| 00:04 | So welcome back, this is neuroscience three. Today we covered history of |
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| 00:11 | . Last lecture we left a few from that particular lecture to discuss for |
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| 00:18 | . And we're gonna start talking about and glia some of this information is |
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| 00:22 | to be some of the basic cell review and some aspects and some of |
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| 00:28 | is going to be new information or that is unique to neurons and glia |
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| 00:34 | particular. As a reminder, you find all of your lectures. So |
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| 00:42 | of your lecture one and lecture to . H. Video points. You |
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| 00:49 | scroll through them and a little bit there will be transcription that is going |
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| 00:56 | be available. You can jump through lecture if you miss certain parts of |
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| 01:05 | . All of the information against us the syllabus on the blackboard. This |
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| 01:11 | where you will find all of the that we've discussed uh for the history |
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| 01:18 | we covered. You don't have to the dates of these individuals the times |
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| 01:26 | which they lived would have a general and understanding of the accomplishments and their |
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| 01:33 | to the development of the modern day . Most significant things that they discovered |
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| 01:41 | postulated or theorized about that led us forming our modern day view of the |
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| 01:50 | nervous system and neuronal communication. And spent quite a bit of time talking |
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| 01:57 | loss of function on in general localization specific function in the brain. We |
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| 02:04 | about how language areas, there are language areas and we discussed Broca's area |
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| 02:12 | for expression of language and Monica's area for reception of language. We also |
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| 02:20 | about Phineas gauge uh as an example a patient that not only recovered from |
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| 02:27 | penetrative traumatic brain injury, but also person that showed us that there are |
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| 02:34 | of the brain that are not responsible hearing or vision or speech or motor |
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| 02:42 | but rather responsible for emotions for control behavior, memories, for cognitive |
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| 02:52 | And that was the case with the gauge. We discussed how different environments |
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| 02:59 | the animals on the outside as as organs and shapes of their various organs |
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| 03:07 | to the local environment for survival and procreation. So uh these changes are |
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| 03:14 | reflected internally inside the brain circuits and the brain maps that represent different parts |
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| 03:23 | the brain and def parts of the that are represented in different locations in |
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| 03:30 | brain. And certain animals, like will spend a lot of time. |
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| 03:34 | their olfactory system. So their olfactory are large. They will use whiskers |
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| 03:39 | some matter sensory sensations. So they a whisker pad map. Animals like |
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| 03:45 | or non human primates, monkeys would by far more superior systems developed for |
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| 03:52 | somatic sensory uh functions such as hand for example, rather than whisker functions |
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| 04:00 | humans. You will have a very hand map but you wouldn't have a |
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| 04:04 | map because we don't have a whisker and of course we have the visual |
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| 04:09 | that's very sophisticated that we use a of brain space to analyze process visual |
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| 04:16 | and also recreated. We talked about in the 19th century microscopes became powerful |
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| 04:23 | to resolve single cell but we needed . So there was Golgi stain that |
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| 04:28 | used by ramon alcohol to reveal individual and Charles. Carrington coined the term |
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| 04:34 | synaptic of synapse. Now we talked particular theory versus neuron doctrine and also |
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| 04:41 | uh how far ahead of his Ramon alcohol was in proposing that the |
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| 04:49 | between neurons and neuronal networks are Uh And we talked about another type |
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| 04:57 | stain which is missile stain which is to Golgi stain where only a fraction |
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| 05:02 | neurons picks up that stain with neurons pick up the Golgi stain will reveal |
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| 05:07 | morphology, precise arrangements of their process done right so mamma's axonal processes. |
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| 05:15 | stain will not do that, but stain will stay in all of the |
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| 05:19 | and all of the glia. It help you distinguish between neurons and |
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| 05:24 | It's not the best way to do without any additional histological or staining markers |
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| 05:30 | do so. But it's great for and allowing us to understand the style |
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| 05:37 | of different regions of the brain. this method the missile stain was used |
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| 05:42 | dr comedian broad mond that describe different that are different functional areas are determined |
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| 05:49 | observing variations in the structure packing destined layering and such in the cells that |
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| 05:56 | these different functional areas. Um electron was needed in order for us to |
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| 06:03 | resolving and looking into individual synapses which 20 nm of space and looking into |
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| 06:10 | , discrete neuronal units. Then we about how most of the contacts and |
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| 06:15 | will take place on dendrites and in on these small protrusions that are known |
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| 06:21 | dendritic spines. Most of the synapse go to be formed there. And |
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| 06:26 | these elements are the most plastic elements means that during early development were actually |
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| 06:33 | with a lot more connections in our . A lot of things are interconnected |
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| 06:37 | specifically and there are more synopses and we use certain parts of the brain |
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| 06:44 | exposed to certain uh sensory and environmental and patterns also we carry certain genetic |
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| 06:55 | . All of that results in us certain connections that are stronger. And |
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| 06:59 | means pruning a lot of these dendritic and allowing for certain other dendritic spines |
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| 07:05 | strengthen and others to weekend. So a part of the learning process and |
