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00:00 | Yeah. So we're reviewing the syllabus Exam one. This is neuroscience. |
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00:06 | is the meeting electric 10. We start talking about neural transmission as's |
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00:12 | Your exams go and your grade a of each of these midterms will contribute |
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00:19 | your final grade. The final exam also not cumulative. So it is |
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00:25 | like midterm three exam. Um, some of you have expressed the desire |
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00:37 | you would like to keep potentially just exams for an average of the final |
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00:45 | . I'm dropping the third exam. is the lowest score. Um, |
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00:52 | will consider that, of course, you may want to consider that usually |
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01:00 | examine term Exam one is the highest grade, and typically Exam two and |
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01:09 | is too, too few points below the average of midterm Wang. Because |
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01:15 | one contains a lot off basic information introductory information and the complexity of material |
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01:24 | in subsequent section Thio that we're starting in that section three later in the |
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01:33 | I have requested with Casa One more and I'm waiting for them to respond |
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01:40 | the previous years, which were different and not our typical year off 2020 |
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01:48 | the previous years, I have given a pop up quiz during class, |
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01:54 | that pop up quiz counted as additional that students could add to their |
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02:02 | Essentially, it served as a self for your grade. Your curving yourself |
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02:08 | taking this quiz and seeing how many you can gain extra. So if |
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02:14 | quizzes had anywhere between 5 to 8 , each question worth one point. |
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02:20 | between 5 to 8 points. if you answer all quiz questions, |
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02:26 | could potentially jump into different grade for of the midterm exams for the |
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02:34 | the miracles course Now what? I enquiring with Casa. Of course, |
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02:39 | cannot do a pop up quiz, it will have to be a different |
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02:44 | that is your midterm to on the three. It will have to be |
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02:49 | somewhere in the middle of this second that I am requesting Casa if I |
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02:56 | give you a 10 minute quiz this is pretty extraordinary year, and |
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03:03 | requires a separate event scheduling for This will not take place during |
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03:11 | Well, uh, potentially have to place outside the class. But it |
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03:17 | have to be at the much shorter window where everybody will just have one |
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03:26 | two hours to log in to take 10 minute quiz. And if Gaza |
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03:31 | me to do it during the class maybe we will allocate Onley half a |
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03:36 | off the claws for everybody to join take that quiz for 10 minutes, |
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03:43 | , likely will cover in our Follow that material will have the 10 |
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03:51 | quiz within this half A Now, that you can go on to casa |
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03:56 | leave, zoom well down to Casa take the quiz during your regular |
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04:02 | Our let me see the chat some questions and mentum was with which material |
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04:16 | be on the quiz on the The if I if we do have |
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04:21 | quiz, I will confirm with you week that we are able to do |
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04:26 | with Casa. Once we have the material is gonna have to be |
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04:32 | much material from the previous lecture. is really testing whether you're attending the |
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04:38 | . Those quizzes originally were designed as quizzes for those that attempted class. |
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04:44 | if you were not in the class day, there was no makeup |
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04:49 | This was basically a privileged to those that attend the class because those that |
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04:55 | attend the class, I do it those are folks that are not necessarily |
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05:00 | interested in improving their grade. if you're attuned, you're attending the |
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05:06 | and reviewing all of the materials in timely matter. As we study |
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05:11 | you will be prepared for the But I will not specifically point to |
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05:15 | area from the coming lecturers will be in that quiz. Uh huh. |
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05:22 | you have to stay and keep up the materials, attend the lectures in |
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05:26 | to score really well on the It's a different way of studying. |
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05:30 | will not be a review session. you take this quiz. They will |
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05:34 | be sample questions that were given. is just testing. Whether you're attending |
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05:39 | class following the material boom, this your curve. You give it to |
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05:44 | . Okay. So I will follow on how this will proceed with Casa |
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05:52 | give you an update next week. . So today we're launching into talking |
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06:01 | neural transmission. Uh, neural transmission synaptic transmission. The slide says that |
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06:11 | in two weeks. Well, you have an exam in two weeks. |
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06:13 | an older slide. My office used be an S r to science and |
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06:19 | building, too. This tall What I call Soviet building. |
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06:25 | and, uh, it was on second floor 2. 42 g, |
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06:32 | offices and H B S B. is using biomedical Building one on the |
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06:39 | floor. My email is the And so all of my contact information |
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06:43 | the exam technical issues You can please me directly if I don't respond in |
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06:50 | is origin. Please repeat your As I explained to you, if |
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06:54 | still don't get a response, maybe a problem with me receiving or you |
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06:58 | the email. So maybe chat me after the class. I will address |
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07:05 | with you. I haven't heard in couple of days, but typically everybody |
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07:08 | is back for me within the day their respective issues and much sooner in |
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07:17 | where I see it's something that needs be addressed, that speedy, um |
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07:23 | the speedy way, so Today we start talking about the connections between |
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07:31 | The first course section, we understood neurons are neuronal anatomy and glial |
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07:41 | And what you have thio think about all of the folks here that you |
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07:49 | know on the slide your Monica we use Golgi stain. We describe |
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07:56 | discreet individual neuronal units who reconstructed from stains these beautiful circuits who argued that |
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08:11 | are discreet units and was a proponent neuron doctrine using his boss sustained Golgi |
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08:20 | . Sir Charles Sherington is responsible for coining and describing this term of the |
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08:26 | and what is happening in the synapse that is happening now again, the |
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08:32 | toward the middle of the 20th What's interesting is in about the same |
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08:40 | . Time is the third player that in a very famous scientists auto Lowy |
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08:46 | makes the discovery off this chemical neural . So in the first part of |
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08:53 | course, we described how these neurons an action potential at the acts on |
