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00:02 | So today we will be discussing neuronal And when we first talked about the |
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00:07 | experience for example watching the we talked um precise uh like my cross |
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00:17 | What all of these techniques allow us do is visualize unusual cells visualize individual |
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00:23 | cellular components. This is a nice about grading spines about the great experience |
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00:29 | visualized and reconstructed and this is all of the structure. So typically when |
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00:37 | talk about morphology of the cells, of them rides anatomy of the dendritic |
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00:43 | season. We're talking about structural imaging it doesn't have function in it. |
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00:50 | when we talk about static or structural versus functional imaging neurons are functional. |
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01:00 | increase their metabolic turnover rate, they a lot more oxygen, they consume |
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01:08 | and there's increased blood flow to the of the active neurons. We're talking |
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01:17 | imaging neuronal activity on the experimental neuroscience . We can image ionic flux is |
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01:25 | there are guys that are sensitive to islands, calcium sensitive guys and they |
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01:31 | show us fluctuations of calcium in different . For example, down drive |
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01:39 | There are guys that are sensitive to islands such as sodium such as |
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01:46 | So we can trace individual ion movement the cell specific ion movement. We |
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01:54 | image neuronal activity and glial activity. we talk about neuronal activity, it's |
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02:02 | , real activity is slow. So experimental setup with the demand for the |
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02:09 | and the speed of cameras resolution might very different depending if you're imaging a |
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02:14 | fast neuronal calcium flux is are much Uh What do you need image those |
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02:27 | supplies of ions of calcium. They're fluorescent tags on the ions. And |
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02:34 | the concentration of these ions goes the fluorescent signal changes, we can |
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02:39 | image vault that you already talked about expressed all the indicators jetties. And |
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02:45 | one of the papers you have and image single molecule like a receptor |
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02:56 | An experimental nurse on. So we tag and pour some first and see |
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02:59 | they move from the extra synaptic spaces the synaptic spaces. All of these |
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03:05 | different imaging techniques that can be used now functional. So when you're talking |
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03:16 | structure is one thing, but you're about flux is and ions changes in |
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03:21 | , glucose consumption, calcium voltage These are all functional changes. Talk |
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03:29 | the different levels that you go into uh supplementary uh reading here that we |
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03:41 | . It's much better resolution. I'm and we talked about different levels in |
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03:47 | you can measure and measure activity that described. The macroscopic club, messous |
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03:55 | level. Macro is. You're looking a certain part of the brain |
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04:00 | You're starting to understand what cells are to inhibit. There may be or |
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04:05 | subtypes of cells are located and what function is. Circuit centric. When |
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04:11 | starting understanding what are the subtypes of on the circuit how they're connected single |
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04:17 | level and the sub cellular level. can look at the activity in either |
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04:22 | spines and dendritic shafts or selma or . And then you could potentially compare |
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04:29 | activity in different cellular compartments essential. within a single dendritic spine compartment, |
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04:36 | can image activity quite successful. So is the experimental setup configurations for different |
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04:47 | of this genetically expressed voltage imaging. way that we already talked about |
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04:54 | The way that these molecules work is they get expressed in the plasma membrane |
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05:01 | they have a fluorescent marker that is to the podium. And therefore it |
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05:10 | gives you a signal, a voltage sensing signals. So it senses the |
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05:18 | as it travels across plasma membrane. different iterations of these uh sensors and |
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05:26 | molecules. But once you have that genetically expressed are applied on the tissue |
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05:34 | can actually measure different levels. So can fix the head, right? |
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05:41 | the animal's head is fixed. But imaging activity in the whole animal as |
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05:48 | animal is performing a certain behavioral Would say the animal is smelling something |
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05:54 | the animal is looking at something. . You can have in many instances |
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06:01 | experimental setup in minusca. Oh oh like a little head microscope, Like |
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06:07 | lens that get mounted typically has like optic wire that comes off the little |
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06:14 | scope. There's an advantage here because animal is freely moving. So as |
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06:21 | to being stationary and fixed head position reacting to certain stimuli. Now the |
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06:30 | can move around with movement, there's with artifacts, there's problems with artifacts |
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06:37 | experimental functional imaging. There's problems with in clinical functional image, such as |
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06:44 | the person as the pet scan or . R. I. F. |
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06:48 | . R. I. Scan. they move small movement can give you |
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06:55 | . Sometimes their own diagnosis too. why movement is an advantage. But |
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07:03 | you have to have a mechanism when doing these experiments to well, how |
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07:06 | I gonna account for the movement? attacks, which ones are going to |
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07:11 | movement artifacts And you're measuring activity And why does it matter because brain |
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07:20 | is soft? So if you have on a certain level of tissue that |
