© Distribution of this video is restricted by its owner
Transcript ×
Auto highlight
Font-size
00:00 So welcome back. This is lecture off neuroscience and we will be wrapping

00:09 talking about neural transmission and hopefully beginning talk about, um, central nervous

00:19 , different parts and functions of the . Still admitting a couple of people

00:24 in late. Now, if you , we talked about different systems and

00:29 pointed out that the interesting thing about I'm allergic systems and me and societal

00:36 histamine, dopamine and acetylcholine norepinephrine, is that they're expressing these very specific

00:44 along the brain stem and the days forebrain and that their projections and go

00:50 the neocortex, the cortical matter, cortex into the columnists and the cerebellum

00:56 well so. This is in contrast the and the cannabinoids that have produced

01:02 and the South there produced on And there is a couple of

01:06 How can it be deep polarization? suppression of inhibition If you're suppressing excited

01:11 signaling so within the cannabinoids will discuss they regulate both but the inhibitory

01:17 If it is a gap allergic synapse will inhibit release of in condition,

01:22 too much inhibition. They will control . There will reduce inhibition. If

01:27 exciting ter synapse and it's too much . They will control excitation.

01:34 in a way, being one of systems and this negative feedback fashion retrograde

01:39 from post synaptic cells where they're produced pre synaptic Lee, where their respective

01:44 receptors are this retrograde fashion and controlling synaptic transmission both excited Torrey and Gob

01:51 synopsis and inhibitory excited her in the the glutamate ergic synopsis and military activity

02:01 the Gabba Logic synapses for glutamate It's that you really believe the whole glutamate

02:08 the cycling of glutamate we distinguish between I am a tropic kinds of glutamate

02:14 sampa NMDA and kind of glutamate Um, we talked about the fact

02:22 the early phase of the E P P is due to the ample receptors

02:26 upon the release of glutamate binding of to the emperor receptors opened immediately.

02:32 in order for the late phase of E p s p to be contributed

02:38 these NMDA receptors, plasma numbering is deep polarized and so magnesium block will

02:44 . The cell will leave the channel channel. Now you can have the

02:49 off positive. Current and re polarization happen through the flux of potassium

02:56 the flux of potassium through both emperor NMDA receptors. So we talked about

03:03 M D A receptors as, having called being called coincident detectors because

03:10 , coincidentally detecting the glutamate release and made binding and lice into a factor

03:17 as well as deep polarization, which pasta? Not so. It's confidentially

03:21 the pre synaptic activity on the posson activity. Where's the Amper or non

03:27 ? Ample kinda channels Glutamate binding. sufficient to open these channels. Interesting

03:32 of potential and with an M A receptor magnesium will leave when

03:39 when when the number of potential D magnesium block will be alleviated. There's

03:45 to be flux of ions through an D. A channel, and it

03:49 , ah, higher conduct its channel Amper channels or not an MBA Ampang

03:55 near channels. Uh, these, , Tampa and an M D A

04:00 will also have their respective blockers are . Tampa Kaine. It will be

04:06 by sea and Q X chemical called and Q X and NMDA receptors are

04:12 by chemical called a PV. Uh . When we talk about the

04:17 these air, the fast glutamate Iona channels are the ample channels As soon

04:24 glutamate binds open and responsible for the phase of the PSP and an M

04:29 . A channels are responsible for the phase of the E P S

04:33 and they are slow, and they're because deep polarization needs to happen in

04:40 for these channels to open. um, we talked about a binding

04:47 for a PCP and M Kato one PCP. It's ah list of drug

04:53 the streets on and is referred to angel dust a lot of times.

05:00 one thing is that some of these that are out there are so potent

05:06 so powerful that they can, permanently of the brain function. And so

05:14 is known thio induced hallucinations. It induce acute schizophrenia where somebody essentially goes

05:22 a psychotic state of mind and doesn't for weeks and potentially go into a

05:27 state of schizophrenia from just a single of some of these substances.

05:35 J. Lo one is a very substance that binds only open and then

05:42 air receptors on again. That's for to start thinking about. Why only

05:48 ? Because the configuration the three dimensional of the channel, has changed.

05:54 confirmation of the channel has changed, now open channels can be bound by

05:58 substances. Is supposed thio channels that closed because they opened up this new

06:05 acid binding sites on the protein the number tropic glutamate receptor site differently

06:12 non mdn NMDA receptors, the actor protein complexes and M D A.

06:19 . If you were to recorded minus million balls, Interesting member and potential

06:24 the presence of glutamate would be almost present. Minus study. You will

06:30 opening of an M D A Channels M D A. Current through an

06:34 D channels will reverse zero million volts will flow in the opposite direction when

06:39 cells are de polarized and in this , held at the positive holding paternal

06:46 eso in the presence of regular which is 1.2 million Mueller. On

06:51 outside of the cells, you have blockade of an M D channels and

06:56 the presence off glutamate and magnesium release glutamate. But magnesium blockade thes channels

07:03 not open. But in the experiment the right, you're recording the same

07:08 through an M d receptor. But really is glutamate and you remove extra

07:13 magnesium so there is no magnetism and cellular solution. There's no magnesium

07:18 and in that case you demonstrate that can open an MBA channels and there

07:23 be conducting a lot of current interesting close to resting member of potential proving

07:29 point that magnesium is was blocking the on this on the leftist. Proving

07:35 point that deep polarization is what helps the channel. I eat removed the

07:41 block. Okay, so these air experimental conditions on the left this regular

07:47 concentration extra cellular, 1.2 million Mueller the presence of glued in a There

07:52 not much current that these potential student receptor in the same experiment you have

07:58 , but now you remove Eszter Salamon . And now you have the current

08:03 on opening of this and then be receptor channel. So if we recall

08:10 the first block, we discussed ivy and these air the current voltage

08:16 And we said that the amount of depends on their on the change in

08:22 voltage. So in this case, looking at to currents here.

