| 00:01 | So today is lecture nine of cellular . We will actually continue talking about |
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| 00:08 | plasticity which we didn't finish talking about . Lecture and start talking about the |
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| 00:14 | imaging of your own selectivity? This so far doesn't have the camera |
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| 00:20 | Maybe the camera will turn on But when we talked about, when |
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| 00:26 | talked about synaptic plasticity, we talked long term and short term forms of |
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| 00:34 | plasticity for short term or STP talked facilitation. This is an example of |
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| 00:42 | here and uh we talked about facilitation sometimes can be followed by depression and |
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| 00:50 | usually happens during the train of stimulation what we would call conditioning stimulants and |
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| 00:57 | in particular in this case we're conditioning stimulus and we're talking about great code |
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| 01:05 | one of the ways uh that the encode information. One of the fabulous |
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| 01:11 | for learning and memory. We also a L. T. P. |
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| 01:15 | is long term plasticity and it is term plasticity. Long term pronunciation on |
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| 01:22 | . The long term depression typically follows some stimulus. So if there is |
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| 01:30 | stimulus that happens following a sampling of signal they slide and following that stimulus |
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| 01:38 | conditioning stimulus. If you have a term persistent increase in their response along |
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| 01:46 | same pathways long term potential creation that decrease that's persistently long. It's long |
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| 01:55 | depression. So the stimulus short term that repeated multiple times. Can cause |
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| 02:05 | term change in synaptic plasticity that can hours, sometimes days and sometimes even |
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| 02:14 | talked about how can the same synapse L. T. P. And |
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| 02:18 | . T. V. So how is it just a frequency code or |
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| 02:25 | other cellular mechanisms that are behind And we've spoken how if you have |
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| 02:33 | high frequency stimulation you're likely to cause increase in intracellular calcium levels that will |
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| 02:43 | through an FDA receptors that would favor relation. And till the system toward |
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| 02:50 | or potentially asian and low frequency stimulation evoke low levels of calcium that will |
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| 02:58 | protium foster to schism. Therefore depression uh the weekend signal safe houses. |
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| 03:10 | now spike timing dependent plasticity. Uh the next thing that we're supposed to |
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| 03:18 | about. But in in the previous it's uh seven. Yes sir. |
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| 03:48 | we talk about spike turning the plasticity should talk about what are some of |
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| 03:57 | of this short. Ah Both cases can be proposal and if it's free |
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| 04:11 | I think it could be housing levels the pre synaptic terminal that increase because |
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| 04:18 | so much deep polarization present up between old educated channels, neurotransmitter availability and |
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| 04:28 | dynamics. So there may be an production and synthesis of war transmitter or |
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| 04:37 | facilitated diffusion americans, retrograde messenger Sign on. So this is an |
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| 04:52 | one in the sense that we have that goes from pre synaptic terminal. |
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| 05:01 | pre synoptic terminal that's where the neurotransmitter released? Not so permanent now. |
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| 05:38 | terminal. Where neurotransmitters being released and we have receptors so we're highlighting particular |
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| 05:49 | have a significant influx of calcium receptors particular but also this is pre synaptic |
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| 06:02 | this is synaptic post synaptic aly the may send messengers from this cell back |
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| 06:11 | lease called to this pre synaptic mineral can also regulate or in this case |
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| 06:19 | or decrease with its facilitation, increase , decrease short term plasticity signaling regulation |
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| 06:27 | neurotransmitter polyps. So imagine if you real pumps that are overregulated in their |
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| 06:38 | . That means that they're clearing glutamate fast. Not as much glutamate is |
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| 06:43 | . Therefore it's likely to have less available less you polarization less differentiation because |
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| 06:53 | less active. Bus unethically the big is an M. D. A |
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| 06:59 | activation as a coincidence detector. Synaptic we have ion redistribution meaning that you |
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| 07:11 | have a receptor redistribution. You actually protein receptors that can be inserted into |
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| 07:18 | plasma memory. They can be brought laterally from extra synoptic space. So |
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| 07:27 | is synaptic space. Everything outside the extra synoptic space they can be brought |
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| 07:33 | the synapse. So if you bring extra receptors and serve extra receptors you |
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| 07:41 | a way of strengthening the accidents but also have internalization. So just like |
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| 07:47 | can put new receptors into the synapse from inside of the cellar from lateral |
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| 07:55 | . You can also internalize the existing you internalize and then be an apple |
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| 08:02 | . You can weaken the synapse We're having enough that the except it's not |
