| 00:03 | So for the first lecture for this that we discussed, we overview the |
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| 00:12 | parts of the central nervous system with you all should be familiar with, |
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| 00:18 | , The peripheral nerves that are coming of the spinal cord. The 31 |
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| 00:23 | a little bit about the history of the brain. Tripper nations where the |
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| 00:28 | neuro surgeries to alleviate pain, fluid build up or blood and the |
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| 00:35 | to discover the anatomy of the Starting from ancient Egypt, where heart |
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| 00:40 | still the most important organ, highlighting people that contributed to our understanding of |
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| 00:47 | , body relationship, but also how brain was controlling through what's thought to |
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| 00:55 | channels or pipes, the muscles and behavior of us as described by rene |
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| 01:01 | cart cognito ergo. Soon as his phrase, I think therefore I am |
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| 01:10 | Luigi Giovanni who showed that nerves were pipes, but they were electrical wires |
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| 01:18 | of generating electrical signals and conducting electrical . And then there was a search |
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| 01:26 | delineation of specific areas of the brain are responsible for different functions. And |
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| 01:32 | technologists were trying to localize specific functions the brain, but they were trying |
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| 01:39 | describe the abilities and as are ascribed different parts of the brain and would |
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| 01:47 | pair on the surface of the So phrenology was an interesting science, |
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| 01:54 | it's really Broca's area and dr broker discovered the area responsible for expressive |
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| 02:02 | barnacles, area for receptive aphasia and we also discussed economic and global aphasia |
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| 02:09 | and this showed us that there is only a specific parts of the brain |
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| 02:14 | for specific functions and utilization of specific but multiple areas, for example for |
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| 02:22 | multiple areas of the brain are involved processing function. This is gauge example |
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| 02:29 | us that essentially while there are parts the brain I would get injured and |
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| 02:37 | could lose vision or feeling or Finance gauge lost his eye, but |
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| 02:47 | injury in the frontal cortex has resulted alterations of his behavior. Executive |
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| 02:54 | control of his aggressions and a lot the studies of specific functions were also |
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| 02:59 | with cortical stimulations. Ramon alcohol used boss's invented Golgi stain and was a |
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| 03:07 | of the fact that individual neurons or doctrine. Individual neurons and discrete units |
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| 03:14 | very forward thinking and suggesting that connections synapses between neurons are plastic and |
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| 03:21 | Carrington coined a lot of what we the synapse and this term synapse. |
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| 03:28 | So this is Golgi stain which states a fraction of neurons and reveals their |
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| 03:33 | and that I mean remote alcohol reconstructed anatomy of many different cellular subtypes. |
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| 03:39 | understanding and the experimental neuroscience goes from microscopic levels from single molecule single center |
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| 03:48 | south cellular network, macroscopic areas, behavior as a whole in the clinical |
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| 03:56 | . When we study neuronal activity, typically use noninvasive techniques and we talked |
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| 04:02 | imaging technique, positive emission tomography. different tasks would essentially activate different parts |
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| 04:10 | the brain. Different neuronal circuits in part of the brain. We also |
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| 04:14 | about noninvasive electrical E. G. later in the in this section. |
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| 04:23 | we discussed how you need electron microscopes resolve the synaptic space of about 20 |
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| 04:31 | to start describing the precise morphology and and it would reveal us these dendritic |
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| 04:39 | . Using infrared microscopy. We can cell selma's and we can target the |
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| 04:46 | of choice with micro electrodes and do patch clamp and other types of recordings |
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| 04:52 | what we understand from doing these recordings also monitoring activity in the nearby glial |
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| 04:59 | such as astrocytes. We understand now astrocytes are intricately involved in neuronal communication |
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| 05:06 | this is what we call tripartite pre synaptic neuron one. Post synaptic |
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| 05:12 | two. And the third player in synapse is astrocytes. They don't produce |
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| 05:17 | potentials. The community communicate through these waves. But as you can see |
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| 05:22 | they have actually transporters for the these black dots and neurotransmitters that neurons |
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| 05:29 | . And we have these transporters for in particular and also they may have |
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| 05:36 | own radio transmitters that either activate neurons get transported into police synoptic neurons and |
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| 05:43 | back into the glutamate neurotransmitters. So play intricate part in the synaptic communication |
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| 05:52 | also regulate the levels of ionic concentrations they increase locally within very active and |
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| 05:59 | synopses. And we talked about in last slide how there are different systems |
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| 06:07 | chemical communication in the brain. There systems such as glutamate and Gaba which |
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| 06:12 | spend the next 23 lectures and within and Gaba neurons would be widely distributed |
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| 06:18 | the brain. But then there are other neuro modulator or amine systems such |
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| 06:24 | norepinephrine, such as serotonin, such acetylcholine. And these are quite |
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| 06:32 | The selma's are located in local civilians only a few €100,000 would be producing |
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| 06:41 | for the whole brain. And these indicated very diffused non specific spring sprinkler |
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| 06:47 | system projections throughout the cortex into the cortical spinal cord areas as well. |
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| 06:54 | will have a few nuclear produces central that then projections through the axons will |
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| 07:02 | it and release it widely throughout the as well as rafting nuclei for whether |
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| 07:07 | serotonin. So there are different ways which there's chemical communication and if you |
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| 07:14 | glutamate as excitation switch on, use analogy and gabbas inhibition switch off for |