08:30 we're looking at a compound GPS speed . Mhm. But we're looking at

08:37 recordings. One of these recordings of 80 million volt holding potential. Your

08:43 clamp is holding the cell of minus million bowls from the second situation.

08:48 cell membrane potential is held at minus million volts de polarizes cell. And

08:54 the third here on the top. cell is how the positive 20 million

09:01 . You're taking two measurements. During experiment, you're releasing glutamate, and

09:07 taking two measurements. Glutamate release are to re stimulation. Corresponds to

09:14 uh, lying right here. Come here. This is this is

09:21 Or maybe or good image stimulation or made application. And you're taking two

09:27 . You're taking the early measurement. this is this dash line. The

09:33 dash line on the left is the measurement. And then this is a

09:39 scale of 50 milliseconds and some 20 Later. 20 milliseconds later, you're

09:46 a second measurement. Each of these measurement points you're measuring the strength of

09:53 current at three different holding potentials minus minus 40 plus 20. So when

10:01 trace what is happening, Thio the measurement at the first dashed line here

10:09 the left, you record straight You get a linear ivy blonde in

10:20 linear TV plod corresponds to the early of the E p s b,

10:26 corresponds Thio the Ampara. Sabra. this graph has two plots the linear

10:34 that is shown in black. And you have these, uh,

10:42 here. These triangles represent current measurements the on the Y access and the

10:50 access is your voltage s o minus million volts minus 18 million balls.

10:57 had a current of about minus 200 amp airs. True, at minus

11:06 million volts, you had a current about 100 negative people out. There's

11:12 25. You had about negative 50 empire. So this early component shows

11:19 is a linear ivy plot. So shows that the Ampara receptor channel has

11:27 linear ivy plot. Things get a bit more complicated when we look at

11:34 second line here which measures the lead in the current. The amount of

11:42 that is present at the late component what it measures is now in

11:48 In particular. We're looking at the circles where minus 100 million volts and

11:55 80 million volts. You don't see current If you look at the late

12:01 , there is not no current There's recover at monos 80. You

12:06 get the fast excited Torrey Potential that's by an m d by Ampara But

12:13 don't have any measurement. Here is zero million valves recurrent nearly zero p

12:19 in Paris. When you dip rise the cell and you dip Polarize

12:24 Positive 40 Where this circle is Now seeing a significant late current that you're

12:31 here. This slave current is shown blue so anything that you see in

12:38 is the late current on that late and blue corresponds to NMDA receptor and

12:45 shows that it opens it about minus minus 40. It's conducting P come

12:53 , it reverses. It starts starts decreasing so you d polarize the

13:00 minus 20 it starts decreasing and notice the circles and the triangles both reverses

13:08 millennials. So this is the reversal for both Ampara NMD air separate channels

13:17 then, as you increase the potential positive 25 million volts. Now you

13:23 a significantly the current shown here because now you're tracing the second line to

13:31 this current, and it shows that the d polarized potentials positive 40 2050

13:39 volts an MBA receptors are preferring to in the opposite direction. So physiological

13:47 for an MBA function, of are in the negative ranges. But

13:53 illustrates that you have a reversal for empire and an MBA. Zero mil

13:59 that the early component, measured through first dash line, represents Ampara,

14:05 it's a linear I V plot that second late component measured by the second

14:12 line, is nonlinear here, and shows a reversal of zero. It's

14:17 linear and represents an M d a . It's non linear because until you

14:22 deep polarization, you have magnesium So you have nearly zero people hunters

14:28 current being conducted here, and then current increases as you alleviate the magnesium

14:34 and then there's no magnesium and conducts lot. Finally, we have,

14:41 , open triangles and we have open . So and the in the in

14:49 in the in the situation where we're looking at the neuro pharmacological manipulation as

14:57 mentioned that each one of these receptors m d A and ample receptors will

15:02 their own respective blockers. So a is a blocker for an M B

15:10 . So in this situation, you're not just measuring the early and live

15:16 . Now think about how much you now, using a voltage climb your

15:22 the potential and different holding potentials. are applying glutamate or you're stimulating

15:29 No matter. GIC fibers, you're the early components the current some five

15:38 following stimulation and the component 25 milliseconds stimulation approximately. No, you understand

15:48 the early component is the linear I plot was just ample channel. That

15:52 component is nonlinear and envy. A . Now you're using nerve pharmacology.

