| 00:00 | Welcome back today. We are here , 26, which is our fourth |
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| 00:13 | is going to be our second lecture neurons and going into glia. Maybe |
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| 00:18 | finish glia today. Maybe we will we will have to end the lecture |
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| 00:24 | a few minutes earlier today. Uh of 5, 15, maybe around |
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| 00:30 | , 10. Um and uh let's . We will continue with the material |
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| 00:37 | we finished talking about last lecture. in particular, we ended up talking |
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| 00:45 | side of skeletal elements and we talked three types of side of skeletal |
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| 00:51 | And we said that these side of elements are also quite dynamic. And |
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| 00:58 | mentioned that the more rigid structure, of skeletal, so to speak. |
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| 01:04 | in general, and the larger micro will be located around the Selma's. |
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| 01:10 | also they will be providing these micro highways or ectoplasmic transport and cellular transport |
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| 01:18 | general. And the smallest molecules active which comprise the micro filaments. Uh |
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| 01:28 | will be located on the outer edges the plasma membrane, supporting the outer |
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| 01:34 | of the neuronal membrane uh shapes And you have the slide in your |
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| 01:42 | . But instead of using this we're going to talk about Alzheimer's |
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| 01:48 | Using this slide and in particular throughout scores, we will highlight several neurological |
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| 02:00 | . And you may want to, you're taking notes on the paper, |
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| 02:05 | a little bit of space underneath the disease because we will come back and |
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| 02:10 | about certain pathology of Alzheimer's disease and second section of the course. Uh |
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| 02:18 | so that's that's important that maybe you some space for yourself. So you |
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| 02:22 | continuity from from what we talked about . And in general, when you |
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| 02:27 | about a disease, first of we're interested in neurological disorders. There |
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| 02:33 | many different brain uh uh and body were interested in the brain diseases and |
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| 02:44 | disease and many neurological disorders. Alzheimer's is the most common form of dementia |
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| 02:52 | Alzheimer's disease. You can start thinking it for many different levels. First |
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| 02:57 | all, what is the prevalence of disease? What population is it the |
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| 03:05 | ? Is it the teenagers or is the aging population? Yeah. And |
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| 03:12 | and older, that's correct. You a higher chance and there's higher prevalence |
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| 03:18 | Alzheimer's disease in the population. So a disease of aging of an older |
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| 03:26 | . It's not a normal part of . Right. And when you think |
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| 03:31 | uh Alzheimer's disease, when you think symptomology, the symptoms of the |
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| 03:39 | What are symptoms of the disease? people with Alzheimer's disease having fever and |
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| 03:49 | or they what what is what is issue? Memory loss? So, |
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| 03:56 | loss comes potentially as the symptom that into mind and in early stages. |
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| 04:04 | disease typically has an onset when disease , there are early stages of the |
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| 04:11 | . Right? And early stages of disease will be associated in particular with |
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| 04:16 | short term memory loss first before there long term memory loss. Then after |
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| 04:22 | onset of the disease, there's a what we call progression and the severity |
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| 04:28 | the disease. How worse does that get? Right? So there's there's |
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| 04:37 | stages of the disease, there's early stages progression and there are late |
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| 04:43 | of the disease and typically the latest is the worst is the pathology and |
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| 04:50 | Alzheimer's disease. If their early symptomology short term memory loss, not remembering |
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| 04:58 | or faces, there are more significant that start happening, a spatial disorientation |
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| 05:08 | a person does not know where they're or how to find their way back |
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| 05:12 | or sometimes have to find their way to their room. There is a |
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| 05:18 | fine disorientation. People with Alzheimer's may losing sense of time, whether it's |
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| 05:26 | or night, it's if it's dusk dawn, uh then there are some |
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| 05:33 | uh sure we're all gonna get this alert. Then there are other problems |
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| 05:43 | a person with Alzheimer's disease would experience the more severe and the more this |
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| 05:50 | progresses, it's going to be associated more severe symptomology. There's going to |
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| 05:56 | a neuro degeneration, there's going to loss of neurons in the brain. |
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| 06:02 | as a consequence to that the person not gonna be able to essentially control |
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| 06:09 | their vital functions uh such as eating eventually breathing human. So it's a |
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| 06:16 | of the brain that is not just loss and which is the early onset |
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| 06:21 | early stages of the disease but essentially lead to death because of the significant |
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| 06:27 | degeneration in the brain. So So let's talk about, first of |
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| 06:47 | , what we're looking at here. first of all why we're talking about |
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| 06:51 | is it's relating to the side of elements and as you can see here |
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| 06:57 | a normal neurons and normal neuronal And in Alzheimer's disease, if we |
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| 07:04 | at the cellular level pathology and network pathology we're seeing are two major pathological |
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| 07:14 | we call hallmarks of Alzheimer's disease. of all, inside the cells we |
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| 07:21 | Nurofen brutally tangles and entanglements of neural which starts messing up the external transport |
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| 07:31 | communication within the south. So this what is happening on the inside of |
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| 07:36 | cells intracellular early extra cellular early there this um amyloid precursor protein um also |
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| 07:46 | as a P. P. That abnormally cleaved from the membranes of the |
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| 07:51 | and it gets aggregated as amyloid There's an extra cellular of amyloid plaques |