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07:25 | come out of focus a little bit there's different regional changes that happen as |
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07:31 | moving, you can have a fiber . It's really interesting in a really |
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07:40 | animal where you basically uh instead of local field potential recordings, you are |
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07:51 | signals and selectively the signals by these indicators with this optic fiber. So |
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07:59 | you're using optic fiber, like an , these voltage sensors will change and |
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08:07 | gonna be able now to insert this and pick up the optical changes. |
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08:13 | why it's likened to feel potential. likened to feel potential because it cannot |
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08:18 | up activity from a single cell. accept activity from numbers of cells from |
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08:25 | of cells. Okay now obviously you a higher magnification 20 X 40 |
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08:34 | You can have imaging in the circuits society capital Circuit, C. 01 |
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08:41 | one parameter cells and you can look it in the tissue or in |
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08:50 | So if you have a stationary animal instead of the camera and this macro |
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08:55 | you want to have a micro view could potentially do these experiments in vivo |
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09:01 | but typically not freely moving. You're at the level of a single cell |
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09:09 | circuit. So these are two very images to to review as as as |
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09:17 | we cover this material. Let's look little bit about in an example and |
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09:33 | brains and talk about a specific structure rodent brains for barrel cortex. So |
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09:41 | rodents do is they are internal animals when they are out and about and |
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09:49 | exploring they explore the environment by smelling . So olfaction and they will contain |
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09:58 | very large or factor involved. So lot of the brain tissue is basically |
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10:05 | to the primary factor information processing. way in which road and sense the |
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10:13 | is the whisk around, whisk around they have a whisker pad and they |
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10:22 | at certain frequency which is typically within low theater range like few hurts. |
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10:28 | moving these whiskers a few cycles a and they're touching things the size of |
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10:36 | walls, piece of cheese whatever they . So this is very important for |
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10:41 | , the sense of olfaction and some sensation. Somatic sensation is especially from |
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10:49 | . For us humans, it's a of sensation. If you want to |
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10:54 | something, we use our hands And rodents will use their paws, |
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11:00 | can move things with paws will pick up, but they will actually explore |
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11:06 | of touching things whisking around and that that there's gonna be a lot of |
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11:12 | area dedicated to the rodent whisker This is the whisker pad. These |
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11:20 | the new brisa or individual whiskers is hair follicles and rodents typically have 12345 |
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11:29 | of whiskers on each side. The are not unique for whiskers actually have |
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11:34 | dog and she has whiskers in funny like on her cheeks and like bottom |
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11:39 | the neck, which is interested in . So, Madison's recording home |
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11:44 | Um but you know, she's my . So I can't look inside her |
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11:51 | , but here's the map for the in the primary somatosensory cortex of the |
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12:00 | . And you can see that this brisa, the whisker pad. This |
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12:06 | a huge area from the entire amount sensory cortex. It's dedicated to this |
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12:12 | pad and it's really beautiful system because one of these whiskers in the primaries |
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12:20 | sensory cortex has a barrel has a structure, anatomical structure where each |
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12:27 | you can see 12345 rows of Each barrel here in this matter, |
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12:34 | cortex will be processing information from grow from a single whisk. So |
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12:41 | it's beautiful because you have this outside of rose, a number of whiskers |
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12:49 | you look and you stay in the , medicines, the cortex in the |
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12:53 | . And you see these barrels these as a precise exact number of barrels |
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12:58 | a number of whiskers. So if rodent is missing a couple of whiskers |
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13:03 | will also be missing a couple of , if they have an extra one |
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13:07 | two whiskers, they may have also this matter sensory cortex an extra one |
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13:13 | two barrels. So that information from bristle. When you're touching the whisker |
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13:20 | , all of that information is traveling the trigeminal nerve. So all of |
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13:25 | amount of sensory information from the neck and your head is processed by |
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13:33 | nerve, five or trigeminal nerve and why this is called the trigeminal |
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13:41 | So there are sensory nerve endings that , can imagine a simple fashion kind |
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13:47 | wrapped around these nerve terminal around the follicles. So every time this hair |
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13:55 | this hair this person moves and the follicle, the hair rooms inside the |
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13:59 | follicle, it will activate the trigeminal . The trigeminal nerves that have the |
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14:07 | branch, acts on that form the and send the information through the central |
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14:14 | all the way through other structures, into the final destination of S. |
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14:21 | which refers to primary amount of sensory or area S. One M. |
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14:28 | refers to primary motor cortex. Area M. One and this once |
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14:34 | demonstrates very neatly that if you have , 5 rose and a certain number |
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14:42 | whiskers on the pad you'll find that anatomy in the cortex and guess |
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14:46 | You can then move whisker two in C. Which is C. |
