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BIOL 4315/6315 Neuroscience (19763) - NEURO 2020 EXAM I REVIEW SESSION
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00:00 So this is the first lecture on first slide that I showed you,
00:08 I'm gonna remember Thio try to show the slide at each review session for
00:15 exam. The reason for it is want you to look at the slide
00:19 see what you knew, Uh, the end of August and what you
00:26 now, append of September. And think that if you're looking at neurons
00:32 synapses and thinking, you're starting to the anatomy of these neurons, the
00:39 of the surrounding glial cells, how form these networks, how they're
00:43 some types of cells, then you're the right track. And so I'm
00:48 walk you through some of the material we covered again. This is not
00:53 say that only the material that are you can ask any questions during the
00:57 from any material. I would suggest I really would like to say that
01:04 is sort of the introduction section in in these eighth, electricity can be
01:11 up into introduction and history of The second section is neurons and
01:17 understanding neurons and glia. And the section of this first exam is what
01:25 action potential and understanding the channel kinetics some of the physics that go behind
01:34 understanding the action potential. Okay, what I'll do is I'll walk you
01:39 sort of the history key elements here take a short pause, maybe 10
01:45 minutes into it, have you a opportunity to ask questions. All
01:51 so now when we started talking about , this is a reminder of your
02:00 . Uh, that is essentially the and electoral follows it. We talked
02:05 prehistoric times and brain tripper nations. recall why they were done. Recall
02:11 they were found throughout the world and many different cultures. We then talked
02:18 Imhotep That was a part of the when Smith Surgical papyrus, where he
02:25 27 had traumas and the thinking if introduced about medicine, the brain and
02:32 distal effects off the brain that can seen in the periphery at the same
02:38 . Still, considering heart is the important organ where the switch starts taking
02:43 with Hippocrates, the modern father of . Remember, we talked about Hippocrates
02:49 believing that the brain is the most center. And during the Dark Ages
02:56 is, ah, lack of although there is a lot off during
03:02 period. We talked about gallon, , that he worked with, um
03:10 was a part of the gladiator scene he was able to access, and
03:15 was dissecting pigs and sort of a thinking dwelled until the Renaissance interested the
03:24 questioning gallons anatomical descriptions introduces understanding off , thinking that ventricles so very important
03:34 between gray and white matter. On psychology side, we have Renada
03:41 who initiates the reflex theory and also about this connection between the mind brain
03:49 Go sum. I think. Therefore am which I often like to say
03:55 eat. Therefore, I think Be careful what you eat, because
03:59 will influence how you think. So is in the Western Mind Body
04:05 which is also noted in Africa. will contain the other parts of the
04:09 . At the same time, he's to something, thinking it's a fluid
04:14 theory, thinking that some fluids maybe from the ventricles, pumping some
04:20 of information through the pipes into the to move muscles And would you
04:25 Lonnie, using by electricity, then that nerves air, not pipes or
04:30 they generate. Elect truthfully. Or this and we talked about major parts
04:37 where this electricity and also chemical transmission be taking place in the central nervous
04:43 and the peripheral nervous system. CNS a cerebral Sarah battling brain stem the
04:48 of the brain, the spinal cord goes from brain stem down your vertebra
04:53 then has a spinal nerves coming after off the spinal cord. And,
04:58 course, the peripheral nervous system, and parasympathetic, which we don't really
05:03 . This course, the main lobes the brain, the frontal, the
05:07 focus separating it from the parietal lobe the back of the brain occipital
05:12 Sylvian fissure here, separating the temporal , the back of the brain and
05:18 with little brain is illustrated here is , so we now know that these
05:23 have very different functions. We talked the anatomy off the spinal nerves,
05:29 we know now a lot more about . We said that there's a dorsal
05:33 which we now know the dorsal component root ganglion cells to the uni polar
05:38 releases glutamate, and it takes a from the periphery. And it's affair
05:43 travels into the spinal cord. And there it activist motor neuron and motor
05:48 will send the Baron back into the because of construction by releasing its Tell
05:57 or Siddle Colon. I said It's all colon or pseudo colon. I
06:01 know why it's the same thing in Colon. Uh, Then we talked
06:06 chronology, and we said, You , it was really important to start
06:09 what parts of the brain are responsible what functions. So Joseph Gow sort
06:15 ah, main character for foreign He was strong standing that you could
06:21 the functions of the brand by reading cover off the book by reading the
06:28 indentations, bumps of protections on the itself on the skull to determine how
06:35 attitudes, psychological tendencies and innate features reflected in you within you as an
06:43 , Really a combination of I would , superficial anatomy and psychology.
06:49 that's that's what it is. They're onto something. But not until
06:55 us the discovers that broke US area spot here. You had a home
07:02 question? Which numbers? Broca's Which numbers is Vernon CAS area?
07:06 remember that home or question, and when I say which, which
07:15 area is as it relates to Brockman but broken. Determined specifically, this
07:21 of the brain is responsible for expressive . We talked about receptive aphasia,
07:26 would be due to damage to Vernon area and involved difficulty understanding or written
07:33 spoken word. And then we talked economic amnesia Feige in global aphasia.
07:38 please review these and there's gauge one the most famous characters in neuroscience.
07:44 remember. I mean, can't forget person Can't can't forget this guy.
07:49 couldn't remember certain things after he had injury in his head. And
07:53 you recall this was a demonstration that could have a pretty pretty significant and
08:00 injury to the head, but that don't lose all of the functions.
08:04 not like all of your functions are all of a sudden, to certain
08:08 that it's specific, you know, functions were lost, illustrating to us
08:13 damage to the frontal lobe was also for controlling executive functions and aggression,
08:19 he turned out to be quite According to some of the accounts following
08:24 injury, Charles Darwin introduces the theory evolution that the environment shapes us.
08:30 shapes our organs and it shapes the in our brain. It shapes the
08:36 and the finches. It shapes the and anatomy of the turtles external
08:43 But we look inside the brain. actually see them. We have very
08:49 anatomical, what we call cortical map features that critical maps that represent organs
08:56 are important for us and the organs are important for us, such as
09:02 , such as listening. They will very complex maps and representations in the
09:07 and for other animals such as whisk oring and sniffing around this important
09:13 rats would have a whisker map represented there. So matter sensory cortex,
09:18 is really adaptation to their environment, they have to do, which is
09:23 reflective in the evolution off the brain and reshaping of these cortical maps as
09:29 is currently happening to us as we . A swell. Okay, so
09:34 would say that this kind of a the first, uh, section off
09:38 first off this three sections that I'm toe talk about. I'm going to
09:44 into neurons and glia. Unless there questions and you can amuse yourself,
09:49 can ask the question. You can write a question. What were the
09:56 parts ago? So if you take eight lectures, I think you could
10:02 them roughly in tow. The history neuroscience. North Korean action Potential?
