| 00:00 | According. So last lecture we finished this slide and the slide is important |
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| 00:07 | today we're gonna talk about the exciting inhibitory circuit. But from the very |
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| 00:13 | we talked about how excitatory cells and are typically production cells. Talk about |
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| 00:19 | capital serpent. Those including the interject these dramaturgical cells. They can talk |
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| 00:27 | other excited to dramaturgical cells and they also talk to other inhibitory gaba ergic |
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| 00:38 | . You recall the inhibitory Gaba They are pretty much local network cells |
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| 00:46 | the parameter cell axons will project out the adjacent regions of the brain. |
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| 00:54 | excitatory cells can have excitatory synapse into cells. Excitatory cells can excite inhibitory |
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| 01:04 | , inhibitory neurons can talk to each so you can have inhibition of inhibitory |
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| 01:15 | and of course the inhibitory neurons and talk to the excitatory cells inhibiting |
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| 01:26 | So that's why we looked at this last lecture which essentially shows this kind |
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| 01:35 | a arrangement that we're discussing uh in particular arrangement, what we saw oops |
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| 01:45 | getting cut off in this particular What we saw oh the inhibitor synapse |
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| 01:56 | excited to synapse and the facts of inhibition through Gaba A which is chloride |
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| 02:06 | and hyper polarization and through Gaba Makgoba tropic receptors that will cause the |
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| 02:14 | of potassium and causing further hyper So this is post synaptic aly so |
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| 02:20 | Bhasin optically prison optically inhibit ourselves that gaba, post synaptic lee they can |
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| 02:26 | Gaba and Gaba B police sign They also have Gaba B auto |
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| 02:34 | So if there is a lot of here it actually will activate Gaba B |
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| 02:41 | and these Gaba B receptors control the of calcium and calcium is necessary for |
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| 02:47 | particular binding and neurotransmitter release. This an excited tourist announce. So now |
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| 02:58 | kind of arrangement here that we're talking synaptic lee that you're seeing Gaba gaba |
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| 03:05 | . Or in this case an D. A receptors there will also |
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| 03:10 | present. So this post synaptic cell be inhibitory cell that will have glutamate |
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| 03:18 | and excited their synopsis on them and can have Gaba. So that's exactly |
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| 03:24 | it is. And this cell can inhibitory cell or this cell can be |
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| 03:27 | to resell because either one of the can receive excitatory or inhibitory inputs. |
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| 03:34 | in this situation where you have glutamate calcium that enters quickly can activate calcium |
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| 03:43 | in campinas too. And it through B receptor or through relation of potassium |
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| 03:53 | boston optically will essentially cause the flecks potassium and hyper polarization. So glutamate |
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| 04:00 | is supposed to be D polarized, d polarizes the pasta pneumatic cells through |
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| 04:05 | NMDA receptors that we discussed calcium influx within calcium can actually hyper polarized through |
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| 04:14 | activation and direct activation of the potassium is and when you have hyper polarization |
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| 04:21 | an M. D. A receptor not going to be active. So |
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| 04:25 | is in the situation where essentially glutamate influx of calcium person optically can activate |
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| 04:36 | synaptic gap of B receptors and cause polarization but there are also pre synaptic |
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| 04:43 | but be receptors on the odometer GIC on the glutamate axles. So if |
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| 04:50 | is a lot of this activity here this inhibitor synapse and there's a lot |
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| 04:55 | firing and signaling of the inhibitor neurons release of gabba. Then this gaba |
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| 05:02 | can activate gaba B. Hetero receptors . There God would be order receptors |
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| 05:09 | they're it's activating the same cell from it was released and the same synapse |
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| 05:15 | here. It's activating excitatory style and different synapse. Excitatory synapse. So |
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| 05:21 | of Gaba here and Gaba B activation again reduce the influx of calcium and |
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| 05:28 | control the pre synaptic glutamate release. you have basically inhibitory control or gaba |
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| 05:37 | signaling precision, optical and pasan optically optically regulates it either order regulates or |
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| 05:44 | regulates the release of either inhibitory or neurotransmitters and post synaptic alie binding to |
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| 05:55 | or gamma beads causing post synaptic hyper and glutamate through influx of calcium. |
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| 06:05 | calcium doesn't contribute that much to changes voltage across the membrane doesn't contribute much |
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| 06:15 | PL. Um But calcium is an messenger and activation and sufficient influx of |
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| 06:25 | through in this case glutamate an D. A receptor post synaptic alie |
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| 06:32 | activate gaba b potassium channels. So somewhat somewhat complicated right? Even if |
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| 06:40 | look at this excitation excitation excitation to inhibition inhibition inhibition to excitation. We'll |
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| 06:47 | about some of these rules and arrangements which neurons function in the brain and |
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| 06:53 | aren't that many rules. But so have these interactions of excitation and |
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| 06:59 | These last two slides are basically gonna us that if we learn how different |
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| 07:06 | to inhibitory cells are behaving during normal , we learn what functions they |
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| 07:13 | We can start looking for abnormal activity understanding how seizures for example begin. |
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| 07:19 | we'll come back to to some of slides and will also understand that these |
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| 07:27 | interactions between exciting or inhibitory neurons are in different layers. These are different |
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| 07:34 | of different layers across the campus in case and that there's going to be |
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| 07:40 | activation of these different neuronal networks as wave of activity may synchronize across larger |
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| 07:50 | of the campus and involve many So this excited for connectivity. Excitation |
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| 07:56 | is very important to synchronize excitatory cells each other. The inhibitor is also |
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| 08:02 | to synchronize inhibitor networks and then inhibit cells and excited ourselves can control each |
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| 08:09 | . Can control the levels of inhibition levels of excitation and so there are |
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| 08:16 | different rhythms in here. This illustration a better rhythm which is very important |
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| 08:21 | learning and memory, slower rhythm and very fast rhythm. It's called sharp |