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| 07:59 | lot of times will be referred as plaques or dementia plaques but that is |
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| 08:09 | formation and entanglement outside the cells into plaques which eventually sort of gets rigid |
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| 08:19 | little bit calcified. These plaques are stationary. They can migrate. They |
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| 08:26 | multiply in different areas of the brain the same time. They can start |
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| 08:31 | taking over the brain space and affecting production of the action potentials in the |
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| 08:38 | on initial segments, therefore affecting the between neurons and neuronal networks. So |
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| 08:45 | are the two cellular pathological mark One is an intracellular, the other |
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| 08:52 | , the plaques are outside the cell this is on a microscopic level, |
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| 08:58 | the macroscopic level, severe Alzheimer's Advanced stages of the disease, on |
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| 09:05 | macro gross anatomical level would be noticeable gross changes and the structure of the |
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| 09:15 | . The shrinkage, especially the shrinkage the gray matter and loss of the |
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| 09:20 | matter, loss of neuronal populations or degeneration, degenerating neurons, dying |
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| 09:29 | And as you can see, overall and shrinkage of the overall brain as |
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| 09:37 | to what would be a healthy brain an individual at the same age as |
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| 09:43 | concerns markers. It is, there some markers that are being developed to |
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| 09:49 | up some of these things, but can only pick up things from the |
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| 09:55 | because of the blood brain barrier. can't always pick up things from the |
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| 10:01 | . And that is that is kind a it's a very good question and |
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| 10:04 | it's kind of a limited of what can looking for as markers. Maybe |
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| 10:10 | are some things that would indicate potentially possibility of developing Alzheimer's disease. But |
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| 10:19 | you have advanced stages of Alzheimer's you can potentially image the information of |
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| 10:26 | plaques inside somebody's brain. But typically is also not done because it's not |
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| 10:33 | for diagnosing Alzheimer's disease. But uh can look and see if there are |
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| 10:40 | of these amyloid plaque formations. if you wanted to see what's happening |
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| 10:45 | the brain, you would have to the cerebrospinal fluid and to sample service |
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| 10:51 | cerebrospinal fluid, you would have to a spinal tap. And that is |
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| 10:58 | , something that is not typically Uh what can be done also. |
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| 11:05 | , very good question. So, now, what I would like for |
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| 11:08 | to know is the cellular, the the gross anatomical changes in Alzheimer's |
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| 11:16 | What is a symptom versus what is pathology uh of the of the |
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| 11:24 | What is the prevalence of the whether it's a developmental disorder or it |
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| 11:31 | prevalent in the aging population uh and may even get to talk about another |
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| 11:37 | today. I think we will. , yeah. Uh so how is |
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| 11:47 | like the flood, whatever they're testing to permanent then. Right, |
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| 11:54 | How do they determine if it's Alzheimer's form of attention? Well, I |
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| 12:03 | , honestly, the definitive diagnosis of disease still, I think it's the |
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| 12:09 | postmortem to demonstrate that you have the of these plaques and and and just |
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| 12:18 | and just getting a little bit Maybe it's a part of normal aging |
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| 12:25 | a lot of people would experience, not as agile as many things as |
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| 12:30 | getting older. But the formation of plaques and the pathology that we're talking |
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| 12:36 | here may not be present in those . So if we can detect that |
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| 12:41 | do have this pathology with either the or with the imaging or postmortem to |
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| 12:47 | confirm that it was indeed that you know. So, alright, |
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| 12:53 | see if I can do this presentation without losing part of the image. |
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| 12:57 | we talked about the skeleton side of elements and the reason why is because |
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| 13:02 | talked about transport and we talked about this transport would be impaired inter cellular |
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| 13:08 | by the euro, february tangles in disease. So done right. This |
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| 13:13 | also something that you think the neurons have these branches and this is a |
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| 13:18 | karam, it'll sell we'll talk about parameter. This is one of the |
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| 13:22 | excitatory cells that you will find in serie a growth parameter cells. So |
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| 13:28 | looks in three dimensions and these phenomenal have the apex or the top. |
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| 13:35 | is called the ethical when you also the base of the pyramid. And |
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| 13:40 | the member is coming at the base the is the basil head rises and |
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| 13:45 | off the some of the bottom base phenomenal cells of this pyramid. You |
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| 13:50 | have an axon that comes out the can divide into acts on collateral. |
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| 13:57 | that branch off and it will branch locally and these parameter cells projection |
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| 14:04 | That means that they will project this for information because they're excitatory cells into |
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| 14:10 | adjacent brain networks and communicate information to neurons. Axons as we talked about |
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| 14:18 | myelin ated an external terminal. You a lot of mitochondria, you need |
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| 14:26 | . You have synaptic vesicles that are very close to the plasma membrane and |
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| 14:31 | what are called active zones. And vesicles are ready to fuse the plasma |
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| 14:38 | to release the neurotransmitter which will then across this physical space of 20 |
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| 14:44 | the synaptic cleft and will bind to post synaptic receptors. Post synaptic lee |
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| 14:50 | the areas that ejects supposed to these synaptic terminals and they refer to as |
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| 14:56 | synaptic densities densities of the post synaptic in the following year. So um |
