| 00:00 | Welcome Thio Cellular Neuroscience. This is first lecture of this very interesting course |
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| 00:09 | this first slide illustrates the brain and Ronald circuits. So on the |
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| 00:19 | you obviously have the cerebral cortex, central nervous system, the cerebellum, |
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| 00:25 | brain stem going into the spinal This is the central nervous system. |
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| 00:31 | now, if we were Thio, in. And what is happening in |
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| 00:35 | one of these microcircuits or macro You would see that you have billions |
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| 00:45 | neurons that are making trillions of these specialized connections that we call synopsis. |
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| 00:59 | a single neuron that is shown here has its soma. It has a |
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| 01:06 | and it has these accents. Most the synapses are formed between accents and |
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| 01:12 | drives and accents and sell most of called accent dendritic access. Somatic, |
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| 01:18 | accidents can also contact our other accents those synapses air called Axel economic |
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| 01:25 | A single neuron like that, but a complex anatomy and morphology can be |
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| 01:32 | hundreds of thousands of synapses. So job of this neuron on single neuron |
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| 01:40 | thio integrate to calculate information sometimes from , sometimes from thousands, sometimes from |
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| 01:48 | of thousands of synapses contacting it and make a decision whether that information that |
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| 01:56 | being sent is going resolved. this neuron. And if it is |
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| 02:02 | it enough to produce an action potential when it produces an actual potential, |
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| 02:08 | causes a deep polarization that travels down accents. And as it travels down |
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| 02:15 | axons, it releases neurotransmitters in these . And once again the cycle |
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| 02:24 | so neurons are interconnected with each but neurons air also surrounded by |
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| 02:31 | And so this is what we refer as a tripartite synopsis. Communication between |
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| 02:36 | and the surrounding glia, which is much involved in the synaptic communication between |
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| 02:43 | . So at the same time, different parts of the brain, you |
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| 02:46 | activation of different neurons and neural Thio varied degree and these neural circuits |
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| 02:59 | lobes in the brain. They produce of activity. These rhythms of |
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| 03:06 | calm and certain frequencies and they travel waves that interconnect adjacent circuits. And |
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| 03:16 | these rhythms of activities sort of like sort of activity of excitation up and |
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| 03:21 | down excitation often inhibition down in this is communicated across different brain centers. |
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| 03:32 | certain brain centers that are dedicated to information. Primary sensor information processing like |
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| 03:38 | lobe in the back in the primary cortex is dedicated to visual information processing |
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| 03:44 | the I in the temporal lobe, have, ah, primary auditory cortex |
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| 03:50 | dedicated to auditory sensor information processing. then there are major areas in the |
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| 03:59 | that are dedicated thio joining information from modalities from multiple sensory modalities. Hearing |
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| 04:13 | , vision, emotional, state of and physical state of being as |
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| 04:23 | So you have neuron is and networks oscillate that produced the ways that communicate |
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| 04:31 | ways to each other. You have of the brain that are dedicated thio |
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| 04:35 | sensor information processing, and then you areas in the brain that recalled association |
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| 04:41 | that will associate these very complex census sensory senses and also internal environment |
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| 04:51 | Thio to produce A to produce the activity of the brain to produce understanding |
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| 04:58 | pictures that have multiple sensory and multiple aspect and cognitive aspects and physical involved |
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| 05:06 | well. So the overview of the nervous system again is we have the |
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| 05:15 | cortex which is divided into the major . The frontal lobe, the parietal |
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| 05:21 | exhibit, all with temporal lobe and cerebellum, so about on a lot |
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| 05:27 | times, is referred to as a brain, and you have brains Town |
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| 05:32 | . Problem the brain stone, which located in your neck from your neck |
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| 05:37 | , you have spinal cord that goes about number two, number three and |
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| 05:45 | vertebra. Where the proper spinal cord . It turns into what we call |
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| 05:51 | it a quinoa Horses scale under, , loose, no longer proper structure |
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| 05:57 | a spinal cord, with loose projections the nerves going into the lower extremities |
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| 06:03 | the body here. So, together projections of censoring and the motor |