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| 07:10 | . You're forming new synapses, potentially growing new dendritic spines and have new |
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| 07:17 | options trying to contact those spines if are forgetting things are potentially weakening existing |
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| 07:24 | spines or maybe you're even eliminating the experience because there's a finite amount of |
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| 07:30 | that we carry and there's importance to types of information may be given at |
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| 07:35 | time of the year semester or a or school undergraduate versus graduate versus something |
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| 07:43 | , you know. So these are plastic elements and good experience and their |
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| 07:49 | . Normal development is very important for their own collectivity processing. We ended |
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| 07:56 | stopping at this slide here and what slide shows is that modern days we |
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| 08:05 | actually visualize neurons without staining and in case we can use infrared microscopy |
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| 08:12 | And so this is a setup where have a microscope and underneath that microscope |
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| 08:18 | that lens you have a slice, a brain slice that brain slices exposed |
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| 08:24 | artificial cerebrospinal fluid. So it's being in the same Aquarius solution or a |
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| 08:32 | environment that it would have in the itself in the super spinal fluid and |
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| 08:38 | is being oxygenated. So the brain that there's still lungs that are supplying |
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| 08:44 | blood vessels that are supplying the oxygen these neurons in the brain. We |
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| 08:49 | identify individual neurons, individual psalms of neurons using infrared microscopy without any |
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| 08:57 | And to do that, you need infrared camera or IR camera which through |
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| 09:02 | set of mirrors points to information obtained the slides, points of information from |
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| 09:08 | back into the infrared camera where you this image displayed on the tv monitor |
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| 09:16 | that allows us not only to visualize south visualize layers and networks but also |
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| 09:25 | us to perform neural physiological or electro recordings from these neurons whereby a small |
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| 09:34 | electrode gets inserted or gets attached onto cells. And that micro electrode which |
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| 09:41 | typically made from more silicate glass of electorate will typically contain an internal electorate |
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| 09:51 | to match the internal Aquarius environment inside cell. Which is different from what |
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| 09:58 | found in the extra cellular environment outside cell. And using these bar silicon |
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| 10:05 | electors, we can record activity from neurons. We can record activity from |
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| 10:11 | neurons at the same time or from networks of neurons be it and um |
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| 10:16 | vitro which is in the slice preparation in blocks or in viva, which |
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| 10:24 | harder to do because we actually in case have to visualize the electorate. |
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| 10:28 | we can potentially do these recordings also vivo which is in the whole brain |
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| 10:33 | whole animal brain. So this is microscopy and this is a setup that |
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| 10:43 | fairly sophisticated but it uses light So we don't get the electron microscopy |
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| 10:51 | here but we get here very good . This is about 10 micrometers across |
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| 10:59 | diameter. He's done right for about micro meter diameter and the tip of |
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| 11:06 | micro lectures is a little bit less a micro meter, typically in diameter |
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| 11:10 | well depending on the types of recordings you're doing with these cells just to |
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| 11:15 | the scales in the perspective. So in the lab and modern experimental neuroscience |
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| 11:23 | have the ability to visualize individual synapses even visualize organizing these synapses. We |
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| 11:30 | about how you can see individual vesicles mitochondria using electron microscopy, not just |
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| 11:36 | synapse. We can visualize the dendritic and dendritic shafts that have all of |
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| 11:44 | different arrangements with the experience. The precise morphology, detailed morphology of the |
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| 11:51 | , the dendrite, the soma solo changes everything. And we can study |
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| 11:56 | in experimental neuroscience from a single the single cell level to a small |
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| 12:06 | level to a larger network level. we can go experimentally from micro studying |
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| 12:15 | of single molecule where we can study only the physiology but also potentially image |
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| 12:24 | a single molecule interacts with neuronal network what does a single molecule do. |
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| 12:30 | we can do that. We can go from micros from this microscopic scale |
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| 12:36 | macroscopic scale which means that we can information from larger neuronal networks that don't |
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| 12:45 | necessarily microscope but can be viewed nearly the naked eye or uh just a |
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| 12:54 | of ex uh magnification. This is neuroscience when you step into the clinical |
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| 13:05 | and when you are talking about what happening in neurology which is a branch |
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| 13:13 | of neuroscience and the clinical sciences, and other branch neuropsychiatry um all of |
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| 13:22 | information you're learning in this course will contribute to understanding many different disciplines but |
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| 13:31 | when we're talking about studying activity of brain clinically, we're talking about noninvasive |
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| 13:41 | of the brain. This is uh done in slices where advancing micro electorates |
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| 13:52 | the south and if somebody has a dysfunction, if they have tumor growth |
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| 14:02 | the brain, we cannot do this the clinical setting. So typically you |
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| 14:08 | imaging, functional imaging or in general of the brain that gets done. |
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| 14:16 | , for example, positron emission tomography a type of functional imaging. What |
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| 14:24 | means is that it is imaging the of neuronal networks and the difference between |
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| 14:32 | experimental techniques versus the clinical techniques as experimental level. You can resolve single |