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| 07:23 | activity. Then these neuro modulators and neurotransmitter ISI add a lot of color |
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| 07:30 | dimming effects to that control of that switch. Let's see if there's something |
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| 07:38 | audio is weird. Can someone asking record you some recording this. I'm |
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| 07:44 | post this after the recording. So is pretty basic lecture and recovered this |
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| 07:52 | fairly well. And I think that happy to take any questions if there |
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| 07:58 | over chat or you can mute yourself long as you meet yourself later. |
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| 08:04 | not, I'm just gonna move on the next section when we talked about |
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| 08:10 | and glia. When you can can speak to all the additional readings |
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| 08:18 | Mostly read the interesting conclusions. I've read the text associated with figures. |
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| 08:25 | you're in good shape then and I I was going to go over that |
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| 08:29 | go over some other things. But , it's a good question. So |
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| 08:35 | we started talking about neurons, excitatory , inhibitory gaba neurons that these major |
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| 08:42 | acid neurotransmitters involved in fast neural transmission inhibition. And also there are ion |
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| 08:50 | tropic and measurable tropic synaptic receptors to these excitatory glutamate or inhibitory Gaba neurotransmitters |
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| 08:58 | be binding Glia is also very We talked about several types of glia |
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| 09:04 | particular highlighting astra sites and involved in blood brain barrier involved in the neuronal |
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| 09:09 | and synaptic activity regulation information illegal. size which form myelin sheets around axons |
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| 09:18 | insulate axons. Micro glia, which long inflammatory response and immune response in |
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| 09:26 | brain following infections and regulation of release the cytokine molecules. Now when we |
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| 09:34 | about neurons and glia cell subtypes are that many. But when we talk |
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| 09:41 | neurons is over 100 different subtypes of and so the neurons can be classified |
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| 09:48 | different subtypes based on their connectivity. example if their projection neurons or their |
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| 09:58 | , they're projection neurons. that means they're going to connect them between neuronal |
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| 10:04 | or different parts of the brain. they're into neurons that means that they |
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| 10:07 | typically exert their activity locally within a network based on excitability, excitatory |
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| 10:15 | inhibitory gaba neurons, other cells specific or molecules that those cells may express |
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| 10:23 | as other neurotransmitters are the neuropathy ties uh you can cells can neurons can |
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| 10:32 | expressed in europe baptize and neurotransmitters. action potential firing signatures and neurons will |
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| 10:40 | ultimately certain output in the form of potential and this action potential. Different |
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| 10:47 | of cells will produce different frequencies and of these action potentials. Most neurons |
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| 10:54 | four functional regions. The input, integrated region which is the selma |
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| 10:59 | I'll regions which is the axon output which is the axonal terminals or the |
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| 11:06 | . So the easiest way to first classified neurons was based on morphology. |
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| 11:11 | are you know polar summer bipolar, civilian polar some are most of the |
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| 11:18 | in the cns or multi polar motor of the spinal cord is also multi |
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| 11:25 | parameter solving which we learned quite a is a multipolar selves inhibitory interneuron multipolar |
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| 11:32 | . Giant bushy park in Gc 150,000 is a multipolar self, we spent |
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| 11:40 | a bit of time discussing the circuit now you understand even better because we |
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| 11:46 | first spend time talking about the cells self subtypes in the sea. |
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| 11:51 | One area of the hippocampus. And you know in the C. One |
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| 11:55 | and see three area are the connections C. Three areas traffic collaterals connected |
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| 12:03 | C. One area. And so projection cells are excitatory cells will project |
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| 12:08 | outputs outside of the C. One. And there's really three different |
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| 12:12 | of these excitatory cells. There's so are located in three different layers where |
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| 12:17 | item from a dollar orients per the layer is very much dominated by the |
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| 12:23 | all cells in general. The whole circuit contains 80 to 90% of the |
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| 12:29 | parameter cells and only terms of 20% these other cells will be the inhibitory |
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| 12:35 | that is dominated by the excitatory But there's only three different subtypes. |
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| 12:40 | distinguished by being located morphological ian three players and expressing called indian C. |
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| 12:48 | . Plus or lacking C. C. B minus the output, |
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| 12:54 | output of action potentials of these These parameter cells three different subscribers will |
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| 13:00 | very similar to what you see here this diagram. Not very much |
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| 13:06 | However they inhibit the inter neurons that found in the C. 01 area |
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| 13:11 | the campus. They can be distinguished on their morphology based on the locations |
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| 13:17 | the soma CNN drives. And also yellow cups which represent the synoptic formations |
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| 13:23 | they inhibit the synopsis onto the parameter in Ghana predominantly located in the stratum |
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| 13:30 | layer. So these cells can be more theologically but when they cannot be |
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| 13:36 | more theologically or the location of the projections such as between basket cells to |
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| 13:43 | basket cells. For then we have do additional staining for potential markers that |
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| 13:51 | just unique to us sell to It turns out that so two contains |
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| 13:57 | in them and sell for contains CCK the morphological li they're indistinguishable but their |
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| 14:05 | intracellular markers is slightly different. And because of the fact that they're different |
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| 14:14 | markers. There's different expression of channels these plasma membranes and because of the |