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| 08:08 | enough is not having enough incident detection so on. So receptors are super |
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| 08:18 | for this lateral diffusion. They move fast from extra synaptic spaces into synaptic |
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| 08:25 | and uh says titanic plasticity. A of farms when you have uh intense |
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| 08:33 | and movement of these uh proteins uh can be likened to titanic stimulation of |
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| 08:42 | muscle and what that means is that tonic stimulation, is there so much |
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| 08:49 | the bicycle release that the muscle gets up and just contracted position of kind |
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| 08:54 | flies. So um production and release retrograde messengers boston optical so if the |
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| 09:06 | is retrograde messenger control at the pre side there is also a production and |
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| 09:12 | of that retrograde messenger influence the short plasticity is the some of the |
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| 09:20 | But again we're talking about excitability, calcium coincident protection and fortifying the synapses |
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| 09:30 | proteins or with And our understanding of the receptors are being trafficked inside the |
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| 09:40 | of the 1998 we thought that it fairly you know uh static situation and |
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| 09:50 | you were just fun changing the function the receptors at the level of the |
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| 09:56 | was correlating correlating the early 2000s who that there is internalization and also insertion |
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| 10:06 | their cells from the plasma membrane to post synaptic um cells rights 2002 We |
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| 10:17 | that there was this lateral movement from synaptic spaces into the synaptic spaces. |
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| 10:24 | now we understand that there is the . That there is an assertion that |
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| 10:32 | is an insertion and internalization and extra space is that there is movement from |
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| 10:38 | synaptic spaces. In synaptic spaces there's lateral movement within the synapse itself of |
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| 10:44 | receptors rearranging themselves. So when you're about short term plasticity, you're talking |
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| 10:53 | the processes that are taking place seconds minutes. Like we're talking about analogy |
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| 11:03 | you remember somebody's phone number and you a few minutes but if you don't |
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| 11:07 | that you don't reside it and store in your long term memory, it's |
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| 11:12 | a few minutes later you won't recall phone or partially on the phone. |
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| 11:18 | different. There you go. 10, 10. Yeah. So |
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| 11:31 | you're talking about seconds and minutes, is happening at the level of the |
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| 11:35 | . If you're talking about the critics year insertion of the receptors internalization |
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| 11:43 | this is taking seconds, milliseconds, minutes. Now if you're talking about |
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| 11:51 | term changes that are gonna take hours days or weeks then inevitably somehow you |
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| 11:59 | to start infecting that intracellular machinery and of the processes that are going to |
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| 12:05 | happening at the level of so much and what makes long term potentially ation |
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| 12:20 | several factors in familiar factors plus the of existing receptor channels insertion of new |
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| 12:29 | inside of the south or from the synaptic number of occasions production of new |
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| 12:35 | . Yes with produced new receptions. you can tickle the transcription mechanisms of |
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| 12:41 | south and start using neuro sectors transcription activation inside the cells. So a |
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| 12:50 | of things that are long lasting are at the level of the synapse assertions |
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| 12:56 | . But also now we're starting to about touching upon nuclear machinery of the |
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| 13:06 | . This is familiar, familiar to . This is the setup. We're |
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| 13:13 | the shop of collaterals that are coming of the city three area of the |
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| 13:18 | and you're recording feel potential activity or single cell activity in this case this |
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| 13:27 | E. P. S. Or excited by potential slope. It's |
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| 13:34 | to the amplitude of that response. the slow uh uh well correlated but |
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| 13:42 | better measure of increase the signal. you can see that there's certain stimuli |
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| 13:49 | can be produced along the shop of uh pathway here that causes potentially |
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| 13:59 | We call it early LTP and a train. One train of stimuli. |
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| 14:04 | high frequency stimulation is enough To evoke early LTP. But you can see |
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| 14:11 | the change here is maybe 50% from baseline following the stimulus following one trade |
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| 14:19 | it looks like it's maybe not as lasting but in any case it's the |
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| 14:24 | . Now if you repeat that stimulus train of stimulus four times that conditioning |
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| 14:31 | four times you see a late LTP longer lasting. And so for the |
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| 14:39 | of long term potentially ation as we about you can have changes here with |
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| 14:45 | flux is retrograde signal messengers. One these messengers is nitrous oxide, another |
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| 14:52 | is covered in oxide and other one cannabinoids. What lady L. |