15:58 applying a PV which is an M a receptor blocker. So this blue

16:04 , which represents an M. D current. I think it's blocked by

16:09 PV. So this line, the line here and gets reduced to the

16:14 line and the bottom line gets Thio no current here and this is

16:19 these open circles indicate. So in presence of a PC in the presence

16:25 V. P V. If you this late and m d component you

16:29 really see, it maintains itself close zero line. It doesn't mean that

16:35 linear ivy plot. It just simply that it is close Thio zero that

16:41 no current is flowing through an D. A. With south

16:45 There's virtually no leave current that's being in the presence of NMDA receptor

16:52 And if you want to prove how specific is this blocker to an

16:57 . D a receptor? How specific this blocker Teoh to the late

17:04 Then you do the measurements in the component in the presence of a PV

17:12 , and in this case you have triangles. What you have is that

17:19 triangles still show you a linear plot you still measure significant amount of karm

17:26 the early component. So this proves a PC does not affect emperor receptors

17:33 does not affect the early component off E. P s p A PV

17:38 is a blocker. A PV instead a blocker of NMDA receptors and by

17:48 virtue blocks the late an m d current. So again, Alfa is

17:56 , and M d A is not PV receptor blocks. The late component

18:00 not affect the early component. This really good. Exam crashes to so

18:09 gated channels you have We're gonna talk calcium from Tajani or development of these

18:18 and cellular location. So first of , what's interesting is we talked about

18:23 channel. So we said that ampoule , unlike an M D A.

18:29 therefore amenable to sodium and potassium, they're not always permeable to calcium.

18:34 there are ample channels. There in fact, promotable to calcium

18:40 Okay, And that all depends. go back to the building blocks off

18:45 amino acids and amino acid sequences. , the primary, the secondary,

18:52 treasury sequences. And this is quite that if you look at this membrane

19:00 two sub unit in the calcium what you see is that in one

19:08 , if you have glutamine in the of amino acids, if you have

19:15 , which is a cube in the , then that Ampara receptor general can

19:23 the passage of calcium if you have . But if you have an edited

19:31 of that Ampara receptor, and you both versions basically that get expressed naturally

19:38 that immersion you have Argentine in a amino acids. Substitution all of a

19:46 makes this entire protein structure impermeable to . So if you go to the

19:55 days of this course and the history we discuss Roderick MacKinnon trying to understand

20:02 one of these sequences is important now have to think about which one of

20:10 Amina acid building blocks is important. , it's It's a break. You

20:21 one brick to the other, then of a sudden you're doors. Don't

20:26 for your doors only let in certain that's again very, very powerful.

20:33 if you have home ology now, sequences and you can identify the sequences

20:38 individual I mean our assets and substitution delusion of individual. I mean our

20:44 . Somehow, by manipulating the and you can achieve quite significant

20:53 just geological changes of the level of channel. Um, so this is

21:01 experiment where you have a Q where have glutamine and you're recording sodium current

21:10 ample channel you're applying. L glued name l glutamate eso You're stimulating essentially

21:18 glutamate channel, and you are recording current, and you're also recording calcium

21:24 through that channel, and you have second version, the edited version of

21:30 channel. Now you replace this glutamine with Argentine are and you stimulated with

21:40 . And you, of course, record sodium currents. The channel is

21:44 permissible to sodium, but all of sudden no, the child was no

21:50 preventable. Thio Calcium, single amino substitution or editing of a single amino

21:59 can be quite profound, because calcium again may not be contributing as

22:05 Here to the member in potential change ah, as opposed to the influx

22:11 calcium is very, very important. cellular downstream mechanism, secondary cellular secondary

22:21 mechanisms and such who Tajani um in structures and quite a few brain structures

22:31 early developments that we're already starting to now about brain structures and early

22:38 The synapses at First Express only an D a. Receptors. Very,

22:44 interesting. So then you would say if they express an M D

22:50 And what happens if gloomy? Maybe released. Well, those synapses air

22:56 silence synapses if glutamate gets released on synapses that air during early developmental

23:05 have only NMDA receptors possum optically. is no Boston optic deep polarization.

23:13 what they're called silence and absence. you have tohave ample receptors, an

23:21 receptors will dipaula rise the membrane and will open up in MBA channels.

23:26 until you have expression during the development ample receptors in these synapses CNS

23:33 those synapses remain silent. But they're silent all of the time, and

23:39 can actually produce very large waves of and developmental stages that will produce Parson

23:47 deep polarization. But they're called silent there will not be activation of Amper

23:54 , and you will have to have lot in a lot of activity and

23:57 polarization in order to activate them, just blue made for leads. The

24:02 interesting thing that we talked about sub and there's a sub unit composition shift

24:08 M D A. Receptors. Because the FDA, receptors are coincident detectors

24:14 Do you receptors are very much involved the plasticity and mediating and ah,

24:22 of forms off. Synaptic plasticity are we call in India, a sector

24:29 . So if an M D receptors properly will have that synaptic plasticity.

24:34 not, it can affect many different of learning and synaptic plasticity. Doing

24:42 development. You also have some unit shifts, so on em dia receptors

24:49 have subunits and R two and R b, and you will have the

24:54 of these subunits shift during the Also changing the function of these receptor

25:01 . So this sort of ah shift the sub unit composition or editing off

25:06 channels can happen as a normal part the development. Normal part of the

25:12 . Any of these channels and synapses from silent, where just in India

25:18 with now with ample receptors, they active synopsis, and it's very important

25:25 you have activity, dependence and cellular where these channels are expressed. So

25:36 have a lot of changes in the of these channels with age. During

25:41 early development, you have shifts in composition of the sub units, the

25:47 patterns and with age and activity. , um, remember that AMP.