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| 15:06 | of the synopsis from these axons are in passing and some of these synapses |
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| 15:12 | terminal that they reach some spatially terminal destination. So all of these things |
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| 15:20 | will repeat itself. And we talk synaptic transmission in great detail in the |
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| 15:26 | section of this course about dramaturgical and , allergic synaptic transmission and other types |
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| 15:32 | chemical neuro transmission in the brain. axons are responsible for not just producing |
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| 15:40 | action potentials but there is a need acts of plasma transport. There is |
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| 15:44 | slow ectoplasmic transport of about 1 to millimeters today there's a fast ectoplasmic transport |
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| 15:52 | about 1000 millimeters a day. And can it says tied up axons later |
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| 15:59 | this course about maybe two lectures or , we'll watch a short movie about |
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| 16:04 | action potentials and how the initial axons the giant squid. Axons were isolated |
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| 16:11 | the squid and they would be tied with a string after an injection of |
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| 16:16 | die. And you would literally how long does it take for that |
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| 16:20 | to carry that die a certain And you can also to do that |
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| 16:24 | radioactive labels as well to trace the of how molecules travel within axon. |
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| 16:32 | you can have fast and slow modes traveling. You have interrogated transport. |
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| 16:39 | interrogate transport is everything that is going the base from the soma, from |
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| 16:44 | major biochemical factory and the near the of the selma. And it's carried |
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| 16:51 | the periphery. And retrograde are things are in the periphery, let's say |
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| 16:57 | the external terminal. And they need be returned back for re processing or |
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| 17:03 | degradation or something else back into the regions. And so for a territory |
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| 17:10 | from so much to the periphery, would have these motor molecules that would |
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| 17:16 | be like arms that will carry different under greatly and retro greatly. You'll |
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| 17:22 | another motor that is dining and that carry different substances back into the soma |
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| 17:31 | the periphery. Uh retrograde transport can very useful tool when we want to |
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| 17:43 | the connectivity of neurons. So a of the chemicals that will discuss that |
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| 17:52 | on this list here and a couple viruses uh can be used as |
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| 17:59 | What that means is H. P. Here stands for horseradish peroxide |
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| 18:05 | and H. R. P. be injected let's say in a region |
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| 18:13 | the brain and you want to know this region of the brain is connected |
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| 18:20 | . Right? So you can inject patch of this H. R. |
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| 18:26 | . And because it is retrograde transport means it goes from the periphery into |
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| 18:33 | . This is a really good way trace from the periphery where these axons |
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| 18:38 | connected into their neuronal somatic network And two days later after this retrograde |
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| 18:48 | , this H. R. Gets taken up and gets transported and |
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| 18:53 | the neurons that are connected to this area of the brain that can be |
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| 18:59 | the skin for example. So herpes rabies virus, they are capable of |
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| 19:12 | transport of this retrograde travel. And if you tag these viruses with some |
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| 19:20 | markers were talking to experimental neuroscience, tag these viruses with fluorescent markers or |
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| 19:26 | dyes that you can expose. You also use viruses to study the connectivity |
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| 19:33 | to study the retrograde transport and to different neuronal networks. Uh some of |
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| 19:41 | viruses like Herpes simplex virus that causes and and adults. It actually is |
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| 19:52 | of both interrogated and retrograde. So can interrogate raid, lee travel into |
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| 20:04 | periphery and it can retrograde lee travel neuronal south and stay there dormant. |
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| 20:12 | there's some viruses that will be capable this bidirectional uh travel capability, so |
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| 20:20 | speak. Round trip. Not one I think both are equally bad because |
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| 20:50 | we're talking about connectivity, if you the connections there, then you kind |
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| 20:54 | communicate. Even if you're alive, it's good that you're still alive but |
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| 20:58 | are irrelevant because you're not communicating to . If you're still receiving that may |
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| 21:05 | be relevant. So you're still listening you're not participating. You're not talking |
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| 21:11 | . There's no network. Um or now, if, you know, |
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| 21:25 | is all. So if there's no there's no salary, I'm saying that |
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| 21:33 | are bad, but there is, know, there's no nucleus neuro |
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| 21:37 | If you listen at the connectivity while , you know, maybe not all |
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| 21:42 | it is lost. And so it's definitely more severe at the level |
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| 21:46 | the soma nucleus in particular, you , and when we're talking about, |
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| 21:53 | know, there's programmed cell death apoptosis there's also a necrosis. So those |
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| 21:58 | have two ways in which once the like gets turned on, they |
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| 22:03 | there's there's a response to basically you know, and that's neuro degeneration |
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| 22:10 | advanced stages of alzheimer's disease. And are many neurodegenerative disorders apart from alzheimer's |
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| 22:17 | , this is great for connectivity. kind of tracers. And we have |
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| 22:25 | looked at the slide. I want remind you how important it expires. |
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| 22:29 | this is also something quite unique to because there's a great expanse of |
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| 22:34 | They can be made into larger, larger than Britain spines that can be |
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| 22:41 | at receiving information and encoding that information the rest of the branch and sending |
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| 22:48 | information into the soma. They come different shapes. Uh They contain holy |
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| 22:56 | complexes, they contain mitochondria. That they have their own energy source right |