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| 14:59 | P. You may actually induce not changes at the transcription level here where |
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| 15:09 | actually influencing secondary messenger cascades, intracellular , cyclist, cyclist, and the |
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| 15:19 | , penises that in the nucleus affect transcription factors which can now change the |
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| 15:28 | levels of different regulatory molecules or different molecules. Or even the neurotrophic factors |
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| 15:37 | can contribute to neurotrophic factors such as . D. M. S. |
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| 15:41 | for brain derived neurotrophic factor can contribute sustaining that long term change at the |
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| 15:49 | of the cell and beyond these molecular this case nuclear cellular overall cellular amount |
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| 15:58 | single synaptic changes for receptors that relation insertion. Now, in addition to |
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| 16:04 | you're also doing structural changes which are rearrangement of silence skeletal parliaments in the |
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| 16:13 | experience increases of the surface area. potentially ated decreases in the surface area |
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| 16:21 | if you're depressed the activity along this building new synapses structurally actually having little |
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| 16:31 | of the dendrite number but off and a new spine or driving away is |
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| 16:39 | it expands altogether because they're depressed, nonfunctional and they may not be necessary |
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| 16:47 | for that part of the brain for task for that moment. So this |
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| 16:59 | uh done right here and you can that spines and this is an interesting |
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| 17:09 | uh the color here which you can the green or yellow red. It's |
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| 17:16 | quite right. Maybe it's orange color amplitude. The highly localized glutamate application |
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| 17:28 | what you're seeing is that if before . T. P. You see |
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| 17:32 | small response in particular the spine and spine was small after you do sell |
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| 17:40 | actually have a structural change and the change both. So you have a |
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| 17:46 | change in the sense that you change architecture and the size of the |
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| 17:51 | The functional change because we change the of activity. And now you can |
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| 18:01 | what you're seeing at the level of 10 drive which we're seeing with the |
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| 18:05 | of the luna made here with your optical we also the electrical reporters go |
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| 18:12 | and talk more about uh optical activity in sports. So so remember we |
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| 18:24 | about silent synopsis and I mentioned silent when we talked about an N. |
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| 18:30 | . A. And really good explanation the silent synopsis that became only the |
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| 18:41 | and the functional synopsis that became So some of this is maybe a |
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| 18:52 | thinking in the recent years but it's a good way to kind of try |
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| 18:59 | understand that there are major changes in receptor opposition during the development. |
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| 19:07 | okay. And here we come to founding dependent plasticity. It's another form |
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| 19:17 | synaptic plasticity that we're in this and gonna jump into the next lecture |
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| 19:32 | Or should I do that? I Yeah, this is explain things. |
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| 19:41 | but the story too. Okay, will spike down in the system. |
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| 19:50 | focus for the most part on the . Code. Rate code is not |
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| 19:57 | timing code, but what a spike spike timing is. And nineties uh |
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| 20:14 | concept came about when you talk about term LTP. Remember Donald was in |
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| 20:19 | late 40s, early 50s. This substrate is the stimulation of the capital |
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| 20:25 | ship collaterals with 100 hertz. And LTP didn't happen until 1973. Discovery |
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| 20:33 | spike timing dependent plasticity doesn't come about the 90's we talked about how you |
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| 20:39 | to do dual or triple recordings on cells in order to confirm that there |
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| 20:44 | back propagating action potential. And then actually have a way to kind of |
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| 20:51 | the back part. We're getting So when we talk about pre synaptic |
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| 20:57 | , pre synaptic is neurotransmitter release your release on the pre synaptic is linked |
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| 21:11 | the action potential on the pre synaptic , boston optic is boston optic |
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| 21:20 | Um If this is pre synaptic neurotransmitter . This is our pretty post. |
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| 21:32 | happens is if the cell is excited . if the stimulus is strong enough |
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| 21:39 | cell is excited enough this is done uh goes into the soma that goes |
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| 21:52 | another acts on here. And if soma is excited enough it's going to |
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| 22:02 | an action potential here and it produces action potential. This action potential is |
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| 22:09 | to back propagate. So forward propagating this direction is going to these power |
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| 22:18 | back propagating action that trump is going influence the synaptic plasticity. So now |
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| 22:28 | is supposed to be selma. So is supposed to be down drive. |
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| 22:34 | was supposed to be axle in Tax on. So there is a |