10:10 . So any questions from this part far? No. Great. I'm
10:20 on, then moving on to neuron , Glina, Thio These guys here
10:29 we talked about neurons and glia. talked about these very important players.
10:34 talked about the fact that to visualize properly you need microscopes and you needed
10:40 . So know your stains, because game in the brain is mostly in
10:48 stain. So what stains and we're about? We're talking about gold.
10:54 staying? Yeah. Um what are features of gold? The same.
11:01 me think. I only see a of neurons. Only small fraction of
11:05 . A few percent of just, absorb the stain. And when
11:11 you can expose not only their but the process is the Democrats the
11:16 and this brilliant, really in Spanish ceremony Carvajal was responsible for making these
11:25 drawings of neuronal circuits and insightful on in neuron doctrine as opposed to the
11:33 theory. And this gentleman on the of rice, Sir Charles Sherington
11:39 was responsible for coining terms synapse describing is happening at the synapses specialized connection
11:47 two neurons. Okay, near anatomy cell morphology. Using histology so histology
11:53 air histological stains and later we developed a histological states using, you
12:00 history, chemistry. Eso these stains . This Golgi stain was incredibly important
12:07 the development in history of neuroscience and three people, you should know all
12:13 them receiving noble prices. Missile What's the difference? It stains all
12:17 the south, but it doesn't stay the process is very well. They
12:21 you to distinguish between glia and but it is mostly for the side
12:25 architecture of the so most on the of these cells the architecture of the
12:31 Oh, architecture of the cells. , using this missile stain, you
12:36 your opinion broad Hman who used the and identified all these different areas based
12:44 the structure and caress director. Correct arrangements off cell layers and their directionality
12:54 the cell layers being arranged using in stain. So this is where you
12:58 get your answer from Focus and Vernon area. Then we developed electron
13:05 Standard line microscopes were not able to synapses. Electron microscopes were able to
13:10 synapse zero nanometer resolution synapses about 20 in space. And so we discuss
13:16 . Now we can see individual synapses not only done drives, but these
13:22 spines and the Boston African, the synaptic termine also pinching on these post
13:28 standard experience. And we started introducing idea that these spines are actually plastic
13:34 so on your electric supporting materials. will now see that there's a article
13:38 for yourself enhancement, your knowledge, enhancement on the drink plasticity, especially
13:45 you're a graduate student. You may look at that article now this is
13:51 recording so we can do now without , the financial infrared contrast recordings that
13:57 us to visualize neurons and the form and later we talked about how these
14:03 we can form different types of electric recordings, uses patch clamp recordings.
14:10 this is exactly the status that you see that are computer controlled, single
14:14 controlled voltage clamp recordings and wholesale patch recordings that we discussed in the late
14:21 of this course. Of course, view of the brain is that we
14:26 in serious processing and in parallel in means that from periphery from the sensory
14:35 from peripheral organs such as vision such years or so, we start essentially
14:45 forming, um, or complex and complex understanding of these sensor information through
14:51 circuits in Siris. But in we process information that there's a
14:55 and that's really for protection off the . We talked about the current you
15:01 different circuits. So this again starts to dendrite Some of these different
15:06 um, neuron. So it's quite need, causing the plasticity and also
15:11 up different parts of the brain as discussed, And this, uh,
15:15 also having ability to track single cell synapses and even single molecules at this
15:23 . So I think maybe this could the end. I may have misspoken
15:28 when I had that neurons and glia , but I cannot there. That's
15:32 I wanted to get toe. So are some of the basic things in
15:36 and glia that we talked about and the transcription. Translation. Do we
15:41 this, You know, post genomic micro race and how they're done to
15:47 changes across many different genes. Thousands genes and different brain structures or different
15:54 and infected or diseased brains versus normal . Organelles that are pretty basic and
16:01 find them anywhere. TTP. The consumes a lot of energy. This
16:05 this is something really interesting to think . The brain consumes about 20% of
16:13 total body energy, 20% of the body energy. The brain weighs only
16:20 £3.5. You do the calculation. percentage of the total body weight that
16:27 So the brain is a system that a lot of energy. It's the
16:32 is driven out of equilibrium. That's nonlinear, dynamic system plastic system and
16:39 plasticity in the dendritic spines on the is in part due to the fact
16:46 you have fluid mosaic model, and have podiums that are moving with
16:50 So we watch the movie and fluid model within the plasma membrane, and
16:56 have a supporting side of skeletal structure . So recall the micro tubules,
17:00 filaments of micro filaments, and that have micro tubules that are important for
17:07 that you can have, um, micro tubular transport, the disease of
17:13 that we discussed on that. The element acting elements would be found in
17:18 most periphery distance sides of cell because can reshape quickly. And they can
17:23 change the actual anatomy of them that or collapsing and Reddick spines protruding them
17:30 together on such now, uh, gonna go into sharing another screen.
17:41 can see that window. Yes, that's the screen that we talked about
17:45 Alzheimer's disease, and in particular, really talked about the hallmarks of Alzheimer's
17:55 . Uh, the reason for it discussed it here is actually for for
18:02 number of reasons. But let's review a list off neurological disorders that we
18:08 so far on some of the things we have to know so Alzheimer's disease
18:15 about hallmarks of shrunken brain. Talked the plaques, email plaques or beta
18:22 plaques. We've talked about how protein , and we said that these tangles
18:27 tangle up our micro tubular highway, impairing the transport and also the communication
18:33 the cells and these plaques can impinge the Exxon's and impinge on the synopsis
18:38 essentially caused these, uh, areas are calcified and highly inflamed in the
18:47 . So this is the pathology of that we talked about this symptomology of
18:52 that we talked about it would be stages would be short term memory loss
18:57 anxiety in particular. So almost a others eso recall the slide.
19:05 I'm going to go back and share material again. After Alzheimer's disease,
19:12 talked about den drives and accents, we describe them. We talked about
19:17 transport, distinguish between interrogated transport from soma into the periphery, bound max
19:25 retrograde from the distant lands for free the soma engines. For it,
19:31 essence front, are great dining for transport that uses thes micro tubules
19:36 ah, highway to transport them. if you tangle it up. It's
19:40 bad news. Retrograde transport tracers. you can use the horseradish peroxide
19:45 We can also use viruses or retrograde a herpes virus and Rabies virus that
19:50 retrograde lee travel from that zonal terminals the perimeter and through the South.
