deep plots and review of the linear D.

38:17 So this is the I. Plot. And this is the demonstration

38:22 the reversal of the current and the of the current and the opposite direction

38:26 zero millibars. Just like you're seeing . This is the simple oneK

38:32 And this is actually a D. for something that will be discussing quite

38:38 bit in the next section as acetylcholine channels. And we'll talk about that

38:45 they have a linear plot. So this is examples of rectification. So

38:54 told you I was gonna take But I think between this image here

38:59 the board uh and the recording and description here in the slides I think

39:08 should be able to sufficiently answer the from the exam that I may have

39:13 to this material. Local anesthesia. It's actually light agonist for sodium and

39:25 the periphery is cocaine but most importantly what I would like for you to

39:32 is lidocaine because lidocaine is a local which means what already may have mentioned

39:39 When you go to get your teeth the doctor may ask you do you

39:49 local anesthesia? You probably say Um Sometimes uh dental offices is nitrous

39:59 . So it's more of a kind a falling asleep feeling something you're inhaling

40:03 lidocaine will bind to the nerve endings should be proceeding the pain and the

40:11 when you're having a small surgery on teeth because you don't feel that.

40:17 then quite often when lidocaine wears off it won't stay bound to that receptor

40:24 . So some substances bind to receptors quickly and they get unbound. Some

40:30 them bind and stay there for a exerting their effect. Some of the

40:35 will have that substance locally concentrated sort keeps binding even if the other molecules

40:40 that keeps binding. But then what after you come home and you had

40:46 tooth done three or 4 hours Oh pain again. Right. And

40:54 you leave the dentist's office, if had local anesthesia, then you would

41:00 when you go home, you know it starts wearing off and the numbness

41:03 coming off, you should take some , you know some Advil or Tylenol

41:07 whatever works for you. So that's to control the pain uh in a

41:14 binding site for this molecule. And this this structure can have so many

41:22 uh nooks and crannies and three dimensions these different molecules to come in and

41:29 up to them and regulate their Now, quite often when we talk

41:38 these channels, You know, you often wonder well, okay, so

41:43 channels are just so small, it's molecule, like it's a channel.

41:48 do you isolate activity from one How do you really know when you

41:52 out that patch of the membrane with that has sodium potassium calcium? How

41:58 you really tease out? What if two, both educated sodium channels?

42:03 if there's three? And they all kind of a similar kinetics and you're

42:07 average over over three different subtypes of educated sodium channels. So to get

42:16 specific than you can use other tools other systems. So frog do sides

42:23 huge eggs and you can over you can isolate something so you can

42:28 the voltage gated sodium channel of interest you can over express it in these

42:34 Exoo sides. You can have very lectures recording activity and because it probably

42:41 the dominant thing that that the egg expressing, you'll be able to record

42:45 strong cars. So this shows an potassium channel that has been over expressed

42:52 these very large cells. And then can record very strong currents and you'll

42:59 why do you want to do Because if you can amplify something and

43:04 plasma membrane and that patch, you have 10 of those multi educated sodium

43:10 and 10 of that is and 10 that is and you really cannot tease

43:13 apart using the techniques that we talked electrophysiology and and uh and even

43:20 So, but you can still tease apart based on their on their

43:27 And so once you take something small or two channels and you amplify through

43:32 system into thousands and tens of thousands channels. Now you can see something

43:39 much larger scale. Now you can back into more complex systems, back

43:43 the mammalian systems back into neurons and for the equivalence of these types of

43:50 in these types of kinetics. So type of amplification allows you to really

43:58 things better. Now the purpose of action potential, the main purpose of

44:05 action potential is something that we're going talk about a lot and the next

44:13 and that is to cause the release the neurotransmitter. So what we've covered

44:19 this section because we've covered the fact the action potential gets produced here.

44:29 why does it get produced here in axon initial segment? Because this accident

44:34 segment will be loaded with voltage gated and voltage gated potassium channels, neurons

44:43 their strategy where they're going to place different subtypes of channels and receptor channels

44:50 voltage gated channels that they express. like a little city. Okay.

44:56 gonna decide what I'm gonna do by here. And you will find a

45:02 large expression, very high number of and potassium channels expressed in the axon

45:10 segment here, which makes us a place to produce the action potential.

45:18 on the den rights, not on selma, but in the axon initial

45:23 . Why? Because it is loaded both educated civilian and educated potassium channels

45:31 play into the dynamics of action potential we talked about the cell, if

45:37 recall this neuron is going to be excitatory input. So if it's receiving

45:43 inputs that will be polarized. If is receiving inhibitory inputs from someplace else

45:49 will hyper polarized. These are great synaptic potentials and this is gonna be

45:55 transmission and neuronal networks that will start in the next section. But if

46:02 shell is excited enough, this particular needs a little bit of current and

46:09 will produce an action potential. Once action potential is produced it will get

46:17 that each note of ranveer and each of ranveer will have the same shape

46:23 amplitude as it did at the accident segment. And the reason for it

46:30 those of Ron beers are unde. ated areas on the axon and are

46:38 with voltage gated sodium and voltage gated challenge. So this charge breaks through

46:46 , this action potential and then it through the axon. And in this

46:54 of ranveer it breaks through again and itself and then travels again through the

47:02 part of the wire until it reaches terminal where again produces the same size

47:10 potential as it did the facts on set. So there's a theory or

47:17 of dynamic polarization that was initiated by to how. And according to him

47:24 you remember his diagrams, he said there's arrows flying flowing into dendrites and

47:30 . So he says there's a problem antennas receiving the inputs and then he

47:35 arrows from axons flowing in one So he says that there's one direction

47:41 which these neurons communicate. But he right for the most part of the

47:45 synaptic transmission and this action potential that here at the axon initial segment and

47:53 down the axon and reproduces itself with axon terminal. It's a forward propagating

48:03 potential. So it is moving in polar direction. But with Monica,

48:07 they didn't know because there was no potential recordings in the late 19th

48:14 beginning of 20th century. He didn't that there is gonna be a small

48:19 that gets generated here that is actually to propagate. This is propagating,

48:26 is regenerating and this small cars is to propagate back into the soma into

48:33 dendrite is called the back propagating action back propagating spike. So in your

48:50 documents you have in your supporting documents out in the folder by accident.