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08:58 | segment these action potentials through solitary really, we, uh, ree |
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09:09 | produce themselves each note over on beer that when this action potential which is |
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09:18 | if the acts on initial segment reaches terminals and you can see that my |
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09:23 | acts on the end of the accent not Miley native and then it's pleasant |
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09:27 | multiple a ramifications where each one of external criminals becomes an individual synapse and |
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09:37 | individual synapses we discussed pre synaptic Lee have mitochondria will have synaptic vesicles filled |
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09:43 | neurotransmitters and plus synaptic Aly and across synaptic cleft. It would have receptor |
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09:51 | to which these neurotransmitters bind and these channels and some of them are G |
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09:57 | coupled receptors is we'll learn and there's whole effect, and that happens. |
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10:03 | optically so this communication between pre synaptic , that zonal terminal plus synaptic cell |
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10:10 | the synaptic transmission. And when we're about the grain, think about this |
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10:18 | your brain contains billions of neurons. 100 billion neurons. Those neuron zones |
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10:35 | through trillions of synapses, can have billion active neurons, billions of active |
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10:51 | within the networks and these networks. active, and they're communicating to other |
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11:02 | , engaging potentially billions of synapses and hemisphere or in other lobe that is |
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11:10 | by a specific task or specific sensory . Incredible computational task. The brains |
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11:22 | £3.5 containing billions of neurons and trillions synapses reacting underwater of milliseconds, synchronizing |
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11:33 | regions of the brain to effectively execute functions. To accept effectively, process |
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11:40 | sensor information. If you took and laid out this census, she, |
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11:50 | , all of the membranes of each cell. In this case, you |
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11:57 | out the membranes, a plasma membranes all of the neurons, all of |
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12:02 | brain neurons, all of the plasma . And you laid it out. |
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12:06 | unfolded. All of the Denver rides on the gendered expired so much and |
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12:10 | laid it flat. That area from single brain would equate to four soccer |
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12:21 | and size. We have many imaginations our cortex. We have many processes |
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12:33 | from neurons and these when they laid , is what our minds are comprised |
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12:46 | . This four soccer fields off very communication that is happening. This is |
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12:52 | fabric of our minds, right? , synapses, neurotransmitters. So neurotransmitters |
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12:59 | will learn today were discovered by at Lowy. And this is one of |
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13:07 | favorite stories in this course, and is by what Allawi in the night |
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13:16 | Easter Saturday, 1921. It's going be 100 years next year. 100 |
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13:24 | 1921. I awoke, turned on light and jotted down a few notes |
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13:31 | a tiny slip of paper. Then fell asleep again. It occurred to |
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13:37 | at six o'clock in the morning that the night I had written down something |
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13:42 | important. But I was unable to the scrawl that Sunday was the most |
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13:51 | day in my whole scientific life. the next night, however, I |
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14:00 | again at three o'clock, and I what it waas this time. I |
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14:06 | not take any risk. I got immediately. Went to the laboratory, |
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14:11 | the experiment on the frog's heart described , and at five o'clock, the |
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14:19 | transmission of nervous impulse was conclusively This is a quotation from Workshop of |
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14:29 | by Otello in 1953. So what the experiment that oughta Louis did? |
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14:39 | is the dream that auto Louis Well, Dr Louis was working with |
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14:47 | Hearts, woke up and did the and a frog heart would isolate a |
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14:53 | heart. And as you isolate a heart, one of the most prominent |
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14:58 | that is innovating. The heart is vagus nerve. It's cranial nerve. |
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15:05 | . And you will learn about cranial . All 12 cranial nerves for with |
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15:09 | end of this section. This is nerve, which is cranial nerve. |
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15:16 | . It has the most extensive It comes from brain stem, most |
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15:23 | innovations throughout the body of the viscera and very significant input onto the |
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15:32 | So the experiments that after that we is he isolated two hearts, the |
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15:38 | on the left he called the donor , and the one on the |
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15:42 | At a vagus nerve, this blue attached it. This this this donor |
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15:48 | , it's sitting in a vessel. this this jar in which is a |
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15:56 | , has, ah, certain The second heart that he prepared. |
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16:01 | call the recipient hard, and that does not have the vagus nerve attached |
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16:08 | it. In this image experiment that did is auto. Lowy stimulated vagus |
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16:16 | in the donor heart on the left he stimulated vagus nerve. So heart |
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16:24 | a muscle cardiac muscle and it's contracting it's beating. So the faster is |
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16:30 | . The faster is the heart When you stimulate vagus nerve, the |
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16:36 | rate slows. Donald. So what did is he collected the fluid from |
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16:45 | jar in which this donor heart was . He collected that fluid after he |
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16:51 | the vagus nerve, and he transferred fluid into the adjacent jaar which contained |
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17:01 | heart. Now this recipient heart, did not stimulate the vagus nerve, |
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17:08 | instead collected the fluid from the dark and apply this new stimulated fluid onto |
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17:17 | recipient heart. And when he added fluid to the recipient heart, the |
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17:25 | trade slowed down. That demonstrated Thio Louis and Thio, all of the |
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17:34 | around the world that the vagus nerve the nerves released some chemical that that |
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17:41 | is found in the solution and the of that chemical causes the slowing down |
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17:47 | the heart trade. And when you that chemical without stimulating the name Davis |
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17:53 | onto their naive or recipient heart, get the equivalent affect. The heart |
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17:59 | slows down. So there is something the fluid. It gets released by |
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18:02 | vagus nerve in the donor heart, that fluid now becomes effectively an equivalent |
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18:09 | the stimulation of the vagus nerve. it contains a camp, that chemical |
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18:15 | a civil calling. So Seal Colleen discovered in this vagus nerve to cardiac |
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18:27 | . Set up and a C Delco became the first known chemical or |
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18:36 | So the take home message here is you fall asleep and you have a |
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18:47 | . If you are having the heart , but you can be bothered, |
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18:54 | , put it down on the You cannot be bothered. Thio. |
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18:59 | it in a graph in a chart an experiment, it can be |
