| 00:02 | This is cellular neuroscience lecture 12. I wanted to point out the articles |
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| 00:08 | are located in your supportive lecture reading . And when we discuss voltage sensitive |
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| 00:18 | , we said that these are the that you can apply onto the tissue |
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| 00:23 | then they will embed themselves into the number. When you look in this |
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| 00:28 | , it talks about genetically encoded voltage , genetically encoded voltage sensitive dyes. |
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| 00:39 | the figures that we cover at great in this article is for example, |
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| 00:44 | one the spatial scales and levels. I could for example ask you a |
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| 00:51 | very detailed question about something in this . And that would be a fair |
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| 00:59 | question that you may have to reread figure legend. You may have to |
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| 01:04 | the paragraphs that introduced this figure and about this figure to really answer |
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| 01:11 | Well, in general, I wanted briefly talk about both of sensitive |
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| 01:19 | We said there are those that you on the tissue and those dies embed |
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| 01:23 | . And then there are those that be genetically manipulated. And a big |
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| 01:31 | of imaging the voltage. And in if you are going to image the |
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| 01:35 | that you have to have very fast temporal resolution, remember we talked about |
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| 01:42 | the spatial resolution is. How many from megapixels you may have in the |
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| 01:48 | . I that is taking picture of outside world and the more pixels you |
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| 01:54 | , the better spatial resolution of that you have. And when you're talking |
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| 02:00 | imaging something over time or imaging the of activity. then you're talking about |
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| 02:09 | resolution, how fast can you sample images? They think I mentioned that |
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| 02:15 | a typical iPhone cameras are sampling about frames per second. That means whatever |
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| 02:23 | happening in that one second, it have 30 windows, 30 images of |
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| 02:29 | ongoing activity. And as you learned the first section neurons are very |
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| 02:39 | They're so fast that they can produce action potentials in one second, a |
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| 02:45 | sound. So when we talk about sensitive dyes and when we talk about |
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| 02:52 | the fact that voltage you're tracking these dyes react to voltage in a |
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| 03:00 | very fast manner. This is a advantage of voltage sensitive dyes but the |
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| 03:06 | by which you can pick up precisely formation of these waves and the spread |
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| 03:18 | temporal spread of these waves. Now are talking about having to have |
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| 03:23 | very fast cameras. And so this also a big advantage of both of |
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| 03:31 | dioceses that you can pick up very activity in addition to dies at a |
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| 03:39 | to voltage that are also dies that ion sensitive dyes. So there are |
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| 03:45 | sensitive dyes, their sodium sensitive There are potassium sensitive dies. There |
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| 03:53 | neurotransmitter sensitive dies, they will be at the flux system increases in neurotransmitter |
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| 04:00 | released and optically. And so this a big advantage of voltage sensitive dyes |
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| 04:08 | to properly image, it would need have very expensive pieces of equipment cameras |
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| 04:14 | microscopes or microscopes, it depends on level you want to image to properly |
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| 04:23 | the neuronal activity in neuronal network So you can also see that there |
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| 04:31 | diverse experimental setups for voltage imaging you some instances may have a mini scope |
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| 04:44 | is mounted on an animal's head and animal is what is called free |
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| 04:52 | So you can perform these types of imaging experiments in evil. You can |
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| 05:01 | it on living animals, not just animals. And if you have a |
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| 05:09 | enough technological setup in the lab and small enough camera that you can mount |
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| 05:18 | an animal's head and measure what is on the cortical surface, what activity |
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| 05:24 | happening while this animal was awake This is a really neat way of |
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| 05:32 | it. Of course you can also optical fibers into specific brain regions to |
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| 05:41 | specific activity. In this case, fibers would be very important if you're |
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| 05:48 | to sample activity deep and optical fibers have an advantage and a disadvantage and |
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| 05:58 | . So if you wanted to image macro view of the cortex active |
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| 06:03 | you'd have to take out a big of the skull. In some instances |
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| 06:10 | may be able to shave the skull such thin layer that it is actually |
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| 06:18 | translucent. Now, these are the where there's a genetic allele genetic expression |
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| 06:27 | coded dies because you don't have to anything on the brain tissue. But |
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| 06:33 | you're talking about applying dies like chemicals embed themselves in the plasma membrane, |
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| 06:39 | you have to open the skull. fibers allow you to penetrate a small |
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| 06:45 | into the skull other than the large . But the disadvantages of course you |
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| 06:51 | have to penetrate the fiber through potentially cortical layers. If you want to |
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| 06:56 | at the activity of the hippocampus. finally, if you have a microscope |
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| 07:05 | you have our hippocampal slice and our graham, it'll sell circuit. Then |
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| 07:10 | can zoom in into these parameter cells have really nice high magnification functional imaging |
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| 07:19 | you can get to a single cell using microscopes. So this is |
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| 07:26 | a versatile technique. It's great spatial resolution from in vitro to viva optical |
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| 07:37 | , genetic expression, chemical application. this is a good article where you |
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| 07:45 | remind yourselves of these subject matters that talked about. And this might be |
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| 07:54 | a good figure for example, to you some questions about or related to |
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| 07:59 | . Now, the the other article we that we discussed was was this |