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| 08:27 | or sharp waves. And uh because the difference in connectivity between excited and |
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| 08:35 | cells, because of the diversity that saw in the hippocampal circuit of the |
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| 08:40 | journey inhibitory cells. Uh we have ability to create these different rhythms that |
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| 08:50 | spatial temporal in nature, meaning that arise in certain special locations and they |
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| 08:56 | certain rhythmic city or temporal temporal patterns them. Okay, so there's uh |
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| 09:14 | slides from today's lecture that was just reminder of what we're talking about a |
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| 09:22 | bit. So now activity, neurons periodic. It's it's and let me |
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| 09:34 | show you where I got this. is the content. You're going to |
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| 09:39 | , reading and supporting materials. We sorry, go to the content to |
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| 09:45 | to the lecture notes And this is dramaturgical cover two through five. This |
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| 09:51 | the eye circuit and brain rhythms. , that's where we are now showing |
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| 09:56 | make sure you have the notes So there's a lot of periodic phenomenon |
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| 10:03 | nature. And the brain is not an exception. And neurons are not |
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| 10:08 | exception. And some neurons have repeated of periodicity that are sustained. There |
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| 10:13 | certain things that we are even unaware some of the vital functions controlled by |
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| 10:19 | brainstem that control heart rate or breathing constantly rhythmically being activated to maintain these |
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| 10:29 | . We have fast rhythms. We have very fast motor activity, that |
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| 10:34 | can repeat much faster mental activity. also have very slow rhythms. There's |
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| 10:41 | phenomenon of of rhythms and with ethnicity periodicity everywhere in nature. So I |
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| 10:49 | the tide data because I like I fishing. There's periodicity in in the |
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| 10:57 | uh and they change as the moon changes. And uh what we have |
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| 11:08 | a scale of rhythms in the brain we have macro scale or scale that |
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| 11:19 | require a microscope. It's macro So we may be able to look |
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| 11:26 | large regions of the brain as they're . Maybe we're gonna be studying a |
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| 11:32 | region in the temporal lobe here of brain. Maybe we're gonna be studying |
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| 11:39 | whole frontal lobe. Did it in frontal lobe, baby. We're gonna |
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| 11:43 | imaging whole brain activity on the macro . Now on a micro level we |
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| 11:54 | these cellular interactions, these different cells connect with each other and we interact |
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| 12:01 | each other using the rules of excitation interactions uh that are based on precise |
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| 12:11 | and precise connectivity between excited during an sells. So structure determines function because |
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| 12:19 | have a certain structure in the hippocampus we have certain connectivity, certain architecture |
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| 12:26 | these layers and certain architecture outsells connect each other. That's what determines the |
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| 12:34 | . And you can look at that at the level of two cells talking |
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| 12:38 | each other, a small network. cells, dozens of cells, hundreds |
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| 12:42 | cells or very large areas of the . So neurons are wired precisely. |
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| 12:52 | then when you think about The rules we're discussing for example, excitation to |
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| 12:59 | from the campus, 21 different cell of inhibitors cell subtypes in Hippocampus you |
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| 13:07 | to extrapolate that and you have to it to billions of cells that that |
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| 13:12 | of thinking if you want to understand whole scale of complexity and function of |
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| 13:20 | brain so the brain is super Now the diversity of cortical function is |
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| 13:27 | by inhibition because for the most part excited for ourselves are going to produce |
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| 13:39 | the same adam of action potentials and or fire anywhere or 27 1st. |
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| 13:59 | if you look at the parameter cells the hippocampus, look at the parameter |
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| 14:06 | and the new cortex they will fire within a certain dynamic range About 4 |
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| 14:15 | seven spikes per second. When we at the inhibitory cells. And even |
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| 14:22 | this image we have two inhibitory cells time an inhibitory cell called basket cell |
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| 14:28 | hip account person targets the soul and regions is excited criminal cell and the |
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| 14:35 | cell is this which has the accents target the most typical the prominent |
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| 14:47 | So now if we look at the subset of the inhibitory cells in the |
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| 15:00 | , what we see is that not they have different morphology but they also |
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| 15:15 | very different frequencies of action potential beiring some of them maybe similar in frequencies |
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| 15:25 | the parameter cells and others may be extremely fast frequencies of action potentials that |
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| 15:35 | go all the way up 2 600 . And in between the frequency, |
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| 15:46 | frequency or the number of action potentials we discussed is one way in which |
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| 15:52 | encode stimulus and the strength of Right? We talked about that, |
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| 15:58 | in this case it's not just the action proton Charles is the language spikes |
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| 16:10 | how fast you can speak is the . But inhibitor neurons will have very |
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| 16:19 | patterns. Some of them will be . Some of them will be delayed |
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| 16:26 | firing and then they will fire continuously stop. So it's not just the |
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| 16:40 | that encodes information. It's the pattern the pattern is important. And the |
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| 16:50 | subset have been inhibited ourselves all of gaba selves that we had in the |
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| 16:57 | are responsible for morphological diversity and functional . Now, is there a path |
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| 17:11 | The 600? And I'm thinking like touch a hot stove or something like |
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| 17:16 | there uh an emergency situations or when that happen? It's actually the question |
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| 17:26 | a very good question. It turns that he's very fast ripples of 600 |
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| 17:33 | . We call them uh in the slide on the previous slide show, |
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| 17:41 | was telling the sharp waves of sharp . So these are also happening on |
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| 17:46 | network level and they seem to be important for encoding new information and learning |
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| 17:52 | information. It does not necessarily have do that? The faster output means |
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| 18:00 | function but faster processing for sure. is the faster out would mean faster |