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19:08 | The brain is also very interesting because brain will replay the patterns did you |
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19:15 | during the day? And by replaying patterns, it's actually tuning the activity |
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19:24 | networks, neuron, all networks and lot of the cells and communicating. |
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19:30 | networks are undergoing plasticity, so synapses becoming potentially ated or they're becoming depressed |
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19:39 | so, replaying the same patterns that your brain during the day. Same |
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19:47 | so now being replayed at different frequencies night and they're very important because this |
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19:57 | learning and memory. This is which you've learned during the day. |
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20:03 | is forgetting things that are averse to physically and mentally through depression, long |
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20:10 | depression of the synopsis, not the of the mind weakening of the |
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20:18 | And so this is very important. lessons here are if you have that |
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20:25 | moment, that clear, buoyant ah moment, try to realize it, |
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20:33 | it's in a notebook or whether it's a chart or whether it's in a |
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20:39 | or whether it's in a musical to your mind works, try Thio. |
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20:48 | it. And if you wake up in the middle of the night, |
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20:52 | may end up getting a noble price materializing realizing something that you have |
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20:59 | This is in the case, Ought Allawi, who discovered the chemical |
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21:04 | transmission. Yeah, the second thing that take home message is that we |
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21:10 | playthings at night, so our brain that we talked about similar brain maps |
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21:15 | get activated. Some of them will strengthened. Some of them will get |
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21:20 | . If you're forgetting things, so have the replay of activity and so |
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21:26 | we play of activity. A lot times, of course, is most |
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21:30 | the time it's, uh, But if you remember, or if |
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21:36 | are very strongly involved in a dream you can come out of that dream |
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21:41 | still remember what you're dreaming, it might be useful thio for self |
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21:49 | , Um, for for discoveries, . So this was the chemical synapse |
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21:54 | the chemical neural transmission that was discovered the brain. And since then we |
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22:00 | that there are two types of the between neurons and the second type of |
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22:05 | synopsis, called Electrical so announced chemical you have release of neurotransmitter, and |
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22:13 | neurotransmitter from the vesicles travels across the cleft 20 nanometer distance, and it |
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22:21 | to the receptors, causing a poss effect, and in electrical synopsis or |
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22:30 | electrical junctions. This is very It is different because you don't have |
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22:39 | same distance. These are very special atomic call densities that form and bring |
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22:51 | cell membranes very close to each An individual gap junction consists off individual |
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23:01 | connections that form connects on, and connects on forums on the cell. |
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23:07 | side applies. We call it pre , and the second connects on forums |
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23:12 | cell to sidle plasma. We can it pasta Nap. Now, what |
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23:18 | understood is that if we bring the membranes close together, that distance is |
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23:25 | physically separating. The two neurons is 3.5 nanometers, but these trance member |
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23:32 | protea ums these heavy channels half channels one side and another they use in |
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23:42 | together, forming these gap junctions. gap junctions allow for the flow of |
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23:48 | and small molecules and notice that it that the ions and small molecules can |
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23:55 | in both directions. This is different when we discussed voltage gated sodium |
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24:00 | both educated sodium channels where allowing for to come in all this gave the |
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24:06 | channels were allowing for potassium to come of the south. In this |
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24:11 | ions and small molecules can go in the cells back and forth. So |
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24:17 | on such as potassium and calcium that discuss can pass very freely between these |
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24:23 | junctions as well. A small molecules as cycling and P, which conserves |
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24:29 | second messenger in the cells can enter leave the cells as the concentration of |
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24:36 | ions or molecules, increases, it go down the concentration radiant because the |
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24:43 | junctions and like voltage gated sodium channels voltage gated potassium channels that we |
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24:49 | They're not gated by voltage. They're open. And so they allow the |
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24:55 | for very fast flux of violence and molecules and bidirectional flux. And that's |
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25:01 | important now. The original experiment and discovery of the Gap Junction was |
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25:10 | uh, firstborn potter in the This experiment has shown here on the |
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25:17 | , where at the very top there , an electrode is inserted in one |
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25:23 | , and that top cell also has recording electrodes. So the electorate on |
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25:28 | left will pass the current current pulse the pre synaptic cell, and that |
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25:33 | you can see will flow down. of it will leak out. Some |
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25:37 | it will flow down, using according the resistance capacitance circuit R C |
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25:44 | and will cause a strong, deep in the pre synaptic self. But |
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25:51 | any delay. There will also be immediate posson optic deep polarization of the |
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25:58 | to only a fraction of that Only a fraction of the ions remember |
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26:05 | size of the current is really the of the ions through the channel. |
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26:10 | only a fraction of this current, a fraction of this deep, polarizing |
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26:15 | will be found in cell number But there will not be any delay |
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26:21 | happens in regular chemical synapses. In synaptic clap, the release of |
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26:27 | that neurotransmitter has to travel through 20 of space to bind the receptors for |
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26:33 | receptors to open. This whole process referred to as a synaptic delay, |
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26:41 | that's an optic delays on the order a few milliseconds. So when the |
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26:47 | potential arrives in the pre synaptic cell vesicles fuse, there's going to be |
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26:54 | five or so milliseconds from the time record an action potential in the Saxon |
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27:01 | to the time that you see a haptic response. And so the synaptic |
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27:06 | because of the synaptic cleft because of space of neurotransmitters, have to traverse |
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27:12 | order to buy into the parson OPIC . That is not the case with |
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27:19 | gap junctions. There is no synoptic , Uh, but you can see |
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27:27 | only a fraction. So there's no of the signal in the post synaptic |
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27:32 | , only a fraction of the polarization the voltage. Only a fraction of |
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27:36 | currents that air coming from Sal Juan be found in Cell two, but |