25:55 and M D heiress address again? cells will strategize. Were put these

26:00 , they will put them pasta. , Piccoli in the synapses are the

26:06 on initial segment the nose of ranveer with ample on an M d.

26:10 . With opera. Snow cells have receptor. They have different channels are

26:17 , potassium, calcium channels, pre Aly amping and the pasta in

26:23 Remember, we talked about the fluid model of the plasma membrane, and

26:28 said that these pro dance move through membranes and the travel. So ample

26:35 , in particular very fast Emperor receptors be located extra cellular early, and

26:41 all of a sudden they flow in the extra synaptic Aly and then all

26:45 a sudden from these extra synaptic spaces they don't get much access to

26:50 they position themselves through plasma membrane through movement into the synapses. So both

26:59 when an M D A. and this dynamics of the receptor insertion

27:05 internalization expression level, also good in perceptions will very much contribute to long

27:10 potential ation. Too many different forms learning and memory. Now, when

27:17 talk about I am a tropic glutamate , it's one thing on medical tropical

27:23 receptors. What we see is when activate medical tropical with them interceptor it's

27:29 to G protein coupled, uh, . And it's linked in particular Thio

27:40 prosper in Arsenal P I p. die false faith and activation off possible

27:47 pace. See, uh, an at the level off the membrane,

27:54 then converts P I p two into A G, which is the vessel

28:01 , and that SL glycerol will target kindly see at the level of the

28:08 the second part of this pathway the of this pathway activation and the break

28:15 of P. I. P. in D. A G, which

28:18 membrane bound and into I P which stands for a new hospital

28:24 I'd be three, will act as secondary messenger and it will bind to

28:30 channels that are expressed on the surface under plasmid particular. Um, and

28:37 from smooth er. You'll have a release of calcium from smooth and so

28:45 particular into the side of plaza, you can essentially raises the level.

28:52 cytoplasmic calcium by activating Netivot, tropic protein coupled receptor. And we discussed

29:00 you know you have very important kindnesses as calcium, ical module and kindness

29:06 Kindness is important, important in memory learning, and we also mentioned that

29:13 is certain levels of kindnesses which force a late molecules and proteins they eyes

29:21 . For group, there's a certain of phosphate ASIS, which deep us

29:26 a late this abstract appeal for group lot of times forced correlation Press relations

29:31 channels may influence their function, but relation may be very important. Thio

29:37 and keep the Amper channel functioning and properly. And when you have deepest

29:44 of these channels by phosphate ASIS, can reduce the function of certain

29:49 Okay, so the expression of these protein kinase c, other kindnesses calcium

29:56 module on Chinese, which could be by intracellular calcium levels and interactions of

30:03 Chinese is and foster tasteless, locally cellular early by the pieces of the

30:09 and regulating phosphor relation of the channels molecules. It's all a part of

30:15 intricate post synaptic cellular machinery that keeps function off the cells intact and allows

30:25 certain mawr things to happen when they're in tact. Gabba signaling. So

30:33 pretty much now finished with talking about , signaling. We understand that you

30:39 glue dermatologic signaling I on a I understand I V curves and dynamics

30:46 the metal tropic signal we look at . First we talked about GABA and

30:52 understand that binding of GABA we'll open Gabba a receptor. This is the

31:00 on a tropic Gabba receptor. The of the Gabba. Every chapter will

31:04 the influx of chloride. Okay, Gaba receptor is essentially also can be

31:13 the gala gated chloride channel. Gabon this channel when Gabba binds to this

31:19 , chloride flocks us through the We also have very important molecules neuro

31:28 storing molecules that bind to Gabba And that's why when you're on steroid

31:35 , that tells you not to do things. It tells you don't consume

31:42 because alcohol is ethanol. Ethanol also through GABA. A receptors binds to

31:50 receptors, okay or operate heavy If you're taking benzodiazepines, bend those

31:59 the as opinions or benzos. A of times are some of the most

32:05 anti epileptic medications, so by stimulating receptor, you stimulate inhibition and

32:14 You have abnormal amounts of excitation. called hyper excitability. There's too much

32:20 in one way in which you can that X citations by increasing inhibition.

32:27 . You have benzodiazepines that combined to receptors and open the GABA ah receptor

32:36 the same way the Gabba molecule barbiturates or sedatives also have a binding

32:46 on the GABA receptor. So in eyes of being, for example,

32:51 the popular uh, literatures referred to Valium, it was sedatives. Barbiturates

33:00 also sedatives. When you're taking these , you have to be very careful

33:06 if you are being treated for that you're not consuming nothing. All

33:10 your being treated for steroids for co , you're not consuming alcohol that you

33:17 that these molecules can have interactions that single receptor and then you have different

33:28 . First of all, with It's interesting because with ethanol in first

33:35 in the addition. Okay, now gonna translate it and Teoh a happy

33:44 situation. Uh, one or two keeps you pretty inhibited. One

33:54 one drink you just yourself because you're addition. Then what happens is that

34:00 you overstimulate the inhibitor of receptors, no longer responsive, so there's no

34:08 any ambition. So after three or drinks, the shirt is coming off

34:14 jumping on the table. There's gnome inhibition because a little bit of ethanol

34:21 you. Elated ambition keep normal. of gabba activated. A lot of

34:25 will flood the brain. Well, eventually the cortex, I'll say

34:31 too much of this inhibitory, agonists here, ethanol mine ambition is

34:38 up inhibition has a half life. these receptors, they can,

34:44 potentially ate their function, or Bagan their function. So these agonists,

34:52 different molecules can overtime depress the function these receptors. Where there you need

34:58 , Maura, Benzodiazepine, amore, off a certain pharmacological drug to see

35:06 effect. Okay, they get You have sensitization. So now the

35:14 is binding thio the Gabba receptors, there's no longer any conditions. That's

35:19 you're standing, dancing on the You lost all of their divisions.