19:55 you would use these viruses tagged with dire if you use a poor
20:00 Peroxide is to determine what parts off periphery or the skin is connected to
20:05 neurons, or what part of the and the brain is connected to another
20:09 . Brain Dunn drives and then doing spines recall. This is where plasticity
20:15 . This is the most plastic, reactive parts of the off the
20:20 and this is the second disorder that talked about. This falls under autism
20:25 disorders in particular. Fragile X. you're called fragile X, so abnormal
20:33 spine anatomy formation density can, uh result in natural reinterpretation, and it
20:45 associate. It is a model for X syndrome, which is a part
20:50 the autism spectrum disorders, which were discussing the pathology in this case,
20:55 the right, we discussed it. has thio intake through these and it
21:00 . Thousands of them, excited inhibit their inputs and integrate that
21:04 Sedentary inputs from glue, maybe a ometer GIC receptors and excited tourist
21:09 inhibitory inputs from Gabba Gabba ergic cells the Gabba receptors and the inhibitory synapses
21:16 themselves. So, again, this just a repeat of that. We
21:21 it for functional regions that could be . But in a sense you still
21:26 the input the integrative, uh, , the component input component to integrative
21:33 . I'll and the output component beat the muscle on 11 Your honor,
21:38 some instance system the capital right? then we said, Well, how
21:43 you classify all these? The for sometimes. And I said, the
21:46 has maybe about 150 different cell And I said one way in doing
21:51 , it's through the anatomy, so follow your anatomy of the South.
21:55 is, you know, polar This is bipolar is sued. Alina
21:58 solve. This is our doors over . And so this is motor neuron
22:02 that listen to grow thrown in the the spinal cord. And this is
22:06 parameter all cell excited, very seldom on campus that we discussed. This
22:11 why we out branch for, Kenji . On the cerebellum, we can
22:14 a 250,000 synapses. The cell has very quickly within milliseconds, integrating some
22:20 , calculate that information and the Selma produce action potential. Some of the
22:26 rights are spiny and others are And, of course, it's not
22:31 just to know morphology of the You have to know the connectivity have
22:35 understand if these local cells that stay a local service or whether the projection
22:40 . Most of the projection self so Torrey cells overwhelming majority of local into
22:45 or inhibitory cells, excited to reverses whether they have south specific markers with
22:52 gabble when they release Gabba, they also release neural peptides. Oneself can
22:57 a couple of things and can stained many, many different specific markers there
23:02 those specific cells. And, of , the firing signatures or the signatures
23:07 the action potentials that they can produce replaces within. This complexity replaces within
23:13 context of that hippocampal. Certainly where said that have been hippocampus, you
23:18 21 different subtypes of inhibitory cells and flanking and controlling the activity of these
23:24 projection excited terry cells that are not diverse in nature. And it is
23:30 the activity by projecting synopsis, having control over the integrative properties and their
23:36 based on their anatomy thes different inhibitor excited ourselves, their distinguished one from
23:43 based on their anatomy based on the potential firing properties and the intracellular markers
23:50 we cross stained while we're doing the cellular recordings. So we talked about
23:56 cells form their own dialect, Lee different dialects of producing different patterns of
24:03 potentials during the selection physiological recordings. we said that glia, which is
24:09 neurons, are very important. We about in the periphery. You have
24:14 cells to produce one segment off Axiron segment of an accident and CNS,
24:21 have a liquid emphasized where you have segment of an accident is produced by
24:25 process outgrowth from that a liquid And then we talked about how if
24:32 have Mylan issues, you can have conditions with discusses multiple sclerosis, so
24:40 writing that down, then There you , uh, neurological Degenerative disorders list
24:46 also shark out narrative disease. So point here is that if you
24:53 ah, model multiple sclerosis, which a shiver mouse model here, has
24:58 mutation. Chromosome 18. You have to have to Bad Ali.
25:02 you have deem island Nation and you this shivering like you can think of
25:07 like it's almost actually, um, Thio model multiple sclerosis because this is
25:16 of the symptoms, not the pathology , de Milo nation and multiple
25:22 What else we want? We know multiple sources. Autoimmune disorder, very
25:28 about multiple slows. Okay, as tremors, people have tremors and
25:34 even can have seizures because in proper , flow doesn't control the muscle contraction
25:41 causing these tremors. And it's not in the periphery. Of course.
25:45 also the D myelin nation CNS. talking about not just the CNS sending
25:50 signals into the spinal cord so you rebuild us by by injecting a
25:57 Acting this animal, this animal model the normal gene So was potential.
26:03 were addressing a gene therapy how you repair one data illegal and potentially repair
26:09 FINA talked about phenotype. Try got this peripheral too much bmp 22.
26:16 talked about the features of impaired bodily deformity. So we talked about
26:22 we can combat that with Grace is it's diagnosed early enough. Now we
26:28 of put it all together. We the movie about micro glial cells that
26:33 during the injury and start cleaning up debris and the most dynamic units in
26:37 brain. Smallest units not only with process outgrowth but the movement of the
26:42 through the tissue itself. And we the Astros side we're gonna have decided
26:51 Myelin Nation and ostracized them was really for us because the ostracized is taking
26:55 of the synapses. Astra site is and defusing increases local increases in potassium
27:05 . Calcium concentration has NT feed. blood brain barrier is the last checkpoint
27:13 things to enter into the interstitial space the space where neuronal networks and the
27:19 fluid as and separated by tandem all forming a layer separating it directly from
27:28 fluid on the pendant dependable south with being potentially, um, stem cells
27:36 into other glial cells. War into and another cell that is not showing
27:43 this diagram. We weren't really cool about this radio glial cells. We
27:47 that radio glial cells and it's not started as a lot of when neurons
27:52 travel to find their final destinations would could and can be a precursor.