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| 23:05 | and the spine we're talking about the about one micrometer cell in size. |
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| 23:12 | that's why I say that there is biochemical independent units because of the |
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| 23:18 | several complexes and because of the stores the energy, they can actually adjust |
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| 23:24 | of these receptor membrane proteins that might the solid to be inserted inside |
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| 23:31 | Uh and so the development of these spines. The shapes as you can |
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| 23:38 | , there are three different shapes. study spine in green, right |
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| 23:45 | There is a spine and purple right and there is mushroom shaped spine. |
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| 23:53 | it's like a mushroom cap here in . So they're predominantly several different shapes |
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| 23:59 | these pines. And there is an of the spines. And this |
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| 24:05 | especially during early development is very As I have mentioned. And I |
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| 24:13 | talking in this course about the concept plasticity that the highest levels of plasticity |
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| 24:19 | present and during early development into early and when we are born, we |
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| 24:28 | a lot of things that are a more interconnected with each other and we |
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| 24:34 | a lot more synapses than what we up in having when we are |
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| 24:41 | And in this situation that means that connectivity in the brain is very |
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| 24:47 | but it's quite non specific and because the genetic environmental sensory inputs, we |
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| 24:56 | refined the anatomical connectivity between neuronal networks the process of plasticity. So we |
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| 25:04 | these and we can prune this dendritic and a lot of them will get |
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| 25:09 | . So the ones that are not , they will get eliminated the synapses |
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| 25:15 | dendritic spines that are very active, will remain there and they may become |
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| 25:22 | . So they become more powerful more . So as I mentioned that we |
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| 25:32 | talk about another form or another disease and we will talk about a |
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| 25:41 | It is called fragile X. Fragile is one of the most common autism |
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| 25:57 | disorders and under the spectrum of autism disorders, you have many different syndromes |
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| 26:17 | many different conditions. Now when we about autism. So, fragile X |
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| 26:26 | not sound familiar to you, but sure everybody has heard or encountered families |
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| 26:34 | individuals that have somebody who is diagnosed autism? Right. And typically when |
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| 26:43 | think about autism now, do you about young Children, you think about |
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| 26:50 | age people? Or do you think the elderly populations? You're correct |
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| 27:14 | a lot of it has to do the onset of when you diagnose the |
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| 27:19 | . So with Alzheimer's disease onset and symptomology that you're seeing is, as |
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| 27:25 | mentioned, 55 plus Is a higher where that means that the prevalence of |
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| 27:32 | in the population increases. If you're or older. Now with autism, |
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| 27:40 | is typically diagnosed in the developmental stages the first few years of life. |
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| 27:48 | is not to say that there are adults or even sometimes elderly people that |
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| 27:56 | autism, but it is diagnosed at stages. So it is a developmental |
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| 28:06 | . And in this case, fragile has a genetic component. So it's |
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| 28:12 | genetic developmental disorder. Okay. And the pathology of this disease is is |
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| 28:29 | is abnormal formation of these dendritic You can see that this is a |
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| 28:38 | dendrite from a normal infant that shows densities and arrangement and shapes of these |
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| 28:45 | spines. And on the right, seeing here Now these elongated spines that |
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| 28:53 | much much, much longer. Some them are completely absent from certain areas |
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| 28:58 | the den rights. And one of biggest features of fragile acts is mental |
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| 29:05 | . Pretty severe. Mental retardation, mental retardation and Children that have fragile |
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| 29:15 | syndrome. There's a fragile X chromosome site. That's why it's fragile |
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| 29:21 | It can occur in girls and but it is more severe in |
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| 29:27 | And uh apart from having retardation and ability to learn and sometimes express |
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| 29:38 | they also quite often have seizures and . Okay, so I'm gonna add |
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| 29:48 | spectrum disorders. It's an umbrella under fragile X false. Okay, The |
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| 29:56 | of the disease is linked to the the genetics and we won't get into |
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| 30:02 | of what is being expressed or I don't have time for this. |
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| 30:08 | . And then the last thing is . And what is this? If |
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| 30:22 | have one disorder already, which is acts and then that child starts having |
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| 30:30 | and no seizures become repeated. Where child is diagnosed with epilepsy, epilepsy |
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| 30:36 | now a co morbidity. Too fragile . So if the first diagnosis was |
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| 30:43 | acts, this this child has fragile . And mental retardation. And then |
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| 30:49 | an onset of seizures in epilepsy, becomes a co morbidity. What does |
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| 30:54 | mean morbidity morbid, dead co morbidity two things are now potentially going to |
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| 31:01 | killing the fragile acts. This mental , abnormal connectivity in your dendritic spines |
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| 31:08 | in your synapses as well as abnormal in parts of the brain causing seizures |
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| 31:14 | epilepsy causing neural degeneration in another way that individual's life and leading to potentially |
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| 31:25 | death and shorter lifespan. Yeah. the caused by uh generation that comes |
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| 31:32 | stages or is it something uh It's it's it's a good question actually because |
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| 31:44 | doesn't have to necessarily and sometimes there no clear answer who came first or |
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| 31:50 | happens first. Because if the child very little, they may not be |