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| 06:13 | you also had interactions between the central system and the peripheral nervous system, |
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| 06:19 | that a system that I would add that is over doing the tags books |
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| 06:24 | mess enteric nervous system. There's a enteric nervous system that's surrounding the viscera |
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| 06:30 | organs in the abdominal cavity that is much complex and very much intricately involved |
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| 06:39 | the CNN s, and there's an discussion of the microbiome and effects of |
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| 06:46 | on the mental, even neurological, , health spinal cord is, you |
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| 06:56 | , will communicate Information from the muscles and joints is all the sensor |
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| 07:02 | will travel through the dorsal side of spinal cord through the dorsal root ganglia |
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| 07:08 | enter into the spinal cord and spinal can produce reflexive behavior, so censor |
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| 07:17 | that comes from the skin. If step on a nail, reflexively will |
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| 07:23 | the muscles and withdraw your leg from now. And, of course, |
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| 07:27 | will inform your central nervous system and cognitive centers that you just stepped on |
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| 07:34 | nail that it was painful. But not going to go through that process |
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| 07:38 | the level of the spinal cord. going to be a reflexive behavior, |
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| 07:43 | there are some reflexive behaviors. Sometimes involving just one or two synopsis. |
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| 07:49 | lot of times, their policy synaptic a gagging behavior or vomiting behavior, |
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| 07:56 | may say, is multi synoptic in many different centers in the brain |
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| 08:01 | But withdrawing your hand from the fire a sharp object is reflective of the |
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| 08:08 | of the spinal cord that later gets through the ascending fibers into the central |
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| 08:13 | system. And there it gets uh, perceived cognitively and adjusting whatever |
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| 08:22 | or whatever behavior needs to be adjusted the time. All of the sensor |
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| 08:28 | goes through dorsal root and all of ventral information. All of the modern |
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| 08:32 | not just, uh, relax if also cognitive motor commands. I am |
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| 08:40 | thio wave my left hand That is coming in the hand from the spinal |
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| 08:46 | from the motor nerves of the spinal contracting or relaxing, deposing muscles, |
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| 08:56 | one set of muscle and relaxing the set of muscles. So this is |
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| 09:02 | we know, and this is sort the basics of the C. N |
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| 09:05 | . And I'm gonna highlight a few what I consider very important findings in |
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| 09:10 | history of neuroscience. So going back 30,000 years, BC, all around |
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| 09:17 | world Mesopotamia, Egypt and South America regions where Peru's now especially very prevalent |
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| 09:28 | Indians is a technique that's called brain Nation. And why I find this |
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| 09:36 | interesting is because brain Trumper nations were a za potentially the first neurosurgery in |
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| 09:45 | history off neuroscience and neurology and later . Thes brain trapper nations where precise |
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| 09:54 | symmetric openings in the skull to access tissues underneath the skull. They were |
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| 10:02 | multiple times, and a lot of they would be found in multiple locations |
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| 10:06 | the skull, and they were not same as just gash or or or |
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| 10:15 | . The skull has followed during a brain injury, but rather that there |
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| 10:20 | a whole method off anesthetizing the person performing the brain. Trapper Nation thought |
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| 10:27 | spiritually released the evil spirits. thio alleviate the pain and pressure, |
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| 10:34 | , headaches, potentially internal bleeding, inside the brain and so on. |
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| 10:42 | this is very important that we have tools and the documentation off these brain |
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| 10:48 | nations going back to 30,000 years ago a tool off fixing off, trying |
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| 10:55 | do something with a brain to fix problem. Then another very important part |
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| 11:02 | the neuroscience history is the part off , uh Edwin Smith Surgical Papyrus, |
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| 11:09 | was written by Imhotep in Egypt. , on and, uh, it |
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| 11:17 | 48 cases of injury. 27 had cases. Although Egyptians don't consider brain |
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| 11:25 | important, they say it's matter of skull. They suck it out, |
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| 11:28 | , with these tools through the nose preparation for embalming. But what is |
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| 11:35 | important is that Imhotep realizes distant the of central nervous system injury. So |
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| 11:42 | really recognizes there's a lot of building on pyramids. There's a lot of |
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| 11:47 | going on wars. But when he is that somebody can have an injury |
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| 11:52 | the head and they may lose the in the arm so that the CNS |