35:24 gon everybody's your best friend, so is just puts in sort of a

35:30 life situation. But these out of benzodiazepines game. For example, if

35:36 are a severe epilepsy case and you status of Galactica's, which is,

35:42 , Grandma's seizure, you have about minutes to exit out of the seizure

35:48 you can cause permanent damage to the , brain, tissues or even

35:55 So benzos benzodiazepines would be administered in case very fast, especially in Children

36:04 have status of Galactica's. It would a suppository administered through anise, because

36:12 where you have the highest circulation and the person is experiencing a severe seizure

36:19 that has a tonic Kalanick component, means it has motor component off

36:26 and it's very difficult maybe to access mouth of that person for them to

36:32 a pill. So that's why it presented in the form of PSA Posit

36:37 . It's the rescue situation to bring person out of the seizure Now,

36:43 regular days, that person who has might be consuming a combination of different

36:54 as a benzodiazepines and some other anti drugs that might be acting through different

37:02 , not through Gabba Channel. But you have to understand, is that

37:08 air psychotropic, pharmacological drugs and when person takes a certain amount of these

37:18 , they can be loopy with Children that have to take pretty high

37:25 of benzodiazepines to maintain the brain activity they don't go into seizure activity.

37:33 can present themselves almost like drunk like and like drunk because advances the same

37:41 that that presents a similar type of like behavior. Okay, so this

37:47 Gabba Channel, Gloria Channel and You didn't think it made so much

37:53 to you every day. Whether you a drink of beer or wine or

38:00 interested in pharmacology or taking steroids or , roids are are familiar in one

38:09 or another, with benzodiazepines and Welcome, Thio Neuroscience, where now

38:16 here trapped for good. It's great be here so Gaba Receptor will allow

38:24 chloride. Channel gap would be a . It's the same Gabbert that will

38:29 to gather be a receptor Gabbert being again will like through Geep Rodin's and

38:36 look what it can do. It close calcium channel posson optically, and

38:41 can open potassium channel. Guess what when you open potassium channel and potassium

38:47 leaving the cell. There is the of potassium. There is a there

38:52 hyper polarization. Mhm. So what is when there's Gabba released on,

39:00 gonna be synopsis that will contain gabba gabby receptors both. When gabby binds

39:07 gabble receptors, there will be influx chloride. There will be initial hyper

39:11 polarization. Gabba binding to gabble Bureau with a certain delay off 10 milliseconds

39:19 . So activation of this Jeep road couple complexes and the flux of potassium

39:25 contribute to further high propeller ization of plasma membrane. So Gabba is I

39:32 a Tropic with Gabby is measurable, . Let's try to put this all

39:38 this context and let's see you can . This is this is a lot

39:43 things in here that we're discussing. at the look at the keys

39:49 PSD stands for Boston optic density blues A receptors, Right? Green is

39:59 Dearest chapters. Then you have potassium . You have calcium channels. You

40:08 NMDA receptors. Mhm. So first all, let's talk about this.

40:15 is what we're talking about Is there this This is glitter Matar GIC synapse

40:20 on the right. And with you glutamate in flex and calcium is

40:27 Calcium is necessary to control the glutamate . What is shown here is Gabba

40:32 receptors prison optical. He can control calcium influx. So if you have

40:38 view receptors pre synaptic Lee, they control vesicles release. Okay, these

40:45 glue dermatologic synopsis But the same can in Gabba Allergic synopsis. Okay,

40:55 remember Gabba be activation and the cannabinoid can also control calcium can also control

41:02 secular early release in both little mate goblets in absence. Uh, now

41:08 have glutamate release here and you have of calcium through an m d A

41:14 . So there you have activation off Chinese too. And then it shows

41:19 this calcium kind a student can now the activity of Gabba be receptors.

41:25 , These Galibier receptors open potassium channels Matic. Um, okay, so

41:34 understand that. Okay, So this our hyper polarization through God would be

41:42 . What about here? So this this is this is Boston optically there's

41:47 gabble binding here. This is through call module and activation of Gabba B

41:53 . But you can also have gathered binding. So here is strong that

41:58 , when you have these synapses, the excited or inhibitory, most of

42:03 neurotransmitter chemical will be in the special . But some of them it is

42:08 to spill over. All right, is called still over a gabba.

42:13 is Ambien, Gabba Gabba binding to , but they will open chloride

42:20 Gabba binding to Gabba V will open channels. This is a mechanism that

42:25 understand so causing initial hyper polarization and causing more hyper polarization for potassium

42:35 And then if there is spillover from synapse here into the exciting Terry

42:41 Now, if you activate Gabba beach and excited Terry Synapse because of the

42:46 of inhibition, now you can control synaptic activity. Good. So once

42:57 , you can read the description but the taking of messages for you

43:01 start putting these together. All of signaling molecules that we're talking about

43:07 particularly here, excited their inhibitory signaling and glued in eight and in this

43:14 , gather a signaling chloride and gather signaling, which effects potassium channels.