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| 14:21 | properties and channels of these cell problems membranes express. We have these different |
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| 14:30 | interneuron subtypes that are responsible for the of these diverse electrical patterns. So |
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| 14:41 | cells will produce a pretty constant rather frequency firing pattern of excitation. The |
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| 14:49 | neurons will contribute all of these different that are called dialects where action potential |
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| 14:56 | the same language but the frequencies and patterns of the action potentials represent the |
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| 15:03 | . This is an experiment that illustrates microscopy patch clamp physiology on two neurons |
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| 15:12 | using bio Sidon filling or neuro biden these two cells that recorded and across |
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| 15:19 | using immune artistic chemistry for self specific as well as neural biden to confirm |
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| 15:25 | specific sub type of cell that I from in this case and criminal |
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| 15:31 | All alarms, Cell plasma membranes are and so all of these foster lipid |
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| 15:38 | layer, cholesterol molecules, trans membrane , membrane associated proteins, lipoproteins, |
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| 15:45 | , membrane channels. They all are within this possible lipid bi layer which |
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| 15:51 | the hydra filic polar had and hydrophobic acid tails. And the structure this |
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| 15:59 | the structure of the movement of the with them. The membrane is fast |
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| 16:05 | of new molecules and new proteins into membranes is also fast and the underlying |
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| 16:11 | supported by cida skeletal elements and the types of site a skeletal elements. |
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| 16:18 | largest of micro tubules which form the tubular highways that are very important for |
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| 16:25 | transport neuro filaments, media intermediary filaments micro filaments which are the smallest comprised |
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| 16:34 | active molecules. And these three silence elements will be supporting the underlying structure |
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| 16:41 | boundaries of the plasma membrane, their will be also contributing to the outer |
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| 16:47 | that form the dendritic spines formation of spines. Their densities proper distribution along |
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| 16:56 | shaft is an activity and environment dependent . These are the most plastic elements |
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| 17:03 | the brain. The synopsis experiences somewhat independent because they contain poly ribosomes |
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| 17:11 | They also contain mitochondria seen here through microscope images. And there's several different |
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| 17:19 | of the these spines come in and spines are very important for normal, |
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| 17:26 | communication, the neurons communicating. That form multiple synopsis on the selma's and |
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| 17:32 | dendrites and dendritic spines and dendritic spines where most of the synopses are formed |
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| 17:38 | most of the neurons and in cases abnormal development of dendritic spines. We |
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| 17:47 | about fragile X syndrome. Please review of the most fragile X syndrome as |
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| 17:54 | genetic developmental mental rental station. And can see neurons have to process thousands |
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| 18:02 | inhibitor and excitatory synapses and having a anatomy and having a proper distribution of |
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| 18:09 | spines will affect the processing and communication can lead to mental recommendation and fragile |
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| 18:16 | . Falls into the autism spectrum So uh it's all good to to |
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| 18:24 | review if you miss this particular section the lecture now, neuronal communication axons |
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| 18:34 | segment here will produce action potential and action potential will get regenerated in between |
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| 18:41 | myelin segment and nose of ranveer and will cause the release of the neurotransmitter |
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| 18:48 | the synoptic external terminals. Action potential we talked about is dominated the rising |
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| 18:55 | by sodium influx and the following phase potassium the flocks and the channels are |
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| 19:01 | in order to conduct sodium a volt these channels that mediate action potential. |
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| 19:07 | vault, educated channels. So it deep polarization to action potential threshold |
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| 19:14 | If the resting membrane potential, the is approximately -65 million vault. I'm |
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| 19:20 | potential missile is receiving excited to inhibitory inputs, excited for inputs. |
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| 19:25 | receives enough of the excitatory inputs. will open up both educated sodium |
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| 19:30 | well educated sodium channels will cause this fast deep polarization. An influx of |
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| 19:36 | followed by e flux of potash and polarization back to resting membrane potential levels |
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| 19:44 | versus absolute refractory periods, absolute refractory . You cannot absolutely evoke in our |
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| 19:49 | potential. Another additional deep polarization, you can with force the very strong |
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| 19:54 | during the relative refractory period. The refractory periods may differ in the different |
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| 20:01 | subtypes and if it's a long refractory , it may take a while for |
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| 20:08 | action potential to be generated that's resulting slower frequency of action potential, firing |
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| 20:15 | rather than refractory periods may allow themselves produce another action potential faster, resulting |
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| 20:23 | higher frequency firing rates. And some the cells. Okay, so this |
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| 20:28 | some of the things that we discussed briefly. Just to remind that this |
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| 20:33 | what's happening during the action potential and these areas where the action potentials |
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| 20:42 | which is excellent initial segment and then nose of ranveer. They contain very |
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| 20:49 | densities of these voltage gated sodium channels potassium channels that are involved and are |
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| 21:00 | for sodium to influx in potassium T and to generate action potential when the |
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| 21:07 | potential arrives at the synaptic terminal, causes the deep polarization at the synaptic |
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| 21:14 | prison optically action potential will cause an of vault educated calcium channels. |
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| 21:21 | just like the deep polarization here opens gated sodium channels and causes the action |
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| 21:27 | when the action potential brings that deep to the pre synaptic terminal opens voltage |