27:59 stem cells pluripotent precursor cells to other or neuronal Sometimes. And then we
28:07 talking about blood brain barrier. And discussed the blood brain barrier not only
28:12 the context off anatomy and how Astro processes play very important role in
28:19 uh, blood brain. Uh, enters from the blood into the
28:24 a very important player at this but also how this plays into the
28:31 development. And we also discussed the that if you don't have an effective
28:38 that is in the form of a or another delivery format, that you
28:46 need to consume a lot of drug get enough of it is through across
28:49 blood brain barrier and therefore you should very cognizant of all the potential side
28:55 that a systemic side effects not in brain regulated side effects. So this
29:00 all important if you're thinking about pharmacology your pharmacology, different treatments,
29:06 start development and such. Okay, I'm gonna take a pause, and
29:13 gonna see if there is any questions the section on neurons and glia,
29:22 in shot. Or like I you can amuse yourself and just ask
29:26 question. What did you say the of radio glial cells was we'll also
29:38 it's in the actually, in the of the previous slides where we talk
29:43 radial glial cells as guiding neuronal migration process outgrowth. So they're guiding these
29:50 . And if you go to your where you have class supporting lecture
29:55 there is a movie that shows how issues radial glial cells to hang on
30:01 them uses a lot us to find final destinations. And there also are
30:07 south polluted, potent precursors south for . We are or neuronal. Sometimes
30:16 Yeah, excellent. Any more questions this on this part? I have
30:24 question. Doctors I Berkus, Did say that the panda Mel's cells are
30:29 cells? Yes. We think that have or may have polluted, potent
30:37 like stem cell like properties. I have one question. Could you
30:51 what the particular theory and the other was again? Sure, So maybe
30:57 me share a slide. So ridiculous thought that basically, when in early
31:25 Nure Anonymous and signs that started addressing , what is this brain? What
31:30 it? One structures, that many , many connected structures. When you
31:35 out the brain, it seems to all interconnected because there was no
31:40 You really couldn't see individual cells? . A lot of scientists took the
31:47 that well, you know what the is is one continuous census IAM with
31:55 stands for like a network of living . But instead of being individual wrapped
32:03 and its own membrane and communicating to other through synapses, they said,
32:08 know what? It's just one continuous of Plas Mick entity with millions of
32:16 in it. So he didn't think the cells or the neurons in the
32:21 where individual or discrete units that they not connected physically thio other units.
32:28 thought that they were all physically connected this plasma member, one plasma member
32:34 sheet surrounding this really, really complex of the brain in the spinal
32:39 So that's a particular theory. The doctrine actually is happening at the same
32:44 when biology previous classes. You may heard the cell theory and neuron doctrine
32:53 or the south theory in case of doctrine. It's relevant to the nervous
32:58 that each one of the neurons, one of these South, that you
33:02 each one of these black cells are from all of them and that they
33:07 to each other through very, very areas that we call synapses physically have
33:13 not connected to each other. They not touch each other. There's 20
33:19 of space between the synapses between the . Okay, so this is a
33:25 doctrine, which is an opposition to theory and other interesting fact. Waas
33:35 sort of a lesson fact was that Golgi, who invented the Golgi
33:42 believe them particular theory. The no Hall, his student gorgeous student using
33:51 Golgi stain and making these drawings. was a huge proponent of neuron doctrine
33:57 that both of them accepted noble prize . So does that answer the
34:03 Yes, it does. Thank Great. Any more questions on
34:08 On this section? On neurons and . Let me just check Chat real
34:28 . I'm sorry. I have Um, so for the total memory
34:34 conduct and a memory circle, like see that we have some problems,
34:38 that mean Medina in the test will ahead like some calculation. So could
34:42 get the right paper for this Okay, so let's talk about
34:55 So then we move over the into new section I'm gonna move into the
35:00 section is I'm answering your question Very good question. So we talked
35:05 all this law. We talked about there is a separation of charge across
35:11 membrane. And then we talked about d samina assets have built into
35:18 and these proteins are channels, and channels are selected for certain ions.
35:23 we call some of the things we about, iron selectivity, and we
35:28 about the fact that there's two Grady of concentration ingredients and electrical ingredient driving
35:34 science across plasma membrane either from outside in or inside out that we have
35:40 TPS pump, which uses a teepee energy in order to transport in just
35:48 direction across against concentration, radiant of ions. So for each to ion
35:58 , that transports potassium ions. So transports inside the south exports three psyllium
36:06 out through these pumps. And then we delve into mawr of the physics
36:13 physics representation of the plasma member. another thing is, we have toe
36:18 that we talked about the circuit. please review the patella tendon reflex
36:25 Ah ah, that we've discussed What are the subtypes? Morphological subtypes
36:33 our sensory neuron inhibiting to neuron and neuron. What types of neurotransmitters
36:40 Louise. Okay, so recall these circuit there's three cells that are involved
36:47 dorsal root ganglion, cell inhibitor, , the spinal cord and the motor
36:52 . We know that they all have polarities off morphological lee, different
36:59 and that they also excited her inhibitory understand the circuit. Well, then
37:05 went on to talk about Ionic movement plasma membrane, and we said that
37:10 is actually to force is it's not a chemical radiant But that is also
37:17 electrical force, or electro motive, that now builds across plasma membrane and
37:24 what we call the Librium potential forgiven such as potassium. We also said
37:29 charge separation is across plasma member. so if you look into into the
37:35 of Saul inside the neuron or outside cellular space further away from the
37:40 it's charge neutrality. This equal amount positive and negative charges. Accumulation of
37:45 negative charge on the inside of the and positive charge on the outside of
37:51 number of things is just across the membrane. And so we introduced this
37:56 of the driving force here also, we said then reviewed. The same
38:02 be for Sony. Um, that depend on the chemical and electrical
38:08 And then we said it's these The four important species of violence had
38:13 up this resting member in for and we said that they have different
38:18 molar concentrations on the outside of the versus the inside of the cell,
38:23 can also be represented by ratio the outside vs inside of the cell and
38:30 each one of these ions sodium, chloride and calcium have their own equilibrium
38:35 or their own reversal potentials. So when we talk about reversal potentials
38:42 , what we're talking about is calculation each individual ion using nursed equation,
38:49 will not need a calculator for the . This is one answer Thio.
38:54 part of your questions. You will need to calculate anything of this
38:58 but you will have toe Recognize, example, he calcium does this formula
39:04 30.77 million volts Log calcium outside versus inside is correct. And I may
39:11 you a question by and starting a value main sort of value of 61
39:17 . And if you don't know, equation that one of the variables is
39:23 , see, then you would not the answer that he calcium two plus
39:27 have 30.77 Um, if you plugged . If you see a formula that
39:35 the ratio of the potassium outside is times less, I'm sorry outside is
39:41 times more than on the inside. you'll say something is wrong with
39:45 There's more potassium on the inside, this is a wrong representation of that
39:49 . Test your knowledge and understanding off formula, but not the actual
39:55 Two Nuns equation will allow us to individual equilibrium potentials, the Goldman equation
40:02 , uh, use and introduced the term. The membrane is mostly permissible
40:08 potassium, a trust 40 times more than it is to sodium and that
40:13 now permeability and concentrations, uh, both ions, potassium and sodium.