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| 22:44 | trump. Pre synaptic action potential causes synaptic neurotransmitter release which causes post synaptic |
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| 22:57 | . And if it is strong enough meaningful enough the polarization is gonna develop |
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| 23:02 | action potential in the post synaptic And so it was noticed that if |
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| 23:12 | produce these in orange or pre synaptic without trials we signed up that is |
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| 23:22 | followed by post synaptic. So we this free before post. This is |
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| 23:30 | synaptic and orange before post synaptic three before post. What was noticed |
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| 23:39 | that on the why access here you a change in synoptic leads after you |
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| 23:50 | a certain stimulation protocol. But when looked originally at the range code we |
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| 23:58 | that we're taking a baseline response then stimulating a certain frequency and we're trying |
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| 24:05 | figure out if that baseline response one of BP. Or went down |
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| 24:14 | T. V. And so our stimulus was based on the frequency. |
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| 24:22 | here in spite bombing dependent plasticity is on the order of that invasion pre |
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| 24:36 | or post. Right? So which is making sense of? This cell |
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| 24:46 | ? The self would respond to What was noticed is that if the |
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| 24:52 | fires first the cell response three fires post. And the cell response post |
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| 25:01 | an action potential in the back propagating control. Within a few lower seconds |
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| 25:09 | get a very strong increase in the response. So this conditioning now is |
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| 25:18 | just based on frequencies based on the . Pre synaptic versus possum attic and |
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| 25:26 | on the interval or delta T. of time that elapses between pre synaptic |
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| 25:37 | post synaptic stimulation. So that interval time is within 10 to 20 |
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| 25:45 | Pre synaptic five post synaptic responded. we talked about the communications with |
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| 25:51 | You know in several seconds of somebody respond here. It takes several |
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| 25:58 | So here 20 milliseconds if this southeastern like sell fire. So 20 milliseconds |
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| 26:04 | the cell responds. This relationship is strengthened. That also was maybe this |
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| 26:14 | has a relationship with another pre input it responds to immediately within milliseconds |
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| 26:23 | What was also notice is that if reverse the order. This is the |
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| 26:27 | of the communication. This is the of communication and the direction of the |
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| 26:34 | in the south. But you produce actual potential in the cell boss tactically |
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| 26:41 | then an action potential after in the synaptic. And what was found is |
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| 26:50 | if that happens within a very short of 10 to 20 milliseconds you get |
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| 26:57 | get depression with his synapses. It's if things are out of order and |
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| 27:03 | . This fires this fire is This doesn't make sense in this two |
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| 27:10 | communication basically or simulation of response. this is your free before post and |
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| 27:25 | before free. Does everybody understand Now? Instead of just the shock |
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| 27:35 | certain frequency, you actually have the synaptic versus post synaptic which you didn't |
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| 27:41 | in these experiments and stimulation of sharp for days. And you're also looking |
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| 27:48 | the interval. Now the delta. . Correlates to frequency in a |
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| 27:54 | Right? The close of the window seeing similar pattern here. The closer |
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| 28:00 | faster the communication, the more likely is to potentially eight. But we're |
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| 28:05 | seeing that the faster the communication and certain directionality, the more likely it |
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| 28:10 | potentially eight. The faster it is the rug and the directionality, the |
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| 28:15 | likely it is to get trust. this is the classical indie classic heavy |
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| 28:28 | spike timing dependent plasticity. Window heavy this after Donald had. That was |
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| 28:35 | this is proposed post pre induced static . Seeing the relative spike timing is |
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| 28:42 | the sole determinant governor governing timing dependent it's that's five timing dependent plasticity is |
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| 28:53 | malleable but the magnitude C. So magnitude of either potentially asian or depression |
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| 29:02 | be changed and the temporal requirements can modulated. Wait a second. Just |
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| 29:10 | us that this is the rule proposed three. I get it fine. |
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| 29:15 | know why look at this from what are you saying? It doesn't |
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| 29:24 | . The order doesn't matter in some . So which in which case is |
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| 29:28 | order doesn't matter the timing still now if you're still within this 10 millisecond |
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| 29:34 | you're changing. That's helpful to either depressing. But now the order doesn't |
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| 29:45 | . And what can change the It's called neuromodulation of spike timing dependent |
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| 29:59 | . Despite plasticity. This article, the way is a very S. |