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| 08:06 | and we discussed this article in relationship external and dendritic recordings. Uh you |
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| 08:17 | maybe you saw some of these figures we talked about spike timing dependent |
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| 08:25 | But there's some concept here of target specificity of frequency dependent synaptic transmitter released |
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| 08:32 | parameter cell terminals. This for example something that we talked about short term |
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| 08:39 | . So an increase in the post response during the high frequency stimulation. |
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| 08:46 | right. So there's there's a lot images here. But these are some |
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| 08:51 | the images for example that we talked because we discussed This is a matter |
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| 08:58 | sensory cortex here. At least amount sensory cortical fibers is C2 whisker experiment |
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| 09:07 | discussed the maps of activity that you . It gets into greater detail so |
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| 09:14 | can see how extensive this article and studies are. Ah So I don't |
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| 09:22 | if I can ask you a lot questions about about this article but there |
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| 09:31 | be on some of the figures and is quite extensive and it is relatively |
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| 09:39 | but also cellular cellular neuroscience driver. it could be an especially this circuit |
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| 09:49 | example, some matter sensor circuit that discussed. Um Just review that because |
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| 09:56 | is a good labeling questions that that always come up. Mhm. And |
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| 10:04 | we talked about voltage sensitive dye we talked about the Samata Toppy in |
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| 10:12 | amount of topping means that there is point by point representation of some matter |
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| 10:20 | map of the body and head and map that is encoded in the |
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| 10:26 | This is what's the matter topic This is so matter topic map that |
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| 10:32 | is a map of the hand and map off the off the lips and |
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| 10:39 | in some matter sensory cortex and in . The map that takes up a |
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| 10:47 | of the space a lot of the . Um Matter is the map that |
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| 10:53 | dedicated to the whisker pad. So is a a Samantha topic matt a |
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| 11:01 | of the whisker pad and the periphery the level of the primary somatosensory cortex |
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| 11:09 | . S one primary somatosensory cortex. brushes is the debris map that is |
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| 11:17 | by a barrel. So we have barrel cortex here and as you can |
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| 11:22 | this this barrel cortex is the connectivity goes through the trigeminal nerve ganglion and |
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| 11:33 | eventually through other tissues into the primaries matter sensory cortex. So we talked |
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| 11:40 | how you can block the activity or can manipulate activity and how you can |
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| 11:46 | how there are changes in the maps this activity. Okay, so if |
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| 11:54 | can dig up this article and I be able to find it. It's |
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| 11:59 | long range connectivity of mouse primary somatosensory cortex. I will upload this this |
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| 12:06 | so that you can have these figures then we can maybe remind ourselves one |
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| 12:10 | time about it on Wednesday. so voltage sensitive dye imaging. We |
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| 12:19 | talked about other types of imaging calcium and we talked about the fact that |
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| 12:29 | neurons will be drawing blood that blood contain and carry oxygen and nutrients to |
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| 12:37 | active brain centers. And as neurons more and more active and fire more |
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| 12:44 | more action potentials, they actually There are so much swell and as |
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| 12:52 | Osama swell, if you were to the light on them, the reflective |
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| 12:59 | of a thicker neuron versus thinner neuron be different. And so these reflective |
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| 13:09 | are can be detected by using intrinsic signal image ng. And you will |
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| 13:18 | it will these this stride cortex will a lot more sense Following the next |
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| 13:27 | or 2 1/2 or so. But is a structure in the cortex of |
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| 13:33 | primary visual cortex area if you These tribes represent activity and neurons that |
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| 13:41 | processing activity from only one eye. these tribes are called ocular dominance |
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| 13:49 | And so this illustration showed us that have first of all very extensive microvascular |
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| 13:56 | and if you look within the brain have these micro vessels that only separated |
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| 14:03 | distance. One micro vessel into connection another is 50 micro meters in |
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| 14:09 | So it's penetrated throughout neurons. And you can visualize the activity, You |
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| 14:16 | visualize the blood flow and you can activity. First of all using intrinsic |
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| 14:21 | signal imaging. So if you were stimulate only one eye and you look |
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| 14:27 | the primary visual cortex you would see beautiful stride lines that represent neurons that |
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| 14:36 | responding to the signal from only one . And you don't need any |
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| 14:42 | Now is it as fast as So are these processes like calcium and |
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| 14:48 | not as fast. A lot of signaling in the brain is done by |
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| 14:57 | . So are we measuring leo Are we measuring neuronal calcium flux? |
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| 15:05 | there are actually two temporal resolutions? calcium neuronal calcium fluxus and gets neutralized |
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| 15:13 | fast. Will calcium? It's slow leo calcium waves as specific glial calcium |
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| 15:22 | are seconds in length. So you then if you had a really good |
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| 15:29 | you could say that you want to really fast optical activity are really slow |
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| 15:35 | activity or I'm gonna collect it at fast speeds And then I'm going to |
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| 15:39 | a filter just like you can filter activity, you can filter optical |
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| 15:46 | So then these processes such as blood . Are they as fast as |
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| 15:55 | They're even slower. So you're talking hundreds of milliseconds to seconds, maybe |
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| 16:05 | minutes. We have a significant change the blood volume flow and that is |
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| 16:13 | in the oxygen and that is reflected the swelling? This may take |
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| 16:18 | Yes let's say between neurons and so . Is it because of the the |