40:20 you can even not chloride onto this and therefore me abilities. Now you
40:25 calculate the overall down brand potential, is VM so up here you have
40:30 k e k n a, C l, individual ion equilibrium,
40:35 . And VM is the some of important, most formidable on most,
40:40 , important ion. So you can that remembering potential pretty much can be
40:45 sat by. Calculating off the concentrations the permeability is for potassium and
40:52 And so this is the nurse This is now the Goldman equation.
40:58 then we moved on to talk about buffering how if you increase extra cellular
41:04 concentration, you will d polarize the members. And if you could increase
41:08 beyond 10 million Mueller. So normal is 3.5, about $5 million.
41:13 you increase is a 10 or 12 Mueller, you're actually reaching the threshold
41:18 action potential generation. So we talked how now, uh, Leo cells
41:23 be responsible for spatial buffering for absorbing high concentrations of potassium and buffering it
41:30 this interconnected processes within Astra size and exercise through the A specific network preventing
41:37 local rises and concentration being potassium or or even neurotransmitters in some cases.
41:44 we talked about that their channel dynamics and that this channel dynamics are they
41:52 a particular structure talked about Shakur flies mutation that made flies shake gene mutation
42:00 using these mutations that using toxins using Roderick MacKinnon was able to derive the
42:08 of the voltage gated Tucson potassium It's important we talked about the conserved
42:14 acids. And then we talked about fact that he also determined the poor
42:18 inside the channel which serves us essentially a sieve, molecular sieve or
42:26 coming in or leaving through that and that the conservative, you know
42:32 could then, by studying the flies food flies, shaking flies we could
42:38 . If they have Kamala Ji and structure of the protein, and we
42:43 it's an important part of this program the fly, then it might turn
42:47 to be a very important part in human, which could then be used
42:51 subsequent drug development as well. So started talking about action potential, but
42:58 question was about the Your question was number and equivalent circuits and the take
43:05 message here is that again you will need to calculate the circuit. There's
43:09 here that you're calculating, but you to realize that you have very important
43:13 , that you have the term off force, which is the difference between
43:18 and potential in the Librium potential. that onslaught equals ir can be
43:23 Driving force equals I r. And driving force VM. Here I equals
43:31 times G, in this case, conductors, because G is equal one
43:36 r. So you derive that your current will depend on the conduct INTs
43:41 the driving force and the conductor's through channels and overall conductors through a number
43:46 all of the channels times, individual conduct. And we said that each
43:51 of these channels and peace of the can be represented with equivalent circuit physics
43:57 . Each one of these will have own membrane resistor conductor, and we'll
44:04 have of battery electro Motive force. so this this this started to hear
44:13 had a question. What is passive ? This is just passive circuit on
44:17 right here on the top. It show any flux. And if there
44:21 any flocks, that is probably not dominating in any direction, then there
44:26 is no net flux in the passive . Uh, not necessarily would with
44:36 it to the bottom, which is an active circuit. And now you
44:39 see the conduct insists of sodium coming outside to the inside, protection from
44:44 inside to the outside, the pumps against concentration. Here it is very
44:49 to positives. So we talked about properties of the capacitors having good capacitor
44:55 large membrane areas opposed to resistor, the membranes are R C circuits,
45:01 combination of resistors and capacitors. There's resistance into the cell that resistance,
45:06 bigger the sell, the smaller the . But the capacity is the bigger
45:11 cell that higher the capacitance on before have this charge loading, which states
45:17 . And we have the ivy properties the electrical properties. Electrical curves for
45:24 membrane overall of for individual channels that discuss later in the course. So
45:29 you will not need to do a here. But you will have to
45:33 what is flowing where I'll say during speak of the action potential, you
45:39 have this type of circuit on I will say, you know,
45:44 different type of question. But now other message here is that the permeability
45:50 changes. And if we had a permeability for potassium addressing member of potential
45:56 the action potential, the permeability is highest sodium. That's so. When
46:01 talked about action potential, we had review the Smallville clam circuit and take
46:07 message. Here is that voltage clamp you to clam the potential toe,
46:12 the potential. It allows you isolate currents at different holding potentials and
46:18 the voltage clamp and setting that number potential of different levels. You can
46:23 different currents of interest, and now contest where the ions actually exhibit their
46:28 . So you calculated it now You contest by using voltage. Clamp
46:34 and you can see above 52 million , which is the equilibrium potential for
46:39 you. Don't you no longer see inward current, but instead that current
46:43 becomes a little tiny blip of an current Sodium is now, instead of
46:49 into the south's flowing from inside the out of the cell it reverses.
46:54 as you can see, the dynamics these currents during action potential of such
46:59 inward current is early. It's but it's transient, and as deep
47:04 is sustained, the outward current, is potassium current, is late
47:09 but it is sustained throughout the deep . So we discussed that this deep
47:15 during the rising phase of action potential influxes of some off sodium channels,
47:21 up and potassium. The flocks is sum of individual potassium channels opening
47:26 and we distinguish between the dynamics of channels being very different. Then we
47:31 last couple of lectures we home did on the sodium channel, so I'm
47:36 going to go over that much over . But we talked about both
47:39 sodium channel, both educated, both educated Passion Channel. The voltage
47:46 sodium channel we said as a sensor us for the poor loop. That's
47:51 . And later we also talked about as six, which is important for
47:56 okay and binding. Now we talked sodium channel kinetics how it has to
48:03 , So I'll review this really quickly you get deep polarization. Sodium channel
48:09 gates are now open up in number and Sodium Channel opens. And that
48:14 because the vaulter Sensor sliding up this and changing the confirmation off the whole
48:19 . But as it changes the confirmation opens activation, gave his ball and
48:23 represents inactivation, give an activation gate and closes the Channel four as it
48:30 , the Channel Port will stay there the member and potential gets hyper polarized
48:35 at least the threshold for the action generation. ATTN. That point there
48:40 be Dean activation, the inactivation gate leave and the activation gable clothes and
48:46 sensor will reposition itself back in its position. Now the number four.