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| 21:33 | calcium channel influx of calcium is important allow for the the secular protein complex |
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| 21:40 | bind with the membrane protein complex and cause the fusion of the vesicles and |
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| 21:45 | of the neurotransmitter into the synaptic cleft will activate the past synaptic neuron uh |
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| 21:54 | neurotransmitter in the synaptic club. But actual piece of the membrane is endorse |
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| 22:02 | toes back and recycled back and refilled the subsequent neurotransmitter release. So in |
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| 22:08 | for the neurotransmitter release to take place about deep polarization and calcium influx. |
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| 22:15 | So you have to have action potential opening of the voltage gated calcium |
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| 22:22 | The major amino acid neurotransmitters in the and the spinal cord of glutamate lie |
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| 22:30 | and Gaba in particular when we talked the C. M. S. |
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| 22:35 | mean the cerebrum we're talking about major neurotransmitter glutamate and major inhibitor neurotransmitter gaba |
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| 22:45 | in the spinal cord into neurons is and google icing on the CMS neurons |
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| 22:51 | a co factor for an M. . A receptor activation as we discussed |
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| 22:56 | . So gluten maybe gets converted into by glue tannic acid deco box |
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| 23:02 | That's all of the cells that have expressed God will be inhibitory cells and |
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| 23:09 | could stain the hippocampal circuit for And all of these 21 different subtypes |
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| 23:15 | cells will actually stain for God. they will all be inhibitory. But |
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| 23:20 | will also have their specific cell markers provolone and their distinct morphology, external |
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| 23:27 | or firing properties at the level of number. In addition to the amino |
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| 23:34 | neurotransmitters, glutamate and gaba. We have decent means as we discuss these |
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| 23:39 | means are expressed in certain specific parts the brain so as opposed to glutamate |
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| 23:49 | gamma cells that will be found broadly different core tickles of cortical regions that |
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| 23:56 | means are actually expressed in very specific . Eyes which is a seed alkaline |
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| 24:03 | um um serotonin pathway. Cata cola which is tyrosine, dopa, |
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| 24:12 | norepinephrine, epinephrine. And for the you should just know that it means |
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| 24:19 | in the specific nuclei and there's cata mean category which includes these amine neuro |
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| 24:28 | and then there is serotonin category in choline category. Now as we discuss |
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| 24:37 | will have these glutamate transporters and one's is released in the synapses can activate |
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| 24:43 | a tropical automate receptors and A. M. D. And metabolic tropics |
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| 24:47 | as metabolic tropic and glue are Glutamate will also be recycled back into |
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| 24:53 | pre synaptic terminals through the glutamate neuronal and reloaded back into vesicles for the |
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| 24:59 | release. But a port will get back into glial cells through glial glutamate |
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| 25:09 | converted into glutamine glutamine with Tammany Cynthia and then transported back given back to |
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| 25:18 | glutamate neurons with Tammany synthesizing degree of subsequent movies. So again tripartite synapse |
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| 25:26 | this is how we will influence the of William gaba of glutamate in this |
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| 25:34 | . Now glutamate transporters present optical, will be located on the excitatory dermatologic |
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| 25:40 | to reload these vesicles. Glutamate on ergic cells, inhibitory cells will have |
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| 25:47 | transporters will be transporting it back and it into the vesicles. So |
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| 25:53 | they don't get wasted to get recycled reloaded into the vesicles with Sergeant department |
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| 26:01 | . We talked about buddha made being major neurotransmitter which is also a natural |
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| 26:10 | endogenous ligand. And glutamate is an to all three types of psychotropic Tampa |
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| 26:18 | . M. D. A. kind made receptor channels in this case |
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| 26:23 | are channels that are ligand gated or gated. Unlike voltage gated channels. |
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| 26:28 | the binding of glutamate is enough to on N. D. A chance |
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| 26:33 | them to conduct sodium inside and potassium this conductance of sodium coming inside the |
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| 26:40 | will cause a synoptic deep polarization to activation and excitatory synapses and M. |
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| 26:46 | . A receptor is different binding of is not enough. We also need |
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| 26:51 | as a co factor to have efficient uh opening of this receptor and you |
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| 26:57 | deep polarization because the FDA receptors are with magnesium. So you need to |
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| 27:03 | the magnesium blockade and m d A as we talked about they have a |
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| 27:09 | of different binding sides, two different and the NBA receptors in general will |
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| 27:16 | a lot more once they're open as to non NMDA receptors. So these |
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| 27:23 | ion A tropic and M. A. And the non M. |
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| 27:26 | . A receptor. And then we metabolic tropic receptors. So this is |
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| 27:30 | example of metabolic tropic receptor with neurotransmitter to the receptor which is not a |
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| 27:38 | both ample N. M. A receptor is our actual channels that |
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| 27:42 | conduct ions through them. But metal receptors are G protein coupled receptors and |
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| 27:48 | binding of this now transmitter will cause catalysis of the g protein complex subunits |
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| 27:56 | will then affect nearby channels they can for a late at a P. |
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| 28:02 | group onto the nearby molecules membrane bound or channels and influence the activity in |
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| 28:10 | fashion. So when we talked about M. D. A receptor is |
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| 28:15 | actually brings me a good point to about what is in your lecturer class |
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| 28:23 | materials, the hippocampal inhibitory circus, already discuss hippocampal inhibitory circus. And |
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| 28:31 | you can understand what we talked about and if you can review this figure |
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| 28:38 | and maybe see anywhere in the text it talks about the figure legend. |
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| 28:42 | if you understood everything that I said you're in good shape. Okay so |
