| 00:02 | Next on our material agenda was olfactory . So now we understand a lot |
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| 00:09 | about this olfactory epithelium cellular network and that there are a progenitor cell |
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| 00:14 | Tacular cells. You actually after COVID-19 COV two lecture know very well that |
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| 00:22 | cells uh uh have a stew certain cell system, tacular cells and |
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| 00:28 | olfactory receptor neurons do not the olfactory neuro endings are hanging here in the |
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| 00:35 | cavity. And this is what is for binding the odor molecules. And |
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| 00:41 | si factor receptor neurons will express unique receptor protein. So will react different |
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| 00:48 | different odor molecules convert through a cyclo T P. And the cyclic A |
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| 00:56 | , the cyclic MP regulated mixed Catron will allow for influx of calcium and |
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| 01:04 | calcium influx. In this case, contribute to membrane depolarization to a large |
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| 01:12 | here, this uh thick arrow. in addition to depolarizing these uh |
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| 01:19 | it will also open calcium regulated chloride and fluoride. In this case will |
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| 01:26 | leaving the cell and negative charge, the cell will also further contribute to |
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| 01:31 | depolarizations. So these are the receptor that are located on the dendrites. |
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| 01:37 | the factor receptor neurons that will generate potentials that are graded potentials. And |
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| 01:45 | these potentials strong enough, so if is enough of the odor molecule, |
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| 01:49 | if the odor is really strong or close enough to the odor and you |
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| 01:55 | enough of it, it will generate large enough receptor potential that will generate |
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| 02:00 | potential controls on these olfactory receptor And we will conduct these action controls |
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| 02:05 | the olfactory nerve. We also saw the olfactory receptor neurons are arranged in |
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| 02:13 | of this mosaic and has very broad . And each one of the colors |
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| 02:19 | represents a subtype of cells that expresses unique uh odor receptor protein. And |
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| 02:25 | certain odors like citrus odors will activate receptor proteins on the green subtype of |
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| 02:32 | receptor neuron and generate a lot of potentials. But it will also bind |
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| 02:38 | the blue neuron that will have a different odor receptor neuron. It will |
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| 02:43 | bind the citrus smell and will generate smaller number of action potentials. But |
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| 02:48 | is other cells like the red one will contain another ulfa receptor neuron will |
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| 02:54 | likely. And in this case, not going to respond to the citrus |
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| 03:00 | . And so if the green cell to citrus odor and the great extent |
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| 03:05 | to floral odor to a smaller extent doesn't respond to a odor. So |
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| 03:11 | one of them, we use different will stimulate different factor receptor proteins and |
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| 03:17 | and Olfa receptor neurons that are scattered the Elum. But once their axons |
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| 03:26 | through the form plate here form these fest administrations in the skull and |
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| 03:33 | the olfactory Gle located. In there is a new order of organization |
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| 03:41 | all of the cells have a specific where all of the factor receptor neurons |
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| 03:47 | express the same ol factor receptor protium all converge in the factor evolved into |
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| 03:55 | single glu Mario. So each glama have a very uh strong uh uh |
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| 04:03 | input coming from Olfa epithelium that gets into a specific region based on the |
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| 04:11 | Olfa receptor protein expression of these LF receptor neurons. As we saw from |
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| 04:18 | olfactory involved, there are projections that into that olfactory tubercle. And from |
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| 04:24 | , they travel into the thalamus into medial dorsal nucleus of the thalamus. |
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| 04:30 | from there, they project into the cortex. But there's also a pathway |
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| 04:36 | bypasses this uh conscious perceptive interpretation of and directly project some factor bald secondary |
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| 04:47 | neurons to the factor cortex and some temporal lobe structures such as the limbic |
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| 04:56 | and the hippocampus. Therefore, the input and simulation has a very close |
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| 05:03 | and a strong stimulation to memories and . Each one of these smells will |
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| 05:11 | a different cortical map of activity that can be recorded with intracellular calcium sensitive |
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| 05:19 | dyes or voltage sensitive dyes. In case, a minty smell or fruity |
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| 05:24 | will produce a certain activation of the specific and olfactory bulb. But besides |
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| 05:33 | bulb, you can also record the information. And this is the cellular |
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| 05:39 | . All of the cells in green activated by piny smell, all of |
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| 05:43 | cells in red by citrusy smell. so this is uh a map, |
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| 05:50 | cellular map for different smells uh that be different for different odors. So |