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| 16:28 | that there are different receptors or is because of like this incident by the |
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| 16:34 | from the signaling is more faster. because of the function you will find |
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| 16:41 | of the calcium in neurons per synaptic and it's both educated calcium channels that |
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| 16:48 | fast and you will find the other of calcium is from under plasmid |
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| 16:55 | Um So you would see these rises internal calcium flux is and neurons so |
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| 17:02 | would be a little bit slower. on the other hand are it's it |
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| 17:12 | active calcium transport but it also has passive um concentration gradient dilution of calcium |
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| 17:23 | if there is a local rise. will slurp it up and slowly just |
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| 17:27 | with potassium and and in the cases excitation we will produce the slow calcium |
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| 17:35 | . So it's just the two different dynamics really. And I believe that |
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| 17:46 | and those glial calcium waves will be spatially specific when you're talking about synapses |
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| 17:55 | both educated calcium channels in particular. it will be less spatially specific because |
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| 18:01 | inter connectivity glial cells have a lot gap junctions to um So it's a |
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| 18:08 | a very good questions but there's definitely different temporal scale. So now when |
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| 18:14 | talking about oxygen, you're talking about swelling, you're again on a much |
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| 18:21 | scale. So if you had a great equipment ideally you want to have |
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| 18:29 | objective or a lens that gets you down to single cell level or two |
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| 18:35 | cell level. And also gives you bit of a macro view and gives |
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| 18:42 | an option to do it really fast then post experiment gives you an option |
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| 18:47 | process different frequencies of whether it's fast movement slowly. Onek movements like slow |
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| 18:54 | waves, really slower processes related to flexes and the blood flow. |
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| 19:04 | so there is uh the resting activity vary. So when we talk about |
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| 19:14 | in the past, we said, look at this map of activity. |
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| 19:18 | a person is reading a book, have the occipital lobe lighting up where |
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| 19:23 | person is listening to words, who have the temporal lobe light up when |
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| 19:29 | person is speaking words and you have broker area motor cortex light up. |
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| 19:36 | what is addressed resting activity? What the sentinel ST resting activity might very |
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| 19:50 | from moment to moment, a person person. And activations associated with behavioral |
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| 19:55 | would be superimposed on this random So when you're looking at any activity |
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| 20:04 | general, when you're looking at either activity recordings or optical activity recordings, |
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| 20:13 | lot of times you will have background you have to be able to either |
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| 20:20 | out that background and think of it insignificant because you're trying to pick up |
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| 20:25 | circum stimulus in certain response or you to consider that ongoing background this resting |
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| 20:34 | of activity. This ongoing background is that's important. That's a history. |
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| 20:40 | if something happens, that's something the will build upon, the history of |
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| 20:48 | activity at this resting state your your brain regions might be having individual |
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| 20:57 | . So, however, this does seem to be the case when a |
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| 21:01 | engages in a perceptual behavioral task, are decreases in the activity of some |
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| 21:07 | areas at the same time that tasked brain areas become more active. One |
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| 21:14 | above the decreases and increases in activity related to the task. For |
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| 21:20 | if a person is required to perform difficult visual task and ignores irrelevant |
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| 21:26 | we might expect the visual cortex to more active and the auditory cortex less |
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| 21:33 | . This is suggesting that the activity the maps of activity are constantly |
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| 21:40 | dependent very much on the importance or attention to what you are performing or |
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| 21:48 | task that you're performing at that Two further observations suggest that there's something |
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| 21:55 | and significant about the wrestling brain First, the areas that showed decreased |
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| 22:02 | compared to the resting state are consistent the nature of the task has |
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| 22:10 | it appears that the areas showing decreased during behavioral tasks are always active at |
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| 22:18 | and become less active during any So this is the figure that talks |
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| 22:25 | this default mode of network from nine . D. T. Or pet |
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| 22:33 | studies and we'll talk about pet and a second, summarizes data from experiments |
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| 22:41 | nine different tasks involving vision, language memory. The blue and green patches |
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| 22:46 | the figures show brain areas which activity from the resting state when humans engaged |
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| 22:53 | any of the nine tasks. So the particular task does not seem |
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| 22:59 | account for the activity changes. the patterns in the brain activity changes |
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| 23:04 | consistent across human subjects. It's not subject, one brain. These observations |
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| 23:11 | that the brain might be busy even the state we call arrest, that |
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| 23:16 | resting activities are consistent and that these are decreased when the task is |
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| 23:24 | So in the figure of data from , the of these P. |
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| 23:29 | Imaging studies involving different behavioral tasks were to produce these lateral and medial views |
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| 23:35 | the brain. The brains have been inflated, so activity in the south |
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| 23:41 | can be seen. Brain areas are blue and green were more active during |
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| 23:47 | rest periods and during the behavioral So that's quite significant. So we |
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| 23:58 | uh from neuroscience in the past that are these association areas and association areas |
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| 24:06 | the place where different information for different such as listening or seeing, |