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| 14:40 | single synapse in the clinical setting and positron or pet scan images. You're |
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| 14:48 | looking at populations and networks of neurons regions of the brain that may be |
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| 14:56 | . Of course, pet scan is only used for imaging activity, it |
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| 15:00 | be used for detecting abnormal growth. can be used for detecting inflammation and |
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| 15:08 | cell growth, not just in the , but throughout the body. But |
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| 15:12 | our purposes. It's really interesting for to know, we can study electrical |
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| 15:17 | and image single cell single neurons. can we do in the clinics and |
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| 15:23 | this illustrates. For example, is scans can also be used to image |
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| 15:28 | parts of the brain are activated as individual is performing different tasks. So |
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| 15:34 | this image shows on the top Left a is the occipital lobe in the |
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| 15:42 | of the brain broad months area 17 primary visual cortex? Area v. |
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| 15:48 | is activated when the person's task is look at the words. So the |
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| 15:55 | is actually under the scam. It's an easy procedure because you have to |
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| 16:05 | radio active active label injections done into blood. So you become radioactive for |
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| 16:15 | a couple of hours that allows for pet uh demographer to detect the changes |
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| 16:23 | neurons that are active. They're going demand oxygen, they're going to demand |
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| 16:30 | . The active neurons and there's going be the difference between the neurons that |
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| 16:34 | active and the ones that are And we can image those differences. |
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| 16:38 | this is the map on the top for looking at the words next to |
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| 16:43 | is the map we're listening to the . And you will see that now |
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| 16:49 | the person is listening to the it's their temporal lobe that is |
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| 16:56 | And also the area that you know Nicholas area when you're speaking words, |
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| 17:06 | what happens. You are now looking the frontal area that would overlap with |
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| 17:14 | area. And also looking at the major motor cortex which would be responsible |
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| 17:24 | generating the speaking pattern, the motor for speaking the words. And then |
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| 17:30 | ask the person to think about the and you're doing these scans as you're |
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| 17:38 | the person to do a different Look at the words, uh listen |
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| 17:43 | the words, speak the words think the words and you can see that |
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| 17:48 | parts of the brain get activated in these different tasks. And when the |
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| 17:55 | is thinking about the words, the that were sort of a primary sense |
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| 18:01 | information processing areas like the primary visual that's no longer activated when you're thinking |
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| 18:07 | the words. Because your primary task not to look at something. A |
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| 18:12 | task is to think about what that means. Um so you can see |
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| 18:20 | what we call brain activity maps or maps that represent how different regions of |
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| 18:28 | brain can be activated as a person performing different tasks, listening, |
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| 18:33 | thinking of wars and such. And can clearly show that the thinking map |
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| 18:39 | very different from any one of these maps and that any one of these |
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| 18:44 | maps is clearly spatially temporally in activity these hot spots or maps of red |
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| 18:51 | are clearly very different. And that's kind of a level of understanding for |
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| 18:57 | the brain activity that you would have the clinical setting and what we strive |
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| 19:05 | . We strive to blend this experimental in this century. From single cell |
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| 19:14 | all the way to noninvasive brain imaging nobody needs to have their skull open |
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| 19:20 | order to have enough memory or pet done on their on their on their |
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| 19:26 | . This is not invasive apart from radioactive legal injection. This is not |
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| 19:31 | . So if we can solve this we're imaging the overall activity in this |
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| 19:38 | maps while we also at the same if we could know what's happening at |
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| 19:42 | level of single synapse a single neuron . And basically this is sort of |
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| 19:47 | holy grail For understanding neuronal function non and imaging neuronal function on them basically |
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| 19:56 | having the ability to do it from Microsoft Microscopic Level two all the way |
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| 20:02 | macro. So these imaging techniques such Pat, there's also F. |
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| 20:11 | R. I. Or functional magnetic imaging. We'll talk about this |
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| 20:15 | And of course they show the brain action to confirm that certain functions are |
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| 20:20 | out in specific areas of the Each function is observed by more than |
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| 20:25 | neural pathway. When one neural pathways , others may compensate. Making localization |
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| 20:34 | specific brain function to see. Because you lose one of the fingers on |
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| 20:38 | hand there's no need for a map that sing finger anymore in this amount |
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| 20:44 | sensory cortex or in your motor And so the adjacent cortex is going |
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| 20:49 | be plastic and it's going to take the area cortical area that is not |
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| 20:54 | used also. Uh if you think parallel processing or parallel pathways we have |
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| 21:01 | years. So if you lose coke , if you lose hearing on one |
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| 21:06 | you still have hearing another two Then there's pathways from two eyes still |
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| 21:12 | into one that crosses over the one stays on the same side to cross |
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| 21:18 | . So there's a lot of redundancy parallel processing. Yeah. Uh It |
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| 21:30 | take days typically two to start We're talking about dates. Yeah but |
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| 21:40 | depends on the time along the development the animal. Early in the |
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| 21:47 | You'll see examples, you can change anatomy by depriving an animal of a |