48:51 cell again is ready to be stimulated deep polarization and go to number
48:55 Number two open and trans simply open channel again. So we discuss this
49:01 it relates to the absolute and relative period's. Also, um, and
49:10 , we also discussed the different modes recording patch clamp recording using voltage clamp
49:17 , which will allow us to test conduct. Ince's how well ions are
49:22 through these channels like sodium channels. we have different types cell attached
49:26 out and outside out. Recording number out will expose cytoplasmic domain to the
49:32 world. Experimenters world experimental conditions I will expose the xlu, the
49:38 of that protein, to the experimental . And then we moved on to
49:43 about toxins to say, Look, have evolved clown, but we need
49:47 and thes toxins are important because they certain things. And we discuss these
49:52 and enough detail for me to ask questions about ttx about sacks, a
49:59 light okay, and there is additional that is posted on, but we
50:05 you review the material from lost the lectures. You will. You will
50:13 all of the information that is necessary you to know, so I don't
50:17 to repeat myself, but maybe get your questions. But once he used
50:20 blockers tt access specific for sodium gated sodium channels. Tokyo's Narahashi and
50:27 article that was posted for you guys about how tetrodotoxin blocked the voltage gated
50:33 channels and block that action potentials but that he needed a voltage
50:38 He needed a combination of the voltage and tetrodotoxin in order to isolate the
50:44 , blocked the currents and show that tetrodotoxin has no effect on voltage gated
50:49 channel because it has no effect from outward conductors has shown in blue as
50:54 to etcetera. Salamoni have shown here the right, which blocks potassium channels
50:59 does not affect the inward sodium So inward sodium current is there doesn't
51:05 sodium channels and locks potassium channels so don't get this outward potassium car.
51:10 you had a home. One How this cocaine interact with sodium channel
51:16 may show up is a test and then we reviewed I V
51:22 okay? And we talked about how you open the channel, some of
51:25 channels are linear. They have linear V curves, which means that for
51:29 same change in the current, or the same change in the voltage current
51:35 dependent voltage voltages dependent on current in linear way the same amount of people
51:41 ization will cause an opening of a at certain level on This is how
51:47 construct ivy plots or, uh, voltage plots. And we talked about
51:53 a lot of these flaws are actually , but they're nonlinear that they're non
52:02 . And then the last toxin that discussed was lighter came. Okay,
52:05 review what we discussed about lighter cane the most common local and the state
52:11 aesthetic. But there's an important feature liner game that you should recall,
52:18 on the fact that it has a side on the inside on the side
52:22 Plas mix side of this office protean sodium channel program. So if you're
52:30 single channels, that's great. Sometimes hard to distinguish activity of single
52:34 so you want to go to systems they will allow you to amplify
52:37 express these channels, determine the exact and go back into more complex system
52:42 now, mathematical calculations and a lot data actually find the channels of interests
52:49 mawr complex systems. And, now, we before we talk about
52:56 generation off action potential if you um, I provided you with a
53:06 , which I think you should know . Thio draw that slide. You
53:13 understand essentially everything on that slide. 13 influx, potassium e flux driving
53:22 equilibrium, potentials for alliance member and resting number and potential value action Potential
53:28 value. A positive feedback loop for deep polarization. Sodium, demobilization,
53:35 . Why doesn't reach the liberal potential sodium? Because driving force decreases.
53:40 because the inactivation gate closes, then driving force for potassium increases have huge
53:46 of potassium going outside, leaving the going outside, and then you have
53:51 reconstruction rebuilding of this chart separation across number in the slow, much slower
53:56 by sodium, potassium pump. So the channel sodium channels open and they're
54:01 there and this absolute refractory period where cannot generate another action potential because they're
54:07 up, sodium channels have plugged There's no more deep polarization. So
54:11 have the hyper polarized because my at least to the action potential threshold
54:15 the law. And in this blue , this relative refractory period zone is
54:20 you can generate. Now There is of being activated that channels that have
54:24 Deion activated on closed. So if is a stimulus coming in during the
54:29 factory period, that piece member and this cell will be able to produce
54:33 action. Then I would like to with you yet about that screen.
54:47 . This is our ivy plots. you remember, I said, What
54:51 I place a ivy plot? And said that it crossed zero line?
54:55 zero current Ramana Satan. We said would represent potassium. Potassium is going
55:04 . Potassium is leaking from the south the outside, and we said,
55:10 is going inwardly is an inward card it reaches positive 55 reverses.
55:16 of course I did all of uh, drawings here, but you
55:24 make your own drawings. I was thinking of posting this one because they're
55:31 abstract art with something like this would interesting. Linear versus rectifying Reversal of
55:37 Sadie Russell Positive. 55. You be able to identify them. Potassium
55:42 r. Sodium with Lisa Linear channel and it's so this is something to
55:48 again. What is the difference between and rectifying again? The rectifying?
55:59 see this linear on the left So it's a It's a straight line
56:04 me and said for the same amount voltage that you change like this.
56:09 you will have the equivalent amount of change, but in rectifying if you
56:16 , let's say here you have inward . You can see that if you
56:21 this this blue line do you know same amount off current and people
56:28 So if you have this current negative here you have low conduct INTs inward
56:35 that is low. But if you to positive one become emperor or hundreds
56:40 members of current one that a number current the same equivalent as you did
56:45 the negative, but you inject the amount of positive current. Now you
56:48 see that you remember and potential value changed tremendously or you can view the
56:54 way for the same change in the of potential value you see, Go
57:00 from zero value to the right or the left, and see where
57:04 where you have more conductive where you more and changing the voltage. And
57:09 this is rectifying, which is essentially to conduct ions in a in a
57:15 direction, in this case, does that answer your question?
57:20 it does. Thank you. So , go ahead. Can you go
57:28 ? So you said that this was conducting because it shapes outwardly the second
57:38 picture on that's life. Yeah. , uh, let me actually mature
57:48 her. Your question correctly. You go by this diagram here. And
57:54 if when I said outward current you know that outward current will be
57:59 for different ion, depending on the potential. So you really the inward
58:04 in this case is this bottom deflection on the outward current was the top
58:11 . So when I said outwardly rectifying , its's preferring Thio rectifying the outward
58:17 like in this blue line here. how would you tell something was inwardly
58:24 . You would do a measurement of curve and you may end up measuring
58:29 that would look like this. okay. And so that's that.