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| 28:47 | that now fragile X information that is to autism spectrum disorder that we discussed |
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| 28:59 | one gene and I want you at to be familiar with this abstract of |
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| 29:05 | fragile X syndrome is and how it to our class material on dendritic spines |
|
| 29:13 | we just discussed now an M. . A. Receptor and then the |
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| 29:18 | receptor we have this one pager that very well. It's more than one |
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| 29:25 | . But you really need to pay to to this uh one page. |
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| 29:31 | then you can start paying attention later because it starts talking about synaptic |
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| 29:35 | And we also started discussing that. that's a good one to review for |
|
| 29:39 | M. D. A. You have the same one that comes |
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| 29:43 | the Gaba receptor physiology. Okay so only one questionable thing in there that |
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| 29:50 | says that God is a major inhibitory in the spinal cord but it's actually |
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| 29:57 | think we had a discussion about that glycerine, that's the major. But |
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| 30:02 | are some Gabbert into neurons ourselves and cord as well. Let's see blood |
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| 30:10 | barrier and neuro degeneration of Alzheimer's This is something that is coming later |
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| 30:17 | the course, modulation of spike timing plasticity. We just started talking about |
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| 30:25 | single cells to networks there's some figures that we talked about last lecture and |
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| 30:34 | was describing to you these multiple recordings single cells. So if you find |
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| 30:39 | figure and you didn't understand completely the and when you reviewed it you may |
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| 30:46 | needing extra read or something. Then are welcome to use this as |
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| 30:53 | Um Exploring the brain. Chapter 19 Epilepsy. So there are some |
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| 31:03 | OK Some figures here that we started about the brain rhythms. Uh and |
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| 31:13 | welcome to to to to just basically that a supplementary reading material. |
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| 31:24 | But it will come maybe more relevant we talk about about epilepsy be because |
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| 31:32 | is relevant to brain rhythms which we covered. But it will be more |
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| 31:37 | when we start talking about epilepsy. so there's more material that is to |
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| 31:41 | and more material that I'm going to with you and upload. Okay. |
|
| 31:49 | . Just to confirm, we'll be 30, maybe 40 questions. So |
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| 31:56 | a man have to be converted. special and it needs to be |
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| 32:02 | There's a lot of it there's a of dramaturgical cells and glia just have |
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| 32:08 | glutamate transporters in particular ostracized so that just the way the circuit is |
|
| 32:18 | Okay now let's see where we were were here at the Meadowbrook tropic |
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| 32:24 | I just shifted because we talked about M. D. A receptor. |
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| 32:27 | if you're talking about coincidence detector it's all described in that one pager and |
|
| 32:36 | . There's another jasper's review on glutamate we address and the figures that are |
|
| 32:45 | . So by all means review these and I'll also show you how it's |
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| 32:50 | to the upcoming exam. Right? so let's venture back into the metal |
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| 32:55 | signaling. And we looked at the as we talked about and then we |
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| 32:59 | about looked about the structure uh non emperor receptor Show em one and 2 |
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| 33:08 | three and 4 uh trance member in units with the flip flop region and |
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| 33:15 | C. O. H. Intracellular . This binding of the kind |
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| 33:22 | Uh and the fact that when the goes in the S. One and |
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| 33:29 | . Two regions, they kind of around the agonist. And so the |
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| 33:34 | the clasp is the strongest effect. full agonists would be a stronger clasp |
|
| 33:40 | the partial agonists and just clasp lightly these two regions. And we discussed |
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| 33:46 | we talked about ligand binding domain versus terminal binding domain. Trans membrane domain |
|
| 33:54 | about agonists antagonists modulators, competitive competitive antagonists will be competing for the |
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| 34:03 | site as the agonist. Noncompetitive will be competing. And then we talked |
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| 34:10 | how ostracized sides and metabolic tropic dis of glutamate through metal tropic glutamate |
|
| 34:18 | Five will increase calcium signaling will increase signaling. This is a partial where |
|
| 34:24 | talked about reactively aosis and this and fibrosis. Um ah this figure that |
|
| 34:34 | discussing is also described here and basically shows you another way in which you |
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| 34:41 | have abnormal dis regulation of glutamate through and glia because glee is so intricately |
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| 34:50 | in regulating this excitatory neurotransmitter levels in brain. So again you have to |
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| 34:57 | deep polarization and then the receptor and and advising in order to alleviate the |
|
| 35:03 | block. Um We then ventured and about how you would record different activity |
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| 35:11 | channels and we talked about how in the frequency of action potential who responds |
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| 35:17 | the strength of the income and stimulus for patch clamp recording most techniques cell |
|
| 35:24 | wholesale inside out with the inside intracellular of the protein channels exposed to the |
|
| 35:30 | experimental environment. The outside our technique the outside of the protein channel of |
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| 35:36 | is exposed to the experimental environment. you can target these channels with different |
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| 35:42 | antagonists on either side, especially the of permissible and record through these neuronal |
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| 35:49 | these pipettes record neuronal activity, record activity. The intracellular versus also recordings |
|
| 35:58 | is very small tip almost no dialysis it's not a great way to amplify |
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| 36:04 | signal and the whole cell has a of dialysis and you can control the |
|
| 36:09 | much better. But you have to sure that you match up the intracellular |
|
| 36:14 | to the neuronal solution. Most of would be done in vitro versus the |
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| 36:21 | which are blind without visualizing the cells the whole seller mostly visualizing the |
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| 36:27 | Most of these visualized recordings will be in vivo. So using this patch |
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| 36:32 | recordings who can record activity from individual . And this is recording from an |
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| 36:37 | . D. A. Receptor that that magnesium blocks and M. |
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| 36:41 | A. Receptor and hyper polarized And if you remove the magnesium this |
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| 36:45 | the physiological concentration of magnesium outside the . $1.2 million approximately. And if |