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| 11:58 | there's distant the facts that are related CNS injury Onda. Another important thing |
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| 12:06 | those that are interested in emergency Imhotep is created what we call the |
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| 12:13 | classifications. Okay, you get triaged board, and those days it was |
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| 12:22 | , and to be treated may be and not to be treated. Now |
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| 12:27 | wait. What's interesting is we have different modern medicine. Everybody will get |
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| 12:33 | , but notice what's happening when the care system gets strained? No, |
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| 12:39 | this surgeries. So maybe treated right to be treated much, much |
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| 12:46 | Don't treat it now. Mhm, treated Now you have to make a |
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| 12:52 | up. Isn't a person Kogan, , on the ventilator, Or is |
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| 12:57 | somebody else that is going in Or should they wait because it's not |
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| 13:00 | deadly are not to be treated where are reports, actually, and some |
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| 13:06 | overcrowded hospitals now just the lock off and potentially ventilators so that those that |
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| 13:17 | very, very severely ill and very old that may be abandoned at |
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| 13:21 | moment, not treated because of the of the health care systems. And |
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| 13:25 | about it. Okay, think about from the perspective that you know, |
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| 13:32 | Stree, AJ and modern medicine. fantastic. But when we get into |
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| 13:37 | health crisis, we go back to of the basics that we saw centuries |
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| 13:44 | . Renee, the card. I him up Not because you need to |
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| 13:48 | and forever the cognito Ergo, sum , I think. Therefore I am |
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| 13:54 | . Remember, the card is uh, he is credited with Western |
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| 14:01 | body distinction. Again, this is . My body distinction worshiping spirits, |
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| 14:09 | . Herbal medicine is happening everywhere in , Africa, Mesopotamia. But what |
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| 14:15 | the card ridiculous pretty well is that thinks that body is a machine, |
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| 14:24 | in his theories fluid mechanical theory and there is a communication between the spirits |
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| 14:29 | the brain and that there is some that moved from the brain from the |
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| 14:34 | into the periphery that then move your and allow you to contract the |
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| 14:40 | Uh, but what's important is that also introduces the concept of reflexive |
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| 14:46 | So something that is reflective withdrawing hand the fire versus something that is, |
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| 14:52 | think, therefore I am because I the higher powers of my brain as |
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| 14:58 | interact with the fluid mechanic model. body. Andi Luigi Golani is the |
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| 15:06 | in the 18th century that stimulates frog and frog nerve, and he sees |
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| 15:14 | when he stimulate it with electricity, frog muscles and nerves contract. |
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| 15:18 | he says, that definitively proves that are not water pipes traveling across from |
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| 15:26 | brain from the ventricles. But these are actually more like wires. No |
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| 15:33 | and nerves are more like wires, they can produce electricity and they can |
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| 15:37 | contraction and they can communicate with each , and they can cause a cost |
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| 15:41 | of the muscles on. Once we of a game, that understanding of |
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| 15:48 | , so the brain has reflexive the has cognitive performance functions, philosophy, |
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| 15:55 | , all of these things. Contemplation infinity. We've now start being very |
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| 16:04 | . Where is the seat of Where is the seat off pain? |
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| 16:09 | is the seat of emotion? Where the seat of all of these wonderful |
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| 16:14 | that humans have on this? Is goes to the concept of brain |
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| 16:20 | Localization? Where is that function? And for knowledge, Isda's wrong is |
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| 16:27 | where where the first wants to start addressing and dividing the brain into different |
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| 16:34 | , What is shown here is an , an image, all the skull |
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| 16:38 | that skull has all of these different on it. And each one of |
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| 16:44 | outlines and circles and ovals represent a part of the brain that is responsible |
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| 16:52 | different faculty. So according to Joseph Nephrologist system, the brain is the |
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| 16:58 | of the mind. The mind is of multiple was composed of multiple distinct |
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| 17:04 | faculties. Because each faculty is each faculty must have a separate seed |
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| 17:11 | in the brain at 35 areas that noted on what's called the size of |
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| 17:15 | organ. Other things being equal is measure of its power. So they're |