58:37 the point is that membranes and cells have ah combination of these channels with
58:43 different curves, some of them some of them awkwardly rectifying, reversing
58:48 different controls. You know, some them reversing it overlapping potentials. And
58:54 why I had that crazy diagram with these lines because really, the cell
58:58 have to compute from about anywhere between or 20 of these different curves coming
59:06 different channels in order to give a response in the plasma membrane. Good
59:14 . So I'm goingto go back to if we have a few slides of
59:20 material to go through. This is rectification. I think this is maybe
59:25 main slide, and I encourage you look at that article again that I've
59:31 . But I hope that this was too confusing for everybody. But we
59:36 have this back propagating spike. So trying to solve How do we get
59:40 backwash of this current coming in and does it mean was back propagating action
59:44 cultural? And so we talked about subtypes of sodium channels. That maybe
59:50 , which is a high threshold, a lot off positive current. In
59:54 Thio for that vaulter sensor to shift open up the channel. And so
60:00 you have incoming deep polarization that may inhibitory input that passes through the cell
60:07 interests, remember this very specialized place on initial segment acts on hillock.
60:12 is where the action potential is going be produced that bypasses the zone of
60:18 receptors, which are located closer to summer. Because the current by itself
60:23 not strong enough, Thio, open these channels, not the receptors,
60:27 these both educated sodium channels. But it enters this yellow zone, which
60:31 a little further away from the that yellow zone is inhabited with low
60:38 in a V 1.6 channels which require current in order for the voltage sensor
60:43 slide and has sensitive alter sensor to up the channels and generate an action
60:49 list explosion combustion action potential will propagate and to drama or forward. I'm
60:58 , Ortho drama were forward propagating action . And then you will have now
61:05 these n a V one point to deep. Polarization is still coming in
61:09 action potentials being generated. Now you the summation of these positive d polarizing
61:15 the campus and positive current that is from the action potential. Some of
61:21 positive inputs on this zone with the starts opening up high threshold channels.
61:27 it z high threshold because there's this current from synopsis and positive current from
61:33 action potential in the Yellow Zone and up in 81.2 channels and generates back
61:40 action potential. And so we talked how back propagating action potential is very
61:48 in synaptic plasticity and important spike, dependent plasticity. And we talked about
61:55 the longer time period it takes from cell for other cells to stimulate the
62:01 for the South to respond, the relevancy that cell has because in the
62:07 things have to happen on the water , funeral seconds. So if you
62:12 inputs being activated, de polarizing inputs activated, cell doesn't respond within a
62:19 milliseconds, and these synapses are feeling it. Been meaningless. They're talking
62:24 somebody that doesn't respond to them. this back propagating Spike informs the rest
62:28 the cell and participates in what we spike, timing, dependent,
62:32 And it is the timing between the coming in the synaptic inputs and the
62:38 that gets produced here. This spike to the action potential that gets produced
62:43 axle initial segment. It's a spike defendant plasticity of this back propagating spike
62:49 you block the back propagating spike, produce the forward propagating spikes. You
62:54 have these synapses and the dendritic spines plastic or you cannot have them plastic
63:02 all. The hostess city changes. if you respond within a few
63:10 ex editor signal you strengthen the But if that time period shifts to
63:18 of milliseconds to hundreds of milliseconds, actually depress the synapses. So you
63:23 the signal. You're saying it's I'm busy and fast processing something
63:28 Right now. He's a kind of of the learning rules, I
63:32 And so you are substrates of these and memory in general, uh,
63:40 our brands. So I think we was probably the last slide. Maybe
63:45 was another slide that said, Why I care about generation of action
63:50 Give you a home or questionable Freshman was about which direction we done
63:57 its preferred to propagate on that point view, Teoh. A couple of
64:00 that are posted online for years on blackboard. Okay, so bring on
64:08 questions. Let me check the For some reason, I can't see
64:13 chant. Okay, let me check , um, during the relative refractory
64:23 with the sodium channel be dean activated closed. But it goes. Dean
64:29 a little bit more hyper polarization They will, dean activate and close
64:35 different hyper polarization levels because a little depends on the local thermodynamic changes and
64:43 local immediate environment. So that's a question. Okay, wait. So
64:51 say that it's being activated. So means that, um if a stimulus
64:57 added during the relatively faster period with channel open, I couldn't hear you
65:09 . Could you repeat it? If the If, Let's say the neuron
65:15 that the relatively factoring period with the . Like if you add a stimulus
65:21 that time with the channel open, , but at the absolute that the
65:28 you can you can. You can you can inject the Houston Power station
65:34 it, and then we'll it will . Not it's a joke. Of
65:40 , if you, you know, the system with so much power,
65:44 things will happen. But you cannot another action potential during. That's why
65:49 absolute. There's absolutely no way you an action potential. But during the
65:55 period, if your stimulus is relatively relative to the position off your number
66:04 potential, you can generate a Okay, also, E. I
66:10 a lot of questions. Um, saw on the sample exam that you
66:16 on blackboard. There was a question had a question on. It was
66:21 five, and it stated whether, all All right, let me look
66:28 it. Thank you for pointing out there is a sample exam. It's
66:34 in your folders and blackboard. Somebody . Okay, So for number
66:44 it says Ionic, conducting strength and depends on membrane potential value, so
66:53 know conduct Ince's like, um, current over the driving force.
67:02 Like, but I'm kind of confusing I would answer that question. Me
67:09 . So I'm opening an example like , uh, legal number five.
67:23 said, um, there must be different question they're looking at or
67:32 So it's the final exam sample. number five. Oh, yeah.
67:39 . That Z fine. Yes, . The question is not so
67:52 actually, so I only conduct and The current amount of current depends remembering
68:02 value. Yeah. Yeah. And would be true that it will be
68:07 . Okay, So direction on the of that current with dependent member and
68:13 value. Um, And that was example I showed you with the reversal
68:19 sodium. Remember that blip going in opposite direction. So as you change
68:26 number of potential as you shift the of potential beyond what the Caribbean potential
68:33 for sodium and the positive values you would then have a reversal of
68:39 current. Okay? This currently the thing as conducting. I'm so
68:46 Like yes. You're conducting currency Yes, on. Do you can
68:58 of it interchangeably? the strength of current or the conductor's through the
69:03 Conductors of ions through the channels, channels, conducting ions. Is the
69:10 okay? Yes, because ionic conduction flow of charge and current is flood
69:17 per second. OK, it's all . ITT's current can also be viewed
69:22 change of charge across the resistor and resisters the plasma membrane and how does
69:30 charge? Change it flows or it conducted across the channels and that conductors
69:40 charge across the channels is the Okay, our thanks and the amount
69:49 that current will depend on the And that's why the resistance conduct Ince's
69:56 inverse of the resistance. If there's resistance, if the channels open,
70:01 pipe is wide, then you have lot of water flowing. Third,
70:06 you use the analogy of like a hose Now, if you have very
70:13 hose, you're not going to be to pump much water through that
70:17 It has a lot more resistance, not as much conductors or current would
70:25 , not as much Water would not as many ions would flow.