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| 24:16 | feeling, touching, whatever they all put together. So this almost suggests |
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| 24:24 | potentially these areas become more active a and the less active during the direct |
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| 24:38 | stimulation of a defer of either distinct concurrent sensory pathways. So now this |
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| 24:51 | imaging and this imaging also shows some the structures individual cortex And it talks |
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| 25:00 | in Vivo two photon calcium imaging lets see activity and thousands of neurons with |
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| 25:08 | cell resolution. So we're still talking some of the principles of imaging we're |
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| 25:14 | talking about here. Although this refers the ah visual cortex and the structure |
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| 25:22 | visual cortex will come back to it the next hour. But this particular |
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| 25:29 | okay, essentially allows you to get down to single cell resolution |
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| 25:40 | And what technique is that? It's photon microscope. So it's not just |
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| 25:46 | regular microscope, you may need to to two photon microscopy level. It's |
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| 25:53 | very powerful microscope, very expensive, over $1 million dollars and if you |
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| 26:00 | it fast probably a million and a or two sometimes even before with all |
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| 26:06 | bells and whistles. Typically universities would coupled to a few of these setups |
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| 26:14 | different imagery in different cells, not in brain cells. Okay, so |
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| 26:22 | section basically that we talked about just pretty much covered the levels of imaging |
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| 26:32 | how you can get from sub cellular the way to macroscopic with techniques. |
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| 26:38 | some of the things tools that you consider in doing that if you were |
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| 26:43 | engineering? Obviously you know you start about these things too. Ah Well |
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| 26:51 | there a better way to image? Are there other tools there are other |
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| 26:59 | that we won't have time to You can actually activate neurons with the |
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| 27:06 | that are called option molecules that are channels you can activate open and close |
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| 27:14 | channels with lasers and light in the that we haven't talked about But there's |
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| 27:21 | techniques here. But I think this a pretty good overview of what you |
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| 27:25 | do with experimental neuroscience techniques. Now the imaging that we talked about the |
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| 27:33 | imaging. We typically talk about how got my X rays done at the |
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| 27:39 | office. That's the most common type static imaging. That's non functional imaging |
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| 27:47 | we're all very familiar with. And dentist office uses it for a reason |
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| 27:55 | X rays are very good for imaging , bones tissue and the difference between |
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| 28:01 | soft tissue and the bone tissue that something abnormal with the soft tissue. |
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| 28:05 | may show up as well through Ah The dentist's office is also a |
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| 28:13 | example because now they have these rotating rays so they take they rotate around |
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| 28:23 | jaw and they give you a really three dimensional image of your job. |
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| 28:30 | and maybe even 10 years ago you be able to do that. Typically |
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| 28:39 | would have a few pictures taken. pictures would be developed and then it |
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| 28:45 | take some time maybe a day and they would have the the images. |
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| 28:49 | very computerized Now it's very fast. that thing that you're here in the |
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| 28:55 | is C. E. T. or M. R. I. |
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| 28:59 | sometimes pat but not as often. if you hear cT scan that's commute |
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| 29:06 | tomography. And it's essentially multidimensional X . It's still static imaging. It's |
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| 29:15 | lot more sophisticated than that dentist setup going around your jaw. In this |
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| 29:22 | you pretty much have a 360° axis rotations or slices. So if you're |
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| 29:30 | about the brain here to hemisphere okay go down. This is the |
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| 29:39 | of the great, you're talking about tomography. It's often referred to of |
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| 29:50 | many slices and a lot of times wanna focus in on some structure and |
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| 29:57 | just image the whole thing because you that there is maybe pathology and that |
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| 30:04 | wanna image that pathology. And so would be referred to as as slices |
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| 30:10 | plans and you can have hundreds of slices of planes that we rode a |
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| 30:20 | that will image at every possible angle structure of the intros. And we're |
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| 30:29 | about 100 256. And the resolution ct scan that you get is maybe |
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| 30:38 | 100 micrometers. So you would never course get any single cell resolution. |
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| 30:47 | it's very advanced computer tomography is that produce this 100 micrometers and typically it's |
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| 30:56 | on the water of centimeters. So but it is still an X ray |
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| 31:10 | technique and emery you typically hear magnetic imaging. Mhm. For us the |
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| 31:21 | important thing is when you do an . R. I. You can |
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| 31:24 | either M. R. I. M. R. I or |
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| 31:27 | M. R. I functional R. I. The regular MRI |
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| 31:31 | functional MRI both. There's no X use for in general for functional |
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| 31:39 | R. I and for pat or emission tomography which is described in the |
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| 31:45 | slide. You're monitoring these slower processes blood flow, brain metabolism, let's |
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| 31:54 | consumption of oxygen, consumption of M. R. I. You |
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| 32:00 | a hydrogen atom has one proton. bounces between high and low energy state |
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| 32:08 | this bouncing between high and low energy . The frequency of which bounces which |
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| 32:15 | state protons absorb energy is called the frequencies. So that's where the resonant |
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| 32:21 | of the uh magnetic residence imaging comes . The magnetic part comes in that |
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| 32:30 | actually surrounded by a magnetic coil that very powerful And the more powerful the |
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| 32:42 | , the more of a spatial resolution can achieve. And often the MRI's |