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27:40 | will freely pass. And if you to dip polarized cell, too, |
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27:44 | scarrans will flow in the reverse direction cell one if you with the reverses |
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27:51 | . So what gap junctions allowed to is they allow for a very fast |
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27:58 | between cells and cell networks. And happens is a lot of times each |
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28:07 | of these lines you can interpret in video as a separate network signal. |
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28:15 | you're looking at each one of these . Let's hypothetically assume is corresponding |
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28:24 | a group of 10 neurons, and can see that the top group of |
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28:29 | neurons is having a very slow oscillation . Okay, it's very slow oscillation |
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28:38 | the middle group Of these 10 this is an average is adding a |
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28:42 | oscillation. This is the third group having yet another oscillation, our voltage |
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28:50 | in the network. But they're not and the reason why you would have |
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28:55 | different rhythms is because you have different properties in the cells. Processing the |
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29:02 | coming in different channels with their I curves within the snap works off the |
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29:09 | and the synaptic delays that are happening these communicating neurons. What gap junctions |
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29:17 | to do is they allow for these all three networks to synchronize within the |
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29:24 | beat. So now you have a strong signal from the first cluster slightly |
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29:32 | signal and implicate from the second cluster the weaker one from the third cluster |
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29:36 | neurons. But all all of these are synchronized. All of these neurons |
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29:46 | now synchronized in time and having gap having the ability for the ions to |
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29:56 | across freely in a very fast way one of the advantages where the gap |
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30:03 | allow for the cells to synchronize. when we talked about glial cells, |
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30:09 | discussed that glial cells, especially the sides, they do special potassium buffering |
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30:17 | there is local rises and potassium One Astra City process will slurp up |
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30:24 | potassium, and what happens is that will distribute it through the processes of |
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30:29 | one Astra side with Astra sides and legal south are interconnected through gap junctions |
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30:36 | so that Sam potassium increases in potassium will now be able to freely cross |
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30:44 | cells that contain gap junctions and Astra . In that way, through these |
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30:51 | junctions will be ableto buffer, especially Increases in potassium concentration also spread the |
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31:00 | of calcium, by which exercise communicate lot of that communication that is through |
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31:06 | Gap Junction channels. Okay, so points here. It's synapses different from |
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31:14 | Junction. You have synaptic cleft synaptic channels and the synapses are typically unit |
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31:26 | . In the gap junctions this distance to 3.5 nanometers, and the heavy |
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31:31 | connect to form. A continuous channel two cells, which allows for very |
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31:37 | signaling of islands and small molecules without delay, allows for synchronization of cell |
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31:45 | . And it's not only the glial that will have gap junctions, but |
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31:51 | a few neuronal sometimes will also be through gap junctions through these electrical |
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31:59 | so essentially neurons will have two types synapses the chemical synapses and the electrical |
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32:07 | and the communication between neurons between networks neurons happen through both the chemical and |
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32:15 | electric. Constant lapses. I think noticed maybe a question or two on |
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32:20 | chat. How do cardio ourselves, keep the same amplitude when two polarizing |
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32:39 | whole heart, they communicate through the junctions too? Well, that's a |
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32:50 | good question. I mean, we're really talking about the hard, but |
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32:54 | is one of the advantages in the , in this case, in the |
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32:59 | muscle, not in the neuronal populations South and the cardiac muscle do have |
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33:05 | junctions. And precisely. There's a example because this is where you have |
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33:12 | contraction off the heart and the heart that synchronizes. So you have the |
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33:17 | and a V notes and connect itself Gap junctions and engage networks off other |
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33:25 | in the muscle, causing this Eso I hope that somewhat answers your |
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33:31 | . It's not completely clear to Um, maybe I'm not understanding |
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33:37 | but we are mostly going to focus gap junctions and communication between neurons, |
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33:43 | you're correct to point out muscle cardiac muscles. Heart contains a lot |
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33:49 | gap junctions now chemical synopsis. We know a lot about chemical synapses. |
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33:58 | we zoom in on the pre synaptic terminal, we will see that it |
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34:01 | again contains a lot of mitochondria, happy synaptic vesicles that have bunched up |
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34:07 | close to the areas where they refused the pre synaptic plasma member in those |
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34:12 | Serve referred to as the active zones you have higher densities of the your |
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34:17 | . Vesicles some of them fused with plasma member and other sir primed and |
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34:22 | to get fused and others are being before they're away and being transported closer |
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34:27 | the external terminal Plasma member. So now the collapsed on them. |
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34:32 | aside, you have receptors that are of the Boston optic densities, and |
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34:37 | response of the most synaptic cell will depends on the receptors that are in |
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34:43 | South rather than the neurotransmitter that is from the pre synaptic. So we'll |
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34:48 | this example in a second synopsis. here is your home or classroom. |
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34:55 | are down score of vesicles and how different from neurotransmitter vesicles. So this |
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35:01 | here on the right, what you is we're seeing our electron microscope |
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35:05 | You should be able to recognize that should be able to recognize the boundaries |
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35:09 | the external terminal here. Zonal terminals off. The mitochondria need energy for |
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35:17 | bicycle release. Recycling off the vesicles be filling of the vesicles. You |
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35:22 | see that some of the vesicles air further away from the plasma membrane and |
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35:26 | are gathered very close to the pre active zones and others you can even |
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35:31 | event are using starting to fuse through plasma member and juxtaposed pasta. |
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35:37 | Piccoli. You also see a Nah, pick cell and you can |
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35:41 | on the other side of the pasta south the pasta napping densities. And |
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35:45 | are the collections off the receptors that be bound by these neurotransmitters coming from |
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35:52 | synaptic vesicles so synapses can be formed the dem drives of the South, |
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35:59 | as one acts on contacting another dendrite those air called accident. Really, |
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36:05 | can be formed on the Selma's off neurons, and those air referred toe |