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| 18:09 | . Yes. If I gonna my is gonna tell my hand to move |
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| 18:14 | just like this or go really my neurons are gonna be firing a |
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| 18:19 | pattern for my hand to move very . So now what kind of inhibitory |
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| 18:28 | we have in the brain and in brain we have cells that form inhibit |
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| 18:36 | re loops with excited ourselves. And also in some instances projection inhibition. |
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| 18:44 | some of the inhibitory cells inhibitor into can project out of these local |
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| 18:52 | But interesting for the for the for most part and for these principles but |
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| 18:58 | were operating is that excitatory sauce are inhibitory sauce for the most part of |
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| 19:04 | . But there are some exceptions and are some inhibitor projection cells and certain |
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| 19:11 | networks in the brain. So this phenomenon, we're gonna come back to |
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| 19:19 | everything. We just talked on that . How do we study periodicity? |
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| 19:24 | is one of a great uh books I like in neuroscience called rhythms of |
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| 19:31 | brain by sake. And what you're jockey did with the army of pos |
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| 19:41 | and graduate students is he studied this phenomenon. He was trying to understand |
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| 19:48 | frequencies. What are the important What are these different frequencies mean? |
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| 19:53 | . What is 47? Is this different code? 4 to 7 hertz |
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| 19:57 | 600. Is this a different code firing versus versus burst firing. And |
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| 20:04 | we look at this here, this sort of like a circle of |
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| 20:09 | Oscillations illustrate the orthogonal relationship between frequency time and space and time. An |
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| 20:15 | can appear over and over giving the of no change. The circle of |
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| 20:21 | just gives an impression. Alternative the evolves over time. Like Monterey, |
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| 20:27 | forward order of succession is main is main argument for causality. One period |
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| 20:35 | corresponds to the perimeter of the circle . It's a phase and amplitude |
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| 20:43 | this is a phase right here, is the period, this is the |
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| 20:50 | of this fluctuation in the brain, call it oscillations. The neuronal networks |
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| 20:57 | turning on and off, turning on off. It's very rarely that there |
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| 21:03 | sustained activity in one neuronal network. usually means that there may be a |
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| 21:09 | dysfunction actually. So we have the , Y, Z. Three dimensions |
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| 21:18 | space and then we have time. we have the space time concept. |
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| 21:28 | I'm here. If you look at , the Panta rei the cycles are |
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| 21:33 | shape and the start and end points the cycles form an infinite tackling the |
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| 21:38 | endless universe. So there's different ways can look at periodicity is like, |
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| 21:47 | I just made another circle around the . I'm one year older or |
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| 21:53 | And then, Well it's really just fluctuations we're going to. So everything |
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| 22:01 | life things that we're doing, things were repeating and we recorded these phenomenon |
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| 22:08 | the brain. There's a story really interesting story of hans berger that started |
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| 22:18 | E. G. Recordings and E . G. Stands for electroencephalogram |
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| 22:24 | Uh And uh what we now know that if we place these E. |
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| 22:32 | . Caps on people's skulls we can up through the scalp and the hair |
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| 22:40 | everything else in between. We can up these fluctuations of electrical signals by |
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| 22:47 | grid of the electrodes is sitting on surface of the scalp. So the |
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| 22:53 | arises then when you pick up activity this. Is it activity from one |
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| 22:58 | ? One action potential E. Is is that what it's recording action |
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| 23:04 | ? Is it activity from two Is it excitatory activity? Is it |
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| 23:09 | inhibitory activity? So you would assume up is excitation down as inhibition but |
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| 23:19 | definitely not one cell or a few in order to become activity. Electrical |
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| 23:26 | that comes from the brain gets filtered the meninges that surround the brain, |
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| 23:33 | filtered by the skull bone, it's by the scalp by the hair while |
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| 23:40 | try to put the electorate right on scalp. So you have significantly filtered |
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| 23:46 | signal and the significant amount of the has been lost. That is actually |
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| 23:52 | the brain that you're picking up. nonetheless there are very clear differences when |
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| 23:58 | put an eeg cap where you have waves with eyes closed, beta waves |
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| 24:05 | eyes are open, alpha waves again eyes are closed. And when these |
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| 24:13 | were recorded, E. G. were recorded. There were dominant bands |
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| 24:19 | these rhythms. These dominant bands are here. For example. Delta is |
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| 24:29 | And that frequency of 0.5-4 in the range. And that dominant frequency ranges |
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| 24:38 | with drowsiness. the frequency of 4-7 stay to Is everything drowsiness pathology. |
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| 24:51 | wakefulness and also learning and memory. is learning in memory. Sharp weighs |
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| 24:57 | and about his learning and memory also an intense mental activity. Alpha relaxed |
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| 25:06 | . So each one of these frequencies the self that synchronized to produce these |
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| 25:15 | indicate a different behavioral in different mental , uh eyes closed, open, |
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| 25:25 | , awake, intense thinking and so . So you would place the |
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| 25:35 | G. On the surface of the and you would pick up these |
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| 25:45 | And another way that you can record activity in very rare cases. This |
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| 25:52 | an example of intra operative recordings. this is an image where photograph where |
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| 25:59 | skull has been cut open and you see meninges around the brain tissue have |
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| 26:05 | cut open and now you're placing the of the electrodes right onto this brain |
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| 26:13 | , then you would only do it you're doing a surgery. Brain |
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| 26:19 | So you would you would do something this because this is a lot more |
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| 26:25 | and less filtered. And the information you would pick up from E |
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| 26:29 | G E. G. In many is being used to detect not only |
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| 26:37 | changes in alpha and beta E. . S used to pick up a |