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| 32:52 | be labeled as two T, three five t 70. That refers to |
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| 32:59 | strength of the magnet. The more or Tesla has had, it has |
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| 33:03 | stronger as the magnet. The stronger the magnet, the more of the |
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| 33:12 | matters you have to take around It has a very very solid |
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| 33:18 | Typically they're placed in the basements or floors of the buildings. If there's |
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| 33:24 | basements and of course anything that is should not be in the vicinity of |
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| 33:32 | equipment because it is a powerful magnet you turn it on So it takes |
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| 33:40 | the radio waves that are admitted by and it allows to image oxy hemoglobin |
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| 33:53 | deoxygenated hemoglobin ratio. When the brain become active, hemoglobin molecule will carry |
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| 34:05 | oxygen. And in this case if have oxygenated hemoglobin flowing through the blood |
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| 34:14 | this mask, micro vasculature, not of it is being used and its |
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| 34:20 | are not very active. But the neurons become very active, they start |
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| 34:27 | oxygen and they start d oxygenating or human myoglobin. Ating they start eating |
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| 34:37 | the oxygen from hemoglobin molecules and you now a much greater ratio of deoxygenated |
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| 34:47 | molecules that you're tracking. So you're measuring the ratio of oxygenated versus deoxygenated |
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| 34:59 | with FMR in positron emission tomography, also similar type of oil, |
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| 35:10 | The subject will be laid into for , but typically you have radioactively labeled |
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| 35:18 | with possibly charge ions and bloodstreams. have protons and electrons and emit electromagnetic |
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| 35:26 | photons of light that gets picked up the coils and then pat you're looking |
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| 35:33 | glucose consumption. So you're tracking in to de oxy glucose levels. So |
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| 35:43 | techniques again, they're great because they us these macro Views of off the |
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| 35:51 | when I talked about going down specifically cm while you are going down to |
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| 35:58 | specific level. then just macro hold of the brain and brain activity and |
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| 36:05 | can get down with F. R. I. To about cubic |
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| 36:12 | area that will be essentially representing whatever cells of the network of cells or |
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| 36:19 | circuit is. And that cubic So if you picked up this is |
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| 36:27 | cubic centimeter, This is one cm is 1000 micro meters. Mhm. |
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| 36:45 | lives however many 10 micrometer, neurons cells live, it's what's going to |
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| 36:54 | represented but it is going to be , slower functional, not nearly as |
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| 37:04 | as the other dies if we're talking . And there's a lot of very |
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| 37:10 | expensive and long post processing that is with that too. Post processing, |
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| 37:18 | that you really have to clean up images, run them and understand a |
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| 37:25 | of it is still the subtraction before after. If you're doing stimulus or |
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| 37:33 | when you're doing functional energy, you to look at the function. If |
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| 37:37 | looking at C. T. you want to look at the |
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| 37:41 | you can get a high resolution without to function as well in a different |
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| 37:47 | to understand it better. Maybe. inevitably, if you're looking at the |
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| 37:52 | , these are the two clinical techniques will be available for for this. |
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| 38:01 | , so this concludes our imaging section the course and you can find this |
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| 38:08 | , you know where and I'm gonna into your Mhm lecture materials. Our |
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| 38:29 | notes, he's on the visual system it talks about visual system. three |
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| 38:43 | Because it's all three lectures in one students. But don't worry, I |
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| 38:55 | uh I'm not gonna rush through it . But I think that some of |
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| 39:03 | may find this not so difficult, if you haven't seen it before. |
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| 39:09 | the whole point is that the life into the retina, Life comes into |
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| 39:16 | retina. So when the live penetration the retina, we're gonna understand this |
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| 39:22 | system because we understand the cellular components understand the network components of the visual |
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| 39:30 | . And it's a great example of sensory system. So if you haven't |
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| 39:37 | a neuroscience, 43, 15 ports again, don't worry because this is |
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| 39:43 | great Way to understand one sensory And you already looked at some matter |
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| 39:52 | system which is somatic sensory system, . It was quite simple here. |
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| 39:56 | has a whisker pad, the rose numbers of whiskers. And then you |
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| 40:00 | this barrel cortex and each barrel is from one whisker. And I can |
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| 40:05 | the activity of whiskers with all of beautiful imaging techniques inside the brain and |
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| 40:10 | cortex to see how the barrels interact and so on and so forth. |
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| 40:15 | now when we talk about the visual , the information which is the |
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| 40:21 | different wavelengths of light will come into retina and it will actually activate these |
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| 40:28 | receptors. This photo receptors are part the neuronal network and the retina and |
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| 40:37 | photo receptors are connected to the bipolar and bipolar cells are connected to ganglion |
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| 40:44 | and the ganglion cells will form the nerve that will exit out of the |
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| 40:50 | . And there are certain features in shape of the retina and how this |
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| 40:57 | of cells is distributed throughout the central the peripheral retina, particular in the |
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| 41:05 | of the retina, directly in the of light, directly in the path |
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| 41:10 | light or what we would call direct rays of light, directly in the |
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| 41:16 | of light through the lengths the light in to the back where the retina |
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| 41:22 | located in the back of the directly here in the center you have |
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| 41:28 | area that is called the phobia. this phobia is interesting because you have |