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14:52 | And when you move physically that whisker . Two on the outside, you |
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14:58 | see that activity in the barrel It's matter sensory cortex corresponding to whisker |
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15:04 | . Two is significantly increased. This a really really neat experimental system because |
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15:11 | can do manipulations that are very precise into single whisker on the periphery. |
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15:19 | you can observe very precise map of in the primary somatic sensory cortex. |
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15:26 | let's look through this image here. this is a single brief C. |
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15:36 | . Whisker deflection and you can see this is C. Two. Whisker |
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15:42 | . And you can see in the of medicines, the cortex first activates |
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15:46 | barrel very small area for barrel And you can see the activity from that |
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15:55 | area that expanding and spreading. So is the map of activity of brain |
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16:02 | of activity if you may and when activity spreads. Now you're talking about |
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16:07 | brain wave for that activity is traveling the interconnected networks in the brain and |
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16:16 | into adjacent regions potentially into M1 Because as you move the whisker that |
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16:22 | may want to move back is going be a motor control. So you |
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16:26 | see activation here eventually of this M1 . So at first you have very |
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16:33 | specific map that corresponds to just that Whisker that you're activating. And later |
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16:39 | see a significant spread of that map that activity through the interconnected networks at |
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16:46 | time. Why we should spreads is tens of milliseconds. Okay, so |
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16:53 | activating a single whisker within 30:40 in will engage other parts of the |
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17:01 | not just the primary amount of sensory through the interconnected networks through these brain |
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17:08 | . Now this is A. Where we have a control experiment and |
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17:14 | in the first condition we're wiggling whisker . Two. And in the second |
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17:21 | we're stimulating whispery too. And you see that C. Two and |
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17:27 | To reform distinct maps. You can that it's not the same barrel. |
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17:32 | it's two distinct barrels. And later some 26 milliseconds time you can see |
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17:38 | spread of the activity from C. and C. Two. Cool. |
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17:44 | there are multiple experiments by which you manipulate the system. So you can |
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17:52 | cut the whisker. And that's a cool experimental manipulation because it's not very |
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17:59 | . It's not like blinding somebody. not you know you are cutting off |
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18:04 | whisker and then you can see what anatomical changes of follow. You can |
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18:09 | in this case block that C. whisker activity with C. N. |
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18:19 | . X. On a Tv and . N. Q. X. |
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18:23 | a PVR glutamate receptor blockers. So . N. Q. X. |
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18:27 | an alpha glutamate receptor blocker signaling receptor an M. D. A. |
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18:35 | a P. D. Is an . D. A receptor blocker. |
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18:40 | if you block glutamate receptors happen in . D. A. By injecting |
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18:46 | into the region of C. Two the sea to barrel column. What |
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18:51 | do is you locally inhibit in the activity from C. Two. So |
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18:56 | you stimulate whisker C. Two but don't see a map anymore. You |
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19:02 | see a little bit of adjacent Maybe it's by adjacent whiskers being widely |
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19:09 | . But then when you activate To whisker you still see that |
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19:14 | Okay so now you wiggle see But you block the signals in the |
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19:19 | locally in C. Two and you longer see the spread of this map |
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19:24 | . So you can block the identity individual barrels and you can block specifically |
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19:32 | zero whisker to and it will not zero whisker to. And the map |
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19:38 | zero whisker to this is another way which these voltage sensitive dyes that we |
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19:50 | be incorporated the plasma membrane. So kind of experiments that we're looking at |
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19:56 | typically done with old sensitive dyes or another type of indicators that we discussed |
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20:05 | , like calcium indicator. But we to do this a lot of times |
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20:12 | imaging cortical activity. And if we're cortical activity we can image voltage which |
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20:18 | to neuronal number and potential changes. it's really good. And this is |
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20:24 | another way in which you can incorporate sensitive dyes into neuronal tissue. You |
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20:31 | apply these as chemicals instead of genetically them, you can apply them as |
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20:38 | make a window in the brain. can apply the dye on the surface |
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20:42 | the brain. These dye molecules of quick little warms. They incorporate themselves |
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20:48 | plasma membrane and as the voltage changes this is a sodium channel that conducts |
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20:57 | inside or outside the south. Deep will cause a certain confirmation will change |
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21:03 | these dye molecules that will indicate where strong activity. You will have read |
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21:11 | it's weak or inhibited activity. You'll areas of blue and now when you |
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21:16 | at this red and green traces you see these two red and green |
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21:24 | . What these traces are comparing is comparing the imaging that is obtained by |
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21:31 | fluorescence and electrical signal as the electorate implanted in the same region. What |
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21:39 | observing here is it's 1-1 that the signal through the camera tracks precisely with |
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21:49 | electrical signal that is recorded in the area of the brain. So intracellular |
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21:59 | is blue and V. Is the activity is red. So it tracks |