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| 26:43 | epic activity. E. G. indicate area in the brain that is |
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| 26:52 | nearby a damaged area that happened or or growth abnormal growth. But you |
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| 27:06 | know where abnormal activity is. So may see abnormal growth on the left |
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| 27:12 | of the brain. The eeg you pick up abnormal activity, but you |
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| 27:17 | know precisely this abnormal activity is right where that growth is. And so |
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| 27:22 | wanna have a better spatial resolution and would do these intra operative recordings something |
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| 27:38 | want to get. Well, I mean just how people are |
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| 27:48 | They would continuously record them and they see them inactive state and they would |
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| 27:53 | to the drowsy state and they were and the rhythms would change and they |
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| 27:57 | pick up all of these differences This is pretty stark, eyes open |
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| 28:01 | eyes closed. You know, so that's how they know that something changed |
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| 28:06 | . But other behaviors. Yeah, were eluded over time with studies. |
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| 28:12 | uh a lot of the E. . Recordings can be long term |
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| 28:16 | In fact when they do recordings for activity if a person doesn't have a |
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| 28:23 | and four hours of recordings but they say still can find a solution, |
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| 28:30 | may have them overnight. And so this is how it started and they |
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| 28:36 | noticing different changes in ethnicity as part the first of all day cycle |
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| 28:42 | alertness and later defining it more precisely this is for learning and memory and |
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| 28:49 | this is a new field. So book came out in 2000s. We're |
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| 28:54 | trying to understand how these different rhythms generated and this comes out you know |
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| 29:00 | studies by Jackie come at the heart this how these different rhythms generated by |
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| 29:04 | cell subtypes. What do they You know um what do they |
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| 29:10 | But this intra operative recording would allow to pinpoint a much smaller region. |
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| 29:15 | you want to do that. If cutting somebody's brain out there's no recovery |
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| 29:19 | function, especially in adult brands. you want to make sure that the |
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| 29:24 | of the brain you're eliminating is as as possible and E. G. |
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| 29:28 | not going to do it. So would have to use these inter operative |
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| 29:33 | methods before the surgery. So Neocortex a six layer structure. This is |
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| 29:43 | most superficial layer is wong 23456. this is on the surface of the |
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| 29:53 | is layer one. And what you in layer five is you have a |
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| 30:00 | of parameter cells that project there. pickle dendrites to layer one. You |
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| 30:07 | have parameter cells in layer 23. projector a pickle done rise to layer |
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| 30:14 | . And so what is the main source? The main signal source in |
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| 30:21 | . G. Which represents again, of synchronized cells that are being |
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| 30:26 | The main signal sources from the optical of the parameter cells. It doesn't |
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| 30:34 | that this is the main source or of that electrical signal because inputs can |
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| 30:41 | from thalamus here from joe Nicollet axons lateral nucleus for example can come in |
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| 30:48 | innovate layer for but most of the we're going to be picking up from |
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| 30:54 | . G. From the surface from den drives where there's going to be |
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| 31:00 | of the current source and current sink the optical portions of these down |
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| 31:08 | So this is what we're picking up the activity uh off of essentially current |
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| 31:21 | and sinks at the optical then rise parameter cells. And then that gets |
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| 31:27 | through all of the good stuff that just mentioned. So this intra operative |
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| 31:35 | referred to subdural grid placement following It's a craniotomy. Uh Top right |
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| 31:46 | the opening of the cranium of the . And then you have the grid |
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| 31:55 | and there's subdural because duro modernism and . So you peel them in images |
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| 32:02 | the recordings of subdural from the very of the brain. So apart from |
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| 32:18 | I mentioned, recording changes in different alpha, beta gamma and so |
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| 32:26 | That represent different behavioral states. G. Which represents network activity, |
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| 32:33 | going to be used for recording epileptic . And this is an illustration of |
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| 32:42 | cap. Now these caps in modern can have hundreds of electrodes so the |
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| 32:48 | specificity can be quite great but it gets filtered and we still don't know |
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| 32:54 | exact origin of that electrical signal. just know where we're picking it up |
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| 32:59 | . But in this case we have through 16 electrodes. And you can |
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| 33:05 | early synchronization in be in a the is having what is called an aura |
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| 33:15 | often that precedes a seizure. These sir present and epilepsy and seizure |
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| 33:22 | These auras are present and migraines And that's typically it's either feeling it's |
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| 33:30 | a little bit loss of some sensory visual stimulus or something like that. |
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| 33:38 | for migrants. It has a very visual stimulus. Uh And then you |
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| 33:45 | see that there is origin of this and starts like this abnormal activity. |
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| 33:51 | starts maybe in one or two traces . What E E. G. |
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| 33:56 | measuring is the difference between the two comparing the signal between two adjacent |
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| 34:04 | So you can see that maybe somewhere this area. 12 13 14 |
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| 34:12 | There is initial abnormal activity synchronization and is abnormal activity. So that means |
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| 34:20 | for the most part, activity in brain is really going to be indistinguishable |
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| 34:26 | from the calculations and apart from the . But you will not have these |
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| 34:32 | unless you have a pathology in this this is abnormal activity that starts in |
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| 34:38 | electrodes and very quickly it spreads into electrodes and then it spreads into from |
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| 34:45 | hemisphere spreads into the other hemisphere and abnormal synchrony throughout the entire network. |
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| 34:52 | this is a spread of abnormal activity abnormal synchrony. This is how epilepsy |
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| 34:59 | seizures quite often originating one focus one point and from there that abnormal synchrony |