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| 41:35 | like a crater and that crater or a little cup that directs as much |
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| 41:41 | possible of that beam of light into very center After that. And of |
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| 41:48 | you constantly move your eyeball. And if you want to focus on something |
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| 41:53 | great detail, you'll always place your in the direct access into the phobia |
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| 42:01 | those rays of light to come in right beneath. You also have great |
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| 42:06 | and concentration of comb photo receptors and cone photoreceptors, there's two types of |
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| 42:16 | , cone and rod photoreceptors. And the cone photoreceptors is dominating in the |
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| 42:23 | retina and they're responsible for the color and they're responsible for high acuity high |
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| 42:33 | vision. That's where they're dominating the receptors that are more concerned with the |
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| 42:39 | vision or dark vision are also located on the periphery. Now the circuit |
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| 42:47 | such that the photo trans duck When the rays of light and the |
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| 42:52 | of light hit the photo receptors, will transducers convert that signal okay into |
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| 43:04 | electrochemical response in the photo receptors. this is the live molecule. And |
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| 43:13 | have a road option pro day in and this road Dobson protein changes to |
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| 43:22 | when the light strikes it and activates tropic cascade G pro dam transducer isn't |
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| 43:31 | it is active, it activates fast dia stories. Remember kindnesses of hospital |
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| 43:39 | , possible diaspora race. We'll turn cyclic GMP into GMP. And when |
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| 43:49 | convert cyclic GMP into GMP, you the sodium channel So functionally this is |
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| 43:57 | happening that when the light strikes and you have the stimulus here you actually |
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| 44:04 | the flux of ions. It's kind the opposite of what we've been learning |
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| 44:09 | you have the stimulation and a stronger as strongly as the response here you |
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| 44:14 | a reduction with the response in the of life. So these normal levels |
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| 44:20 | cyclic GMP are necessary in order to this sodium channel over. But when |
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| 44:27 | have light activating you have the conversion C. GMP into GMP. And |
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| 44:33 | close the sodium current. So within circuit where I was mentioning to you |
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| 44:41 | have the photo receptors or bipolar cells ganglion cells. There's some interesting features |
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| 44:48 | the circuit. So first of all receptors is where this conversion of photo |
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| 44:54 | will take place and then that the change in the membrane potential will |
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| 45:02 | communicated to the bipolar selves. And bipolar ourselves. And this is all |
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| 45:08 | at synoptic potentials. So these are or sensory potentials, receptor potential sensor |
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| 45:18 | . They're all graded and these bipolar will communicate information to the ganglion cells |
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| 45:25 | retinal ganglion cells and retinal ganglion cells produce action potentials. And retinal ganglion |
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| 45:32 | is the only output from the retina the higher order visual processing centers. |
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| 45:41 | the only axons that come out of retina are for retinal ganglion cells and |
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| 45:46 | only cells that can produce action for Schultz I retinal ganglion cells when you |
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| 45:56 | about exposing or beam of light shining on the retina, not all beams |
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| 46:02 | light going to the center of the because you have a field of view |
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| 46:08 | most of the focus in the field view in your eye is in the |
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| 46:13 | as you move the eyeball there's significant in the periphery that we always |
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| 46:19 | Maybe not always consciously aware. We have a blind spot. That's where |
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| 46:25 | of the fibers that form the optic exit out of the retina. That's |
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| 46:32 | we have a blind spot. But you seen your blind spot lately? |
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| 46:38 | other words, when you look at solid wall of green color, do |
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| 46:45 | see these spots that are missing from eyes? You don't because you actually |
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| 46:50 | in for two. So uh you see these blind spots but these beams |
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| 46:59 | light are striking the center of the because you're moving to it. There's |
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| 47:04 | beams of light that are striking a bit away from the center of the |
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| 47:09 | . There's activation in the periphery. maybe shining a flashlight on the periphery |
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| 47:14 | that activation happens first before you turn head and refocus onto that beam of |
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| 47:22 | . So you have activation. And these beams of light, let's say |
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| 47:26 | shining a flashlight and you have the to produce a small beam of light |
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| 47:31 | that flashlight. Even in the very , just activate the cones. You |
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| 47:36 | shine a little bit of off you can shine a little bit here |
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| 47:40 | the periphery of the retina. Every you do that or every time there |
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| 47:44 | a visual stimulation in the retina you activate hundreds tens or hundreds of these |
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| 47:52 | soft drugs. Okay And 10 or of these photo receptors will encode information |
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| 48:00 | a point by point representation. It's retina topic map. So when there |
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| 48:06 | a space and a point in space the piece of retina is looking at |
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| 48:11 | will be processed. And this is receptive field property. So the receptive |
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| 48:19 | properties in the retina such that you some on center ganglion cells. And |
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| 48:26 | have off center ganglion cells. That that these collections of the photo receptors |
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| 48:33 | on center ganglion cells when you stimulate very center, okay when you stimulate |
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| 48:41 | very center of that, mm So there's a patch of red |
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| 48:57 | There's a whole bunch of these little a photo of herself trips and the |
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| 49:10 | this will take a lot millions but just don't want to leave it |
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| 49:21 | Smaller. Oh and then it received stimulus in one color and this stimulus |