43:19 it can also affect calcium channels, we saw in this diagram here,

43:25 it can affect calcium channels pre synaptic and control the circular release the parson

43:33 . It can affect potassium channels by potassium channels and can cause pasta,

43:39 , hyper polarization, even the inhibitory or through the spillover. Even in

43:45 excited Torrey synapses. Spillover happens when is a lot of gabba being released

43:52 and here order receptors referred Thio. cell that releases GABA pre synaptic Aly

44:00 also have GABA receptors located pre synaptic . That's what the order receptors referred

44:07 . The same synapse. The same that releases Gabba also has the receptors

44:13 gabble or header or synaptic gap would receptors hetero receptor. So you have

44:20 from the inhibitory synapse, and you gap will be receptors located in other

44:26 . So these air the gap would header receptors versus auto receptor. What

44:32 tells you is GABA release can control so on. Release through on your

44:40 . Gabby, released in this pre molecule, can control its own

44:44 released by controlling calcium, shutting down influence. Or it can control release

44:51 nearby synapses through the spillover mechanism. , right? Everybody's on board with

44:59 . Excellent. So now I'm gonna to you some of my early

45:07 Not so early, but it's about years back. The publication that we

45:13 in The Journal of Neurophysiology with my mentor, William Guide Oh, who

45:21 later become a chair off Virginia University Virginia and their science department. We

45:29 studying inhibitor and excited her responses. so I'm using this diagram is an

45:36 thing. So here you have an of Gabba. A gaba is

45:42 Gabba is trying to reach the goal potential for chloride of about minus

45:49 This lady inhibitory component is Gabba be was Gabbert. Be component is due

45:58 potassium channels. Opening potassium makes it more hyper polarized because it's trying to

46:04 the membrane potential to that delivery. , potential for potassium and So what

46:09 have here is you have a synapse the thalamus and part of the brain

46:14 the thalamus, where activation produces excitation excitation. That's followed by the early

46:23 through Gabba ai on a tropic receptor and laid inhibition through g protein coupled

46:32 off potassium channels through, Yeah, receptors. Uh huh. And you

46:39 read about it in more detail. is the only take home message I

46:42 show you is an A. But did really, really cool experiments and

46:48 showed that if you apply by, and see if you apply by

46:54 which is Gaba receptor antagonist, you the same stimulation when you get inhibition

47:02 you applied by jubilant. Now you massive excitation. So this is a

47:11 here that you see, that's followed e p s p you have e

47:16 s p. That is followed by ai PSP and Gabba B I p

47:21 p If you blogged gabba. what happens is that this eh PSP

47:27 becomes massive, massive excited to Nah, pick response with firing of

47:33 potentials. So it's telling you that this this synapse excitation is being shocked

47:40 inhibition through both I on a tropic middle the Tropic gather receptors now G

47:49 structures air different. You have G coupled receptor, which is a seven

47:56 membrane alfa hell exists. 1234567 that on intracellular side and member inside attached

48:05 this Jew protean. And this is the G protein signaling happens. And

48:11 have a lot of different G protein receptor subtypes, too. So for

48:18 Rennick, remember we talked about Mouskouri . It'll Colleen, you have on

48:25 Maybe because this diagram and the stable from a few years back.

48:34 Medical tropical intimate receptors on glue are through 12 12 different subtypes of these

48:43 tropical automate receptors, which means that have a slightly different structure and association

48:49 different G proteins. It could be I gee, inhibitory geek pro

48:55 different G protein complexes, serotonin five 15 ht 25 ht four or five

49:03 . Five Alfa data Oh, a dopamine. 1234 nor up Enough.

49:10 remember, we sent push flow mechanism have to. Not from data is

49:15 person Alfa is the Paul? You have Alpha one Alpha to beta

49:20 data to beta three and they expressed different levels in different cells in different

49:27 of the brain. Okay, These protein coupled receptors that correspond to the

49:33 of norepinephrine Ron or dopamine or serotonin different parts of the cortex. Cannabinoid

49:40 , C B one and C B . So we haven't even discussed CB

49:46 receptor, but you have to g coupled receptors and potentially G p r

49:53 55 which is a third emergent cannabinoid . Okay, so you have two

50:01 of G party, a couple cannabinoid . Then you will understand that the

50:06 CB two receptors, mostly it is in neurons, but it is mostly

50:12 highly expressed on glial cells, especially glia CB two receptors. CB one

50:21 control neural transmission, CB two receptors information, an inflammatory side of kind

50:29 and signaling. Okay, so these receptors g protein coupled receptors at different

50:38 , too. They're expressing different subtypes cells, different parts of the

50:42 and they have different functions. you have a T p a one

50:48 two a two b A t p . Remember, Is this a Dennison

50:54 ? So the molecule 80 p will be signaling through g protein. This

50:59 all G protein coupled neurotransmitters. This all G protein. Remember that they

51:05 have I on a tropic signaling as . This is a transmitter structure of

51:12 signal Colleen receptor, and this is receptor channel. And he is shows

51:19 in order for the channel to you have to binding size for a

51:22 coleene and that acetylcholine has to bind , Alfa and Alfa. You have

51:28 alfa subunits beta, gamma and And each one of these will

51:37 uh, for trans membrane segments called one through M four. So each

51:43 of these subunits will have four trans in segments, so you can see

51:49 you have gabba a receptor and this the code basically for for for different

51:57 . But they take home message here that these structures are very different.