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| 21:53 | input. You can restructure the But if that deprivation was short lived |
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| 21:58 | if it happens during the high period plasticity, that animal can rebuild its |
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| 22:04 | or partially rebuild the circuits. But that deprivation is longer time and if |
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| 22:10 | deprivation falls outside the period of plasticity early development then that regrowth may take |
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| 22:19 | and may not be as robust, there's still evidence in adults that repeating |
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| 22:27 | certain task, for example with one for days will enlarge the brain map |
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| 22:34 | that finger at the expense of the four fingers. So it does not |
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| 22:40 | have to do with deprivation or loss function, it can be an increased |
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| 22:45 | of one finger and now more brain needs to be dedicated to that one |
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| 22:50 | . That's why I always make an with cell phones that we really are |
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| 22:55 | a lot of our brain matter. , a lot of our brain space |
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| 23:00 | these two fingers and this kind of swipe and tap, You know? |
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| 23:06 | that's that that's quite different. Although still type, you know and uh |
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| 23:10 | and still a lot of them still 10 fingers for typing, but that's |
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| 23:16 | always the case also. Um some individuals use two or three fingers and |
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| 23:23 | that's that's where the focus is. then you start losing ability sometimes of |
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| 23:29 | motor tasks with the parts of the you don't use as well because your |
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| 23:34 | has shifted its attention to the parts the body or the fingers that you |
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| 23:38 | use. So. Good question, also know that emotions are localized, |
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| 23:45 | temporal lobe epilepsy and micro stimulation of temporal lobe epilepsy uh is a abnormal |
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| 23:53 | that happens in the temporal lobe. these patients when they're having seizures, |
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| 23:58 | seizures, they are having very severe episodes and it can go from happiness |
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| 24:07 | rage to absolute uh destructive rage. And so you can also evoke emotions |
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| 24:18 | micro stimulation. So there's certain parts the brain you can stimulate like |
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| 24:24 | for example, parts of the limbic and you will evoke different emotions. |
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| 24:29 | if you stimulate certain parts of the , maybe you will evoke an emotion |
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| 24:33 | fear. So there's different emotions that be evoked by adjacent to different parts |
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| 24:39 | the brain group throughout the brain structure consists of multiple processes that occur in |
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| 24:49 | areas of the brain imaging studies reveal different processes called elementary operations. So |
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| 24:57 | towards a sort of elementary operation, think thinking of words is maybe a |
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| 25:03 | complex operation, processing is both serial parallel, which means that parallel |
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| 25:10 | Because we have two eyes, like said, we have redundant pathways coming |
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| 25:15 | those two eyes too. And it's serial. Because the complexity and processing |
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| 25:21 | we acquire the sensor information light enters the retina. Retina doesn't see the |
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| 25:28 | thing. It doesn't even can recreate whole primal sketch of of the of |
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| 25:36 | outside world of the outside image. have to pass that information from retina |
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| 25:42 | the thalamus into the primary visual And that's when you're gonna have a |
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| 25:47 | picture of the outside world. So each station from the retina and to |
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| 25:53 | thalamus and the cortex, the processing more and more complex and gets more |
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| 25:59 | more enriched to the neuronal connectivity. that's why it's cereal too is happening |
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| 26:05 | parallel and in serious where it's hierarchically complex as that sensor information enters from |
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| 26:11 | periphery into the highest cognitive organs and of the brain. Even the simplest |
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| 26:19 | activity requires coordination of processes in multiple of the brain. So we like |
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| 26:25 | said, don't just see with retina retina has to communicate information through the |
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| 26:31 | system which will contain multiple areas of brain that need to be activated in |
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| 26:36 | fashion. Uh such processes appears introspectively . So we don't spend much time |
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| 26:43 | about how we're thinking and what's happening our brains is we're thinking or as |
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| 26:49 | looking at at something or listening to . So it's were we grew up |
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| 26:55 | it, so to speak. You , it's it's introspective or seamless. |
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| 27:01 | now this is interesting because here is image that says no virtual reality and |
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| 27:07 | is virtual reality and it shows the maps that I've introduced to you when |
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| 27:12 | talked about the pet scans. And so you can see that in |
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| 27:16 | case the individual has no virtual And I think it was linked to |
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| 27:21 | game. It was here in the , uh Contemporary Arts Center here in |
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| 27:30 | , which by the way, is and small. It's in the museum |
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| 27:34 | and you don't have to but you donate $5 to go see the exhibits |
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| 27:40 | exhibits are awesome. There, I also in the Museum of Fine Arts |
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| 27:46 | one thursday of the month where it's to go to the museum. So |
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| 27:50 | a great place to go walk around in bad weather or have a date |
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| 27:54 | walk free through the museum. And day I came in into the Contemporary |
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| 28:00 | Center and there was this exhibit about virtual reality of the snowman and you |
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| 28:06 | be playing in front of the computer . Or you could immerse yourself in |
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| 28:10 | reality to play the game. The was pretty cool. You throw the |
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| 28:14 | at the the snowman over there and just explode if you if you got |
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| 28:18 | so they fall apart and they did of the brain. So they had |