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| 30:07 | . D. D. Can be in three stages the neuronal activity prior |
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| 30:12 | the plasticity inducing event despite bombing event is the stimulus that induces and the |
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| 30:20 | of plasticity scene and the long lasting about the ways. So it's not |
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| 30:29 | response response neuromodulation of S. D. D. Orange. So |
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| 30:39 | by ground here you have a prostate neuromodulation At the time of induction you |
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| 30:51 | concurrent neuromodulation prior experiences what happened before really preempts or sets up the |
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| 31:01 | Pride is a system Once you have plasticity inducing event. You're having |
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| 31:12 | You're a modulation and then lasting changes had retrospective neuromodulation and you can see |
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| 31:27 | when I said what can change these ? I posted uh an article but |
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| 31:39 | disorders may change these rules of neuromodulation , interpretation may be different concurrent state |
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| 31:51 | stimuli by the dead part recall. you have fragile ax to have retro |
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| 31:59 | you have in parenting experience your proposed learning spike bounding and frequency rules are |
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| 32:07 | . Therefore your perspective priming and co current state encoding of information is gonna |
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| 32:13 | different. Your degenerative disorders nor did disorders when the stimulus is coming in |
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| 32:24 | addiction retrospective feedback lasting changes in synaptic . So if you have a neurodegenerative |
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| 32:33 | that encoding may not be happening So an example Alzheimer's hippocampal circuits are |
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| 32:40 | . There's no encoding of plasticity inducing . That high frequency just doesn't get |
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| 32:48 | through the circuit because of the neuro in that circuit. Therefore potentially there's |
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| 32:54 | retrospective there's no long term with addiction may alter the circuits of the communication |
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| 33:03 | the circuits and the order to the where it is also a long |
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| 33:10 | So with any substance abuse or any substance use we also change the plasticity |
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| 33:21 | when you change the plasticity you change rules proposed L. D. |
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| 33:26 | L. T. D. Frequency encoding of the information understanding cognitive mental |
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| 33:35 | motor of. So I'm gonna show in your lecture notes uh class lecture |
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| 33:48 | materials here. Um you have this of spike timing and with the city |
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| 33:59 | about spike timing dependent plasticity. You to review closer review the bigger |
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| 34:08 | You can, it's a fairly recent from five years ago like that I |
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| 34:16 | . So that's there also go to pretty cool article here. But when |
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| 34:42 | did my first post dog to be , I did my first postdoc. |
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| 34:49 | I did my PhD at Louisiana State in New Orleans, uh, which |
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| 34:56 | right across the street room, Mercedes Superdome center. Great buildings, very |
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| 35:04 | , very depressing. But every time drive them drive through new Orleans always |
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| 35:10 | my buildings and all this stuff. kids, uh after I finished my |
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| 35:20 | , I was solicited to do my at Charles one. Green is really |
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| 35:27 | Baltimore, very boutique uh instituted as part of the broader neuroscience program at |
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| 35:37 | Hopkins in a moment campus. And mentor was Alfredo Kirkland, he's from |
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| 35:46 | actually. And my best uh Uh Postdoc from uh was choi is |
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| 36:01 | an author of this paper, but a postdoc in my first postdoc I |
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| 36:08 | the most from the other post What concerns the technique, the execution |
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| 36:17 | experiments doing things you learn from your a lot of times more then from |
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| 36:25 | mentors, having a good relationship appears speak normal personal nights need help can |
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| 36:35 | you really quite far along because your may be too busy what they're gonna |
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| 36:45 | being demanding, they're gonna want you perform and it is their fault that |
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| 36:50 | cannot explain sometime. Would you show give you the resources? They're not |
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| 36:55 | acknowledge that either because as a post , your adult nobody is gonna hold |
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| 37:03 | hand in the special boss, it's imposed opposition PhD graduate students. We |
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| 37:10 | hold their hands to have a you budget to place they can break. |
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| 37:16 | understand that you can live as opposed that level of tolerance and how once |
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| 37:22 | can perform and how many resources you and how many things you break that |
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| 37:28 | that fuse is much shorter. But did this really intriguing experiments, the |
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| 37:36 | author of this paper where we induced spike timing dependent plasticity to share. |
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| 37:45 | we saw this isil paternal which is larger and larger magic agonist. And |
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| 37:56 | we applied as a fraternal we saw this L. D. B. |
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| 38:03 | much stronger and much longer. And we kind of looked at different generations |