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| 05:57 | two different molecules smell the same and two different molecules. Mt versus fruit |
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| 06:03 | produce the same maps and factor evolve in the cortex. And even further |
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| 06:08 | volatile molecules that are natural, that mostly from essential oils that we smell |
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| 06:14 | called taps and turkeys and any odor . They don't just generate the maps |
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| 06:20 | the olfactory regions. But as we , as they stimulate different olfactory areas |
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| 06:26 | the brain, the smell information gets with other senses just like some matter |
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| 06:31 | sensory, just like color, just sound. Now you're associated with the |
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| 06:35 | of smell and some memories and some . Therefore, there is a broad |
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| 06:39 | of activation and not just psychological but map of activation through inhalation of |
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| 06:48 | volatile molecules such as turps where each will have its own representative map. |
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| 06:54 | we talked about this fun project, artist project of depicting a city uh |
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| 07:01 | a map of a map it And then we talked about how different |
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| 07:06 | are, have different um temporal scales their volatility, shorter molecules so are |
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| 07:14 | volatile. And then the perfume industry referred to as top notes, longer |
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| 07:18 | , heart notes, longer ones and notes and really long molecules over 16 |
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| 07:23 | , long molecules we count and Therefore, uh we do not perceive |
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| 07:29 | over 16 carbons long and cannabinoids. we talked later lectures do not. |
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| 07:35 | we cannot perceive them, they are than 16 carbon. So we receive |
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| 07:40 | from flowers and from plants, including plant. We're always smelling these essential |
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| 07:49 | the molecules. Um We also talked these two uh terms, the one |
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| 07:55 | I coined a homo psychophysiology and the that uh that exists in neuroeconomics. |
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| 08:01 | I think it's really an important way think about how the brain works, |
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| 08:05 | different senses are related and intermingled and associated with other modalities. And this |
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| 08:13 | very important for basic science re It's very important for medical reasons and |
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| 08:20 | reasons as well as for market economy general. So let me see if |
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| 08:27 | any questions on the chat. I see any questions in the Madison or |
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| 08:34 | . Uh So now we have one uh uh olfactory system or some other |
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| 08:42 | system we have. Now the slide that I'd like to show you. |
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| 08:48 | that amazing how much we've learned since started when you look at the slide |
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| 08:55 | uh I'd like to move now into rhythms and epilepsy. So, uh |
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| 09:00 | we had this in technique invented with of pho gram, it was known |
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| 09:05 | that there are certain patterns of electrical that is being produced in the |
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| 09:11 | And we talked about how electrons of grams or E E G S are |
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| 09:17 | invasive method of placing an electrode cap top of the hair on top of |
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| 09:22 | skull and scalp. And that allows over time to understand that there are |
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| 09:29 | dominant frequencies, alpha, beta delta gamma that fall within a certain frequency |
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| 09:36 | and characterized by these frequencies and by amplitudes and that these different ranges, |
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| 09:44 | ranges that are dominating in the brain different behavioral states, different uh um |
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| 09:52 | alertness states. And we also talked these intracranial recordings which are different from |
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| 09:59 | E G and intracranial recordings will be . So we talked about how E |
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| 10:04 | G S used to record normal normal rhythms, brain rhythms. But |
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| 10:13 | is also used to pick up abnormal activity in the cases of seizures and |
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| 10:18 | . And in that case, if treatments do not work for an individual |
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| 10:25 | may be recommended. And a neurosurgeon the help of a neurophysiologist would place |
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| 10:31 | grid of these electrodes intracranially. So the skull has been open, the |
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| 10:38 | has been, have been exposed, peeled off, exposing the brain and |
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| 10:44 | electrodes are placed on the very surface the brain so that you can |
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| 10:48 | potentially just that very limited area that small or uh or area of the |
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| 10:53 | that is generating abnormal activity such as activity. So to understand rhythms, |
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| 11:00 | want to place it within a certain , we want to understand how rhythms |
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| 11:04 | . And we talked about circle of and, and the system that drew |
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| 11:10 | trying to describe for different rhythms in brain. Although rhythmicity is present everywhere |
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| 11:17 | life. And we have a variety these different rhythms in the brain. |