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36:11 | somatic from accent to Selma. But are also synapses that can be formed |
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36:17 | one Axiron onto another accent, and are referred to access X tonic synapses |
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36:24 | one accent onto another accent. So that you've learned so far, you |
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36:30 | learning about synapses and the dendritic spines in the dendrite. And now I'm |
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36:35 | you that they're actually points of contact communication on the accidents. Indeed. |
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36:41 | there's also Denver dendritic synopsis, which don't understand very well. But we |
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36:45 | that the gun rights communicate with each also through somewhat different but also specialized |
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36:51 | off communication. Uh huh. So is the difference? And how can |
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36:57 | three different types of synopsis influence activity another neuron in a If you were |
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37:04 | exciting Terry solid, you were an solid. You were projecting onto this |
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37:08 | drive. You need quite a view these dendritic synapses in order for the |
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37:14 | to be de polarized enough, for , to produce an action potential, |
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37:18 | that dendritic synapse should be very close the soma. The closer it is |
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37:23 | the soma, the stronger impact that happen, the integrative properties of the |
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37:28 | and the acts on initial segment. it will influence whether the cell will |
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37:33 | an actual potential or not. In the synapses projecting onto the Selma, |
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37:41 | actually have very strong influence on the properties of the south. If you're |
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37:47 | to resell, you can excite the because you're located approximately very close to |
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37:53 | zone that will be responsible for generating potential. That's so much acts of |
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37:58 | segment. So you have very robust from the synapse. If it is |
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38:04 | director of the SOMA robust influence on integrative properties of the self. Now |
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38:10 | the third see diagram, you cannot the integrative properties off the neuron onto |
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38:19 | your synapses notice that the sin So this acts on this contacting another |
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38:26 | . So this this this ax on determine whether this other neuron will fire |
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38:34 | potentials or will not bar will fire potentials or will not. We will |
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38:39 | influence the integrative properties and decision making fire or not to fire. But |
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38:47 | it will exert module A Torrey It will modulate the output of this |
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38:54 | . So in a and B you influencing and you're affecting the integrative properties |
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39:00 | these nerves and then see you modulating output off one neuron onto another |
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39:08 | This is the actual sonic center. , we looked at these synapses. |
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39:15 | certain anatomical features of these synopsis that us Thio just based on anatomy, |
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39:25 | excited Torrey verses. Inhibitory synapses so tourist synopsis are typically as symmetric. |
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39:32 | have as symmetrical, numbering differentiations by symmetrical. I mean that the pre |
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39:38 | active zones are usually thinner and smaller compared to the pasta synaptic receptor densities |
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39:46 | the Pasta Matic side and the vesicles very, very round in the exciting |
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39:51 | cells in the inhibitory solace earmarked by the synapses air actually symmetrical. They're |
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39:59 | , numbering differentiations, the same density size off densities of the membrane and |
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40:05 | or the pre synaptic active zone in past synaptic density and also noticed that |
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40:12 | vesicles has someone of a flatter shape . So vesicles are plasma membrane enclosed |
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40:20 | . Alison Inside this vesicles you have . So exciting story, of |
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40:26 | are glutamate. The glue dramaturgical synopsis the inhibitory cells. That symmetrical and |
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40:32 | ship that's the cults are inhibitory Well, we said that we're going |
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40:42 | talk mostly about neurons in the But it's very important that we come |
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40:47 | and understand the rudimentary circuit that we studied, but in slightly different and |
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40:54 | way. And actually, this is the last time we touch on |
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40:57 | I'm actually going to talk about what call and play potential in the following |
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41:02 | next week. But so you have motor neurons, our favorite multipolar motor |
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41:10 | that live in the ventral aspects off spinal cord and project their different outputs |
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41:18 | the muscle, in this case, muscle and release a single Colleen. |
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41:25 | , you guys know so much. job. So when s until Colin |
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41:31 | released on the muscle muscle contracts and increases the contraction of the skeletal |
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41:40 | Wait, wait, wait, wait A Wait a second. You |
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41:44 | us that if you have a Seattle , it will slow down the contraction |
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41:49 | the muscle and slow down on hard . All more question. So settle |
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41:58 | is inhibitory in the cardiac muscle, down activity off the heart and in |
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42:07 | skeletal muscle biceps muscle, it's causing contraction. It's deep polarizing the |
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42:15 | Why? Why is the Seattle call inhibitory to the cardiac muscle Alexis Editori |
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42:23 | answer lies and the receptors that it . And the response is coming from |
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42:29 | receptors, so look into it. is your home or question number |
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42:35 | And look, let's look closer into anatomy of this external terminal again. |
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42:41 | have the splits of these percent African terminals, each one of these terminals |
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42:47 | an end plate motor and played region the muscle fibers. And if you |
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42:55 | in again, you will see mitochondria we're all familiar with. You'll see |
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42:59 | synaptic vesicles. The synaptic vesicles are with the Seattle coleene, and a |
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43:04 | of them are sitting on these active , primed and ready to fuse. |
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43:08 | when there is an action potential, synapses highly reliable, it's, |
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43:14 | High Fidelity Synapse 121 and action potential results in a twitching a muscle unless |
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43:23 | something wrong. Pathologically with the very powerful synapse. Activation of one |
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43:30 | in the Motown played causes a deep of 70 million balls. How much |
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43:35 | you need to de Pol? Arise South from resting member and potential in |
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43:39 | to produce an action potential. Only 20 to 30 million moles so motor |
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43:45 | played potential or and played potential is huge potential nerve to muscle potential of |
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43:54 | 70 million balls that always results in action potential in the muscle, So |
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44:01 | to 1. So what happens is when the acts on, uh now |
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44:08 | the action potential in action potential, rises the pre synaptic terminals. You |
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44:14 | that there is influx of calcium. because of this deep polarization, influx |
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44:19 | calcium, the neurotransmitter vesicles will fuse the plasma membrane. And as they |