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| 17:19 | that is, this part of the is more developed, which is responsible |
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| 17:24 | a specific function. You'll actually see bump on the outside of the skull |
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| 17:28 | that part of it. So they that the shape of the brain is |
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| 17:32 | by the development of the various In fact, when the skulls of |
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| 17:38 | and young Children are softened the shape around the grown brain tissue, they |
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| 17:43 | him the plates of the skull and then they finally fuse that about |
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| 17:47 | couple of years of age, so skull takes its shape from the |
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| 17:51 | The surface of the skull can be as an accurate in mix of psychological |
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| 17:56 | and tendencies, organs responsible for different aptitudes and character traits of what makes |
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| 18:01 | generous. What makes you generous according foreign ologists in the 18th and 19th |
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| 18:09 | is potentially Area 37 because Area 37 measured by for knowledge, is stool |
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| 18:18 | here measures the angles, the this spherical blah, blah, |
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| 18:23 | It says that is Ah, bump on the skull, and that's what |
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| 18:27 | you generous. That's the generosity So for enologist would come to foreign |
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| 18:33 | , officer would sit you down for of these tools, measure had to |
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| 18:36 | , like, Yes, you you are generous, you know, |
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| 18:40 | 37 is is really big. you know, go home now. |
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| 18:47 | Fern. A logical journal. I the slide 18 48 These different parts |
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| 18:52 | into different functions. Different aptitudes that in eight. And the more you |
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| 18:57 | them, the bigger they become. the bigger they become. The bigger |
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| 19:00 | the bump that could be measured on surface of the skull. Wrong. |
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| 19:07 | , in reality, you can only what's happening with specific functions by looking |
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| 19:14 | the actual brain structures and the discovery the specific brain structure that's called Broca's |
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| 19:23 | happened Thio, Dr Paul broker. had a patient that had a missing |
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| 19:29 | of this brain right here in the lobe that is now called Broca's |
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| 19:33 | And so he's discovered after studying many that people that had Broca's area damaged |
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| 19:41 | this area. They suffered from expressive , expressive evasion lows, difficulty in |
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| 19:48 | thoughts through speech or writing. The knows what he wants to say but |
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| 19:55 | find the words he needs, or strings them in the wrong order. |
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| 20:01 | DSO, we now know that damage Broca's area is responsible for expressive |
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| 20:07 | There's another air in the brain over area, and this broker is important |
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| 20:11 | because he's the first person to Ah, hole in the brain saying |
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| 20:16 | is the whole of the brain in brains that I have collected. |
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| 20:20 | hole is in the same location, the people that have all this location |
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| 20:24 | all have a specific symptom, a function, localization of specific function in |
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| 20:33 | case, a specific dysfunction, a failure and so legions. The |
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| 20:41 | to the brain areas is what through history revealed the functions of different |
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| 20:47 | of the brain. Receptive aphasia is you have damage to Vernon CAS |
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| 20:53 | which is located in in In in parietal lobe. Here on the border |
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| 20:59 | temporal onda parietal lobes. The patient the voice or sees the print but |
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| 21:05 | make sense of words. So it's perceptive or receptive. If Asian there |
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| 21:11 | a gnomic or amnesia. Aphasia, is least severe form of Asia, |
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| 21:15 | difficulty in using the correct names for objects people, places or events. |
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| 21:23 | not to be confused with short term , UH, or poor facial recognition |
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| 21:32 | poor name recognition. That's something that constantly experience, so, but it |
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| 21:37 | at least two there because it it is minor. It doesn't really |
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| 21:43 | your expression. But there's global which is severe and extensive damage to |
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| 21:49 | language areas of the brain. And you have damage to hearing and motor |
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| 21:56 | associated with the language production, these kind of speaker understand speech, nor |
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| 22:03 | can read or write. So this be much larger areas that get affected |
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| 22:08 | are affecting Broca's vernick, Assyrian, other areas of the brain as |
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| 22:14 | And, as you can see, US area, expressive aphasia is very |
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| 22:17 | closely linked to the motor cortex, initiates the commands the motor commands for |