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| 36:51 | remove that magnesium concentration to zero magnesium the south you will see the |
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| 36:57 | He's a conducting system, an D. A. Receptor and reversal |
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| 37:02 | currents through an M. D. receptor. Zero million balls. So |
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| 37:07 | talk about reversals. We're talking about plots, the outward currents and the |
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| 37:12 | currents and I. V. Plot for current for I and V. |
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| 37:17 | voltage. In this case the number potential voltage. We discussed that the |
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| 37:22 | component of the E. P. . P, which is an ample |
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| 37:26 | is a linear component. A little component which is an M. |
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| 37:30 | A. Component measured here at some passed the stimulation and past this initial |
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| 37:37 | measurement. It's a nonlinear M. . A. Component here. We |
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| 37:42 | that the nonlinear NBA component has blocked the T. V. And that |
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| 37:47 | or specific TPV. Therefore it doesn't anything about the early amP occurrence. |
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| 37:53 | also talked about how there are differences the development of progeny are there are |
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| 37:58 | synapses during the development where synopsis only of the receptors and therefore it can't |
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| 38:05 | be activated by glutamine because there's no D polarization through ample receptors. There's |
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| 38:11 | in the sub union composition of these channel podiums and this is happening at |
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| 38:17 | developmental stages and then and ample receptors in and the synopsis no longer silent |
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| 38:24 | some of them will allow for the of calcium but others will not. |
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| 38:28 | that's the difference. All in India will allow for calcium to come in |
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| 38:33 | only some emperor receptors and that difference the substitution of the single amino acid |
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| 38:39 | this very long three dimensional structure of protein substituting one amino acid can influence |
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| 38:49 | this protein channel will be conducting calcium not. Ample receptors can be inserted |
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| 38:57 | plasma membrane. They can travel through membrane a very fast fashion and just |
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| 39:02 | an M. D. A receptor very important for long term plasticity. |
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| 39:06 | term potentially ation which we discussed our election. This is one of the |
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| 39:11 | for example by which little bit tropic receptor activation and actually activate two pathways |
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| 39:20 | and cause intracellular calcium release through an dry phosphate or activation of protein kinase |
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| 39:27 | at the numbering level. And kindnesses be risk responsible for correlation a lot |
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| 39:32 | times was for relation of the channels keep that channel activity or channels open |
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| 39:37 | versus phosphate Asus which deepest farley to away the P. 04 group and |
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| 39:43 | limit the activity of certain channels. you protein coupled receptors or not like |
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| 39:51 | ? Uh M one through M four that we were just looking at here |
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| 39:58 | the amphora suffers when we talk about protein coupled receptors. There's seven trans |
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| 40:05 | segments here, there's no inner channel and there's numbering associated you protein subunits |
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| 40:14 | you can see that all of the acetylcholine, gaba, serotonin, |
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| 40:21 | norepinephrine, catelynn cannabinoids, 80 P a denizen triphosphate. They will all |
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| 40:28 | metabolic tropic receptors Glutamate and Gaba and . The first three will also have |
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| 40:36 | A tropic receptors to usually combined but the rest will only exert activity through |
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| 40:46 | tropic receptors. Acetylcholine glutamate and Gaba cause the flux of ions through ion |
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| 40:52 | tropic receptors. Then all of the molecules will be mediating cellular activity through |
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| 41:00 | protein coupled receptors. Gaba Gaba in binding of Gaba. Gaba A, |
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| 41:07 | is an endogenous agonist will allow for of fluoride and hyper polarization. So |
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| 41:13 | is a target of ethanol, barbiturates steroids and they will have different |
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| 41:19 | size where they can target this receptor , raising the levels of inhibition. |
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| 41:26 | A allows for influence of fluoride activation Gaba B by Gaba Plus in optically |
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| 41:33 | will open up potassium channels and cause more hyper polarization precision, optical it |
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| 41:39 | block calcium channels in particular voltage gated channels influence of calcium and neurotransmitter |
|
| 41:46 | And we saw that later in this that summarized all of these circuits excited |
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| 41:51 | inhibit the enough work connections. So can see that quite often when you |
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| 41:56 | the cells you will see the P. S. Be excitatory post |
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| 42:00 | potential followed by an early inhibition through A. And later delayed inhibition through |
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| 42:06 | B. And then this experiment uh trace number one. What we see |
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| 42:13 | when we stimulate here we see excitation PSP and it is quenched by inhibition |
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| 42:20 | by inhibition by Q. Colon is specific Galloway receptor antagonist. And applying |
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| 42:26 | queue colon. You stimulate and produce same exact stimulus as in trace number |
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| 42:32 | . But now when you block inhibition can see that this excitation becomes in |
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| 42:37 | and becomes very long de polarizing stimuli a lot of action potentials riding on |
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| 42:42 | of these deep polarization, a dropsy with them as a specific blocker for |
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| 42:48 | receptor. And here it basically shows in the presence of hydroxy sack with |
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| 42:56 | you you don't have a significant effect . So by Cuco and this Gaba |
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| 43:02 | antagonists hydroxy cyclosarin is Gaba B. this is a great diagram we discussed |
|
| 43:11 | you have a Gaba ergic synapse releasing and bind to Gaba receptors. Person |
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| 43:17 | hyper polarized the sell through chloride cause PS piece which are graded the same |
|
| 43:24 | E. P. S. S. Are graded potentials and that |
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| 43:27 | different from action potentials which are all none boston optically binding to Gaba B |