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44:25 | to the plasma membrane, they will released into the synaptic cloth. And |
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44:31 | the synaptic cleft. These red dots corresponds to the Seattle Colin receptors. |
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44:39 | so you can see that there is high densities of these acetylcholine receptors that |
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44:44 | located proximal of these, uh, regions to the pre synaptic active results |
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44:53 | ical release. And you can see these, uh, synapses on the |
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44:59 | side they contain what we call All falls and these junction all falls |
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45:05 | the surface area, and they also for the expression of high densities of |
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45:11 | settle Colleen receptors. And so what happen initially is the release of a |
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45:17 | Colin will cause the opening of acetylcholine . He's a ligand. Gated receptors |
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45:24 | deep polarization through acetylcholine receptors will then on voltage gated sodium channels which are |
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45:32 | deeper within that junction. All falls the voltage gated channels will then generate |
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45:39 | action potential, which is different than muscle. The dynamics are different. |
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45:44 | a longer action potential. We won't that much time. Thio look |
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45:48 | It also has a significant calcium component the action potential in the CNS neurons |
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45:55 | not. And so we actually have kind of ah, start understanding. |
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46:03 | settle Colin is released that travels through clap monster receptors causes initial deep polarization |
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46:09 | we'll be learning mawr and more and about the So if you are a |
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46:13 | bit confused at this point about, does assembly potential happens? And how |
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46:18 | this translate into generation of action potential come back to the following a |
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46:24 | Okay, But just so this is important for us to learn today so |
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46:30 | we understand and we understand that these very reliable, very high amplitude functioning |
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46:38 | between the nerves and the muscles. if we're looking to see N s |
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46:44 | we want to describe what we call our system, we have many different |
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46:51 | , and we have neurotransmitter systems. what is a neurotransmitter system? Neurotransmitter |
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46:59 | is the whole system that has a of components that have to exist. |
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47:03 | synaptic Aly Apostle, optically pre synaptic . That neurotransmitter has to be produced |
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47:11 | synthesized and found within the neuron. , that neurotransmitter should have synaptic vesicles |
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47:20 | . That means that that neurotransmitter needs get loaded up into the synaptic |
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47:24 | So you need to have proteins of that will transport the chemicals and in |
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47:31 | them within the membranes off the you need re uptake. Transporters. |
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47:39 | right, so reacting transporters. Synaptic vesicles, transporters and the ones |
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47:44 | are going to transport the vesicles to plasma member and re optic transporters of |
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47:47 | ones that are gonna, uh, the re uptake off off the vesicles |
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47:53 | the vesicles doesn't get wasted. It refilled with neurotransmitters. It has to |
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47:58 | degradation. Enzymes that once the New translator is released in the synaptic |
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48:03 | It doesn't linger there around indefinitely. actually gets either diffused or it gets |
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48:11 | into his constituents. Parts and usually parts reported back into the prison attic |
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48:18 | and goes through the mechanism of re and bicycle transport following that exercise. |
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48:26 | . Okay, so Boston optically you transmitter gated ion channels. Those are |
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48:30 | channels that will bind these mini So these air ligand gated channels, |
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48:35 | different. The Legans or the chemical going to open the channel, not |
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48:39 | voltage change. Boston optically will have protein coupled receptors. G protein coupled |
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48:46 | will also be the binding targets to dinner transmitters, but they're not |
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48:53 | That means that transmitter gated ion channels allow for flow of ions through the |
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48:58 | and actual channel, where G protein receptors are linked to G proteins and |
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49:04 | G protein. So your translator, to G protein coupled with several active |
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49:09 | protein which will turn, will activate protein gated ion channels Boston, AP |
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49:16 | and, of course, Boston optically secondary messenger cascades that will then signal |
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49:21 | information potentially all the way to the of this pot synaptic self and reacting |
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49:27 | the levels of the activity. So criteria, when neuroma stimulated, do |
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49:34 | that neurotransmitter that is synthesized. It be released when that chemical is |
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49:39 | So let's say it's glued in It must cause a pasta Matic effect |
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49:43 | you release them. Chemical doesn't cause possum attic effect. Then maybe it's |
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49:47 | neurotransmitter. After Chemical is released, must be inactivated. It has to |
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49:54 | on Boston optic receptor causing biological If it doesn't bind to the |
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50:00 | it has to be now broken broken down and re up. Taken |
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50:06 | into the present optic terminal. If chemical is applied on the Boston optic |
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50:11 | and should have the same effect when is released buying neuron so it would |
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50:16 | the same effect. If you isolated chemical here and they use non produces |
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50:21 | skull Colin and you're isolated that that's tall colon, it should have an |
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50:25 | . The fact is, if you to stimulate the Vegas now, so |
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50:30 | air the neurotransmitter criteria do we have neurotransmitter systems, you know, our |
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50:37 | do that qualify these criteria. So can see that there's pre synaptic |
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50:42 | There is a synaptic degraded degradation. . There is possibility. Component. |
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50:47 | is a system glutamate. It's a dramaturge. ICS system glutamate gets released |
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50:52 | receptors. There, there there's gonna things that the great glutamate reacting |
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50:58 | Gabba synapses, Gabba allergic synopsis. a gap allergic system that's still Colleen |
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51:04 | allergic synopsis. Right? That's an thing to know for us. Is |
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|
51:09 | impairment? Visit Seattle. Colleen is with which neurological disorder, which neurodegenerative |
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|
51:19 | that we now you haven't impairment in Colleen. Anybody wants to take a |
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51:42 | . Hello will be eventually. Parkinson's have an effect, but it's typically |
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|
51:51 | by an impairment and dopamine systems and allergic impairment. We haven't discussed |
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|
51:58 | so your hint is something that we discussed. Yes, Alzheimer's disease. |
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|
52:06 | Alzheimer's disease what we talked about. talked about pathology. So go back |
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|
52:11 | your announced now where you have you in Alzheimer's disease and you have the |
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|