70:38 , good. Any more questions? ? Oh, Yes. Okay.
70:48 number 10 on that exam, you whether action potential is a greater
70:56 Um, yeah. So So this exam is not necessarily like the best
71:03 for you guys, because it's a exam. That was cumulative. I
71:09 to give you an idea of the exam, and you understand the answer
71:14 this question action potential is all our . And when you talk about synaptic
71:21 , so synaptic transmission and the second we actually talked about graded potential.
71:26 synaptic potentials and action potential is all not. I'm great potential.
71:33 Okay, So what I would say , you have this exam also no
71:41 . And this is all, Exam one, The section relevant
71:48 The final exam. Are you seeing screen now? Which is a lot
71:53 . Yes. It says principal You scored 60 out of 100.
71:57 had a terrible scar, apparently, my exam. Uh, well,
72:02 did that for for a reason. didn't want you guys to have all
72:07 the correct answer. I said I you to scratch your head and all
72:11 and false is easy. But then it comes Thio. If you multiple
72:16 questions, I left them and correct that you could check yourselves and check
72:20 notes rather than just checking. Key. So this sample one examines
72:28 , relevant thes would be examples off questions. You know, Let's let's
72:35 through this. For example. Please correct association above graph A and B
72:40 first look. A. Always When look at the label and questions,
72:45 a hint. Look for what is . Look what the labels are.
72:51 what the access say, Look what numbers say. Okay, what you
72:57 on a says member and potential value this positive 20 positive 40 0.
73:04 currents of deflection going and then flatline positive 55. Okay, I still
73:11 know the answer, but it's my . I'm onto something. What is
73:15 ? 55. Start ringing in your something. It's a value of
73:19 55. What is that value? about. No resting member of potential
73:23 of 65. What is the positive over the town? Shell for
73:28 No, that's minus 80. Was sodium. I think it's sodium.
73:36 sodium? Yes, it's sodium reversal potential for So what is it represents
73:41 to do with sodium? Okay, , Let's go to be What is
73:46 a number of potential value? Flat at zero current? Eso Yeah,
73:54 it is the flow of current this on upward and downward directions. Deflections
74:00 flow of current and you have a flatline. What does that mean?
74:07 , zero for me was the outside of the cell, that of
74:11 The section, of course. let's see what the options are.
74:17 represents sodium current reversal. Who? think that's right. I think that's
74:22 . 55. I think it's Current would reverse there. That's where
74:26 equilibrium. Potential is it's the same reversal. Potential represents PPS peer of
74:32 Island Study B. P. Spc he wouldn't be so bad It asked
74:36 something I don't know about I P p. I didn't study these yet
74:42 potassium. Controversial old potassium did study and it's a deliberate potential. Potassium
74:49 00 No, it's mine to say , no, be Gabba reversal.
74:55 haven't studied Gavin reversal yet. It's completely and relevant to you 100% This
75:01 I PSB reversal haven't studied piece so I would bacon answer sodium current
75:07 and that is the correct answer. is the equilibrium potential. This is
75:13 deliberate potential value which sodium currents would and flown off the direction. And
75:21 would structure these questions in these answers on what we covered in this particular
75:26 in this particular section, which we cover. Gabai, PSP or a
75:30 reversals. Yeah, for this So here we kind of went over
75:36 questions. Actually, you know, your pick your best association. Which
75:42 is which one is potassium channel? ? The answer is correct. It's
75:48 because it has reversal about minus 75 80 mil evolves shown here. That's
75:54 that's why I wouldn't take that you know? So this is the
75:59 you should really go through. You go through the final exam in look
76:02 some relevant questions, but I think this is really most relevant for,
76:07 to see. So let's see, you have a cut off score just
76:22 75 or so? Not sure what means. You get cut off after
76:29 . Um, I'm sorry. You the grade the letter grades?
76:39 not certain natural. If you could the great What did you say that
76:42 ? Graph shows be graph shows You know what it shows you haven't learned
76:47 . Its e p s P reversal be excited. Very positive about the
76:53 on play potential in the Neuromuscular Junction illuminated with staff Terry Wrestle potential ample
77:01 receptor reversal potentials. All that zero . Also, this is a language
77:05 you'll learn and you add these other and other terms onto this reversal potential
77:12 zero mobile minus 80 and I minus for minus 90 even I totally agree
77:20 you. What a pain in a which one is a jeez? Minus
77:26 minus 75. Different book tells me . Different cell will give me a
77:33 different reversal for potassium. So that's I said go by this diagram.
77:41 , minus 90 for potassium minus Core I resting member of potential minus
77:49 . Follow this diagram. My They're gonna be based on this because
77:54 different environments in the brain and calculations different books will give you a slightly
78:01 values. It's not to nail your ha got you. It's not 88
78:07 90. That's not the point. know. The point is Thio really
78:13 you understand that the Zerg liberal potentials play into the action potential dynamics and
78:21 how much of an ion would would through the channels. So great.
78:29 I think we're pretty much out of today. I am recording the session
78:35 I will post this online hopefully shortly and sometimes takes quite a few hours
78:45 me, even to save Zoom and video points to upload it. A
78:51 of you expressed concerns about video If that link directly from my syllabus
78:58 lead you to where you need to , it says it's bad length.
79:02 dangerous. Try searching for it. putting it into Google. You have
79:09 video points to get you to the location. Try a different browser.
79:15 it says it's unsafe and you go video points, I do proceed on
79:19 computer and so hopefully you can get . You have any questions? Please
79:25 to me before Monday. Good luck your exam on Monday, I will
79:34 checking my emails if there is any glitches. The first thing in the
79:42 heirs to reach out Thio cause a if they pick up the phone or
79:47 the answer to your email right away try to get their response if it
79:53 work. If it is extremely try Thio. Even email me and
80:00 c Casa Support honor as well. if you're emailing me directly, put
80:07 people soft number so I can address fast. Have you know people solve
80:15 but it's a couple of steps for to get to them. I don't
80:18 them hyperactive all the time. So that. Hopefully nobody will have
80:24 Not many of you. Just a experience and technical glitches during the
80:31 Good luck. Have a great weekend on good luck on the exam next
80:37 . I think I have a
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