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| 38:16 | it. But to cut the long short will be really discovered in the |
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| 38:24 | . Is that this curve okay towards that if we apply different concentrations of |
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| 38:35 | agonists like I. S. We could change the curves by thomas |
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| 38:43 | plasticity. So this curve that we seeing like this originally was described |
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| 38:54 | We could shift it, we could it. We could make multiple |
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| 38:59 | We can make them shorter. We also make them longer. We can |
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| 39:04 | the curves based on the concentration of Oregon ergic agonist that was added |
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| 39:11 | So that tells you that another way which you modulate the plasticity and modulate |
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| 39:20 | curves, modulation of these terms is through are the chemicals through other neuro |
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| 39:40 | . So this is neuromodulation. So not just neuro degeneration, it's not |
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| 39:45 | developmental disorders, it's not something that just because of addiction and it's something |
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| 39:51 | we modulate these curves, we stretch and change them just as a consequence |
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| 39:57 | different stimuli in different chemicals neurotransmitters that being released in our brains, different |
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| 40:04 | of our brains. So this is we know that. The real truth |
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| 40:10 | not consistently lies between the raid spike bombing dependent code and the ability |
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| 40:18 | these curves to be modulated by endogenous and exogenous substances that stimuli as |
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| 40:32 | A lot of the meeting spot. it's uh Professor Anderson Harris talks about |
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| 40:40 | she fell in love with the british . You were calling shape and that's |
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| 40:47 | important for synaptic communication. The good where the plasticity of the most plastic |
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| 40:54 | . So you can increase their decreased their members surface area, decreased |
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| 40:59 | area expression of molecules is somewhat biochemical and responsible have the accomplices and they |
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| 41:07 | have a lot of biotech Andrea for as well. So this is something |
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| 41:14 | we started talking about imaging. It electrical across being imaging that was three |
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| 41:20 | elections across the imaging which allowed or reconstruct the three dimensional anatomy of these |
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| 41:28 | spots. So we started understanding that different shapes forms that the shapes mean |
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| 41:34 | that the distribution along the dendrite of of densities are also important. As |
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| 41:40 | always the case with fragile accent, a static image. We saw a |
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| 41:48 | bit of activity imaging response. But is still static general when we talk |
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| 41:56 | imaging and experiment on their styles, talking about difference levels of analysis, |
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| 42:10 | . They didn't in this case we're talking about just imaging south or |
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| 42:17 | We're talking about imaging activity in You can have this at a macroscopic |
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| 42:26 | . Macro does not require microscopes. , gross anatomical level. Macro is |
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| 42:36 | you can observe with the naked eye the country or you're talking about macro |
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| 42:41 | talking about a pretty large patch of brain area of the brain nucleus of |
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| 42:48 | brain. You're studying this function of macro level. Is that nucleus and |
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| 42:54 | . Is it small? If you're into Mezza SkoP IQ level, you're |
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| 43:02 | at the meses topic level. You increased magnification and what you're looking as |
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| 43:18 | and functional differences or morphological differences in macroscopic nucleus and that macroscopic circuit. |
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| 43:25 | you're looking at maybe red and blue two different subtypes of cells. This |
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| 43:32 | now with even more increased resolution and circuit centric approach. What you're doing |
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| 43:47 | you're experimenting. You're testing says you're the interaction between South within the neuronal |
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| 44:02 | . Now you're interested Which cell is only exciting or inhibitory but which cell |
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| 44:08 | active first? Blue over the red during a different rhythm of activity. |
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| 44:14 | cell is not active at all, cell fires first, which one is |
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| 44:20 | , Which one is post when it to a cellular level. This is |
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| 44:30 | interesting because all five of these levels are placed here in front of you |
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| 44:38 | be done with using voltage indicators or sensitive imaging or otherwise, genetically encoded |
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| 44:50 | indicators here is which is genetically encoded that when neurons show their activity, |
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| 45:04 | can image changes in the fluorescence or properties of these already genetically coded dies |
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| 45:15 | animals brains. So from stargate you can go to a single cell |
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| 45:23 | , you can study what it does the single cell level and look at |
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| 45:27 | sub cellular locations of cellular activity is sell more active on the axon or |
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| 45:35 | . Is it connected to which location another south. And so this is |