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| 11:23 | why do we have so many oscillatory or different rhythms is because we need |
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| 11:29 | perform multiple tasks. Some of them very fast and very precise. Some |
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| 11:33 | them are slower and may take longer and longer focus. And with these |
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| 11:40 | frequencies that are generated by the So activity that gets picked up by |
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| 11:46 | cap of the E E G by electrodes is the network activity that is |
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| 11:52 | in the brain. It's not an of the single cell. These rhythms |
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| 11:56 | created with a variety of different cell that have their own uh unique ways |
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| 12:04 | producing the frequencies of the action controls have their own chemicals, neurotransmitters and |
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| 12:11 | modulators and arms that they release and can influence the rhythmicity and also these |
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| 12:19 | are created because there is external There are certain frequencies of sound and |
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| 12:24 | frequencies of visual stimuli that we can and the networks that we have built |
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| 12:30 | to process these six frequencies. And is surrounding us, what frequencies are |
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| 12:35 | us? The classical music frequencies or techno music frequencies, those are all |
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| 12:40 | the different external stimuli that we're always trained by. So we have these |
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| 12:46 | rhythms And so Ja tried to explain and place it within certain mathematical |
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| 12:51 | we obviously have very slow rhythms, diurnal rhythms or circadian rhythms. But |
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| 12:57 | we have these ultra fast rhythms of to 600 Hertz, 600 cycles per |
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| 13:04 | . And that's because we have cells can generate very fast activity. Some |
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| 13:10 | can generate very fast firing of action and allowing for the networks of cells |
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| 13:17 | synchronize in a very, very fast . But nonetheless, there is a |
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| 13:22 | way. And one explanation is that you place the frequencies, dominant frequencies |
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| 13:29 | the L N Hertz scale here that will be separated by one hall integer |
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| 13:35 | the scale. But these are different . And as I said, they |
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| 13:41 | different behavioral states and different different states alertness, eyes closed, our eyes |
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| 13:49 | . And uh this is another representation E E G recordings and the description |
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| 13:56 | intracranial recordings just like uh with recordings normal activity E E G is actually |
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| 14:04 | to diagnose people with seizures to determine seizures are coming from, to study |
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| 14:09 | dynamics and diagnose people with up to have epilepsy. Because epilepsy uh uh |
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| 14:17 | you have repeated seizures, it's not just to have one seizure. And |
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| 14:21 | this case, we can see that can be generalized. So they may |
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| 14:25 | in one or few electrodes involving one hemisphere in certain parts of the brain |
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| 14:32 | that hemisphere and eventually get generalized and . Generalized seizures will be loss of |
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| 14:38 | . And this information of normal synchronized of normal oscillations can spread through the |
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| 14:46 | brain networks and take over the whole of the brain. And when you |
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| 14:52 | seizures activities uncontrolled, and it can likened to short circuiting of electrical activity |
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| 15:00 | can repeated seizures can lead to neural . It can re lead to neuronal |
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| 15:07 | death. And it is a neurodegenerative where hippocampus and the temporal lobe are |
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| 15:13 | susceptible on our common sides for especially temporal lobe and hippocampus is very |
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| 15:20 | to damage by seizures. And uh susceptible to damage by seizures in |
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| 15:26 | And earlier, we also saw it to damage by uh in other um |
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| 15:31 | conditions including schizophrenia. So we know these rhythms are generated by different cell |
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| 15:39 | that are interconnected in a specific And in order to pick up activity |
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| 15:44 | the level of these electrodes which are on the other side of the |
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| 15:49 | you need to have activity that is from these optical uh uh dendrites uh |
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| 15:57 | the parameter cells in the Neocortex, where the activity is coming from. |
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| 16:02 | in order for E E G to a distinguishable dominant pattern of frequency and |
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| 16:08 | , the activity in these cells to synchronized. So if each one of |
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| 16:11 | cells is receiving a different input, different frequency, different time, the |
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| 16:16 | E G is not going to show meaningful persistent rhythm or fluctuation oscillation here |
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| 16:23 | the sum E G recording. But these cells will receive one common input |
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| 16:29 | will synchronize thousands of cells underneath these E G electrodes, then the sum |
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| 16:35 | G recording at the surface of the scan would show these uh synchronized |
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| 16:43 | So E E G recordings represent information these optical um the dendrites and uh |