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| 43:33 | by Gaba. Open up potassium channels cause the second wave of hyper |
|
| 43:39 | So boston optically you may see excitatory activation and you may see early EP |
|
| 43:48 | and then that early PSB and activation gamma is followed by early I PSP |
|
| 43:54 | is Gaba A followed by activation of tropic receptor and the late I PSP |
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| 44:02 | is mediated by Gaba B. And opening of these per synaptic potassium |
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| 44:08 | Gaba B receptors are also order receptors they will be located prison ethically and |
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| 44:15 | binding to Gaba receptors. Prison ethically block multi educated calcium channels which are |
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| 44:21 | for neurotransmitter release and regulate the release Gaba. This is an dramaturgical |
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| 44:28 | legitimate release and influx of calcium through and activation of calcium. Co modular |
|
| 44:37 | key to can influence the phosphor relation person, attic potassium channels or activation |
|
| 44:44 | gabby receptors person athletically which then will potassium conductance is hyper polarized ourselves essentially |
|
| 44:54 | an M. D. A receptor the number you need deep polarization from |
|
| 44:57 | . D. A receptor to be . So this is in a way |
|
| 45:01 | personality Gaba receptors can control by Person optically if there is a strong |
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| 45:09 | activation. Prison optical it'll be spillover Gaba into these synaptic gaba b receptors |
|
| 45:15 | are located glutamine terminals and then block of calcium and block glutamate release in |
|
| 45:22 | here not only has possum attic effect has a significant place in africa |
|
| 45:27 | both on its own auto receptors and receptors. Gaba hetero receptors located on |
|
| 45:35 | narrows. Let me see if there's questions in the chat on this |
|
| 45:43 | But I think that this is a good diagram that summarizes everything and so |
|
| 45:47 | should study this really well. So we talked about the phenomenon of rhythms |
|
| 45:57 | how these rhythms can be recorded using . G. Recordings and using in |
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| 46:02 | instances intra operative recordings or during their . Are these different rhythms that dominant |
|
| 46:11 | certain frequencies represent different behaviors. We e E. G. S there |
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| 46:17 | the surface of the skull. So of the signals coming from the op |
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| 46:21 | down rights of the parameter cells. Gs will measure activity and comparative itty |
|
| 46:27 | electrodes in different parts of the brain try to predict where the seizures started |
|
| 46:33 | different phases of the seizures. And have different rhythms that seemed to be |
|
| 46:39 | on natural log scale frequency here by integer. It's a mathematical system for |
|
| 46:48 | natural rhythms and they go from very to very fast or the fastest can |
|
| 46:52 | 600 per two second called fast rhythms fast triples. So from early days |
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| 46:59 | that we recorded these rhythms on the and we understand that dominant frequencies of |
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| 47:06 | rhythms. We now also know that are all these different cellular subtypes and |
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| 47:11 | we wanted to understand which cellular subtypes responsible for generating different rhythms. And |
|
| 47:17 | we had to use these multi electric and triangulation in order to pick up |
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| 47:24 | different rhythms. Um We also talked the hippocampus in general is one of |
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| 47:30 | best studied structures part of the limbic , part of the cortical machinery for |
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| 47:36 | and emotions and memory and hippocampus is in semantic memory or storytelling memory |
|
| 47:45 | seahorse or corner Simoni with a specific and very susceptible to damage Alzheimer's |
|
| 47:54 | schizophrenia upwards. The seizures very important learning and memory. And the circuit |
|
| 48:01 | we discussed is this dominant circuit of gyrus, projecting them to see three |
|
| 48:06 | mossy fibers performed pathway coming into dental . Mossy fibers from dental gyrus and |
|
| 48:13 | see three schaffer collaterals from C. to C. A. One. |
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| 48:17 | is a salute that travels through the and back into the surrounding cortical |
|
| 48:23 | Um And we talked about three dominant stratum orients parameter. We already adam |
|
| 48:30 | looked at the C. A. circuits and understand the circus. This |
|
| 48:36 | just a review of the circus. focusing on and then we discuss three |
|
| 48:41 | rules of inhibition feedback feed forward and or winner takes all in the |
|
| 48:48 | And then we talked about our basket are perfectly positioned for feed forward inhibition |
|
| 48:54 | orients cells And these basket cells are and four alarm cell is number seven |
|
| 49:01 | . O. L. M. clara cells or petition for feedback inhibitory |
|
| 49:08 | here and then we discussed how inhibition be activated across these three different layers |
|
| 49:15 | very different patterns spatial town patterns that be representing these temporal rhythms and these |
|
| 49:22 | of spatial temporal. So we record across different areas of the brain and |
|
| 49:26 | we look at the micro circuits will activating different layers at different phases. |
|
| 49:32 | the same time we use the example ripples where we said that parameter cells |
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| 49:36 | basket cells are most likely to fire synchronize at the very center peak of |
|
| 49:43 | fast ripples rhythm and all alarm Again we're talking about these basket cells |
|
| 49:49 | our alarm cells and or alarm cells be most likely to fire right before |
|
| 49:56 | center portion the fastest portion of this and right after that ripple so different |
|
| 50:02 | contribute differently in time and in space generating these overall rhythms. And then |
|
| 50:09 | talked about how these rhythms, you trace them and have these spectrograms of |
|
| 50:16 | field potentials and explain how local field can be likened to E. |
|
| 50:20 | Recording. So we have an experimental of studying and tissue in vitro and |
|
| 50:26 | vivo comparing into E. G. . And these show the darkest areas |
|
| 50:32 | basically have the highest power and the here on the Y axis and the |
|
| 50:39 | seconds is on the X axis. ? Now when we talk about plasticity |
|
| 50:50 | is very recent information. And um would actually advise for all of you |
|
| 50:59 | to view it in full recording instead me running over it because we just |
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| 51:07 | about this two days ago and I to mention that I think that the |
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| 51:13 | that have attended the lectures life and questions and took notes and I draw |
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| 51:21 | things on the board. I'm not how well they show up online. |
|
| 51:26 | took a couple of pictures on my . Maybe I can post them for |
|
| 51:29 | from this plasticity lecture in particular. the point being is that if you |
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| 51:37 | this lecture is life, you're going be in a really good shape. |
|
| 51:40 | you may want to just review this ation depression halves theory of engram and |
|
| 51:51 | . And how we had to prove theory and how we started recording from |
|
| 51:58 | and we started recording from um cells multiple electrodes, understanding what's going on |
|
| 52:05 | dendrites to and that there is this propagating spike which became very important, |
|
| 52:11 | about how spike is generated an axon segment by low threshold. And this |
|
| 52:17 | the forward propagated action potential that will neurotransmitter released back propagating spike is very |
|
| 52:22 | for plasticity in particular. Spike timing plasticity. And then we said well |
|
| 52:28 | plasticity has cellular substrates and we talked rate code. We talked about different |
|
| 52:37 | stimuli is that the reverberation of some happening that there's during that condition stimuli |
|
| 52:45 | may be having short term plasticity, or depression and that the conditioning stimuli |
|
| 52:52 | change the activity long term long term ation of long term depression or how |
|
| 52:59 | frequencies in different grades can cause either . T. P. Or |
|
| 53:03 | T. D. How we sought explanation. Well how come you can |
|
| 53:09 | L. T. D. And . T. P. At the |
|