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| 35:08 | hijacks the circuits and the networks of self and spreads marches on throughout larger |
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| 35:19 | of the brain. In Alzheimer's disease is damage to hippocampus in epilepsy and |
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| 35:29 | is damaged the hippocampus in schizophrenia, damage to the hippocampus. So hippocampus |
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| 35:36 | the hippocampal circus that we were talking . The excitation and ambition. They |
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| 35:41 | to be somehow very important for learning in this case mental stability and and |
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| 35:52 | vulnerable to damage to. With this this is an M. R. |
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| 35:58 | . For ct scanner can't remember of hippocampus in on both sides and it |
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| 36:04 | a significant damage to the hippocampal structures advanced uh stages of schizophrenia and advanced |
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| 36:14 | of temporal lobe epilepsy? And Alzheimer's as well? So it's an important |
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| 36:22 | area that we're looking at and as as the hippocampus and I put hippocampus |
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| 36:30 | it's also the circus that we studied during his circus that we said it |
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| 36:34 | in hippocampus. So if there is future therapeutic solutions to target these |
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| 36:42 | potentially there's something here and this self agonists antagonists, potentially pharmacological treatments that |
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| 36:53 | help these types of conditions, you , which comes first the the damage |
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| 37:01 | the abnormal rhythms like if can someone that and be asymptomatic. Is that |
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| 37:05 | early way to tell? Or they schizophrenia? And then this this is |
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| 37:11 | is an example of seizures in epilepsy schizophrenia. You wouldn't be able to |
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| 37:17 | this type of activity. And Alzheimer's also. You wouldn't unless you have |
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| 37:23 | epileptic component in Alzheimer's disease. So is really E. G. Is |
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| 37:29 | diagnosing seizures and epileptic activity but the that are vulnerable to damage by seizures |
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| 37:37 | epilepsy hippocampus are also vulnerable to damage Alzheimer's disease and schizophrenia. So it's |
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| 37:45 | an important part of the brain and susceptible part of the brand tune. |
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| 37:53 | why how are these rhythms created? are we having so many different rhythms |
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| 38:00 | we talked about different cell subtypes that different frequencies of firing in different rhythms |
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| 38:07 | they can produce an action potentials. have neurotransmitters, gaba glutamate. We |
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| 38:15 | a mean neurotransmitters that we discussed early add color. We have ion |
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| 38:23 | different subtypes of ion channels. All this results and the ability of different |
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| 38:29 | to speak a slightly different dialect to different chemicals, activate different receptor channels |
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| 38:37 | ion channels and produce this diversity from slow to really fast um activities. |
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| 38:49 | else the rhythms created? Its external , What is external entrainment, its |
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| 38:54 | stimuli? We're born and we hear human speech around us that comes into |
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| 39:03 | frequencies. Uh we have certain natural and side and sound that were trained |
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| 39:18 | uh so why so many military Because each one of these different rhythms |
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| 39:29 | a different task. Some of them have to have very precise and |
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| 39:36 | Some of them you have to have slow somewhere in between. They have |
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| 39:40 | be occurring at the same time. should be overlapping each other, riding |
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| 39:47 | top of each other. You can multiple rhythms simultaneously in the same |
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| 39:53 | That means that you can have a oscillation that is slow and on top |
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| 40:00 | that oscillation. You have a fast . So you have two rhythms you |
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| 40:06 | this rhythm that is repeating here and have this rhythm that is repeating |
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| 40:13 | There might be periodicity ease that might harmonies that created between the rhythms and |
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| 40:21 | same networks. Some of the rhythms very slow. The slowest rhythms that |
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| 40:27 | have in the brain are diurnal rhythms circadian rhythms. So day and night |
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| 40:33 | . We have a circadian clock which super charismatic nucleus and it expresses transcription |
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| 40:41 | in the evening that help us fall and changes into a different subset of |
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| 40:47 | factor expression in the morning. That us wake up and this is the |
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| 40:52 | rhythms. But we're not talking about potentials. There are also rhythms that |
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| 40:58 | happening on the order of seconds, four, slow three, slow to |
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| 41:05 | one rhythm. And these are very changes that may happen in the |
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| 41:10 | let's say numbering potential of the cell went up and d polarized for a |
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| 41:18 | seconds of slow rhythm and it could synchronized again. These are network |
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| 41:31 | These are not just individual cells, cells have the ability to produce all |
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| 41:37 | these different frequencies. But when we're about E e G. And when |
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| 41:41 | talking about these rhythms, those are rentals. Alright not individual celeb |
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| 41:49 | Then we can have ultra fast rhythms the way to 600 Hz. Most |
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| 41:57 | the cells will fire within 4 to 40 herds, that sort of most |
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| 42:05 | the dynamic range. And then you the superfast cells that will fire 100 |
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| 42:11 | 104 106 100 hertz a second. each one of these rhythms is encoding |
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| 42:17 | information, distinct levels of computation and levels, ability of processing different |
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| 42:30 | So uh you wonder how These experiments taking place historically and also how they |
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| 42:42 | in the last 20 years. This from 2004. It was uh |
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| 42:50 | So if you now localize the source the rhythm using E. G. |
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| 42:57 | question that Jackie was after and his is what sells contribute to these different |
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| 43:07 | . In other words if you have ongoing oscillation at the network level this |
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| 43:17 | on the network blob our individual cells to this oscillation. Is it that |
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| 43:33 | Farrah middle cells by firing their spikes at the teak And some cells and |
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| 43:45 | inhibitory cells are firing their action potentials and all inhibitory cells are firing their |
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| 43:55 | potentials at the trough here. Which ? We have 21 different cell subtypes |
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| 44:03 | . Cell subtypes do they all fight same time? I know we didn't |
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| 44:10 | that until 2000. So we knew E. G. Rhythm. We |