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| 31:57 | to detect mental reputation. But if child has a seizure and that seizure |
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| 32:03 | gonna have an outward motor component, parents are probably gonna go to the |
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| 32:08 | and now they're gonna be trying to if this child has seizures and epilepsy |
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| 32:13 | they may get diagnosed with seizures and first and then with fragile X. |
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| 32:19 | we wouldn't know what happened first. typically the more neuro degeneration happens, |
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| 32:26 | more of seizures and epilepsy development, would see this is also linked to |
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| 32:32 | next slide to the next image of slide that shows that these lunatics finds |
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| 32:37 | the synaptic inputs that are coming They can be excitatory which a glutamate |
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| 32:44 | of glutamate is the major excitatory amino neurotransmitter in the brain. Or they |
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| 32:50 | be inhibitory which is gamma immuno butyric or Gaba. And those of the |
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| 32:57 | synopses. So on this image everywhere you're seeing green punkt eight green |
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| 33:05 | These are glued dramaturgical excited to a that stain for glutamate receptor everywhere we |
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| 33:12 | seeing orange dots here. These are synopsis and the stainless for the gabba |
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| 33:22 | which is inhibitory receptor. Now I'll you in a second. These functions |
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| 33:26 | excitation excited for synopsis will drive this to de polarize the fire an action |
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| 33:33 | and to communicate that information downstream. these synaptic inputs will try to tame |
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| 33:41 | activity in this neuron and keep it or quiescent and prevent it from firing |
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| 33:47 | hyper polarizing its monthly potential single as I mentioned, can have tens |
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| 33:53 | thousands of these inputs, hundreds of sometimes and a mixture of excitatory and |
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| 34:00 | inputs. And now you can see if you have improper arrangements and improper |
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| 34:07 | , what can happen quite often is of the improper connectivity. There is |
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| 34:13 | an effect where there is a loss inhibition and this imbalance of excitation versus |
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| 34:21 | . If there's loss of inhibition, too much excitation which now gives the |
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| 34:26 | for neuronal networks to synchronize and to producing epileptic activity in the form of |
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| 34:33 | . So it's it's very important that not only precise anatomically, but it |
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| 34:38 | also physiologically these thousands of the inputs balanced in a particular manner between excitation |
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| 34:47 | inhibition to keep us within our brain operating within certain normal dynamic range. |
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| 34:55 | if you go outside this range, maybe pass out a loose consciousness on |
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| 35:01 | bottom end and at the top end go maybe into abnormal synchrony and and |
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| 35:07 | like. So this is what the and inhibition does through the interactions multiple |
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| 35:15 | of the single self and the precise , precise connectivity are very important for |
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| 35:22 | development for learning and for having uh mental state and uh normal connectivity in |
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| 35:31 | brain. Yeah. One can understand have short or no uh that |
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| 35:56 | Yeah, they're not normal. They're . That means the connectivity is going |
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| 36:02 | be. So it is not that completely, you know, and understand |
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| 36:06 | of the structure and all of the of all of them. Good experience |
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| 36:10 | all of the brains. But they seem to have a lot more uniform |
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| 36:14 | and normally developing brains that don't have , relax in the genetic disorder versus |
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| 36:21 | model. And there's a very good animal models where we manipulate the genetics |
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| 36:26 | we can actually reproduce these dendrites that missing dendritic spines. And we can |
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| 36:31 | some of the renovation and some of behaviors that would be associated with this |
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| 36:44 | . No, fragile acts falls under umbrella of autism spectrum disorders. Because |
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| 36:52 | it falls under the umbrella and apple suis seizures is a co morbidity. |
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| 37:11 | there could be other comorbidities also. there could be other diseases that form |
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| 37:16 | the individuals. So that severe neurological presentation. Yeah. Yeah. The |
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| 37:25 | matters. The shape matters. The matters. The location matters. |
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| 37:37 | That would be that would be I don't know if anybody has found |
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| 37:41 | particular shape or expression the higher levels that and correlated it with some changes |
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| 37:46 | function, but you can definitely tell difference here. Yeah. And the |
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| 37:52 | , like keep getting to the fact the shape is important because the shape |
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| 37:56 | the arrangement of the membrane, the skeletal elements underneath it. The elasticity |
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| 38:01 | the plasticity of all of this to dependent on the activity or not to |
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| 38:07 | . So yeah, the number and location. Are they all missing in |
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| 38:12 | middle of the done drives where they're to be and they're located in different |
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| 38:16 | where they're all together and distributed So for people like us, it's |
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| 38:31 | art. Oh uh I can't really that question very well. If people |
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| 38:38 | out, there can be so many reasons why they do and uh in |
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| 38:44 | experience I've seen people pass out because typically have something to do with their |
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| 38:50 | system and with the heart and maybe respiration. So, but if there |
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| 38:59 | too much inhibition, you would get if you exciting inhibitory receptors. And |
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| 39:08 | in this course we'll talk about the drugs that excite inhibitory receptors. Gaba |
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| 39:15 | . One of the big side effects those medications is drowsy in us or |
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| 39:21 | like feeling so a little bit loss gate a little bit of disorientation. |
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| 39:30 | you're being sedated. A lot of sedatives and a lot of the things |
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| 39:38 | will slow down the activity of the would work by activating inhibition. So |