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| 28:24 | person perform this game with no virtual . Virtual reality. You can see |
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| 28:29 | the map is quite different between the will say wow this is a virtual |
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| 28:35 | . Make the map smaller maybe more because it's more realistic and maybe that |
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| 28:40 | be the argument made. But in you can see that having two dimensions |
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| 28:46 | flat screen versus the virtual environment changes brain maps. And so where we're |
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| 28:53 | is we're going into the virtual world taking tests online. We're going into |
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| 29:01 | World or Matter is trying to take there through participating in virtual reality. |
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| 29:09 | data coming out that kids that play games that actually have a really good |
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| 29:15 | of three dimensions and navigation through space directions. Especially if they play like |
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| 29:21 | where they have to chase or move the buildings or towns and stuff like |
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| 29:27 | . So this is all shaping our brains too being a part of these |
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| 29:33 | processes that come out every day. specialists and nervous system already mentioned. |
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| 29:41 | neurologist psychiatrist. Looting personality disorders, . A neuropathologist and all the top |
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| 29:49 | have to have an M. To be a neurosurgeon psychiatrist, |
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| 29:53 | neuropathologist can be an M. Or PhD. And so there's different |
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| 30:00 | to get to where you may want work eventually. If your ph de |
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| 30:05 | wants to work in a hospital, neuropathology is the way to go. |
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| 30:09 | your PhD that wants to work in university uh then maybe being a neurophysiologist |
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| 30:16 | you're a pharmacologist and your anonymous molecular computational neuroscientist, all of these different |
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| 30:23 | implants and the levels already that I've in discussing the molecular to single cell |
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| 30:32 | networks and systems to behavior, What animals sees or how animal we |
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| 30:40 | we interpret the world, the our behavior, our emotional and our |
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| 30:44 | output and cognitive levels to to cognitive . And there's more information here. |
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| 30:54 | think that a lot of knowledge from can there's neuroscience nurse, there's also |
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| 31:00 | rehabilitation. Anything to do with nerve . A lot of the physical nerve |
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| 31:07 | or even your or neurological in Europa and recovery and rehabilitation and also very |
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| 31:17 | sciences that are related to understanding audiology will actually study the auditory |
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| 31:24 | And so you'll have the basis of auditory system if you decide to go |
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| 31:29 | to audiology field, pharmacy pharmaceuticals. of these things are related to neuroscience |
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| 31:39 | . So this concludes our second lecture and now we enter into the third |
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| 31:51 | material which is today is the third and into the pork lecture material. |
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| 31:56 | when we look at the brain and looked at those images of the |
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| 32:00 | 90% of the brain is actually And of the brain is neurons. So |
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| 32:10 | are like chips in a chocolate chip . And there's basically way more of |
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| 32:16 | space and way more of the cellular that belongs to glia which is glia |
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| 32:24 | glue is the dough of the chocolate cookie and one cannot exist without |
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| 32:30 | It's not like you can have a cookie with sugar without chocolate chips that |
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| 32:35 | of happen in the brain, you to have the dough and and the |
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| 32:40 | in order for the brain to function . So chocolate chips are they so |
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| 32:49 | you can have the whole cookie and it too the game and the brain |
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| 32:55 | mainly in the stain. And this to our theme that in order for |
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| 33:01 | to understand the structure of individual neurons neuronal networks or connectivity between different parts |
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| 33:07 | the brain. We need different And there's also a famous saying that |
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| 33:14 | rain in spain is mostly in the . So the gain in the brain |
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| 33:19 | mainly in spain. Uh And once learn more about neuronal anatomy, we |
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| 33:27 | that there are certain features of neurons are just like any other cells to |
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| 33:33 | a nucleus, they have gold conflicts smooth into plasma, particularly rough. |
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| 33:42 | the plasmid particular studied ribosomes, it's surrounded by cyber plastic membrane, |
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| 33:51 | membrane. And so what are the that are quite unique or different from |
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| 33:58 | cells that you may have learned Well, neurons have dead, |
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| 34:03 | So they have these dendritic spines that talked about and that's where the sides |
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| 34:07 | the contacts or whether you're a steak uh neurons also have axons and those |
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| 34:15 | are myelin ated or they're insulated because electrical activity of the action potentials that |
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| 34:21 | generated in the axon hillock will get through the axon to the external |
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| 34:29 | So you'll say, okay, well cells also produce action potentials. Muscle |
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| 34:34 | produce action potentials excitable numbers, neuron , muscular tissues are excitable, Just |
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| 34:44 | discovered. So what's the difference? , neurons are very fast and their |
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| 34:51 | potentials are very fast. Only one two milliseconds in duration, cardiac action |
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| 34:57 | . So skeletal muscle action potentials for longer in duration. So they're the |
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| 35:03 | . Um And that's a unique feature you have to endurance. The other |
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| 35:08 | that is interesting is those molecules that ribosome complexes of mitochondria which is the |
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| 35:17 | of a teepee are necessary for post modifications of the proteins and you will |
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| 35:25 | a lot of these complexes color of complexes. And mitochondria with energy |
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| 35:32 | A teepee and then it expires which you expand somewhat biochemically independence uh to |