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| 44:14 | pick up individual cell activity. And had to come up with some clever |
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| 44:19 | in order to start picking up how this network rhythm relates to individual cell |
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| 44:29 | And the periodicity of these different subtypes cells that are in the network because |
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| 44:33 | part of the network. Right? rhythm we're picking up is from network |
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| 44:38 | cells. I said it's mostly from . That's okay. What happens to |
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| 44:47 | optical Tenderized and excited their cells depends what's happening in the network interactions with |
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| 44:53 | cells and other inflammatory cells. So have this principle of triangulation for determining |
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| 45:00 | heart's electrical access voltage measurements are made the right and left arms, right |
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| 45:06 | and left leg. Left and arm left leg. This is the top |
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| 45:14 | illustrates William Eindhoven's electors. The subject an arm and leg and salt water |
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| 45:20 | to galvanize A meter from the voltage in each measurement. The voltage vector |
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| 45:26 | be calculated. So it's basically the of triangulation here that allows you to |
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| 45:35 | the source of the heart rhythm, heartbeat and when your heart beats. |
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| 45:41 | it your heartbeat is gonna be detected right here in your left shoulder at |
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| 45:48 | same time as it is on your shoulder or there's gonna be a slight |
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| 45:54 | . It's gonna be a delay. so you use you know triangulation of |
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| 45:59 | you do E. K. Recordings you have them on both sides |
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| 46:05 | the body. So you can triangulate . This was the bottom is the |
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| 46:11 | of three dimensional position of neurons by measurement. So there were these tet |
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| 46:17 | of four electors that later became sophisticated more sophisticated and can have like microcircuits |
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| 46:28 | of sensory cortex of threat here. connections between participating parameter south's triangles and |
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| 46:34 | interneuron circles can be determined by the relationship. So what Jackie did with |
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| 46:40 | group is they inserted. These tetro first in the networks of cells and |
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| 46:47 | these sort of a thin plastic Each one of these electrodes one of |
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| 46:54 | electorates has 12345678 million electors. Then they can pick up the signal. |
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| 47:11 | do we have now? So if cell is located here and it |
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| 47:18 | Is it this electrode that's gonna pick information 1st? Or is it this |
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| 47:23 | ? It's this electrode. So you determine by looking at the spike at |
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| 47:29 | shape of the spike excited or inhibitory , excited inhibitor spikes. And you |
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| 47:37 | also say that excited to spike in one the rhythm was going on. |
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| 47:42 | electorate was activated first. Or that was activated first in this region right |
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| 47:51 | was the most active. So that you to triangulate and derive the spatial |
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| 48:00 | of the south around these electrodes as being active. Okay, so synaptic |
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| 48:15 | between participating parameter self triangles and putative circles can be determined by their temporal |
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| 48:23 | . For example, decreased discharge of partner neuron immediately after the spike of |
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| 48:28 | reference cell time zero in the upper instagram reveals the inhibitor nature of the |
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| 48:37 | neuron. So you see this here activity and then there is inhibition. |
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| 48:43 | saying basically if you saw one neuron and the nearby neuron all of a |
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| 48:50 | had a blip a lack of That means that that neuron was |
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| 48:56 | So the neurons that fired was inhibitory on the right now. Conversely consistent |
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| 49:09 | latency discharge of a partner after reference . This is the lower hissed A |
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| 49:13 | here indicates excited during nature of the cell. So here are the sulfide |
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| 49:20 | the responses more activity. Here the fired. And the response in the |
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| 49:27 | cell. You see this black it reduces activity. So this is |
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| 49:34 | I look. It's not clear And you would gather from six or |
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| 49:40 | of these electors in the network as recording the ongoing activity and then you |
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| 49:46 | look at these different cells and this example, I wonder if I'm gonna |
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| 49:53 | it more. Yeah but okay this not the destiny to see it when |
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| 49:59 | so small which sells fire in the first. Do all cells fire at |
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| 50:11 | same time. And this is an of a ripple rhythm. Very fast |
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| 50:17 | . And what you're seeing here is seeing different colors. Here represent a |
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| 50:24 | cell subtype, neuronal cell subtype and these are there. The hissed a |
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| 50:32 | of their spiking activity. So whenever spiking a lot these hissed a grams |
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| 50:39 | high. So this is the answer different cells during this ripple rhythm which |
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| 50:48 | happening at the network level. The sell the green cell and the brown |
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| 50:55 | seemed to be active during the very peak moment of this ripple, yellow |
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| 51:04 | maybe it's a little bit more accurate but it doesn't change much red south |
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| 51:13 | firing when the ripple starts. And there's a purple cell. So in |
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| 51:20 | to produce this ripple rhythm and you different cells in the network, you |
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| 51:29 | Rommedahl cells rather by the inhibitory Or an inventory sells Rommedahl sells, |
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| 51:36 | will be firing at different parts of rhythm to produce the overall network |
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| 51:43 | All parameter cells will fire here all setbacks of cells, one will fire |
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| 51:50 | . The inhibitory subtypes of cells will it here and this is the overall |
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| 51:55 | of rhythm. So that network rhythm that synchronized rhythm and E E. |
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| 52:01 | . Comes from synchronized activity, but activity is determined by each self |
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| 52:09 | It's spiking activity at different phases of ongoing rhythm if the campus is actually |
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| 52:23 | part of the limbic system. So 1937 James Pop says described the limbic |
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| 52:35 | as a cortical machinery for feeling that limbic lobe region that was originally identified |
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| 52:45 | paul broker. So now the whole system is shown here in green and |
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| 52:59 | contains different nuclei and portions that comprise limbic system. So you have the |