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| 39:46 | the inhibition and a lot of epilepsy are designed to raise the inhibitory |
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| 39:53 | So okay well actually these are very questions and we'll come back and actually |
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| 40:00 | about gaba receptor and benzodiazepines and and things. So good. You'll build |
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| 40:08 | this knowledge and this repeats a little . So the major functional zones of |
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| 40:14 | that we have that can be roughly and the neurons come in different shapes |
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| 40:19 | sizes but they will have the input which is typically their dendrites or their |
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| 40:27 | and they can be receiving input from motor neuron the local interneuron, a |
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| 40:34 | neuron other cells. The integration of information and the decision whether the neuron |
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| 40:41 | excited or not is going to be into the in the selma the action |
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| 40:47 | gets produced in the axons and the . I'll units are the axons. |
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| 40:51 | adequate units are the axonal terminals. of the cells, as you can |
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| 40:57 | they don't have done rights. They the peripheral axon soma and central |
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| 41:04 | Some cells will project their axons on other neurons and other will form their |
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| 41:09 | on the muscles and even onto the very cells as well. So there |
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| 41:14 | multiple points of input there multiple points output. But most of the neurons |
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| 41:21 | have these four functional regions the input region of the soma conducted region of |
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| 41:30 | axon in the output. External And when we talk about neurons we |
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| 41:38 | said that there are glue dramaturgical excited neurons and then there are inhibitory neurons |
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| 41:44 | gaba ergic neurons. And does that that the only two subtypes of neurons |
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| 41:51 | as it turns out there is over different subtypes of neurons in the |
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| 41:57 | And from the very early days of golgi stain, Ramon alcohol started describing |
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| 42:05 | neurons and distinguishing between these different neurons on their morphology. And this was |
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| 42:12 | early way to classify neurons into different . And if you look at the |
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| 42:21 | and some of the cells will have body and acts on the dendrite on |
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| 42:29 | . This is an invertebrate neuron. it is unit polar cell, it |
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| 42:34 | only one pole, it's all going , this is bipolar south and this |
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| 42:40 | be found as one of the cells the retinal circuit that you will talk |
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| 42:46 | when we study the visual system. it has the axon, it has |
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| 42:52 | selma and has a dem drive. bipolar because it has both the north |
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| 42:57 | and the south pole. This is unit polar cell, pseudo unit |
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| 43:04 | It does have the north and the pole. No but it doesn't have |
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| 43:07 | denver, it has the peripheral axon top and the central axis on the |
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| 43:14 | axon will be innovating skin and joints muscles. So this is your dorsal |
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| 43:20 | ganglion cell. The sensory neuron of spinal cord and the axon terminals will |
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| 43:27 | into the spinal cord proper through the axle. And a lot of |
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| 43:35 | most of the neurons that we will discussing in most of the neurons in |
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| 43:39 | brain and the cerebral in particular That means they have the north and |
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| 43:46 | south and the east and the west northeast and the southwest poles because they |
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| 43:54 | their then drives projecting in different directions well as axons. This is a |
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| 44:02 | neuron of spinal cord. So this the dorsal root ganglion cell which is |
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| 44:07 | unit polar sensory girl. This is motor neuron that will come out of |
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| 44:12 | ventral side of the spinal cord and send a signal to the muscle for |
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| 44:17 | to contract. This cell is also multipolar salad. Already discussed this |
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| 44:24 | It's parameter salad. This says parameter the campus but in fact this parameter |
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| 44:31 | will be found throughout cerebral and are abundant in the cerebral cortex as |
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| 44:38 | And you can tell that this cell is different from this cell. This |
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| 44:43 | morphological is different this cell and look this. This is the Mackenzie cell |
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| 44:49 | cerebellum. These are the cells that contain up 250,000 synapses. You can |
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| 44:58 | how complex it's like a big bush each one of these little offshoots is |
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| 45:04 | point of contact and the synapse for self and still these cells will integrate |
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| 45:11 | process that information within milliseconds and make decision to fire or not fire the |
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| 45:18 | potential. So some cells will have number of synopsis. That just motor |
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| 45:26 | . Approximately 10,000 synopsis. So its it's vary song where these cells |
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| 45:32 | It varies on their morphology and also number of the synopsis. Okay. |
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| 45:45 | you will you will find them in which is the back of the or |
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| 45:52 | referred to as a little brain. . Sorry. Maybe one which |
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| 46:09 | Fire which ones do not fire? I mean which neurons are active in |
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| 46:16 | not which which are not not active out cannot help but this out and |
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| 46:23 | this is the antennas they're receiving their America. So this cell cannot help |
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| 46:29 | fires and whatnot, fireside excitation or . But once it receives the impetus |
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| 46:35 | will decide. The selma will decide this cell will produce an action |
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| 46:41 | But the synopsis they can be thousands of them are active on all |
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| 46:48 | these branches and they can be for 20,000 excitatory synapses active from 5030 synopses |
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| 46:55 | and they can this activity may happen a matter of like 3 to 4 |
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| 47:01 | . And that cell now has to and process that information. 34 milliseconds |
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| 47:09 | say I'm gonna pass on the signal I'm gonna stay quiet. So yeah |