| 53:11 | synapse if you stimulate these schaffer And this is where these studies were |
|
| 53:18 | in the ceo on region after stimulation the schaffer collaterals and recording of the |
|
| 53:23 | field potentials. Then the question well if we produce high frequency stimulation |
|
| 53:29 | get potentially ation produce low frequency We get depression. How can this |
|
| 53:34 | at the same symptoms? One of explanations was that high frequency stimulation can |
|
| 53:39 | high levels of calcium increase the production protein kindnesses. Their activation was relation |
|
| 53:46 | synoptic podiums, yielding and favoring LTP frequency stimulations, low levels of counseling |
|
| 53:53 | find phosphate assis favoring on phosphor de phosphor relation and L. |
|
| 54:02 | D. So low low levels long changes and plasticity amount of an |
|
| 54:07 | D. A receptor activation is another . So calcium is one how much |
|
| 54:12 | the N. M. D. receptor is activated maybe during low levels |
|
| 54:17 | activation. You have L. D. And high level to produce |
|
| 54:21 | . Not surprising, low levels of , low levels of calcium, potentially |
|
| 54:27 | through an M. D. A is one of the sources high levels |
|
| 54:31 | . High levels of calcium, high of an M. D. |
|
| 54:34 | Receptor activation is correlated with LTP. an M. D. A receptor |
|
| 54:39 | very important as coincidence detector in learning memory and plasticity. And the spike |
|
| 54:48 | between the two cells that are communicating each other is also very important. |
|
| 54:54 | so we ended here by saying that come back and talk about spike |
|
| 54:59 | But we used an egg example that when they communicate to each other. |
|
| 55:04 | have to get a response if the the synaptic cell fires and there is |
|
| 55:10 | response in the soma. Then this should come within milliseconds of time for |
|
| 55:15 | communication to be relevant when we left . The here we just described spike |
|
| 55:21 | dependent plasticity as a leading cellular model behavioral learning and memory. These are |
|
| 55:27 | substrates of learning and memory and I by saying that the truth lies somewhere |
|
| 55:32 | between the rate code and the spike dependent plasticity. The spike timing |
|
| 55:41 | Alright, check it out. Mossy are mossy fibers and their outputs that |
|
| 55:51 | going from dente gyros granule cells into sea A three region of the of |
|
| 55:58 | hippocampus they follow that this is performed inputs come from the cortex go into |
|
| 56:08 | dental gyrus. From dental gyrus. have these granule cells we call them |
|
| 56:12 | cells that form multi fibers. And axonal projections to target to see |
|
| 56:18 | Three neurons not just parameter neuros also neurons here. And the C. |
|
| 56:24 | cells parameter cells or projection cells So they will project into the sea |
|
| 56:29 | . One and target the C. . One region excited or inhibitory cells |
|
| 56:34 | forward feedback inhibition loops and such and excitatory C'E. One projection cells will |
|
| 56:41 | out into the subic Yalom. And I hope that answers your question. |
|
| 56:48 | fibers are really kind of a mossy moss like a parent. That's what |
|
| 56:52 | were called. Mossy fibers originally. . Now the other thing I'd like |
|
| 56:59 | share with you is exam practice questions uh they're maybe not the best and |
|
| 57:09 | don't have the answers because there for to practice with to make sure you |
|
| 57:18 | your own answers. And this is a couple of years ago it doesn't |
|
| 57:23 | that your questions are going to be same. Uh they will be similar |
|
| 57:32 | that gives you an idea of what of questions I may expect. And |
|
| 57:38 | this is now in your folders and apologize for the images. I was |
|
| 57:43 | to adjust. It adjusted and I but so okay you're having a problem |
|
| 57:48 | something like this A. B. . D. This is correct |
|
| 57:53 | Which region? So you go then below what happens in the activation |
|
| 57:57 | So this is how you read True question one. It doesn't mean |
|
| 58:02 | . It's A. B. D. Okay then this question here |
|
| 58:07 | question 14 above the image. So question here about the images, the |
|
| 58:13 | related to this image, Which region the N terminus of glutamate protein channel |
|
| 58:20 | , which region is the N And you would answer, Do an |
|
| 58:29 | somebody. We'll have to check him now. Something about signaling. Okay |
|
| 58:37 | come to this image and you're like wait a second. This is like |
|
| 58:40 | of the image. I know it taking me way too long to adjust |
|
| 58:43 | into this format. So I finally printed in a few minutes before so |
|
| 58:47 | it. I'm just gonna share it than not share it. So this |
|
| 58:51 | sharper collateral pathway of the hippocampus. obviously the images cut off. But |
|
| 58:57 | you knew shopper collateral pathway, shopper pathways from C. Three to |
|
| 59:01 | One. So the answer would be . This is dental gyrus of the |
|
| 59:07 | . Oh oops too bad. It's off. But now you know that |
|
| 59:12 | have to go into uh that you to go into uh let's see I |
|
| 59:28 | to go into this diagram. Going review what's the performed pathway? What's |
|
| 59:32 | dental gyrus here in this area. the C. Three was to see |
|
| 59:36 | on? Okay. And so obviously is not included in full, it's |
|
| 59:47 | off. So once again, well guess uh my professor did not receive |
|
| 59:54 | image so I have to go and this image one more time. But |
|
| 59:57 | a graduate student so I can do . And uh what is this campus |
|
| 60:03 | of the olympics is indicated by this . What I have to know where |
|
| 60:07 | campuses you better know? We talked it too much. So yes. |
|
| 60:15 | so there what is this? This a theater, rhythm frequency. Oh |
|
| 60:20 | a good one. And you have A. B. C. |
|
| 60:24 | Which one is the theta. Me to remember everything. No but maybe |
|
| 60:29 | a gamma delta fast cripples the things we talked about. Okay Donald help |
|
| 60:40 | that cell assemblies frequency of 200 hertz above modular Torrey neurons are controlled hippocampal |
|
| 60:46 | neurons simultaneously equal neurons responding to the stimulus. He suggested that cell assemblies |
|
| 60:53 | rigid and non plastic now. So C. And M. D. |
|
| 60:58 | . questions. Not all of these are maybe in order here. These |
|
| 61:02 | great sample questions so you can go them on the history questions. |
|
| 61:08 | you know just it's not that much so I would know that uh and |
|
| 61:13 | seven lectures. So if we're going have about 35 to 40 questions you |
|
| 61:20 | expect maybe about seven questions or so for each lecture? And on on |
|
| 61:27 | slides, some images. We spend time. So there might be a |
|
| 61:32 | bit more detail or a few more on on those particular images. We |
|
| 61:38 | to know the brain pathways in the with all the red or just the |
|
| 61:42 | stuff pathways and called around. We're black stuff. I'm not sure Jason |
|
| 61:55 | all the road or black. Um think he's talking about the hippocampus |
|
| 62:03 | That's in the lecture. There's red and there's black text. Oh it |
|
| 62:12 | in the very last lecture I Where where is more text. So |
|
| 62:21 | know, I don't know, a bit off here. Oh my |
|
| 62:44 | that's elasticity. So it must be circuits. Mm So what do you |
|
| 62:59 | to know about hippocampus basically three layers should know. Orients pyramid Alice stratum |
|
| 63:06 | . Autumn Major pathways performed mostly fiber collateral and number four is the output |
|
| 63:16 | civic Yalom C1 output which doesn't have a single name to it. Um |
|
| 63:23 | gyros Area C three D Area C area maybe like a fun thing. |
|
| 63:31 | a ship. Like a seahorse Amos corner Simoni, that's why it's C |
|
| 63:38 | region. So um criminal cells, sauce and the perimeter layer. So |
|
| 63:45 | relates to that electro flying by at 21 different subtypes of an inventory sells |
|
| 63:51 | in this diagram which already repeated. does that help? It's the phases |
|
| 64:02 | the op ellipses line, 16 sleights skin. Mhm. Yeah. I |
|
| 64:16 | kelly was helping us look for that with a Jason's question. Okay, |
|
| 64:21 | you. Uh This is the phases seizure. We talked about aura and |
|
| 64:29 | initial seizures, a few seizures in few electrodes and then the spread of |
|
| 64:35 | march of this abnormal activity. And said hippocampus would be susceptible to damage |
|
| 64:41 | seizures, also susceptible to damage and . Alzheimer's disease and schizophrenia. So |
|
| 64:49 | think that we didn't specifically discuss the of seizures yet. We'll come back |
|
| 64:54 | that when we talk about that Okay, good questions. Appreciate you |
|
| 65:08 | here. If there's no more I am wishing you good luck and |
|
| 65:14 | everything this weekend. And good luck your text test on on monday. |
|
| 65:21 | sure you take it on caSA. register for your times, make sure |
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| 65:26 | you are online, doing it It's not at caSA facility. |
|
| 65:33 | so good luck to everyone. Thank . Thank you Dr |
|