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| 53:11 | McDowell is important and fear processing. have the hippocampus here that we've been |
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| 53:18 | about. You have some of the in the thalamus, medial dorsal thalamus |
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| 53:27 | nuclei, mammal, everybody's ventral basal , para hippocampal gyrus and parietal |
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| 53:35 | Singular gyrus? So hippocampus is just part of this limbic system. So |
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| 53:42 | is not only for encoding the So we discussed that hippocampus is responsible |
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| 53:49 | semantic memory. The hippocampus is also in the emotional processing, an emotional |
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| 53:57 | in the limbic system and the limbic is an emotional system in the |
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| 54:03 | It's not visual system, it's not system, it's not a matter |
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| 54:06 | it's the emotional system, fear, , happiness and so on. That |
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| 54:12 | processed and encoded through the different aspects the system, the campus and the |
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| 54:21 | of the hippocampus. Uh this seahorse horses known as hippocampus around your |
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| 54:33 | And the reason why hippocampus is named seahorses because it has this kind of |
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| 54:38 | bending like structure. It also has called demon's horn. This is Eamon |
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| 54:49 | the horns. Eamon was an ancient god. He was depicted as a |
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| 54:56 | with rams had, he was one the chief gods. So this is |
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| 55:02 | version and he was adopted by The Zeus and by romans romans is |
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| 55:12 | for campus. The corner Simoni demon's one of the most famed and studied |
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| 55:22 | in the brain? So we'll talk about hippocampus. Why is it? |
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| 55:29 | is it so famous? Why is hippocampus so much studied in the brain |
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| 55:35 | it has distinctive and easily identifiable growth and as the logical appearance. It |
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| 55:41 | hippocampus right here. This is in rodent brain. So you can see |
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| 55:45 | the humans. It's uh lower here the temporal lobe, the hippocampus. |
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| 55:53 | then and the rodents is higher up . Huh By the trial globe in |
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| 56:02 | . So you can see a very band of dense cell populations. So |
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| 56:06 | thought, oh this is very You can identify it easily, you |
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| 56:10 | slice the brains, you can put in the dense band, you don't |
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| 56:15 | that same dense band. And the , you see several distributed bands and |
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| 56:20 | six layers. So it has a three layered structure with one distinct cell |
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| 56:28 | which is the parameter cell layer. the growth structural and histological levels. |
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| 56:35 | very easy to identify. Very easy study. Very easy to teach to |
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| 56:39 | of the students to. It's important early on it was recognized as a |
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| 56:45 | important part for learning and memory. there is a famous case of H |
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| 56:53 | M. And two Canadian doctors of and Milner described H and M's |
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| 57:00 | He's one of the more famous cases neurology and neuroscience is he kept forgetting |
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| 57:06 | names every day. They had two had to reintroduce themselves to him and |
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| 57:12 | discovered that hmm Had serious damage in and that's how so we're talking |
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| 57:20 | late 1950s and we're starting to understand there are these emotional centers that there |
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| 57:26 | these memory centers Remember that 1970s, lobotomy was a popular procedure. So |
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| 57:38 | even, what is it not even years ago, if you had serious |
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| 57:44 | behavioral issues, they may put a to your brain in the frontal lobe |
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| 57:48 | just cut all the connections. So not like we knew so much and |
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| 57:55 | discovering this and so this is a of important part of the brain involved |
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| 58:00 | memory. It's also highly susceptible to and other neuropathology is Alzheimer's disease, |
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| 58:08 | very sensitive to is he mia anoxia any loss of examination because it's located |
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| 58:16 | within the brain tissues. Uh this a three dimensional representation of hippocampus, |
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| 58:22 | a banana sort of a in a a rat hippocampus. That's how I |
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| 58:28 | to teach my students how to do to isolate the hippocampus and then slice |
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| 58:34 | it. Um and I used to them to do it with their eyes |
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| 58:41 | in their sleep without a scalpel in hand. And it really helped them |
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| 58:46 | because a lot of times you can't very well, even under a |
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| 58:51 | you just kind of have to you know, just do it. |
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| 58:55 | you practice and mentally it helps. , practicing your hippocampus help with hippocampal |
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| 59:05 | . Okay, so we're gonna look this hippocampal circuit. Uh now the |
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| 59:13 | and the major pathways that come They come in from the entire original |
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| 59:20 | . So cortex is around the hippocampus information entering the entire original cortex can |
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| 59:28 | around hippocampus through the excitatory pathways and to the cortical area of origin. |
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| 59:35 | hippocampus will get input from other cortical . Will kind of circle it through |
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| 59:43 | circuit and also communicate back to other cortical regions. So this is |
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| 59:50 | C. Which is internal cortex and of the inputs go into the dental |
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| 59:58 | gyrus gyrus and some inputs bypass Dante and go directly into an area called |
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| 60:08 | . Three. C. A stands corner simone demon's horns. So see |
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| 60:14 | . Three and see A. One say we're about C. Two. |
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| 60:18 | . Two is about here but it's very clearly defined. So we very |
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| 60:22 | can define the dented gyros area here very clearly defined the C. Three |
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| 60:28 | and see a one area. The gyrus contains excitatory cells but they're actually |
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| 60:35 | parameter cells. They're called granule So that's another type of excitatory |
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| 60:45 | And the performed pathway. # one is the pathway that carries the signal |
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| 60:52 | Cortex into the dent age iris. this is a performed pathway brings it |
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| 60:59 | the dental dental gyrus And some of projections you can see from the performed |
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| 61:07 | go directly into c. three. illustrated here now. So there's excitatory |
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| 61:16 | performed pathways. Excitatory pathway. Dente has excitatory pathway which is the granule |
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| 61:23 | that form mossy fibers and mossy fibers the projections here that go between dente |