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22:07 | well with either the network or individual that is inside that network. That's |
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22:15 | it's a great way to study neuronal changes because of the ability to do |
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22:22 | at multiple scales. You now have ability to look all the way from |
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22:30 | macro levels, all the way to cellular law office and because it's tracking |
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22:37 | well with neuronal membrane potential changes for changes, it's a very valuable technique |
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22:47 | study cells from single cells of cellular all the way to large areas of |
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22:54 | brain and networks. And so when do imaging studies, we also reveal |
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23:03 | structure the functional structure. When we anatomical studies we reveal that anatomical structure |
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23:11 | reveals functional structure, function of these and structures equal function, function influences |
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23:20 | , structure and influence of function. all independent of each other. In |
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23:25 | end we have a lot of blood neurons, neurons will suck a lot |
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23:29 | blood. But another very interesting and thing is that neurons that are |
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23:36 | They're going to swell and as they , they're going to change the reflective |
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23:41 | and you can image the surface of brain for what is called intrinsic optical |
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23:49 | with both sensitive dies. There's a that you applied with genetically expressed voltage |
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23:57 | . There's an indicator that you genetically with calcium, sodium potassium sensitive |
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24:05 | you have to apply and die some of an indicator. The huge advantage |
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24:10 | intrinsic optical signal. There is no that is applied. You're purely looking |
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24:17 | the changes in the reflective properties of cells. And you can see here |
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24:23 | called the striatum vortex of the primary cortex. And everywhere where you see |
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24:29 | black lines of these blacks triumph that activation of one eye in the areas |
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24:35 | are not uh lit up or shown darker colors of the areas that are |
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24:41 | to the other. I this is the ocular dominance columns of the visual |
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24:46 | . And it's a really neat way intrinsic optical signal to visualize these uh |
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24:54 | dominance columns. Now you're its activity . So neurons have to be |
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24:59 | There are disadvantages of this technique because can only imagine on the surface really |
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25:04 | penetrate a couple of layers of the , but that's about it. So |
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25:12 | is the cortical surface without that activation one eye. This is the cortical |
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25:20 | . When you activated one eye and change the intrinsic intrinsic optical signal And |
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25:27 | of the neurons and the primary visual responsive to that one, I then |
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25:34 | you have is blood flow and this imaging of the blood flow. So |
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25:40 | correlated to the increases in activity in region is correlated with the changes and |
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25:47 | patterns of the blood flow to that . So more active neurons will do |
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25:54 | demand more blood supply. All right let's uh before we go into the |
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26:05 | . R. I. And things that. These are some of the |
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26:08 | signal imaging maps. We already mentioned in the last lecture a little bit |
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26:14 | uh welcome to read through this a bit. But it's a great way |
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26:20 | image the visual cortex. It's a way to reveal the ocular dominance |
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26:25 | And both of sensitive dye imaging and intrinsic signal optical imaging can be used |
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26:34 | delineate the orientation selectivity. Uh this visual cortical cells. So it's it's |
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26:42 | really it's a really neat technique again can image at the level of the |
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26:46 | network and hone in with enough of uh image resolution using a two photon |
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26:57 | imaging in this case. This is terms of signal imaging. In this |
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27:00 | it's calcium imaging. You can reveal of individual neurons. That's really important |
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27:07 | that you can have the underlying structure you image or sustain and use the |
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27:12 | stain and apology stain but then you the image of the activity. |
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27:25 | is the brain active all the What's happening with the resting states? |
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27:35 | so this is from your textbook if go into a quiet room, lie |
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27:39 | and close your eyes but stay What do you suppose your brain is |
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27:44 | ? So now we're talking about the brain. Not anymore neurons, but |
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27:48 | whole brain, If you answer is much, you're probably a good company |
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27:54 | our discussions of various brain systems that how neurons become active in response to |
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28:00 | sensory information or the generation of Modern brain imaging techniques are consistent with |
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28:06 | view that in response to behavioral neurons become more active in cortical areas |
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28:13 | process on the perceptual information. It reasonable to confirm that the brain is |
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28:20 | in the uh in the absence of processing. However, when the brain |
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28:25 | imaged with positron emission tomography. Now talking about functional imaging techniques that are |
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28:31 | , such as that or F. . R. I. It is |
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28:35 | that it is rest resting state. includes some regions that really fairly quiet |
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28:43 | others that are surprisingly active to the in quiet states is not necessarily |
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28:50 | it's just different parts of the brain important. Mhm. The imaging studies |
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28:58 | the difference between the brain's resting state activity recorded while a person performs a |
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29:04 | , they teach us an important lessons the nature of the resting brain and |