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| 47:28 | there are other types of neurons. are other types of neurons. And |
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| 47:32 | start looking at some of this diversity we'll use the hippocampus as an |
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| 47:37 | Will not look into the cerebellum circuits there are climbing fiber cells and there |
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| 47:45 | this Birkin Ji cells. So there's variety, there's uh several different subtypes |
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| 47:50 | cells and each one of the And the Hippocampus is we'll see there |
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| 47:55 | probably 20 for 25 some types of neurons. And hang on to that |
|
| 48:02 | for a few minutes because we'll walk some of this. Oh, I |
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| 48:08 | very poorly here. Sorry, I will tell the difference in and |
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| 48:18 | in B and C. Okay, , it's a good question. Uh |
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| 48:27 | morphological descriptions, you may not be and you may need to use additional |
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| 48:33 | and a specific for axons with membranes we can do now for sure. |
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| 48:39 | . There are certain markers that will stay within the axons. And we'll |
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| 48:42 | about that also in this course they they received the city of solar |
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| 48:55 | They received the information through from the and they carry that information to the |
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| 49:01 | and the selma makes a decision and it output through the another accident. |
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| 49:06 | called the central accent. Yeah. also receiving information as well as sending |
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| 49:16 | information. Yeah. It's interesting. ? It's unusual. Yeah. And |
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| 49:21 | every size. There's exception to the . And in this neuroscience there's probably |
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| 49:28 | lot of exceptions to rules. And yeah, you think of dendrites mostly |
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| 49:34 | information and here you have an accent that information. So it's it's it |
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| 49:38 | different. It is different in this case. This is a out of |
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| 49:42 | periphery, you know? So then that case if you're not differentiated, |
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| 49:48 | their functions and how do you know urologist differentiated? Uh Well, they |
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| 49:56 | different than the uh No. Well this case you would have to differentiate |
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| 50:02 | two axons. The dendrites and axons very different function. Dendrites don't produce |
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| 50:09 | potentials, physiological thing. Okay. they look more theologically very different. |
|
| 50:16 | produce action potentials and they have myelin them. So morphological lee they look |
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| 50:21 | different than they will have this Myelin around them. And then drives don't |
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| 50:25 | that. Dendrites don't have money. that's something that's very specific to |
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| 50:31 | Yeah. But here you would want say, well, in the pseudo |
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| 50:35 | unit polar cell which is the which one is the peripheral while the |
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| 50:39 | is going to be attached to the . And then we'll look a little |
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| 50:44 | more into this anatomy. So it be more clear and there's gonna be |
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| 50:47 | branch which is central. That's going the spinal board. So all |
|
| 50:52 | Uh some of these dendrites can be as we talked about. They will |
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| 50:59 | them do the spines. But not dendrites have to have spines. So |
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| 51:04 | are some dendrites that will be a too. It's not as I said |
|
| 51:09 | science. There's an exception to the . So we learn about the spines |
|
| 51:13 | you think that all the dendrites and you find some neurons that are a |
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| 51:18 | in their dendrites. Ah In general of your questions are very good. |
|
| 51:27 | to answer what specific subtype of neuron sell you're looking at, you will |
|
| 51:33 | have to employ multiple techniques and you have to use multiple ways to describe |
|
| 51:42 | morphology, the connectivity, the excitability that is still not going to be |
|
| 51:51 | . So you will have to use markers that are self specific or sub |
|
| 51:56 | specific markers to distinguish between these different of neurons. So in this case |
|
| 52:04 | of the cells or production cells and are into neurons. What does that |
|
| 52:09 | ? That means that sir certain cells we already noted that the hippocampal parameter |
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| 52:17 | sell certain cells will send their axons one area of the brain into another |
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| 52:25 | of the brain where they will contact neurons. And these are called projection |
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| 52:32 | because they project from one area of brain or one network and they can |
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| 52:39 | long distances millimeters sometimes even centimeters and into other neurons. And these projection |
|
| 52:47 | are typically excitatory projection cells in general cerebrum you have 80 to 90% of |
|
| 52:54 | of the neurons are excitatory and 10 20% are inhibitory neurons. That means |
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| 52:59 | 80 to 90% of neurons are going be producing glutamate and releasing glutamate and |
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| 53:05 | to excite other cells. And 10 20% of neurons going to be producing |
|
| 53:12 | releasing Gaba and trying to inhibit other to which they are connected. So |
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| 53:21 | this is the projection and projection cells typically excitatory cells and locally you would |
|
| 53:29 | many different neurons that talk to each through axons and talk to the parameter |
|
| 53:37 | and interconnect and this is their axons they do not lead these local networks |
|
| 53:45 | uh structures of the brain or So their local inter neurons and typically |
|
| 53:54 | of the local inter neurons are inhibitory an exception to the rules. So |
|
| 54:04 | cells are excitatory and they communicate information networks and the inhibitory cells into neurons |
|
| 54:14 | they stay within these localized networks and control the activity of the excitatory cells |
|
| 54:21 | they can influence how much of this cell activity is going to be communicated |
|
| 54:27 | the connected adjacent networks. So this morphology, right connectivity, projections versus |
|
| 54:39 | of excitability, excited very self versus cells stealth. Self specific markers. |
|
| 54:47 | know that excited to ourselves will release that inhibit ourselves will release Gaba. |
|
| 54:57 | , so glutamate will be released External terminals. So there's other |
|
| 55:06 | glutamate and Gaba are not the only . Uh there is co expression of |
|
| 55:12 | peptides in excited during inhibitory cells and are multiple cell specific markers. One |
|
| 55:20 | the features that distinguishes these 250 different of cells is that a slightly different |
|
| 55:27 | subset gets expressed in these cells that one cell you look, you |
|
| 55:32 | polar, another one pseudo unit And also not just morphological lee but |
|
| 55:38 | cell specific or intracellular markers that are markets inside the cells. And that |
|
| 55:45 | still not enough. We need to the action potentials and firing signature, |
|
| 55:52 | sequences of the action potentials that neurons produce. And this is the first |
|
| 55:57 | published in the cellular recording of the potential from 1939 and documents that you |
|
| 56:05 | this very fast 1 to 2 milliseconds duration reflection of approximately 100 million volts |
|