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| 45:40 | beauty of in this case voltage So these images, these uh signals |
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| 45:48 | you see light up here. They all all the images. That means |
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| 45:58 | the dyes or the indicators that are genetically are sensitive to changes involved. |
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| 46:05 | not a change in calcium concentration, the change in the membrane potential. |
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| 46:12 | this is why voltage sensitive imaging or die sensitive imaging also encoded die imaging |
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| 46:21 | so powerful because it can give you views from sub cellular all the way |
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| 46:28 | the macroscopic. Now. Uh let's if I have a good uh image |
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| 46:40 | . This is a both of sensitive . It's another way genetically get these |
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| 46:52 | indicators that are genetically expressed in animal . And once they're on the liquidity |
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| 46:58 | , you can actually pick up an change with this illustrates is another version |
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| 47:04 | that. These little squiggly blue warms little dye molecules. This is an |
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| 47:13 | . You're looking at the macroscopic view interested to see in the activity of |
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| 47:17 | animals as part of the brain And you apply the dye molecule C |
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| 47:23 | molecules embed themselves in the flag room . When you shine the light on |
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| 47:28 | molecules here, they reflect the But as the number of potential across |
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| 47:35 | plasma membrane across the channels islands flexing the channel says the plasma membrane potential |
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| 47:43 | these little squiggly warrants. They change confirmation and as they change their |
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| 47:50 | they change their reflective or absorptive properties as they change their reflective and absorptive |
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| 47:58 | . You will see areas of the and red indicating active normal populations areas |
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| 48:05 | the brain that are blue indicating the or inhibited. So with these voltage |
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| 48:15 | dyes or voltage genetically encoded voltage we have the ability to image things |
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| 48:24 | are very fast temporal resolution, not spatial resolution from sub cellular all the |
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| 48:31 | to macroscopic but also temporal resolution. cameras from all the sensitive guy imaging |
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| 48:40 | image information that 10 kHz speak, very powerful. So they're very, |
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| 48:48 | fast. But it's something you do see in a clinical setting. And |
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| 48:54 | is really unique because obviously you don't voltage indicators that you can apply to |
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| 49:00 | genetically express. And then the imagery , there are other things that humans |
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| 49:07 | subjected to that are pretty harsh when doing positron emission tomography imaging, you |
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| 49:16 | injected with radioactive material, you're technically for like 23 hours and you're not |
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| 49:26 | supposed to be in the presence of human provide an hour because of how |
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| 49:32 | you are. And if you're not healthy older have kidney issues, liver |
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| 49:39 | that is procedure, you may not able to do either often or at |
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| 49:45 | . So this is, you there's other things that we inject. |
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| 49:49 | don't have the sense of the guys for the genetic published indicators but we |
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| 49:56 | inject things into humans in order to the brain activity in general. What |
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| 50:01 | talking about imaging is the static and functional static imaging is you can go |
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| 50:09 | have a broken bone, take an ray of the bones is bones broken |
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| 50:14 | it doesn't say this bone has a of inflammation and the muscle cells are |
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| 50:20 | around the broken bones. Now what happening really in uh active neurons and |
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| 50:32 | networks is active neurons consume a lot oxygen and they demand a lot of |
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| 50:39 | flow towards that location. That metabolism . There is changes in ionic composition |
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| 50:48 | signaling in the areas of the brain are very active neurons will produce action |
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| 50:55 | . Glia will produce these slow calcium related to different levels. Voltage can |
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| 51:03 | imaged also. So metabolism can be . How can you image oxygen? |
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| 51:08 | oxygenated, hemoglobin and deoxygenated. That's basis for functional magnetic resonance image blood |
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| 51:17 | . Okay, what will will deliver metabolism? You're looking at processing of |
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| 51:26 | . Active neurons will consume glucose. you're looking at the glucose consumption, |
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| 51:32 | at positron emission tomography, ion That means that there are guys that |
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| 51:39 | sensitive to ions. There's calcium sensitive , there's potassium sensitive diet. There's |
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| 51:45 | sensitive. I want to see the of an ion in the network inside |
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| 51:50 | cell between the cells. We use sensitive dyes both have sensitive eyes. |
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| 51:58 | talked about that. There's a little molecules are genetically coded indicators that are |
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| 52:05 | in the plasma membrane. They change confirmation based on the activity levels and |
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| 52:11 | their reflective and absorptive properties receptor movement be imaged. So apart from having |