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29:08 | functions that it performs the existence of state activity does not itself allow us |
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29:16 | include much conceivably the resting activity might randomly from moment to moment and person |
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29:24 | person, and activations associated with behavioral will be superimposed on this random |
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29:31 | However, this does not seem to the case when a person engages in |
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29:36 | perceptual behavioral task there are decreases in activity of some brain areas. At |
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29:40 | same time the task relevant brain areas more active. One possibility is that |
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29:46 | the decreases and increases in activity are to the task. So when we |
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29:52 | at only the increases of activity that not be a fairly good representation of |
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29:58 | of the areas of the brain that processing that task. In fact we |
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30:01 | to look at the brain areas that go quiet for more quiet as one |
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30:09 | of the brain goes more active which of the brain goes more quiet. |
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30:12 | also should correlate to the activity. example the person is required to perform |
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30:17 | difficult visual tasking ignore irrelevant sounds. might expect the visual cortex to become |
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30:24 | active and the auditory cortex to become active. So we can have the |
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30:29 | tuning and choosing stimuli. But what it getting at here? It's getting |
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30:37 | . Maybe we need to understand the and brain status. Whenever we image |
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30:42 | we stimulate we stimulate schaffer collaterals in . One and C calcium increases. |
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30:50 | subject animals to sensory stimulation, we their whiskers so they're involved in active |
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31:00 | and tasks and we're looking at these that are created by active tasks and |
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31:08 | is this term sentinel sentinel is sort a term that in the in in |
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31:19 | you're a sentinel soldier, your your is to keep the watch some sort |
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31:27 | uh resting state. But it doesn't that the brain is to adopt. |
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31:34 | means that different regions of the brain activated during the sentinel or arresting |
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31:42 | Uh Conceivably, the resting activity might randomly from movement to movement persons. |
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31:49 | does not seem to be the case bit to further observations suggest that there's |
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31:54 | fundamental and significant about the resting brain . First, the areas that showed |
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32:00 | activity compared to the resting state are when the nature of the task has |
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32:06 | , it appears that the areas showing activity during behavioral tasks are always |
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32:12 | addressed and become less active during any . Huh? So now we're talking |
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32:22 | there seems to be brain regions that active when you are performing the |
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32:27 | But when you're not performing the task this brain region is no longer |
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32:32 | There's other brain regions that that are that are not involved in directly processing |
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32:40 | that task. So, uh figure 1 summarizes data from experiments using nine |
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32:49 | tasks involving vision, language and The blue and green patches in the |
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32:55 | shown brain areas in which activity decreased the resting state when humans engaged in |
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33:00 | of the nine tasks. Particular task seem to account for the activity |
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33:06 | Second, the pattern in the brain changes are consistent across human subjects. |
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33:13 | pretty cool. I thought we all differently but there seems to be some |
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33:18 | replicable patterns across our brain. So why maybe a lot of us get |
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33:22 | and think of like you know uh others that don't get along or think |
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33:28 | . Maybe their patterns are a little . You know, these observations of |
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33:33 | brain might be busy even in the we arrest that the rest of the |
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33:38 | are consistent with these activities and Asked this perform the state of sentinel |
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33:46 | or the state of internal meditation. you if you pay its cost of |
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33:53 | now you will say why is this ? Why we're looking when we talk |
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33:57 | E. G. We're looking for and outdoors. The E. |
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34:02 | Technique is not very good for recording brain activity unless the person is performing |
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34:09 | tasks. And you have all of filtering and measuring techniques to isolate certain |
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34:14 | bands data gamma. That represent different . But other than that if the |
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34:18 | is not having abnormal sexual activity, . G. Is not going to |
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34:23 | much and it is not even There's no resting state. E. |
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34:28 | . It's not typically done when you in right, they take your blood |
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34:32 | and things like that. They don't a cap on you for 20 minutes |
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34:35 | say what's your resting state? G. But maybe that is actually |
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34:41 | important. It's just that we cannot that information from E. G. |
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34:47 | not sensitive enough. We can start this information from imaging activity. Uh |
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34:55 | imaging activity. And this is done pet imaging studies involving different behavioral |
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35:03 | You can say that the brain have computer inflated activity in the south side |
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35:09 | be seen. Brain areas colored blue green were more active during quiet rest |
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35:15 | than during the behavioral tasks. So is more during the quiet periods as |
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35:22 | to the behavioral tasks that were being . It's very important. What is |
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35:30 | in any neuron inclusion. What is in learning and plasticity is prior |
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35:37 | Its prior information of what happened was of what is happening in a resting |