| 56:11 | amplitude. That is the action Okay, so let's try to, |
|
| 56:20 | the next 10 minutes, cover the . And as we cover the |
|
| 56:25 | we're almost finished with neurons and gonna into glia. And glia will probably |
|
| 56:31 | about half an hour of our next because we'll only address a few uh |
|
| 56:37 | of glia, few functions of the cells. But what what is illustrated |
|
| 56:43 | , what we're looking at is a piece in that structure that is known |
|
| 56:51 | hippocampus. Okay, hip hop campus , campus hippocampus. We're looking this |
|
| 57:11 | is a is a very interesting structure overall for example have this shape. |
|
| 57:19 | we're looking at one area of the . Okay. And the area we're |
|
| 57:24 | at and the size of this area approximately one centimeter or 1000 micro |
|
| 57:33 | We're looking at the scale of this . So this box is right here |
|
| 57:38 | in that box. And in what is hippocampus already mentioned? Hippocampus |
|
| 57:45 | a structure in the brain that is in semantic memory which is names, |
|
| 57:53 | , stories, facts, recollection of , semantic memory. It is also |
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| 58:01 | to emotional processing and not only encoding that memory through hippocampal circuits but also |
|
| 58:10 | of different in particular semantic memories through hippocampal circuits. Campus is actually one |
|
| 58:19 | the structures that is responsible for learning memory. And therefore, since we |
|
| 58:28 | Alzheimer's disease. Mhm. This is , remembering things, semantic memory. |
|
| 58:36 | discussed. Alzheimer's disease and Alzheimer's This is one of the structures that |
|
| 58:41 | susceptible to damage is the hippocampus. is also very uh excitable part of |
|
| 58:53 | brain and a lot of times in around the hippocampus. There may be |
|
| 59:00 | of seizures and epilepsy and there's also neuro degeneration of hippocampus in many neurological |
|
| 59:09 | . Not just Alzheimer's disease but for , in advanced and severe stages of |
|
| 59:15 | as well. So it's a very structure but it's not a part of |
|
| 59:20 | cortex. It's what is called our cortex are key cortex and what are |
|
| 59:31 | means is that it's ancient or its cortex. And the reason why it |
|
| 59:39 | because it's predominantly a three layer structure gray layer which is stratum stands for |
|
| 59:47 | ready autumn, this wide band layer is strategy from the dollar and below |
|
| 59:54 | stratum orients. So it's a predominantly layer structure that is involved in semantic |
|
| 60:04 | and learning and memory involved in emotional processing and recall of memory. |
|
| 60:12 | It's archaic cortex because it has only layers neocortex. But the cerebral |
|
| 60:20 | what we typically call neocortex is Its new cortex. It's six layered |
|
| 60:30 | . So hippocampus is more simple. three layered structure. Although I think |
|
| 60:34 | the hippocampus is trying to become new . Neocortex is the the greatest and |
|
| 60:40 | latest in the evolutionary development of the brain. The six layered circuits and |
|
| 60:47 | that we have that are responsible for highest cognitive, mental and physical functions |
|
| 60:53 | we can perform. And so our cortex is an older cortex and so |
|
| 60:59 | 63 layers in this case. And we were to stain this patch of |
|
| 61:08 | , this archy cortex glue mainstay it stay all of the parameter cells and |
|
| 61:14 | find that 80 to 90% of all excitatory cells in the area are veronica |
|
| 61:23 | 80 to 90% And if we stay Gaba or later you will learn from |
|
| 61:28 | enzyme God we will reveal that 10-20% the cells are inhibitory into Nunes. |
|
| 61:37 | if we stay for parameter inside of we'll find overwhelming majority of them and |
|
| 61:45 | and growing alive. And if we these parameter cells more logically we would |
|
| 61:52 | that there's most of them located in of them in radiology. Some of |
|
| 61:58 | the glorious layers. But they look same. They have the same dendritic |
|
| 62:05 | . They are essentially indistinguishable from one morphological E. And use a projection |
|
| 62:11 | so they will project their access outside this network into the other adjacent networks |
|
| 62:17 | the brain. So is there more one excited or itself sub by morphological |
|
| 62:26 | . It's indistinguishable if we look at function of action potential so also produce |
|
| 62:32 | same patterns of action potentials. So distinguishing. So how can we |
|
| 62:38 | Well, they live in different Okay, that's our cue. But |
|
| 62:42 | that doesn't mean that they're different sometimes they live in different layers. So |
|
| 62:47 | would stain them for intracellular self specific in this case is C. |
|
| 62:54 | Which stands for pal Brendan. And phenomenal cells will be C. |
|
| 62:59 | Positive and these are the cells and that live in two different layers will |
|
| 63:05 | C. B. Negative. So the excitatory projection neurons you really have |
|
| 63:12 | subtypes and it's really to see be . C. B. Negative except |
|
| 63:16 | two CV negative are located in the Blair's to the and so this is |
|
| 63:23 | on switch the on signal. The for projection sources. They're excited often |
|
| 63:29 | goes on and communicates the life of information into the adjacent now So then |
|
| 63:35 | would do the same for all of Galba positive staining cells you will |
|
| 63:40 | Now I want to see all of inhibitory cells. So these are all |
|
| 63:45 | excitatory cells. And when we stay for different neurons we found out that |
|
| 63:49 | are 21 different subtypes of inhibitory And how can we tell that their |
|
| 63:55 | cells, first of all they stain Gabba, they expressed inhibitory neurotransmitter. |
|
| 64:01 | we know that. And then we at their morphology and their distribution in |
|
| 64:06 | layer. So you can see that of these cells can be very clearly |
|
| 64:10 | more theologically one from another. This the selma, these large protrusions of |
|
| 64:17 | and these yellow cops are the synapses in particular the location of the |
|
| 64:23 | With respect to the parameter cell This cell axons the yellow cups are |
|
| 64:30 | the paris somatic regions of this parameter cells very powerful because the more you |
|
| 64:36 | closer to the integrated region of the and the action initial segment the stronger |
|
| 64:42 | in this case inhibitory effect you can and you can very clearly tell the |
|
| 64:47 | for self is very different from number . Just morphological E. It's not |
|
| 64:53 | it lives in different layer, It different morphological, it has these horizontally |
|
| 64:59 | them drugs and then it has this action that goes all the way to |
|
| 65:04 | top and targets the optical regions of tyrannical self. So you can tell |
|
| 65:10 | morphological if these are different, we can distinguish them pretty well and you |
|
| 65:16 | distinguish a lot of these cells but a lot of them will be looking |
|
| 65:21 | and for example, number two and four, why are they different? |
|
| 65:27 | that inhibit their narrows. They look same Dunn drives going vertically. The |
|
| 65:37 | are targeting the same regions here. morphological lee they're distinguishable this enough to |
|
| 65:44 | . Their locations are the same as parameter will sell. So the only |
|
| 65:48 | that we can do is we can them for self specific markers. And |
|
| 65:52 | turns out that number to sell which call the basket cell is positive for |
|
| 66:00 | a number four cell which looks identical the number two. And they produce |
|
| 66:04 | identical firing pattern of action potentials contacts the same reasons soprano sell, they |
|
| 66:11 | express another marker that is called C. K. Stands for color |
|
| 66:17 | . So I'm gonna try to wrap in the next minute or two. |
|
| 66:22 | quite often uh students ask me if have to remember the markers on the |
|
| 66:29 | and how many different 21 subtypes of express different markers. No, |
|
| 66:34 | The fact that parameter excited ourselves are boring in the variety of their stuff |
|
| 66:40 | . It's only really to provide them positive or negative and maybe the difference |
|
| 66:45 | layer location. But the variety and morphological and functional variety in this hippocampal |
|
| 66:54 | stems from the morphological and functional variety the inhibitory cells that are local network |
|
| 67:03 | neurons and that are not projection And then definitively to distinguish between these |
|
| 67:10 | cell subtypes. You need morphology, need self specific markers and when we |
|
| 67:19 | back on Tuesday you need to know sequence and the patterns and the frequencies |
|
| 67:27 | their action potentials. Because this is dye election. It will tell you |
|
| 67:32 | the two selves look the same and they have the same cell specific |
|
| 67:37 | They speak two different dialects of the language. Therefore there's still different cells |
|
| 67:43 | . Okay, thank you very And I will see everyone on |
|
| 67:48 | Have a good |
|