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| 52:20 | sub cellular ability to image a sub level, We can now tag into |
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| 52:26 | ample receptors with fluorescence and track how travel from extra synaptic spaces. Synaptic |
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| 52:33 | , how they diffuse laterally possible number measure their speed, measure how many |
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| 52:39 | them potentially come in because we can see the increases of voltage. All |
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| 52:45 | these things are incredibly valuable to reveal function of neurons, individual neurons, |
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| 52:54 | or macro function and without it we do otherwise. We would just have |
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| 52:59 | imaging of morphology. This is how cell looks like. This, is |
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| 53:03 | the vesicles look by neurotransmitters. We to know how the activity changes. |
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| 53:08 | in general the brain demands a lot oxygen, a lot of nutrients. |
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| 53:14 | can live longer than two minutes without . Um and neurons will be consuming |
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| 53:24 | as the major source based of energy food, doing intense levels and we |
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| 53:32 | it. So we also have optical cows too. Um optical imaging of |
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| 53:47 | brain. We're talking about all the guys like the surface of the |
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| 53:54 | When neurons are active blood volume and changed to a degree correlated with neural |
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| 53:59 | . Blood flow and oxygenation influence the of like brain tissue, reflected |
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| 54:06 | Can be used to indirect assess neural . Light is projected on the brain |
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| 54:11 | the video camera reports the reflected light what intrinsic signals. They used to |
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| 54:16 | brain activity number of potential for action and not directly measure, What is |
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| 54:22 | really talking about this? And it that if you were to just look |
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| 54:26 | the surface of the brain which is here with the micro vessels and there |
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| 54:31 | some intense levels of activity that there's reflective properties off the brain cells and |
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| 54:40 | tissues that will change because active neurons also swell and as they swell, |
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| 54:47 | gonna stretch on their plasma membranes as stretch on the plasma membranes. It |
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| 54:52 | change the reflective properties of the life is projected on the surface of the |
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| 54:57 | . You can read what is scored intrinsic optical signal intrinsic because you're not |
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| 55:06 | a die, you're not injecting a material. You are just looking at |
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| 55:13 | reflective properties disadvantage is that you can look at the surface and see the |
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| 55:20 | because you kind of go deep into tissue and see these intrinsic optical |
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| 55:27 | The big advantage is that you're not and introducing any other additional chemical |
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| 55:34 | genetically coded indicator or anything into the . So, you have multiple |
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| 55:41 | Uh, if you're smart and have experimental task, most likely you will |
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| 55:47 | two or more imaging techniques just like the clinic, you will do X |
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| 55:54 | samarai or Ct scan. In something else the same way as if |
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| 55:59 | studying activity. You will do The sensitive dye imaging in the and |
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| 56:06 | you will say well but how does compare intrinsic optical cigarette? What are |
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| 56:13 | differences? You can have subtraction of image to another to determine the differences |
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| 56:19 | how different these detect different uh levels activity. This is a really cool |
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| 56:29 | that this is a map of local , blood volume changes, of blood |
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| 56:36 | changes and the surface can be intrinsic optical signal can be red. |
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| 56:41 | is a stride cortex in the visual . And the experiment here is your |
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| 56:47 | one eye and only to stimulate an activists. What are called ocular dominance |
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| 56:53 | . Primary visual cortex is very well anatomical feature that can be illustrated using |
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| 57:01 | including uh intrinsic optical signal industry. there's a little bit more about |
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| 57:09 | This is more about sensitive guy images uh in your lecture notes, uh |
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| 57:21 | actually don't go says that the if you want to review the uh |
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| 57:28 | are different kinds of genetically encoded uh or indicators read about if you want |
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| 57:40 | and let's see where we are. one is actually not available to you |
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| 57:47 | such as saw that. So when come back we'll review some of this |
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| 57:52 | we'll talk a little bit more about rest and activity. So a couple |
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| 57:56 | interesting concepts that will add on When we come back on monday. |
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| 58:04 | won't see you again until monday, guys on the soon can see this |
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| 58:13 | was beautiful as four monitors now. , unfortunately, it doesn't have the |
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| 58:21 | that points like me still over the . I think the images promised. |
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| 58:29 | Yeah, So we'll end here We'll review some of this imaging |
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