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| 22:23 | for talking. My motor cortex is initiating a command for me to talk |
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| 22:29 | next slide. Organizational specific functions. gauge is probably the most famous bigger |
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| 22:38 | in having damage to the brain and away with massive damage. And it's |
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| 22:45 | device that went off. And this rod metal rod went from bottom of |
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| 22:55 | skull through the top, leaving large of the prefrontal cortex damage, |
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| 23:02 | impaired vision and the left eye. for the most part, he was |
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| 23:11 | . He just was very angry He couldn't control his anger. He |
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| 23:18 | control his executive functions. He was and was aggressive and so told us |
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| 23:25 | the prefrontal cortex and he also had the hippocampus and memory are involved in |
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| 23:30 | processes. They're not involved in processing because he was still seeing from one |
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| 23:36 | , and his visual cortex in the of the brain was intact. So |
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| 23:41 | shows you that even really severe damage the brain. And he is the |
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| 23:46 | famous person because he survived the severe we had a specific loss of functions |
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| 23:54 | . But he survived. He and he lived many years after. |
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| 23:59 | get the same job, though, he couldn't control himself very well. |
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| 24:03 | only way the other way that we different parts of the brain is when |
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| 24:08 | already had electrical electrodes that can be and animals that we could stimulate the |
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| 24:17 | brains, monkey brains and unfortunately, the history off human experimentation, human |
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| 24:25 | is well, so historically, what talk about today comes to the end |
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| 24:37 | the 19th century beginning of 20th century these three great man Camelia Golgi. |
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| 24:45 | believed in particular theories. He believed all of these brain cells are not |
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| 24:51 | . That they all combined together, enveloped by the same side of |
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| 24:56 | Mick shall outside of plasma continuity, his student, Ramon Alcohol, who |
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| 25:04 | in neuron doctrine and believed in synaptic . He used the Golgi stained |
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| 25:10 | invented the stain, and the Golgi stains 1 to 3% of all of |
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| 25:14 | neurons in the brain. But when stains those neurons that actually Staines there |
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| 25:19 | most stains there down brides and stains optical done drives and then black, |
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| 25:25 | stains these accents also. So it ramon alcohol that use Golgi stain to |
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| 25:32 | these beautiful neuronal circuits of a lot what we still study is, we're |
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| 25:38 | trying to understand what Ramon alcohol revealed what Sir Charles Sherington coined as a |
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| 25:46 | the term of the synapse. We're trying to understand the inter connectivity, |
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| 25:50 | directionality of the connectivity, the individual and thousands of synapses and hundreds and |
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| 25:58 | of synapses and neural networks. How work together was the anatomy or morphology |
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| 26:04 | these different circuits and systems. And is the function? What is the |
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| 26:11 | ? Mhm to? These are three important figures. Chameleon Golgi invented the |
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| 26:17 | stain Ramon alcohol. He used the stain to describe neuronal circuits and thio |
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| 26:23 | your own doctrine, arguing where each is an individual discreet cell just like |
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| 26:28 | South theory that communicate with other And Sir Charles Harrington said coined this |
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| 26:34 | of the synapse, a very specialized when neurons communicate with each other, |
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| 26:41 | know that, you know, from very rudimentary understanding of brain function |
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| 26:48 | we will talk later in this course non invasive brain imaging and the brain |
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| 26:54 | that are created by different parts of brain. Brain map is essentially the |
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| 26:59 | that is present in a specific part the brain amplitude frequency of that activity |
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| 27:05 | how it is being communicated across different of the brain, and this diagram |
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| 27:10 | that if you activate, if you an individual to do different tasks, |
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| 27:16 | will activate different parts of the And individual looking at the words will |
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| 27:20 | involved simple cortex for vision, listening the words auditory cortex for listening, |
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| 27:29 | words, broke US area and the motor cortex here and then thinking of |
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| 27:35 | . You can see that that map away from the primary visual or the |
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| 27:40 | auditory areas to different parts of the , which now in most cognitive processes |
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| 27:47 | what we also have, is the to image that activity non invasively in |