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| 35:41 | certain degree. Maybe another unique feature that these neurons can have tens of |
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| 35:50 | of synapses, tens of thousands of spines and tens of thousands. And |
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| 35:57 | even hundreds of thousands of synapses formed a single neuron. And they're fast |
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| 36:03 | they have to process these hundreds of of inputs. Some of them are |
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| 36:08 | for some of them inhibitory and integrate of that information within milliseconds and then |
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| 36:14 | an action potential. That's very 1 to 2 milliseconds in duration. |
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| 36:20 | they're they're fast computational units process information a fast manner. You know. |
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| 36:26 | our axons communicating between neurons and then damn rides are communicating to the muscular |
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| 36:34 | . No not exactly. Axons are mostly onto the soma or onto the |
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| 36:43 | . And that's what axons are going cause the release of the neurotransmitters. |
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| 36:47 | once this action potential gets generated here will conduct terminal. This is coming |
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| 36:56 | another cell. You can see the and their transmitter will be to excite |
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| 37:00 | inhibit the cell by binding the chemical its past synaptic receptors on the cell |
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| 37:07 | . So axons can target some of can target them rights and axons can |
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| 37:12 | target other accents sometimes can talk to drives right now we're focused on the |
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| 37:19 | . N. S. So nothing here goes directly into the muscles. |
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| 37:24 | we will talk about neuro muscular junction we talk about these divisions of the |
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| 37:29 | nerve, the sensory dorsal and the ventral. And we'll talk about how |
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| 37:35 | neuron signal to the muscles. But now this is between between den rides |
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| 37:45 | like antennas and they're good exp ein like little antennas and points of contact |
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| 37:50 | neurons. They get all of these that go to then drives the axles |
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| 37:56 | selma's and the soma will get to in a couple of slides with Selma |
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| 38:02 | the integrated portion of the cell that integrate the positive and the negative and |
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| 38:09 | butts. And if it is excited then the axle of the initial |
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| 38:15 | If it's excited will produce an action . But if inhibition wins because there's |
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| 38:20 | to be hundreds or thousands inputs coming the south and the addition overrules, |
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| 38:27 | the cell will stay quiet. And staying quiet it's not going to communicate |
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| 38:32 | information to an adjacent network on adjacent may be connected to. So there's |
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| 38:39 | good questions. I think you'll get of that as we move along with |
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| 38:43 | material. Um It's going to be clear what I've just mentioned to |
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| 38:51 | This is basic stuff. We have transcription, you have RNA. RNA |
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| 38:58 | export from the nucleus. So RNA spliced into messenger RNA and then you |
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| 39:07 | the molecules from the proteins, basic . We have splice variants. So |
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| 39:15 | these uh in tron and Exxon zones spliced basically into the code. There |
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| 39:27 | be some variations during the splicing And in a way we're kind of |
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| 39:31 | splice variants of each other a little because we may have slightly different genetic |
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| 39:37 | and expression of that code and that's but also splice variants. This information |
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| 39:45 | not get spliced properly from the The messenger RNA can lead to a |
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| 39:51 | , the cellular dysfunction or neurological neuronal . So it can lead to pathology |
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| 39:56 | well. So very basic stuff. al's rough and the plasma critical um |
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| 40:03 | has ribosomes and poly ribosomes. And messenger RNA A exits out through the |
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| 40:15 | transporters and the nuclear pores. It's to destinations, there's either side of |
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| 40:22 | Mick, free floating protein or membrane proteins. And we'll talk about a |
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| 40:28 | about membrane associated proteins in this Because we're gonna talk about ion |
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| 40:35 | We're gonna talk about g protein coupled and these are all membrane associated or |
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| 40:42 | some instances trans membrane proteins and structures we will be discussing. So the |
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| 40:51 | and the plasma particular will participate in faith where destination of faith of these |
|
| 41:00 | . The other thing that we have good way to look at what is |
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| 41:07 | in the brain is by analyzing the and we live in the post genomic |
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| 41:15 | . And what this diagram shows is we actually can have these micro race |
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| 41:22 | synthetic D. N. A. we know the sequences that code okay |
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| 41:32 | certain molecules for certain proteins and we these micro rays that are shown here |
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| 41:40 | the slide. And in this micro you can have 65,000 synthetic pieces of |
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| 41:49 | . N. A. Which essentially a specific code or molecule or for |
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| 41:56 | podium. And you have one brain is labeled Red Brain one. And |
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| 42:05 | have brain too which is labeled And let's say one of these brains |
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| 42:12 | normal and another brain has Parkinson's And now you have no stained red |
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| 42:23 | green. You mix them and apply this D. N. A. |
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| 42:29 | rate where it's a micro rate where have little well so you will have |
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| 42:35 | little wells with little synthetic piece gene sequence here, synthetic D. |
|
| 42:41 | A. And Jean would reduce expression brain. one will blow in green |
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| 42:49 | be dominated by green jeans with reduced of brain to will be in red |
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| 42:56 | jeans that didn't change and have the expression will remain in yellow. So |
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| 43:02 | are visual markers of visual tags in . Well, that signal And what |
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| 43:10 | basically tells you is if you have micro array with 30,000 wells in it |
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| 43:17 | you comparing your normal brain to Parkinson's . What you may see is 25,000 |