52:03 trans membrane subunits structures that air channels the G protein coupled receptor that her

52:09 and their combinations, it can almost to be like endless. So if

52:16 talking, for example, about acetyl now let's compare uh, Colin ergic

52:24 continent receptor his eye on a tropic and nicotine caradhras antagonists. Musk arena

52:32 after g protein coupled receptor agonist is antagonist. It's a trap in

52:40 norepinephrine, when you talk about norepinephrine A, they're both g protein

52:46 So you have to start knowing some these details. Glutamate happen.

52:51 They're both I on a tropic with own respected agonists and antagonists. Gabba

52:58 Yeah, Gaba is an agonist. also have chemical agonist Muslim alarmed by

53:03 . We just looked at the bike two slides back. Http.

53:10 P two accident A type receptor subtypes you have agonist today type receptor as

53:16 Dennison and antagonists Caffeine. This is highly relevant. I probably assume close

53:27 90% of you consume caffeine in the of coffee or tea, cheers or

53:37 other form. So it acts through Dennison receptors and it influences glutamate.

53:42 on the Dennison shuts down widow mate . So Dennison will be expressed in

53:47 evening and at nighttime help you sleep and you drink in the morning.

53:53 you wake up and stay awake is glutamate release. Okay, let's play

54:00 games. Gabai ev receptor subunits You're all human calculation robots total

54:10 How many Gaba A receptors. Can we have if you have Alfa

54:19 through six. Data 71 through four 71 through four. No, the

54:26 serve units. How many combinations can come up with? Well, none

54:34 us are robots. The nature does own place. The fact of the

54:38 here is that you have these slight in these actual sub units comprising these

54:47 in these receptor channels and combinations are , the world not particularly completely

54:57 But possibilities are there for us to discovering new and new channels and new

55:02 combinations of the sub units and slide and their amino acid composition slide variations

55:10 their functions and their downstream signaling What these systems do is they amplify

55:20 in the gap junctions and the electrical , you have immediate transfer of ions

55:25 transfer of small molecules to that it . But a small amount of that

55:31 there was no amplification of the chemical . No transmitter binding. The one

55:37 can activate multiple G boat in, , complexes. They can stimulate multiple

55:46 . Is kindness is possible. Cases of production of secondary messengers. The

55:53 messengers can produce kindnesses. Prospectuses that secondary messengers from college economy system fostered

56:01 can influence the function of downstream channels as potassium channels can force for late

56:09 channels and help them keep open. you have massive amplification through the system

56:15 the neurotransmitter entering into the cell and the channel opening. But activating g

56:22 coupled complexes at the level of the membrane. So you have amplification.

56:28 also have divergence. You have a neurotransmitter that combined to three subtypes of

56:37 . Vampire an, M, D and kind eight. Okay, and

56:43 D. A. Was scepter, example, can have different effective

56:48 Three effective systems inside the cells y and Z. You can also

56:54 convergence. You can have convergence on same factors. System transmitter. A

57:02 from one receptor will get to President may see, but so will transmitter

57:07 acting through B receptor, and so transmitter see acting to see receptor.

57:11 may all converge and influence one defector . They may all influence the levels

57:18 calcium. They made all target calcium . One targets calcium channels and the

57:25 well, Khloe's calcium channels and so gather be receptors will close calcium channels

57:30 same effect er system. Okay, neurotransmitters, different receptors. You also

57:38 redundancy and the redundancy and in the that this relates thio parallel streams of

57:46 parallel streams of processing that are at level in this case, off transmitters

57:52 receptors Parallel streams of processing at the off the brain function in general.

58:03 what we have is we have transmitter that can buy into a one receptor

58:09 a two receptor in one receptor can a factor. Three transmitter be through

58:20 years after the different receptor can also and activate affected three. Uh

58:31 There is redundancy here. This this in this redundancy in parallel streams,

58:38 two affected effects effects affected too. have their own distinctive factors and they

58:45 overlapping of factors too. Through these . So is you don't have a

58:56 receptor any longer you may lose access affect her too. With affected 3

59:05 serve a similar function to affect her . So you have a redundancy.

59:09 of these defectors will serve similar Also, what happens if you lose

59:14 one receptor? Can you still get affect your three? Yes. So

59:19 can, through B receptor and transmitter so this affect your three doesn't sees

59:24 functions inside the cells. If something array with a one receptor to this

59:30 and parallel streams of processing a very of keeping the overall brain function,

59:38 injuries and loss of specific neurotransmitter systems relate thio specific function losses and also

59:48 expressions the respectively. Okay, so we're finished with synoptic transmission. Now

60:00 understand how individual neuron with individual neurons made off, how they function and

60:09 they communicate thio each other and what glial cells play in the maintenance of

60:17 function, as well as in maintenance brain activity and synaptic transmission, with

60:24 cycling and with buffering off the ions many other functions of glia play.