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35:44 | because what is happening in the wrestling will affect how the brain reacts to |
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35:52 | . So but the brain and the maps are not quiet. It's just |
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35:56 | the maps organization of the activity in quiet brains changes in three arranges |
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36:08 | And this is uh an article that already looked at when we talked about |
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36:14 | synaptic action potentials. E. S. P. S. By |
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36:18 | dependent plasticity. And this is just beautiful image of the whole system here |
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36:25 | the barrel cortex that we're talking in . So I have the soap and |
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36:29 | on. Show it to you if guys wanna read through the figure legends |
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36:34 | too. Now. Uh Oh that started talking about uh imaging techniques and |
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36:55 | imaging techniques in particular uh different from broken bone. What kind of imaging |
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37:07 | you do? But er excellent. you have uh if you have a |
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37:20 | or computed tomography will C. Is is a sophisticated X ray |
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37:27 | So what C. T. Does it uses a narrow X ray beam |
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37:32 | the road. Very sensitive detectors that placed on the opposite side of the |
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37:39 | . But essentially CT scan or computer tomo means a cut or slice. |
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37:48 | a graphic of a slice. What is you can see that this X |
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37:55 | source here and the detector. It be rotated, it can be rotated |
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38:01 | multiple different focal planes and different angles you essentially target, let's say this |
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38:10 | of the brain, you're interested in and you can send the deems this |
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38:16 | and collect them on this side and you can send them this way and |
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38:20 | the detector on this side and then can send them this way right and |
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38:32 | them on this side. And what does is it really gives you a |
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38:37 | nice three dimensional representation of that So you're imaging it from different angles |
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38:45 | different slices through this three dimensional So you can eventually create it. |
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38:52 | the X ray two brocades, three radio density matrix can be created allowing |
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38:59 | to be computed for any plane through brain. So ct scams what they |
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39:05 | do is they can readily distinguish between matter and white matter. It can |
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39:11 | the ventricles very well and it can brain structures with the resolution of several |
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39:22 | . So what is the diameter of single neuron? 10 Micro Fevers |
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39:30 | So can I pick up single cell millimeters? We're talking about thousands of |
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39:37 | meters. So you're looking at hundreds cells activity average from hundreds of |
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39:43 | In this case it's not even activity it's hundreds of cells that are imaged |
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39:50 | . That's the resolution. Mhm. now magnetic resonance imaging and the whole |
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40:00 | imaging revolution that started with M. . I. In the 19 eighties |
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40:07 | based on the fact that the FBI some Adams act the spinning magnet and |
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40:15 | placed on a strong magnetic field. atoms will line up with the field |
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40:20 | spin at a frequency that is dependent the field strength. So the magnet |
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40:27 | produce a field. And typically these are strong Tesla 35 Tesla seven testings |
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40:36 | can think about it. It's a bit of quantum physics that is not |
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40:42 | really well understood of what the spinning happening. But it's like a |
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40:47 | you know a toy that you uh going in the spinning spinning and then |
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40:52 | can turn sideways a little bit is spinning and go back in this |
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40:56 | This position tilt a little bit so what we're really are seen here in |
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41:02 | . R. I. The magnetic is distorted slightly by imposing magnetic gradients |
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41:08 | three differential access three different spatial access that only nuclear at certain locations that |
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41:16 | to the detectives frequency at any given . So magnetic M. R. |
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41:25 | . M. R. Images What can they do? They can |
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41:30 | between very matter white matter cerebrospinal So it gives you more information. |
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41:37 | if you had a tumor, if had a traumatic brain injury, if |
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41:41 | had an infection in the brain that causing inflammation, what you would do |
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41:47 | you would typically do to scan T. N. M. |
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41:51 | I. And this is still not to show you any functions. So |
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41:56 | have to do functional brain energy and do functional brain imaging which we talked |
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42:03 | is detecting small localized changes in metabolism blood flow. You will have to |
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42:11 | positive uh emission tomography, pet single emission, computerized tomography spect or functional |
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42:23 | resonance imager. Now on the clinical , I have to tell you not |
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42:31 | patient can go through em Ri scanning F. M. R. |
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42:36 | Scanning those coils. You can see confining it is that you're measuring brain |
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42:44 | you're being placed in this little A lot of people are have claustrophobia |
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42:50 | they cannot go through this procedure. lot of Children can still stay still |
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42:58 | lot of times if it is really to do this, they may sedate |
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43:02 | patient. So anesthetized. But guess happens when you invest participation and you're |
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43:07 | for brain activity. You changed his activity. So you're looking for tour |
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43:14 | of the tumor with static imaging of or C. T. That's |
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43:19 | But then if you're looking at M. R. I, then |