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| 43:25 | remain unchanged which will tell you out these 30,000 25,000 don't don't have anything |
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| 43:32 | do with with with Parkinson's processes. then you may find that 5000 of |
|
| 43:39 | genes changed. And then you will that 500 of these genes really changed |
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| 43:45 | a lot. And then you'll find 200 of them went up. Which |
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| 43:51 | that there's more of this gene expressed the brain. And you can also |
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| 43:56 | the reduction or the increase in the . And you will say that |
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| 44:00 | top and 301 down to the expression that gene went up or went |
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| 44:08 | Is it is it helpful? It's really helpful to get a global view |
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| 44:15 | water. The genes the populations of interrelated genes 200 or they're completely |
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| 44:22 | Or either of these 200 or 150 to sodium channels for example. Then |
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| 44:28 | getting to a certain level of But it gives you a good what |
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| 44:32 | call bird's eye view of what is with genetic changes which consequentially can result |
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| 44:39 | changes from molecular expression or protein expression neurons in the brain. But then |
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| 44:47 | know, your mentor will say I these five genes so make sure you |
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| 44:53 | out the two genes that are regulated those two I'm interested in and then |
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| 44:59 | can be like Ramona alcohol and say I think it's the other to mentor |
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| 45:04 | say, well I'm not gonna give a stipend and wants to study these |
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| 45:08 | because at my age is giving me grant to study these two genes. |
|
| 45:12 | let's try to figure out and understand these do, you know? So |
|
| 45:18 | always you know rationale behind and there's both the scientific rationale and then if |
|
| 45:25 | make the financial rationale or strategic rationale for a lab for a mentor to |
|
| 45:32 | certain studies or be interested in certain . So but that's a good way |
|
| 45:38 | to have a general view of what the global changes. And of |
|
| 45:45 | you know this is the whole brain you could say I'm just going to |
|
| 45:50 | this there about, I'm just going take the temporal lobe, I'm just |
|
| 45:54 | to take a tiny little piece that know is amygdala. So you can |
|
| 45:59 | a lot more specific, right, is not just what happened in the |
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| 46:03 | brain versus this, you can say happened in the hippocampus of the Parkinson's |
|
| 46:08 | versus this. What is the genetic in that area. Because that's the |
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| 46:12 | that I'm interested in. My mentor interested in when it makes sense in |
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| 46:17 | disease, to look at that specific and not another one so smooth and |
|
| 46:22 | plasma in particular, we're going through of the basic organ Alice is involved |
|
| 46:26 | protein folding calcium regulation. Um so intracellular stores of calcium right? You |
|
| 46:36 | release intracellular early calcium inside the south of colic. Or free floating calcium |
|
| 46:42 | very tightly regulated because calcium is not a di valent ion, it's also |
|
| 46:48 | secondary messenger, the secondary messenger neurons can influence long term effects inside the |
|
| 46:54 | . So a lot of calcium is buffered and regulated and stored in this |
|
| 47:00 | smooth er golgi apparatus is involved in post translational processing and podium sorting as |
|
| 47:09 | being built. And mitochondria in is source of energy undergoes the what is |
|
| 47:16 | the Krebs cycle. It takes the and stored energy sources such as protein |
|
| 47:24 | sugar, fat uh acid and conversion . There's a production of A. |
|
| 47:31 | . P. And the carbon dioxide there's a lot of ADP that gets |
|
| 47:36 | by mitochondria. So it's the main a main basically engine energy engine in |
|
| 47:46 | all of the energy sources. Uh A T. P. Is also |
|
| 47:54 | to drive certain transporters such as A . P. A. S. |
|
| 48:00 | pumps that pump ions like A P. A. S. And |
|
| 48:05 | use that energy a lot of times work against concentration gradient. And in |
|
| 48:11 | the brain mask comprises suddenly about 3 of the total body mass. So |
|
| 48:21 | you if you were to hold the , it weighs just about 3% of |
|
| 48:28 | total body amounts or so. But consumes about 20 of all of your |
|
| 48:38 | body energy intake and energy sources. it's a small organ, right? |
|
| 48:46 | demands a lot of energy. A of A. T. P. |
|
| 48:51 | lot of oxygen. And that's why talked about how it's sensitive to hypoxia |
|
| 48:57 | oxygen laws. It's a system that somewhat driven outside the equilibrium because it's |
|
| 49:05 | and it draws and consumes a lot total energy that that we that we |
|
| 49:12 | energy sources. Oh yeah of course course. I mean but in general |
|
| 49:22 | brain will draw a lot of energy it's not necessarily that what you're getting |
|
| 49:28 | is maybe I should have talked about and talked about the maps. Um |
|
| 49:33 | a myth Circulating out there that we use 10% of our brain. So |
|
| 49:40 | don't use more than 10% of our . And so you saw these |
|
| 49:45 | you know, they look like you , they're covering different but in fact |
|
| 49:48 | can use you know, if you 100% of your brain, that's not |
|
| 49:52 | . That's probably a epileptic seizure. Mall. Everything is in a short |
|
| 49:57 | in a way that's 100%. Uh don't do zero because that's brain |
|
| 50:05 | Uh And we go anywhere in between . 200%. Like I said 100% |
|
| 50:14 | be bad pathology but we do get . We get overload sensory overload. |
|
| 50:21 | heat strokes and not just you know but also environmental factors that contribute to |
|
| 50:27 | . So it's not like it's uh drawing that exact 20% of all of |
|
| 50:33 | energy sources, but also the brain not quiet when you're asleep. Your |
|
| 50:39 | is not moving well most of the it's not but your brain is |
|
| 50:44 | It's just different areas of the brain are active when there's a disconnection for |
|
| 50:48 | motor function. So we never go this, you know, Sleep Dark |
|
| 50:55 | , where were, you know, consuming zero energy and there's very little |
|
| 51:01 | . It does fluctuate around that 20% the total energy sources that we that |
|
| 51:06 | can intake in general. I don't if that answers your question. Uh |
|
| 51:17 | yeah, like I said, it pretty much go between 10 to and |
|
| 51:22 | but you don't want to be in and very oh, how does that |
|
| 51:32 | to the caloric intake? That's a question. But, you know, |
|
| 51:41 | do digestion and you have metabolism and . So what you're in taking is |
|
| 51:45 | necessarily what is Yeah, but I have a good answer to that. |
|
| 51:50 | a that's a great question for somebody doing like performance, uh neuro and |
|
| 51:56 | science and like durability and performance. because you want to, you |
|
| 52:03 | I'm curious about how much energy the use different occupations and different. It's |
|
| 52:13 | to tell. Um we typically don't ourselves in our functional brain activity. |
|
| 52:20 | know, we have usually limited studies are dedicated to groups of 20 or |
|
| 52:27 | studying a particular function or dysfunction. yeah, but if you were to |
|
| 52:36 | at the brain undergoing grand mal epileptic , you would see everything in |
|
| 52:44 | We see that in vitro and slices you will see that in vitro. |
|
| 52:49 | , and and it can be sustained quite a bit of time and it |
|
| 52:53 | go away. You know, it's not, it cannot be if 100% |
|
| 52:57 | activity brain activity sustained all of the draw for longer than half an |
|
| 53:05 | you actually lose neurons when you So, mm Hmm. Yeah. |
|
| 53:12 | if you having grand mal epileptic which I call a short circuit over |
|
| 53:16 | brain 45 minutes, if you don't that seizure within 45 minutes, you're |
|
| 53:22 | likely going to die. So, these are all very good questions. |
|
| 53:29 | , keep them coming. Even if don't have very good answers for |
|
| 53:34 | Stop. Is that possible to stop 20 minutes? Yeah, you can |