49:06 . Uh you have the supporting Let me this is gonna be the

49:14 slide that we go over actually in whole section. And the last concept

49:20 will go over. So it's something you guys to review for the

49:25 I may ask you a question or on this, but I may also

49:30 back and ask you another question or on the subsequent midterm exam because there's

49:35 be more information that we're adding onto . So remember I told you that

49:41 may have multiple multi educated channel. I also said that one cell can

49:47 multiple multi gated sodium channel sometimes just particular sodium island channel sometimes. So

49:55 turns out that the channels that are close to the selma in this region

50:04 . R. N. A. . 1.2. And this subtype of

50:09 channels called high threshold sodium channels. high threshold which means it requires high

50:16 of current, a lot of current order to open the vault educated

50:20 That's high threshold a little bit further from the soma. In this

50:26 In the axon direction you have maybe and M 81.6 are low threshold voltage

50:36 channels. That means that they require little bit of positive current. Low

50:42 for opening of the civilian general. this is an explanation of how can

50:49 cell produce a forward propagating spy in back propagating. And we talked about

50:59 it can produce the forward propagating It activates the inputs d polarizing

51:05 If they overcome the inhibitory inputs, membrane potential value can reach the threshold

51:12 action potential and the sodium and potassium in here. Boom will set off

51:18 action potential. But then I said going to be forward propagating and back

51:24 forward propagated. The one that's be cloud comes in and you see this

51:29 arrow in wong actually this current although is positive current and quite a bit

51:35 it. It bypasses this area that inhabited by N. A. D

51:43 And it's not strong enough to open 81.2. But then when it reaches

51:49 area that has low threshold require low and maybe 1.6 it sets off the

51:57 which is the action potential, the phase of the action and this action

52:04 three will be forward propagating, it go regenerated note of run there and

52:10 the release of the neurotransmitter as you this explosion and deep polarization nearby.

52:19 A V 1.2 which require high threshold . Now feeling this polarizing input and

52:28 explosion from this it's some positive charge leaks into the area and the combination

52:35 the two is now strong enough to N A V 1.2 and when N

52:41 D 1.2 opens the sodium starts flexing and here you have a very large

52:48 potential already a lot of positive charge you don't have as much of positive

52:55 coming in with the deep polarization. these channels say the only way my

53:00 can go is back into the south produces a small number five back propagating

53:08 potential that travels into the cell, into the south and back into the

53:16 drives. So we have the forward action potential and 81.6 low threshold And

53:27 81.2 high threshold which now sends some this positive input and this positive input

53:33 generate back propagating spike spike. Let is really a fraction system on the

53:41 of a few million volts. So main forward propagating action potential in the

53:46 of 100 million volts. The small propagating action potentials in the order of

53:50 funeral vaults. Yeah. Does this propagation has? Yeah. That's a

53:57 question that propagation has. What is propagating spike. And why should I

54:04 about it? So uh it's uh gonna actually tell me about it briefly

54:16 I said it's gonna be a last and I wanted to uh talk about

54:22 maybe under your review, just kind put some of the things together.

54:27 this very fast communication. And this of union spike is very important for

54:34 plasticity that informs the cell and informs Den writes that this cell has been

54:41 by the influence the cell has a ability to learn and it has a

54:48 ability to strengthen the inputs that caused to fire action potential. So in

54:54 way it's reporting back of what happened saying, yeah, all these inputs

54:59 the spike. It's paid off and just letting you know, we're good

55:03 if you don't produce a spike and don't have the back propagating action

55:09 This network the synapses doesn't tune as as in florida as well. So

55:16 important for plasticity. There's a concept spike timing dependent plasticity and that is

55:24 if this cell fires and you have back propagating spike in in very short

55:32 period from Neutrogena, then they know the signal is relevant, incoming signal

55:37 relevant because otherwise it's fires, fires and we sell a silent,

55:42 , there's no back propagating spike back spike comes to this network a second

55:49 , which is forever and neurons and irrelevant. So there's something about the

55:55 and timing that's very important. You can think of, you have this

56:01 summation that's coming in. Now, you d polarize the cell back up

56:07 again and the den rides, then inputs have a greater chance of having

56:12 sell reach the threshold begin for action . So it's really tuning the pre

56:17 inputs of post synaptic inputs through this propagation. And tuning the plasticity of

56:23 learning rules and the networks. I a question there challenge of the

56:31 but I believe I'm gonna leave that for the for the next uh

56:38 Let me just check. Well, boy, I didn't record the last

56:46 portion here. I talked about different channels. I'm not going to rerecord

56:51 , but maybe I'll re mention this Uh in the review. So also

56:59 you have any other questions about the , I expect to spend about 45

57:06 maybe on the review myself. I a lot of the material and action

57:11 is pretty fresh. Uh and I'll over some of the other concepts in

57:17 fairly fast manner, so maybe seven per lecture, so or less 5-7

57:24 . Uh for each lecture is about lectures that we had. So come

57:30 , bring your questions. All of materials are available to you, and

57:34 see you all on

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