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43:22 | imaging anesthetized basically with brain activity and is going to change a lot How |
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43:31 | an hour, 20 minutes, depending the area that is being studied. |
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43:36 | you're studying really small nucleus, maybe done in that machine 20 minutes. |
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43:42 | you're scanning the whole brain for tumors something else, it's an hour, |
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43:51 | ! People put headphones on spanking. really tells you that you're halfway |
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43:59 | Uh And if I'm arai and I'm right, you do this and you |
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44:07 | , in text scanning have a stable emission admitting isotopes incorporated into different agents |
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44:15 | water rickerson molecules or specific neurotransmitters in and then injected into the bloodstream. |
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44:25 | intense scanning what are the stable isotopes essentially labeled oxygen and glucose, Quickly |
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44:34 | more metabolically active areas, labeled transmitter are taken up selectively to appropriate |
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44:46 | So functional M. R. I M. R. I. Currently |
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44:53 | the best approach for visualizing function best local tablets. F. M. |
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45:00 | . I. Is predicated on the that hemoglobin and blood slightly distorts the |
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45:05 | resonance properties of hydrogen nuclei in its and the amount of magnetic distortion |
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45:13 | Logan has oxygen bounded. I don't know what these little fancy things to |
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45:33 | . I want to visualize the whole presentation month. So here are some |
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45:42 | the images and more images of adult with brain tumor. And then you |
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45:48 | F. M. R. Activity during a hand motion task |
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45:54 | This is a tumor and you can that it shows you the structure and |
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45:58 | the pride is a three dimensional surface up of the same areas. So |
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46:07 | resolution for F M R. 2 to 3 millimeters temporal resolution. |
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46:13 | seconds. Maybe it's going to hundreds milliseconds. We were still talking about |
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46:21 | , advantages of experimental imaging fast, sensitive guys, super fast kilohertz. |
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46:29 | image of the killer hurt speed, herd samples, image sounds. What |
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46:35 | your cellphone frames per second? 30 maybe 60 of the high setting |
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46:45 | frames per second. So it's Right, 60 frames per second. |
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46:51 | R. I F M R. . Uh you're talking about few |
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47:00 | not so fast resolution, few How many cells? No single cell |
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47:07 | . So it's an average of hundreds cells. And that Fox alert that |
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47:15 | of imaging. So the changes in of oxygen and blood flow. We've |
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47:22 | blood oxygenation level and the changes that called old changes. So you will |
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47:27 | bold changes in F. M. . I. It's our situation levels |
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47:33 | it is dictated by the blood you can see that you can have |
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47:38 | nice three dimensional reconstructions advantage you can deep. So with that M. |
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47:47 | . I. Uh that scan you image deep inside the brain all the |
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47:55 | dyes calcium dies. If you have photon fluorescence microscope, you can go |
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48:00 | little bit deeper into the tissue, a couple of millimeters to image. |
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48:06 | you cannot image deep, intrinsic optical , circus signal to these disadvantages but |
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48:14 | faster. So both the sensitive guy optical signal, you can imagine hundreds |
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48:20 | frames per second tries to live your phone but in F. M. |
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48:25 | . I. It's one frame every of seconds. Ultimately, what do |
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48:33 | want Because we want to apply the uses of imaging functional imaging, we |
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48:43 | to implement the same spatial and temporal scales in the clinical setting. So |
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48:53 | we want to accomplish and you guys gonna be responsible for this a century |
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49:00 | creating a very Good non invasive imaging . It can give you a resolution |
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49:09 | you're seeing here on the order of mm area of interest but also give |
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49:16 | an opportunity to zoom in and understand on the serpent level. That would |
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49:24 | really cool or understand it on a cell is then out of these hundreds |
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49:32 | thousands of cells in the area that is a normal task. You know |
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49:39 | moving your hand as a normal task if you have abnormal activity coming from |
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49:44 | part of the brain. If you it up with E E. |
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49:48 | Now if you could apply F. . R. I showed that very |
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49:52 | piece of the brain and is abnormally generating seizures. Now with Mariah have |
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50:00 | of hundreds of cells. What if five bad cells? So then the |
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50:06 | challenge is gonna be okay. So resolved there's five bad cells on the |
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50:10 | that are called the seizures. How I gonna how am I gonna direct |
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50:15 | therapy? How am I gonna take the five bad guys without taking out |
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50:20 | hundreds of by themselves either pharmacologically or the surgeries or something like that. |
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50:26 | how am I gonna do that? know? So it still is a |
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50:29 | challenge. Even if we find our to single cells in this noninvasive clinical |
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50:37 | we still are facing some significant Uh And and then therapy and how |
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50:47 | manipulate the single cells with the small of cells tricks. Mhm. And |
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51:00 | is just in just an abbreviation of we talked about. In fact you |
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51:05 | be looking mostly at the oxy glucose glucose consumption. And then from ri |
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51:11 | be looking mostly at hemoglobin oxygen There's a lot of really interesting techniques |