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| 49:48 | other color and the stimulus and the color and the stimulus. This is |
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| 49:52 | coming onto the. But underneath these of light you have collections of the |
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| 49:59 | receptors and it turns out that within collection of these photoreceptors, the on |
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| 50:07 | ganglion cells are the ones that are . If you shine a beam of |
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| 50:12 | . This is not an electrode. just a beam of life in this |
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| 50:16 | activating this area. The south that located here. The photoreceptors and the |
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| 50:22 | underneath the bipolar cells of the retinal cells will produce the most action |
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| 50:30 | But if you produce another beam of coming from somewhere else. And that |
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| 50:37 | of light where to activate the surrounding then you would produce very diffuse any |
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| 50:48 | potentials during the same stimulation. And is what is shown in that |
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| 50:54 | Conversely there are collections collections of these receptors that if you were to shine |
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| 51:02 | light on the periphery here on the instead of the center you would produce |
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| 51:14 | most action potentials response from the underlying in the retinal ganglion cells. But |
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| 51:21 | you were to shine the light here the on in the central zone again |
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| 51:27 | wouldn't produce much of a different level the actual potential fire. And so |
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| 51:33 | level of the rat and the the of these photo receptors are subdivided into |
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| 51:43 | on and off all and off. And for us collections of cells elections |
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| 52:04 | these photo receptors to communicate that information bipolar cells communicate that information to gangly |
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| 52:11 | which produce action potentials and put the encode that information to be processed. |
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| 52:18 | huh. And the whole retina is processing this luminescence in these center surround |
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| 52:37 | the entire reckoning this will take a to but I'm just filling in our |
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| 52:48 | so this is this is what this is that you have certain cells in |
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| 52:53 | center and if you activate these collections cells in the retina and it's on |
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| 53:05 | ganglion cells that means the ganglion cell connected to the network of photo receptors |
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| 53:11 | bipolar cells that when it's in the of that center surround these are just |
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| 53:19 | properties of their self the fields. this is a matter sensor system Receptive |
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| 53:25 | for the whisker in the cortex was barrel. That's the receptive field. |
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| 53:34 | the field for the visual stimulus of by point representation activated or peripheral |
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| 53:43 | Here it's comprised of all of these fields that are going to take that |
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| 53:50 | or break it down into the center on and off processing is luminescence. |
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| 53:56 | I always say that if you were take and hook up a computer to |
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| 54:00 | retina, what you would see is is what you would see the very |
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| 54:06 | . You take a Photoshop image and it out and you just saw darker |
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| 54:13 | lighter and it was someone in the fashion, pixellated circular fashion. That's |
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| 54:20 | threatened the processes. So if you out just information from the run, |
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| 54:27 | there's a lot of details and they into the way the cell circuit |
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| 54:36 | Um Don't be scared of these details some of them are very familiar to |
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| 54:43 | the neurotransmitters that the photoreceptors release of but we talked about. I wanna |
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| 54:52 | and metabolic tropic signaling for glutamate and bipolar cells it turns out the on |
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| 55:00 | bipolar cells have the better but tropical receptors. And the off center bipolar |
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| 55:07 | have I am back in it wait minute. I on a topic with |
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| 55:12 | METs receptors and that's important because I a tropic versus medical tropic. They |
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| 55:20 | have opposing actions are synaptic physiological cellular actions plus Sinatra. So when |
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| 55:29 | talk about for example glutamate activating apple . We we know that when glutamate |
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| 55:36 | downpour suffering produces gps speed. D the cell. So glutamate deep polarization |
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| 55:44 | this cell will release glutamate and the of glutamate will de polarize the off |
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| 55:53 | . So and you'll understand why it's off center. So because what happens |
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| 55:59 | the lights too, the photo receptors hyper polarized instead of deep polarization and |
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| 56:08 | stopped with a make movies. So lights would stop glutamate release in this |
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| 56:16 | . But the synopsis, this is and if it is excited, releasing |
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| 56:23 | will excite bipolar salad will like set central ganglion cells. But the cell |
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| 56:30 | has measurable tropic receptors if it receives it will actually get inhibited because through |
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| 56:38 | tropic mechanisms that hyper polarizes the So glutamate here the synapse plus stein's |
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| 56:47 | sign conserving, meaning that if this D polarized glutamate is released this is |
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| 56:51 | polarized sign inverting synapse means that if is D polarized photo receptor and releases |
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| 57:01 | . It will not be polarized bipolar hyper polarized. That's why it's called |
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| 57:09 | vernon symptoms and then bipolar cells will released in glutamate and at the level |
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| 57:15 | the ganglion cells you only have The of tropic, ample, chaotic 98 |
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| 57:21 | receptors that will communicate that information. now you understand that the same photo |
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| 57:28 | could be looking at the light or of light release of neurotransmitter, absence |
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| 57:34 | neurotransmitter and linked to two types of cells. So I don't want you |
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| 57:41 | know all of the details of the but do pay attention that there are |
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| 57:45 | types of bipolar cells. And by either in the tropics signaling, it |
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| 57:51 | one thing, it's signed, conservative tropic is signed inverting and now you |
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| 57:58 | see how the same light but in different bipolar cells that converge on the |