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| 61:33 | and see a three area and the fibers will be contacting the excitatory parameter |
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| 61:41 | and all that. The cells inhibitory in the network as well. So |
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| 61:49 | basically layers one in this case to dental gyrus layer two performed pathway to |
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| 61:59 | gyros and C. Three layer You can see that in turino cortex |
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| 62:07 | has layer three. This arrow goes into C. A. One in |
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| 62:12 | into cervical. Um So although there this circular here performed pathway dental gyrus |
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| 62:21 | . Three C. One, there's a bypass from turino cortex directly into |
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| 62:28 | . One. Now from dental gyrus have mossy fibers to see A. |
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| 62:36 | . And from C. A. you have a dominant fiber pathway called |
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| 62:41 | shop A collaterals that will contact onto C. A. One sells the |
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| 62:46 | sauce and they inhibit their inter neurons from C. A. One the |
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| 62:53 | output is going to be to an called Civic Yalom and from Civic Yah |
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| 62:59 | here is going to be an Again going into the deep end to |
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| 63:06 | cortical layers. So we start from cortex we go through the hippocampus and |
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| 63:14 | into the memories are not stored in . They're not uh they're widely distributed |
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| 63:22 | cortical tissues. So there's an organization these memories and how they're recalled |
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| 63:28 | So hippocampus will be activated to encode memories and recall these memories. The |
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| 63:33 | of memories but not to store The storage is gonna be widely distributed |
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| 63:43 | to the six layers correspond to like have any relation with the video |
|
| 63:48 | So cortex is a six layer cortex a neocortex. Is a type of |
|
| 63:55 | . Yeah it isn't. Thanks for clarification. So 123456. And then |
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| 64:03 | the campus is not really six structure more of a three layer structure discuss |
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| 64:10 | orients adam but it has these three substations for processing there and I'm showing |
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| 64:20 | to you because I'm gonna want you know the dominant pathways in the |
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| 64:27 | And the reason why is because this how you start understanding from single cell |
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| 64:34 | excitatory versus an inventory or they can to each other to network in the |
|
| 64:42 | like campus. You have three D. G. C. Three |
|
| 64:45 | one donald regions is spiritual to how are interconnected into the vortex. And |
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| 64:54 | we start thinking okay so that means activity and the rhythms that we're talking |
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| 65:00 | and that the campus all of these are gonna be cycled through the synchronized |
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| 65:07 | of selves in these different layers and these different regions of hippocampus and the |
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| 65:13 | cortex. So this is another view the pathways and when we're visualizing the |
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| 65:27 | with the performed pathway mossy fibers and collaterals. This is transverse sections of |
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| 65:34 | sections through hippocampus similar except that uh convention corona was cross sections in this |
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| 65:51 | of the brain. And if the is sort of like a banana so |
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| 65:55 | did the corona we wouldn't capture these . We have to do transfers in |
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| 66:02 | direction of the actual structure. No I would still if you did |
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| 66:10 | corona section I would still be This is a criminal section. See |
|
| 66:19 | is a colonel section and it looks . It's almost like a little bit |
|
| 66:25 | the banana is being cut a little because it would be like this cut |
|
| 66:31 | here and this is the transfer sections then the transfer sections you very clearly |
|
| 66:40 | the dental gyrus, the C. regions and see one in this dark |
|
| 66:45 | of cells. Is the in the virus. It's the granule cells and |
|
| 66:50 | C. Three and C. One the parameter all cells. So now |
|
| 66:55 | learned about another excitatory subtype of cell granule cell. That's in the |
|
| 67:09 | So this is our stratum orient stratum middle stratum. Ready adam. The |
|
| 67:26 | this I don't know why I put information Stratton for by bulletin conjunctions and |
|
| 67:31 | . Cell parameters shaped cell bodies. cell bodies. Mossy. Um But |
|
| 67:35 | mossy in with large and small cell . Yeah it's a mess out |
|
| 67:41 | You have to know the circuit really I'm not going to demand from you |
|
| 67:45 | know the circuit really well I Understanding the principle that you have these |
|
| 67:50 | interconnections and the importance of the circuit learning memory and you're a pathological |
|
| 67:57 | That's that's what I'm gonna ask you know these dominant pathways. But I'm |
|
| 68:03 | gonna ask you if there's small or cell bodies in in there. But |
|
| 68:07 | talking about this circuit. Alright, looks familiar. Okay so three types |
|
| 68:16 | parameter south and this is in A 13 types of parameter South that |
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| 68:22 | not by their activity but by their markers inhibitory cells to distinguish based on |
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| 68:30 | activity morphology, Synaptic connections, locations this synaptic connections and phenomenal cells and |
|
| 68:40 | firing patterns. Different firing patterns of potentials. So let's see if we |
|
| 68:47 | to get through all of this some of this good stuff maybe for |
|
| 68:53 | lecture can we're out of time now very quickly I'm going to say that |
|
| 68:59 | and what are the rules that govern communication, especially inhibition. What types |
|
| 69:05 | inhibition we have three predominant types of . The first one is so when |
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| 69:14 | herself receives citation input informs inhibitory it excites an inhibitory cell and this |
|
| 69:23 | sell inhibits excited to herself. Citation site inhibitory self, this is negative |
|
| 69:33 | or feedback in division, this is forward. So you can have an |
|
| 69:39 | stimulus coming into the hippocampus, you be coming into the hippocampus and it's |
|
| 69:47 | not only the parameter cell axons but can see it's contacting this inhibitory cell |
|
| 69:52 | here. So the input will come the inhibitory cell first and only later |
|
| 70:00 | , followed by the input to the cell. And in the meantime what's |
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| 70:04 | to happen is when this cell gets inhibitory cell will start in feed forward |
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| 70:11 | inhibiting this excitatory cell and then we lateral in division and in lateral |
|
| 70:21 | You have excitation here coming in to prom. It'll self and these phenomenal |
|
| 70:29 | will excited inhibitory neurons. But those their neurons will not inhibit the same |
|
| 70:38 | yourself but they will inhibit cells located through this excited for itself on both |
|
| 70:46 | . And what this does is basically this neuron then has the villages suppressed |
|
| 70:52 | sides excited ourselves because it receives excitatory activates inhibition and suppresses it and it |
|
| 71:01 | for what it says autonomy. A of neurons neuronal activity by suppressing the |
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| 71:09 | activated neighboring neurons or otherwise called winner all. So in this case the |
|
| 71:17 | is the middle south staking all of signal to itself by inhibiting the surrounding |
|
| 71:22 | through lateral. These are the three rules by which an ambition uh functions |
|
| 71:32 | in the brain in a way it yeah. Yeah but except that it |
|
| 71:42 | be happening through the inhibitory ah horizontal . Yeah it's a good way of |
|
| 71:58 | about. Okay we're gonna end here . Thank you for being here. |
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| 72:03 | will see you all on monday. then we'll have our review on zoom |
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| 72:10 | on Wednesday. I'll let you know monday. Yes, I'll email on |
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| 72:15 | with a zoom link Wednesday. Know here on monday and then not |
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