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51:20 | are emerging in the last 10 There's M. e.g. magnetic electra |
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51:27 | grant imaging. Um there is typically couple of interesting markers that can be |
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51:35 | . Not just uh two D. . But there may be more specific |
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51:41 | neurotransmitters. There are some markers that specific to alzheimer's plaques that we can |
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51:48 | imaging. Uh Maybe even some blood that could be showing up in the |
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51:55 | started. So this is a hot the bounce I feel. But as |
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52:00 | know it's very expensive equipment. So example University of Houston does not have |
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52:09 | F. M. R. Machine. Universities would have those or |
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52:17 | of brain activity. Whole animal or . You have aged. Doesn't Medical |
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52:25 | is multiple. But if you're doing procedure you want to have an |
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52:29 | M. R. I. It's not like oh I can do |
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52:33 | here and there and there and there every door I can walk in. |
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52:35 | course you know this methodist will have own Andy Anderson call Sissy ball. |
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52:42 | a lot of times it still is access to these machines. Still stand |
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52:50 | line wait for three weeks. There's sign up. Uh And it's it's |
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52:57 | challenge for humans. It's a Imagine you go get radioactive sit in |
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53:04 | for an hour because you cannot be human being if you're doing a pat |
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53:09 | you're ready to act that way and go in through machine for an hour |
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53:16 | know and come out. That's Also when we see non invasive |
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53:24 | Yeah, no electrodes being stuck in head. But it is but it |
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53:29 | a challenging, challenging procedure. so that's all I wanted to tell |
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53:36 | about imaging of the brain activity. again, I think it's important to |
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53:42 | that the uh cellular level, we all of these guys forensic optical |
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53:49 | which is not that great result signals level that you have all of the |
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53:54 | specific guys. Guys. Really valuable the value. You can go across |
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54:02 | different spatial scales from. So, their disadvantage if you're doing it in |
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54:11 | slice, you're doing it in you're doing it in devo you're typically |
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54:15 | to a small focal plane. The of the clinic. Again, you |
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54:22 | get the same. You don't get start it. We can tell ourselves |
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54:28 | to our military and maybe that is be the future. Right. If |
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54:32 | can target to specific neurotransmitters, that be really cool. So now we're |
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54:38 | about in general talking about these brain activities up or we call it it's |
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54:45 | or its sentinel state were not But in reality, uh when we're |
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54:55 | activity and neurons, it's related with but it's also correlated hyper polarization. |
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55:04 | it'd be really nice to start taking this information on the level that we |
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55:08 | that people did brain written studies like the micro lectures that did the triangulation |
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55:17 | from individual cells and they can tell sell fired at which cycle of the |
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55:24 | . But now it would be really if in these techniques we could introduce |
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55:29 | and inhibition, dermatologic signaling and the temporal dynamics of these separately. Not |
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55:38 | , you know, active brain And so So next time when you're |
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55:45 | , you know, and in don't go by that urban myth. |
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55:49 | we only use 10% of our Always say that you could probably use |
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55:55 | than 10%, which is probably not . Uh and it's also not good |
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56:00 | have 100% of your great views because called generalized seizure. All of the |
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56:07 | is fully active. All of the are fully engaged. So what we're |
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56:12 | is that there's a switch off going active during the task. These regions |
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56:20 | up in active, this goes down region, activity comes on. And |
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56:27 | I'm also saying is that it's very to start understanding this baseline sentinel |
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56:32 | That may inform us something about the for that network too hard. Sentinel |
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56:39 | would be like what is the sentinel of the heavy and and ground. |
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56:45 | if you know the sentinel state of N gram, you can predict how |
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56:50 | stimulus is going to recreate that the state of the heavy engram would be |
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56:59 | state of neurons in this interconnected circuits active somewhere inactive and depending on the |
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57:08 | of the training supply to this, this graph. Now you can understand |
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57:14 | is active in sentinel state and how sentinel state will affect the end ground |
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57:21 | the stimulus as well. And that's becoming important in seizures and epilepsy, |
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57:27 | a lot of times people throughout the activity or what happened before the |
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57:34 | So they would just analyze, oh can see the seizure happen here. |
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57:37 | let's take the data a minute before seizure and the minute after we see |
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57:43 | stopped at E. G. analyzed us emphasis, logical what's really |
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57:51 | importance these what happened before seizure How what happened before the seizure to |
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57:59 | ? How long was the seizure? , thank you. And when we |
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58:06 | back uh next week monday we will covering the visual system and talk about |
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58:17 | critical period of plasticity and development and into the retinal, articulate pathway meticulously |
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58:23 | move into the sun some of the systems to optimist. All right, |
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58:30 | |
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