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| 58:08 | photos chapter in the presence of why they have the same effect for opposite |
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| 58:18 | in the presence of darkness will have effect, the opposite effect. But |
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| 58:22 | will always fluctuate between this sound conserving , inverting of deep polarizing and hyper |
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| 58:27 | effect. The graded potentials until you polarize the ganglion cell enough to produce |
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| 58:33 | action potential. Remember we talked about inhibitory rules how you can have the |
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| 58:42 | inhibition feed forward inhibition lateral inhibition. in the circuit here, when the |
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| 58:52 | deep polarization in the photo receptors something glutamate. They're linked to these horizontal |
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| 59:01 | uh and horizontal cells. There are types of cells that are in between |
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| 59:06 | cones bipolar cells and retinal ganglion the horizontal cells and the american |
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| 59:13 | We're talking here about horizontal cells horizontal if you release glutamate on horizontal Sao |
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| 59:20 | Gaba ergic south. So that horizontal it's also connected to other horizontal cells |
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| 59:28 | gap junctions. So if you release and you excite one horizontal cell that |
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| 59:37 | cell will excite other horizontal cells. this horizontal cell has a negative or |
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| 59:46 | inhibitory loop onto the photo receptors by gaba um inhibiting the activity. So |
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| 59:55 | the dark actually the photoreceptors are d and they're releasing glutamate and so in |
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| 60:05 | dark they do polarized releasing glutamate and constantly activating the inhibitors house and inhibitors |
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| 60:13 | or keeping a certain level of excitation these photoreceptors. So um horizontal cells |
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| 60:23 | area of retinol elimination releases Gaba and . Control of cone glutamate release. |
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| 60:32 | can think of it. It's controlling . It's also if it is activated |
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| 60:37 | gap junctions that can kind of eliminate areas. Exide broader areas but can |
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| 60:46 | sculpt the spatial specificity of this because you excite nearby cells that are don't |
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| 60:56 | excited photo receptors will inhibit those federal and the ones that you're excited. |
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| 61:03 | gonna be excited for awhile until you this negative feedback began to. So |
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| 61:09 | sculpting in its space and as in and time again inhibition when we learned |
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| 61:15 | it the diversity of that inhibition the of the action potentials. It's all |
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| 61:22 | sculpting the output of the parameter all between the hippocampal regions In this case |
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| 61:28 | about sculpting the spatial temporal specificity of information for the major output which is |
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| 61:36 | retinal ganglion cells going into the You have at the level of the |
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| 61:45 | . You have two types of ganglion not just by the receptive field properties |
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| 61:51 | also by their other properties, morphological but are also reflected in the size |
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| 62:00 | the receptive fields of receptive fuel Ah parvo and magno and non empty |
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| 62:09 | . They're functional and anatomical subtypes of ganglion cells and the major output going |
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| 62:15 | . The T cells are small. have small receptive fields because they have |
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| 62:21 | small processes that can interconnect with with circuits above them. The bipolar and |
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| 62:31 | photo receptor circuits have slower conductance. less sensitive to low contrast. So |
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| 62:40 | less sensitive in the way animals. retinal ganglion sauce. They're fast. |
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| 62:45 | conduct information in a very fast Uh And they are more sensitive and |
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| 62:57 | are larger. You can think of larger receptive fields too because they would |
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| 63:02 | these broader than victories that would gather from more areas in the right |
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| 63:10 | So this is what's happening at the of the retina. And then the |
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| 63:15 | thing that I was going to discuss you before we moved into the central |
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| 63:21 | and pathways which is inhuman. I gonna talk to you about rodent |
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| 63:28 | But from the retina that information goes the lateral ju Nicollet nucleus. The |
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| 63:35 | nerve goes in goes into the lateral Nicollet nucleus here in the thalamus and |
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| 63:41 | the lateral gene Nicholas Nicholas and the that visual information goes into the primary |
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| 63:46 | cortex. So when we were looking the studies of the cortical activity using |
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| 63:52 | of sensitive guys and welcome back to next lecture talking about the structure and |
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| 63:56 | of the primary visual cortex. This where we're looking at, we're making |
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| 64:01 | window on this primary visual information processes we're looking at. So today we're |
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| 64:08 | of time when we talk about the of rhetoric. Nicholas mathlete actually is |
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| 64:16 | graduate student work that I sloth through five years and had a lot of |
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| 64:27 | learning electrophysiology doing these experiments. So tell you about it. It's a |
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| 64:33 | simpler system anatomically compared to human For example human or ah primate, |
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| 64:46 | cat LGN. Ortho columnists of Visual information has six players And in |
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| 64:55 | you have two zones. It's a of and control idle zone and there's |
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| 65:00 | lot of plasticity that happens during early . So we will recite some of |
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| 65:05 | things like critical period of development plasticity the refinements from the early non specific |
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| 65:17 | and function in this path list. very much adult like specific structure and |
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| 65:25 | of these pathways. And then we look into the simple pathways into what |
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| 65:29 | be a human like visual system. , thank you very much. I |
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| 65:34 | let you guys know about the resolution the quiz questions, but also the |
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| 65:42 | and time. The time will be the day. It's just the day |
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| 65:46 | want to make sure I can confirmed thursday. Okay, thanks for |
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| 65:51 | |
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