|
| 53:42 | to do it. And the best is still pharmacologically, still using uh |
|
| 53:50 | of the medications have been around for , 60 years, years of Benzodiazepines |
|
| 54:00 | in the rap world it's known as benzos. So, but in the |
|
| 54:05 | language it's days upon and benzodiazepines are potent uh inhibitors. Uh seizure activity |
|
| 54:16 | still probably the most effective at stopping mal seizures. There's maybe some exceptions |
|
| 54:24 | electric shock, potentially breaking down the , but that's at the experimental |
|
| 54:31 | And that's also when you have a stimulation and implants in the brain, |
|
| 54:38 | brain stimulation, which can be used stop seizures electrically as well. Uh |
|
| 54:43 | is clinical and it's available, but very severe cases because it's a invasive |
|
| 54:49 | surgery. So only medications don't work stopping these severe seizures, Then you |
|
| 54:55 | go into either respecting the surgery of area or implanting an electrode in hopes |
|
| 55:02 | if you detected normal activity, you break the pattern of abnormal activity with |
|
| 55:07 | pattern of electrical activity. Question what's ? Um, musk's neuralink? It's |
|
| 55:21 | mean, it's very interesting. I heard that he fired the Ceo and |
|
| 55:24 | hired a new Ceo. Um let's leave it to uh this discussion |
|
| 55:32 | neuralink maybe later. And of maybe we understand more about the brain |
|
| 55:38 | to, but it's it's very interesting happening with neuralink with artificial intelligence, |
|
| 55:45 | know, Casper dot io with chad . Those are some of the things |
|
| 55:54 | I think your generation should really consider very serious land because it I believe |
|
| 56:01 | will, you know, I'm just to hear the rumble, but I |
|
| 56:06 | believe that a lot of these things influence um the necessity for some basic |
|
| 56:16 | for basic uh professions even that will replaced with artificial intelligence or creative writers |
|
| 56:26 | are non writers that are digital artists are Casper artists, you know. |
|
| 56:34 | it's interesting. So we'll talk about at that stage two because that's sort |
|
| 56:40 | looking into the future. Can we digital into the brain? Can we |
|
| 56:45 | digital of the brain? Can we the brain think the way somehow brain |
|
| 56:51 | interface, basically. Can we make as smart as our brains after the |
|
| 56:56 | learn from our brains. So then could take over the world and run |
|
| 57:01 | around. Uh let's talk about it the course. Now possible lipid bi |
|
| 57:09 | is the membrane of neurons that consists two layers by layer two layers of |
|
| 57:20 | in which has a polar hydra filler or the polar groups are exposed to |
|
| 57:25 | extra cellular fluid or intracellular side of inside of the cell fluid and the |
|
| 57:31 | acid tails. These non polar hydrophobic point inwards to each other. So |
|
| 57:40 | form by layer in between you have cholesterol will contribute to the how tightly |
|
| 57:49 | possible effects are bound together in a the flexibility and fluidity of this plasma |
|
| 57:57 | . The numbering will have some trans proteins that are channels some trans membrane |
|
| 58:03 | that are protein associated proteins, powerful . So the sauce and neurons will |
|
| 58:09 | coated with sugar, carbohydrates, black proteins which are very important for South |
|
| 58:14 | sell recognition and this whole structure of membrane and the shape of the membrane |
|
| 58:22 | the dendrite and the spines in different is supported by the underlying side of |
|
| 58:27 | elements and these side of skeletal they're also not static, meaning that |
|
| 58:35 | side of skeletal elements in particular. small ones acting molecules can prelim arise |
|
| 58:43 | form longer change and they can form chains rather than longer chains. They |
|
| 58:50 | be polymer rise and they can form layer lattices that will be more rigid |
|
| 58:59 | structure. Or they could have just couple of layers for these satis scalable |
|
| 59:05 | , it will be more flexible in the member of destruction. And so |
|
| 59:11 | overall shape of the membrane will change the shape of those dendritic spines can |
|
| 59:16 | change. And the functionality of the can change because you will have a |
|
| 59:23 | of the elements. These are not elements. There's lateral diffusion and a |
|
| 59:29 | of these molecules will move throughout the and they can move really fast. |
|
| 59:35 | the trans membrane proteins can move micro within milliseconds so they can move within |
|
| 59:43 | bus lipid bi layer. If you possible lipid Beiler, you can start |
|
| 59:50 | these elements around and some of them actually get picked out some of the |
|
| 59:55 | lipids and reform into little my seals little organelles inside or outside the |
|
| 60:03 | And this is fluid. So this referred to as dynamical fluid mosaic model |
|
| 60:10 | of the lateral diffusion and because the diffusion and the site of skeletal supporting |
|
| 60:17 | underneath can change depending on the levels activity of demand. That particular piece |
|
| 60:24 | the membrane and the spine requires that it's being really activated a lot and |
|
| 60:29 | needs to become larger. So you to change the side of skeletal structure |
|
| 60:35 | to support. Now the larger member arrangement for that particular dendritic spine. |
|
| 60:41 | this is a very dynamic process. like I said in neurons, some |
|
| 60:46 | these trans membrane proteins can move very fast. The three types of cited |
|
| 60:52 | elements that we have on micro tubules are the largest 20 nanometer in |
|
| 60:59 | For the price of tubular molecules. we have the strands the neuro filament |
|
| 61:05 | or intermediary filaments, also known as filaments. And we have the micro |
|
| 61:12 | which are the smallest elements, only nanometers in diameter and they have the |
|
| 61:18 | molecule. And this is the smallest . And as I talked about acting |
|
| 61:25 | prelim arise and form longer chains. prelim arise and get cut up into |
|
| 61:30 | chains. This is a cross section the axon And the axon, as |
|
| 61:37 | can see on the outside has a and it has multiple layers in this |
|
| 61:44 | . This is the Myelin nation around axons that get formed by leo cells |
|
| 61:50 | the legal tender sides. So this nation is the insulation of the axon |
|
| 61:59 | it to be able to conduct electrical . So the myelin is insulation. |
|
| 62:05 | when Myelin is formed around a axon Alico denver side will wrap it's and |
|
| 62:13 | around multiple layers like that. And why you're seeing multiple layers, multiple |
|
| 62:21 | here in the violin. If you inside the axon which you're seeing on |
|
| 62:27 | inside of the axon looks like small vessels that are running lengthwise here except |
|
| 62:36 | non blood vessels. Their micro tubules micro tubules A lot of times are |
|
| 62:44 | referred to my axons as micro tubular . Micro tubules are very important for |
|
| 62:54 | O. And cellular transport in So you will see abundance of the |
|
| 63:01 | tubules and tubular and molecules that are around the Selma's up the neurons and |
|
| 63:08 | located throughout, especially the axons for external transport through the micro tubular |
|
| 63:19 | This is a fibroblast cell. So is not a neuron cell. But |
|
| 63:24 | it shows is in purple is the of the cell that is stained in |
|
| 63:34 | . You have the turbulent, which micro tubules and in blue. Everybody |
|
| 63:44 | blue here in blue. You have which is micro filaments. And this |
|
| 63:54 | basically illustrates what I have just mentioned you that the larger the side of |
|
| 64:01 | elements that will contribute to the overall of a base uh side of skeletal |
|
| 64:09 | structural rigidity of the cell and are to the transport and the elements. |
|
| 64:18 | smallest elements like acting show the You can see the blue stain is |
|
| 64:25 | clearly defining the very much outer distal of the cell. And this is |
|
| 64:33 | the support of the shape and the and the outer edges of the possible |
|
| 64:38 | . It comes from having tubular in on the inside, having acted on |
|
| 64:45 | outside by having acting on the having acting the ability to rearrange quickly |
|
| 64:51 | the outside. You can change the of the plasma membrane and through the |
|
| 64:57 | diffusion you can change what proteins are in the plasma number and therefore the |
|
| 65:04 | of these different elements and pieces of plasma membrane. So in uh this |
|
| 65:15 | I've actually in your notes have replaced with another slide. And when we |
|
| 65:21 | back we will talk about it. , I will end the third lecture |
|
| 65:26 | because of the rain a couple of earlier. And when we come back |
|
| 65:30 | will talk about Alzheimer's disease. So I mentioned that I replaced the |
|
| 65:36 | I will show you to you in minute. But this will conclude |
|