52:15 | of pathology that we discussed, which there, tangles inside the cells and |
|
|
52:20 | and what blacks outside the cells. we discussed the you know, the |
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|
52:26 | short term memory loss anxiety. We discussed another pathology of shrunken gray |
|
|
52:32 | shrunken brains. Now this is a pathology, which sells air dying in |
|
|
52:39 | Alzheimer's disease. The earliest networks that deteriorated are the colon. Ergic networks |
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|
52:47 | Colleen Networks. Uh huh. So that's That's an important note to put |
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|
52:54 | to your Alzheimer's disease. Note. now we have all of these different |
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|
53:05 | system times, and we have I acid in your translators that we're getting |
|
|
53:13 | know pretty well. This is gamma butyric acid or GABA glutamate glazing Gabba |
|
|
53:20 | a major inhibitory neurotransmitter in the Glutamate is a major excited to know |
|
|
53:27 | . Glide scene is a favorite neurotransmitter is contained and, uh, inhibitor |
|
|
53:35 | turnarounds of the spinal cord. There's to every rule glazing, and the |
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|
53:41 | nervous system in the serene room actually as a cool factor. Too |
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|
53:47 | So whilst in this final chord, is inhibitory in the serene room. |
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|
53:53 | acts as a co factor in promoting and excited Torrey signaling interesting all depends |
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|
54:01 | the receptors depends on the binding size of these molecules to the receptors just |
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|
54:07 | an assault. Tell Colleen it can exact hitori, but can be |
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|
54:12 | Correct. Nicotine Nicholas chapters. The muscle off the skeletal muscles is |
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|
54:20 | going to cause the exciting Torrey effect the muscles. Other times, those |
|
|
54:25 | is up to you to find Okay, Now you have a group |
|
|
54:30 | the means that are very easy to . They're all ending in i n |
|
|
54:38 | . That's a little Colleen dopamine. any epinephrine? I nie histamine. |
|
|
54:43 | any norepinephrine i d and serotonin? the only one with exception. I |
|
|
54:51 | again. These are all very important systems in our brain. Acetylcholine is |
|
|
54:57 | important for no memory for, cognitive executive function dopamine and is involved |
|
|
55:08 | many different aspects. And it's correlated different behaviors. And different neurological disorders |
|
|
55:15 | been ephron and norepinephrine. Is that of the activation and the fight or |
|
|
55:23 | , um means in our brain. is related. Thio inflammatory reaction |
|
|
55:29 | and you'll learn later as we study about Sortino trick systems very widely expressed |
|
|
55:35 | the body. So when we talk neurotransmitter systems, it doesn't mean that |
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|
55:40 | neurotransmitters, such as acetylcholine or serotonin only find in neuron. Serotonin in |
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|
55:48 | means and other neurotransmitters can be expressed the periphery can be expressed in the |
|
|
55:53 | organs and peripheral cells again. um, peptides that we've mentioned. |
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|
56:00 | you will not really have to know much about the baptizes color system kind |
|
|
56:05 | dine Orphan and Kath Elin's n acetyl in glutamate. Neuropeptide y's amount of |
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|
56:11 | Substance speed. I would drop in hormones as active intestinal polyp type V |
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|
56:16 | . P. Substance P. You know mediating pain signals so that a |
|
|
56:22 | we mentioned because we talked about certain of inter neurons and that you put |
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|
56:27 | that have some out of Staten War calling sister kind. And so these |
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|
56:33 | the major neurotransmitter systems. Sometimes what have to start thinking about is that |
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|
56:39 | think of these amino acid neurotransmitters. glutamate has involved in very fast |
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|
56:46 | and I see little coleene and opening mean and theft I Nero transmitters. |
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|
56:53 | you need to have heightened levels of in order to start releasing or co |
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|
56:58 | these neurotransmitters together with gabba or glutamate what you have to realize is that |
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|
57:06 | one of these is dominated in a part of the brain. Therefore, |
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|
57:11 | linked to slightly different function. each nor transmitter system can be linked |
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|
57:17 | almost a specific behavior, so serotonin be link, for example, thio |
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|
57:23 | behavior and appetite. Okay, so is how you have to start thinking |
|
|
57:28 | it and physiological on cellular level with molecules so look like and then on |
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|
57:33 | holistic level, what kind of Where they expressing the brand, what |
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|
57:39 | of behaviors they would be controlling For example. You have traumas and |
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|
57:45 | disease because dopamine is very important and the motor commands and the structures of |
|
|
57:51 | brain straight. Um, that expressed a very important for the organization of |
|
|
57:57 | motor commands. So again, different different part of the brain, different |
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|
58:04 | as it is related to the So let me positive for you to |
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|
58:09 | notes on this one as well and particular. What I mean by that |
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|
58:13 | that you have these classes of neurotransmitter and system neurotransmitter system types that we've |
|
|
58:22 | and this list is incomplete, so will actually add to this list. |
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|
58:31 | happens? I added to this We have gas. Is that service |
|
|
58:41 | ? So you have Naturists oxide and monoxide that actually have the respective |
|
|
58:47 | Nitrous oxide receptor government oxide receptor. you have gas is gas neurotransmitters. |
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|
58:54 | into that home or question that I , what's the difference between vesicles and |
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|
58:59 | score dense core vesicles and neurotransmitter Right. And we're talking about storing |
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|
59:06 | neurotransmitters inside the vesicles and packaging What we cannot do with the gas |
|
|
59:11 | so they're not packaged in the neurotransmitter us. There is a non sort |
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|
59:17 | a nontraditional our transmitters that are very to always make this joke that next |
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|
59:23 | somebody says I'm having a brain so you have too much natural socks |
|
|
59:28 | in your brain, our carbon Too much of the gas was |
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|
59:33 | Going on in your brain can be smart Alex Alexander. And do |
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|
59:40 | uh, that a nontraditional neurotransmitters that important that will mention you should know |
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|
59:46 | the energy molecule 80 p. And and triphosphate actually serves as a |
|
|
59:53 | There are receptors to which a teepee . It's not just an energy |
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|
59:58 | It's also a neurotransmitter. And the of that molecule at Denison is also |
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|
60:05 | neurotransmitter, and it is very Actually. You know why? Because |
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|
60:14 | overwhelming majority of us use a psychoactive that regulates the Dennison receptors. A |
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|
60:23 | receptors shut down the signaling of so Donaldson receptors will essentially make the |
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|
60:31 | less excitable. The synopsis. They're to be less excited if the dentist |
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60:38 | activated and the Dennison is going to expressed at high levels at night time |
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60:44 | then the dentist Similar Decrease in this . Normal synthesis levels in your brain |
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|
60:53 | the morning time between you wake you sometimes feeling groggy and having difficulty |
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|
61:02 | to kind of jump Start yourself for immediately engaged. And most of us |
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|
61:08 | thio psychoactive substance that we know that called caffeine. And when we consume |
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|
61:18 | and caffeine interacts with the Dennison and it blocks the Dennis Interceptor. |
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|
61:27 | promotes the release of glutamate of the . So you glutamate is released. |
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|
61:37 | have a psychoactive effect from caffeine, I'm not just talking about coffee, |
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|
61:45 | drinks, energy drinks, caffeine This is all that we used to |
|
|
61:53 | glutamate signaling, and it's acting through Denison receptors. That interesting thing to |
|
|
62:01 | that we don't think that is a substance. But what is psychoactive? |