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| 27:52 | whole brains for going the lab and activity and individual synapses. This is |
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| 27:58 | special feature, if you recall of and dendrites and a good experience. |
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| 28:02 | very small protrusions that come off the mushroom thin, short study spines, |
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| 28:07 | they described here. And this is place where a lot of the synaptic |
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| 28:13 | , as well as changes in synaptic of synaptic plasticity, takes place, |
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| 28:18 | we have the ability and modern thio, image activity and whole grains |
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| 28:22 | well as in single synapses or single , which, of course, it |
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| 28:27 | doing mostly in vitro studies, apart some potentially in vivo studies, using |
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| 28:35 | very important microscopes and what we can using started like microscope is about 0.1 |
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| 28:43 | meters and the space between neurons is 29 millimeters. So this this space |
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| 28:49 | you see, this s P S stands for posson OPIC density. This |
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| 28:54 | dendrite with post synaptic density and right an ax on with vesicles neurotransmitter vesicles |
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| 29:02 | it looks like the num brains but they're not. There is a |
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| 29:06 | distance of about 20 nanometers between one , one neuron and that in |
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| 29:12 | So if you use regular light you cannot visualize these synapses. You |
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| 29:16 | thio use a con focal microscope or functional imaging, or you have to |
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| 29:23 | to greater resolution. Using electron microscope allow you resolve the individual synapses, |
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| 29:30 | it does. It will visualized these dendritic spines, and we also have |
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| 29:37 | by which we can visualize cells without them these days. And so later |
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| 29:42 | the course, we will talk about physiological recording techniques, especially a lot |
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| 29:47 | wholesale technique comparing the wholesale technique to non invasive, like EEG. And |
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| 29:53 | come back and discuss what is in diagrams. But this is a |
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| 29:58 | It's in my laboratory here, you age that allows us toe play slices |
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| 30:03 | the brain and visualized narrows without any on target individual multiple neurons at the |
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| 30:09 | time and record activity. And in term you could see multiple Otto's again |
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| 30:15 | study from in Viva from clinical You're interested in medical applications for medical |
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| 30:23 | ing traumatic brain injury, emergency image thio Very concrete. Very fundamental studies |
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| 30:32 | a single synapse activity in the single activity in single cells or interconnected |
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| 30:40 | And I'm gonna actually end here. I have another slide I'm gonna end |
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| 30:46 | . The reason why is because I this lecture tripartite synapse in part, |
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| 30:51 | I haven't mentioned the third part just briefly. The third part is |
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| 30:57 | and I'm just going to show you neuron in the circuits and that you're |
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| 31:02 | responsible for like, wow, we to know all of this. We |
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| 31:05 | remember this from undergraduate neurobiology. So shows you your own pre synaptic neuron |
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| 31:13 | to Posson optic shows. Synaptic the release of the neurotransmitters from these |
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| 31:20 | in the synaptic class in targeting of receptors and these receptors of post synaptic |
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| 31:26 | that can be I on a tropic that can also be met over tropic |
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| 31:30 | will come back and talk about it more. Glia is not a passive |
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| 31:35 | here. One of the types of is called on Astra Side. Leah |
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| 31:39 | not passive. Glia will actually collect neurotransmitters. Let's say it's new. |
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| 31:48 | released by the synapse, excited during will cycle these excited during neurotransmitters. |
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| 31:54 | have their own way of Leo transmission communicating to neurons. And there are |
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| 32:00 | in involved in in synaptic plasticity and taking care not only what is happening |
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| 32:08 | the maintenance off chemical maintenance of neural here, but also synaptic plasticity influencing |
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| 32:17 | plasticity, the communication between neurons. why we call it a tri part |
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| 32:22 | , really a three part synapse, synaptic neuron, possum optic neurons and |
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| 32:28 | that there's no way a passive we'll a lot more Mongolian different subtypes as |
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| 32:33 | continue through the course, but this just an example of what we call |
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| 32:38 | canonical circuit tripartite circuit and understanding that is going to be crucial on. |
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| 32:46 | very interesting also. So we'll look of these diagrams. Aziz, we |
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| 32:53 | with the |
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