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| 16:51 | cortical uh regions, superficial regions, cortical regions represent synchronized activity of |
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| 17:00 | Uh It gets synchronized with a common and with the help as well, |
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| 17:05 | junctions. If you recall, we talked about how gap junctions or electrical |
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| 17:09 | are important in synchronizing neuronal activity. we addressed that there are certain cellular |
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| 17:17 | physiological uh abnormalities that are found in side that generate seizures, those are |
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| 17:25 | Intal spikes and the bursting activity when depolarize and produce a number of action |
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| 17:32 | . On top of this deep polarization can be recorded intracellular as well as |
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| 17:38 | , which means it represents a normal activity in the network. And that |
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| 17:43 | is repetitive. It is often formed a common input but also intrinsic number |
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| 17:49 | properties. And here what I would to take away is that APA and |
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| 17:56 | A and glutamate are typically elevated. there's too much excitation and seizures and |
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| 18:04 | or inhibition is typically decreased in seizures epilepsy. So, there's an imbalance |
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| 18:10 | excitation and and typically there is a of inhibition and a lot of anti |
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| 18:17 | drugs will try to boost inhibition by Gaba receptor. We talked about gabba |
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| 18:24 | receptor stimulation will raise inhibition and by inhibition. You are hoping to control |
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| 18:31 | abnorm normal excitation that glutamate. Too glutamate can lead to glutamate exci |
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| 18:39 | Too much glutamate can lead to too calcium signaling can lead to calcium excited |
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| 18:45 | leading to neuronal cell death. Both them causing toxic events in the neuronal |
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| 18:51 | death. Epilepsy is found in 1% the population. 1 to 2% actually |
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| 18:59 | from epilepsy in some regions. It's to 2% as this U shaped curve |
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| 19:05 | the early developmental epilepsies are typically They have a genetic component and the |
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| 19:12 | uh age epilepsy is 55 over where is again, an increased incidence of |
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| 19:18 | occurrences in elder population that typically acquired and they can be acquired as a |
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| 19:26 | of conditions such as stroke, increased inflammation, infections, Alzheimer's |
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| 19:33 | So there are many different causes of , tumors, trauma, traumatic brain |
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| 19:38 | , lesions, genetic component or developmental particular disorders in epilepsy, metabolic |
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| 19:46 | infections, viral and bacterial vascular dysfunctions stroke environmental such as chemicals in the |
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| 19:55 | . And in many cases, the of epilepsy are not known. So |
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| 20:00 | don't know it's called sporadic or There's no way to pinpoint it. |
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| 20:05 | when we started discussing genetic causes of , we looked at what are called |
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| 20:12 | or pathologies in channels. So there genes that code for channels. And |
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| 20:16 | particular case, in greater detail, discuss voltage gated sodium channels. Although |
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| 20:22 | said that they can be mutations to gated sodium channels can be mutations to |
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| 20:27 | channels, can be mutations to calcium , can be mutations to gamma receptor |
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| 20:34 | channels can be mutations to glutamate receptor that can all lead to epilepsy. |
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| 20:43 | mutations to sodium channels are not unique that these genetic mutations can lead to |
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| 20:49 | . But what we discussed in this case, I reminded you of the |
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| 20:53 | of the voltage gated sodium channels is four subunits, six transmembrane segments. |
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| 20:58 | I said everywhere where you see a and the amino acid sequence on this |
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| 21:04 | that is marked in green. There's possibility that these mutations result in generalized |
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| 21:12 | . Generalized all of the brain regions synchronized and involved with febrile seizures, |
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| 21:19 | epilepsies, loss of consciousness, febrile , viral seizures, plus hyperthermia in |
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| 21:25 | seizures and hyperthermia, hypothermic hypersensitivity to where body temperature can arise by one |
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| 21:34 | two C. And a person is likely to go into a seizure everywhere |
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| 21:40 | you see these red dots is a that can lead to SME I which |
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| 21:46 | severe myronic epilepsy of infancy or a . So even on this one single |
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| 21:53 | gated sodium channel, just addressing G, Efs and SME I, |
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| 21:59 | can see a multitude of mutations that take place along the same protein channel |
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| 22:05 | can lead to detrimental. These are severe forms of epilepsy. Again referred |
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| 22:11 | as channelopathy because impaired gene will have improper coding sequence for the amino acids |
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| 22:19 | will lead to an improper function of channels, which can lead to abnormal |
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| 22:25 | in the brain seizure activity, repeated activity and the consequences that can lead |