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|
62:06 | that alters activity and psyche. If brain physiology out during the physiology of |
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|
62:14 | brain is actually out there in the , if your brain is well, |
|
|
62:18 | interesting thing to know is caffeine is addictive, and this is actually quite |
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|
62:26 | . An effective dose of caffeine. of us consume one, maybe |
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|
62:33 | um, speaking Teoh guy regularly that about eight cups of coffee. It |
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|
62:38 | pretty wired to me. I don't how he sleeps. This is the |
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|
62:43 | does alright that z effective those that that it z accomplishing what you're It's |
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|
62:49 | upper. You consumed an upper. by the way, these points of |
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|
62:54 | for this addictive substance exist on every in this country. Whether it's called |
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|
63:01 | or another type of cafe, you have three Starbucks on the intersection, |
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|
63:06 | then you'll have dunking down and selling different type of caffeine on the fourth |
|
|
63:11 | . That's very typical because it is addictive, and the other thing is |
|
|
63:15 | . Does is this few cups of deadly does for caffeine is about 100 |
|
|
63:21 | of the effective. Don't so, effective, does if one cup of |
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|
63:25 | is makes you wired 100 cups of stand to kill you so caffeine can |
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|
63:32 | toxic and especially synthetic cafe. An different form off caffeine, which can |
|
|
63:40 | quite quite strong. So it's very to keep these things in mind as |
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|
63:44 | consume substances every day, you and we're seeing effects from these |
|
|
63:50 | but we don't think of them a . We don't talk about them a |
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|
63:55 | . We don't even discuss that it's glutamate signaling. But now you know |
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|
64:01 | you know better. Finally, we another very interesting class of neurotransmitters that |
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|
64:07 | lipid soluble or their plasma member insoluble . The gas is so the lipid |
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|
64:14 | neurotransmitters they cannot be stored and their vesicles because neurotransmitter vesicles have their own |
|
|
64:21 | membrane that forms the neurotransmitter vested. these are academic acid and and they're |
|
|
64:32 | and for their kanam annoys will actually a separate lecture attendant discourse. But |
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|
64:38 | have these internal cannabinoids that are synthesized our bodies, the two dominant, |
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|
64:45 | and best known as an anti mydd to a G, and you will |
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|
64:50 | understand how their signal. Now our asset can be both the precursors under |
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|
64:56 | and also a decorative byproduct of degradation the contaminants. Those molecules are |
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65:04 | uh, synthesized on demand when there heightened levels of activity and released on |
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65:10 | their membrane, or lipid soluble. , they will cross through the membranes |
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65:14 | will buy into their own respective almost in the para crime like |
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65:20 | in the sense that they're not stored the vesicles right across the road from |
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65:26 | Boston optic densities. But rather they're through the plasma membranes leave. It's |
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65:31 | lipid soluble molecules, and they traveled buy into their respective receptors. So |
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65:37 | a way, there is a bidirectional in the chemical synapses as well. |
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65:42 | of the cannabinoids will travel retrograde invited to the pre synaptic receptors rather |
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65:48 | affecting the loss synaptic side and and Canavan alliance eyes a very important |
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65:55 | It's expressed in the brain. It's throughout the body, different various organs |
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65:59 | express different under cannabinoids, with virtually single cell in our body as an |
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66:06 | noid system, which is really very him for a long time. There |
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66:11 | this, uh, you may have off endorphins and dismiss that the runner's |
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66:20 | runners run long distances. They get is called the runner's high, that |
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66:26 | the feeling of bliss and by the , Ananda in Sanskrit means bliss. |
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66:32 | Ananda mine is a bliss molecule, that makes you happy. Something that |
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66:37 | steal mood, something that makes you makes you laugh. And it also |
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66:42 | inflammation and appetite in your body, other things. So it's actually and |
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66:49 | cannabinoids that our bodies release and the high is not because of them the |
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66:55 | , because there's no endogenous morphine, is no more feeds like molecules that |
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67:00 | synthesized and in our bodies that cannabinoids molecules and their cannabinoids are synthesized. |
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67:08 | and the new and modern science understands the runners hide is good feeling of |
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67:16 | . It happens typically when you run middle miles, so if you're a |
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67:20 | , you know that, too. , mile is not very interesting. |
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67:23 | you're somewhat of, ah, long runner. The random I was not |
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67:28 | interesting. You run. It may for speed, you know, to |
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67:33 | three miles is becoming a little bit interesting. Somewhere on the 2nd 3rd |
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67:38 | , you may be getting that second . It's the middle mile. So |
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67:40 | people run 10-K, which is about point, some are seven point some |
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67:48 | miles this middle miles 2345 is actually a really nice you for a boost |
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67:56 | the runners and after the run. , the whole physical activity that's stimulating |
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68:02 | production of under cannabinoids. This resulting this, uh, this blissful happy |
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68:09 | after the war cough. So in you didn't know, you could go |
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68:14 | out, run a few miles and your own cannabinoids in your own |
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68:20 | And if you wonder what other ways you can generate cannabinoids without injuring your |
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68:25 | because that's when then the cannabinoid system really very active. Is during the |
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68:30 | and inflammation other ways singing one of most effective ways Thio induce under contaminant |
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68:38 | in your body This were singing or . We're having a workout, and |
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68:43 | feeling of bliss. Next time you feel great after work out, think |
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68:48 | you. And and, um, and to a G. So I'm |
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68:52 | to stop the lecture here. And we come back, I will have |
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68:59 | scores. I will have your Casas released. Uh, my next |
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69:06 | You can look at the questions you ask me any questions specifically about the |
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69:12 | . For now, I want you address technical issues you may have had |
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69:17 | Casa. Have only a couple of to look over these because it's occupying |
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69:22 | lot of their space, all of video recordings on their servers. So |
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69:26 | address any technical issues. Example Get . You will see what you missed |
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69:31 | the exam. The questions. You adjust them with me then and I'll |
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69:36 | you know about the Casa quiz if going to do the quiz or if |
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69:39 | have another way and try to accommodate toe help you with your grades. |
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69:46 | . There's any outstanding questions. shoot me an email. Otherwise, |
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69:51 | your weekend, and, uh, will see you next |
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