60:33 now that we understand how the cells the action potentials, other cells released

60:39 and communicate two other Selves. Let's ourselves back onto the macro scale and

60:48 ourselves about the structure of the central system about major parts of the central

60:56 system and major functions off these different of the CMS. So, first

61:03 all, on the left, you brains that are shown to scale.

61:10 you have a rat brain which about centimeter rapid brain A few centimeters,

61:18 brain Japan's a human dolphin brain. . Uh, now this is this

61:29 this image is not to scale on right. The image on the left

61:34 to scale. So if foreign ologists correct and they said that the size

61:41 the muscle being things, all things equal represents the strength, therefore the

61:50 off a certain area of the brain a certain ability. Then again,

61:55 know, dolphins would be telling us to dio and so with elephants,

62:01 their brains are bigger than ours. the complexity and the structure and the

62:08 of the brain is what determines that walk on 2 ft and rule the

62:15 . Or at least we think Until we get hit by nature and

62:20 that we are part off the nature the world. And dolphins developed different

62:27 of the brain and rats developing at parts of the brain to survive in

62:32 respective environments. Was there body their sensory body structures and sensory brain

62:44 . You can see a rat and and lizard brains would be flat.

62:50 are no imaginations there, no self gira on the surface that you would

62:56 seeing on the higher order species. you can see that it gets very

63:01 when you come up to the humans you have a lot of salsa.

63:05 right, which increase the complexity of network structure, increases the surface area

63:13 the ability for the complexity of processing these brains. So you hear a

63:20 lizard brain. It refers to somebody smooth brain. That means it's a

63:29 insult, but it refers to the that these brains air not very complex

63:34 notice and rats. You see these bulbs sticking out in the front and

63:39 rat it too. Guess what those are. Those air olfactory evolves for

63:46 . Now look at the humans. barely see them. They actually buried

63:52 the front here. So we have bulbs, but we don't nearly realize

63:57 on the sense of smell. Is other animals doing their four other parts

64:01 the brain in us is a lot sophisticated and much more developed.

64:08 so now let's look at the Let's look at some anatomy and symptoms

64:14 the anatomy because this is our Somehow we name brain structures, and

64:21 also identify the location of different brain . So first we have dorsal.

64:27 already know dorsal is the doc. is a sensory neurons in the dorsal

64:33 . Ventral side is our motor neuron on the ventral side, the front

64:37 the spinal cord. Well, look the top. Midline corresponds to closer

64:44 midline. You are even the brain the whole animal body. The structures

64:50 called medial structures, and the further you are from MEDLINE to the outer

64:57 of the animal, the brain. you're laterally located laterally and most of

65:03 brain. The front is referred to interior or all rest role, and

65:12 tail cardinal called it eyes posterior You have cuts that are defined in

65:24 of the brain, such as agile cuts, horizontal and kurono

65:29 A little cots are made. Ross to coddle from the front. If

65:35 made to the tail, Rasta wrote cardinal, and it's made along the

65:42 plane. He's in the sagittal Horizontal cots are made along the

65:50 Okay, Kurono cuts are trance verse made perpendicular to the brain structure perpendicular

66:00 horizontal cuts. The major parts of brain again is the cerebral cerebellum,

66:07 and spinal cord serie broom divided into cerebral hemisphere, less cerebral hemisphere.

66:16 in rats, uh, separated by massive satchels, Fisher, the sagittal

66:23 separates the two hemispheres one from The two hemispheres are interconnected with a

66:30 powerful bundle of fibers. This is agile view. So if you want

66:35 make this cut, Ross wrote to , you would then reveal the inside

66:41 sagittal view off the brain. So cerebral, Um, and Serena's our

66:52 and cerebral hemispheres. So first of , cerebral mom is New York or

67:00 , right? Cerebral hemisphere left cerebral . When we talk about the function

67:08 the hemispheres. Our function is contra sensory motor functions and censor information crosses

67:19 and motor information. If it is in the right side of the

67:24 it will control left side of the left side of the brain controls right

67:29 of the body. Sarah Ballon, the other hand, is it still

67:36 ? So Senator Belem is very much in control of the movement of the

67:42 . But it will control the movement cerebellum on the left side. Rights

67:46 on the right side, Brain stone many significant functions. It has massive

67:56 that connects the re broom to cerebellum through brain stem across cerebral cerebellum pathway

68:02 Bella cerebral pathways. There's also served cerebral serverless spinal that way. And

68:12 the brainstem will control major vital body such as breathing consciousness and control of

68:20 temperature. It will also express this cool Raffi nuclei. You like the

68:29 ? I mean, the twist question on the Raffi nuclei norepinephrine. Some

68:34 you got the question on the Nora Locusts, Aurelius nuclei. They're all

68:41 in brains, town, brain. will have cells that dictate and control

68:49 breathing rate. If you injure brain , you can lose consciousness too,

69:02 control of many, many different additional , not just body temperature.

69:09 so we're just starting here today. when we come back, we're going

69:15 talk a lot about different parts of brain. We will talk about the

69:20 of the brain. We will talk CNN's development and how it comes

69:26 And then the next lecture, you find out a lot about different brain

69:32 and their functions, as well as site of architecture of the cortex.

69:37 I believe that we're probably going to all of this material in the next

69:44 trip. Then we will review the . And you should be well prepared

69:49 on your way to take the term . So we'll end here.

69:56 I will see you all in the

-
+