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| 22:32 | neuro degeneration eventually. And so when talked about severe myronic epilepsy of |
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| 22:38 | it's a severe disorder, over 30% these Children cannot be treated by available |
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| 22:44 | medications. Oh, 20% or so from what is called sudden unexpected |
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| 22:50 | And epilepsy typically happens at night. that's why these disorders are referred to |
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| 22:55 | catastrophic forms of epilepsy, catastrophic for and they're developing a catastrophic with parents |
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| 23:03 | they lose their loved ones during uh during night, especially putting so much |
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| 23:09 | in keeping them alive and hopefully seizure . And many of these Children that |
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| 23:15 | um their pictures were under the Driving Foundation or unfortunately passed from Suad. |
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| 23:23 | And this is where we started talking uh alternative. So we talked about |
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| 23:28 | a lot of drugs for epilepsy and will control voltage gated sodium channels. |
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| 23:34 | talk about how gaba receptors will be to raise inhibition. But then when |
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| 23:41 | Children don't have common pharmaceutical medications that available for apple, two seizures, |
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| 23:47 | seek alternatives. And Dr Syndrome, figgy who had Dr syndrome were at |
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| 23:54 | forefront of generating this debate of natural based medications. And right now, |
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| 24:00 | a treatment CBD, the dial 10% that is that is approved medication for |
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| 24:09 | and seizures and drive syndrome. And discussed that in the uh subsequent |
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| 24:14 | but there is also potential uh anti properties in this cannabis plant and other |
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| 24:22 | . Apart from CBD, such as big, it was a combination of |
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| 24:27 | and T H C. And since , you learned of any uh many |
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| 24:31 | molecules that are present in cannabis, turps that have their own biological effects |
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| 24:38 | could have in certain conditions, uh uh medicinal effects. And so we |
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| 24:46 | the discussion here and with this, will end this review also of brain |
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| 24:55 | and epilepsy and check if there's any in the chat. Have you ever |
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| 25:01 | with the brain surgery? Random Um It's a good question. I |
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| 25:08 | I could say that I helped with brain surgery. I observed brain |
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| 25:13 | but one of my mentors who was very talented neurophysiologist, he did help |
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| 25:19 | these recordings, intracranial recordings or So, uh me as a |
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| 25:25 | I haven't really practiced it but observed in the operating room. I have |
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| 25:31 | that have practiced as phd S together and in helping with these ultra operating |
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| 25:40 | data waste calls because more information is the eye. Well, it's just |
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| 25:47 | , it's a different input. So simulation, different frequencies now external |
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| 25:53 | right? Because with eyes closed, no external entrainment, visual entrainment with |
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| 25:58 | open, there is a whole different depending on what room you are, |
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| 26:02 | colors you're receiving. So uh definitely necessarily more but different information I would |
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| 26:12 | and the different frequencies, what kind metabolic dysfunctions are associated with epilepsy. |
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| 26:20 | slower. Uh For example, if talk about some of the metabolic |
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| 26:26 | it could be the systemic dysfunctions in body. Uh or it could be |
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| 26:35 | in mitochondrial function in the brain. So production of E T P or |
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| 26:44 | metabolizing chemicals, neurotransmitters. So it be a glial dysfunction on transport and |
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| 26:52 | of glutamate. For example, let's , or underproduction of A T P |
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| 27:04 | maybe even particular damage of A T production on certain subtypes of cells, |
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| 27:11 | versus neurons or exciter versus inhibitory OK. All right. Thank you |
|
| 27:21 | much for being here. Thank you much for coming, especially those of |
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| 27:27 | coming in person throughout the semester. here online. I hope that the |
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| 27:31 | that you've learned can be applied in future. And if you will be |
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| 27:36 | any health care related professionals or taking exams that you will lose your |
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| 27:40 | use this knowledge to your advantage. , thank you very much for being |
|
| 27:47 | . This concludes our final meeting and session. Please prepare for your final |
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| 27:52 | if you get a chance and you an email for evaluating this course. |
|
| 27:56 | really appreciate uh all of your I'm very happy to hear any positive |
|
| 28:04 | . Of course, happy to hear uh constructive uh suggestions and criticisms of |
|
| 28:10 | to improve this course. This course have all of the materials updated this |
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| 28:15 | for the cameras actually. But I you for being here with me. |
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| 28:20 | study Hard Ace. This exam do well and have a great rest of |
|
| 28:29 | semester and good luck on your Take |
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