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Luis Puelles on neuroanatomy and prosomeric model

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What if the standard anatomical maps of the brain have been wrong for over a century, and the molecular evidence was there all along? Neuroanatomist Luis Puelles from the University of Murcia explains how developmental biology and gene expression mapping overturned the dominant columnar model of brain organization, revealing a segmental architecture that had been proposed and forgotten decades earlier. Subscribe for more from the Convergent Science Network podcast series. Luis Puelles, one of the leading figures in developmental neuroanatomy, joins Paul Verschure and Tony Prescott at the Convergent Science Network podcast to discuss his career-long effort to replace the columnar model of brain organization with a prosomeric model grounded in embryological evidence. The conversation traces Puelles’ intellectual trajectory from an initial interest in how the mind emerges from the brain, through frustration with psychology disconnected from neurobiology, to decades of work on the spatial organization of the developing neural tube. The central argument is that brain boundaries are transversal to the neural tube axis, not longitudinal as the dominant American school proposed since 1910. Puelles describes how he arrived at this conclusion through morphological observation of embryos long before molecular genetics provided confirmation. When gene expression mapping became possible, the data immediately validated his model, showing that genes code for boundaries exactly where his framework predicted them. The conversation explores the historical context of the competing columnar model proposed by Herrick, which extrapolated brainstem nerve component analysis to the entire forebrain without embryological support. Puelles explains why this model persisted for 60 years despite being inconsistent with developmental biology: it offered functional interpretations that appealed to the field, even though those interpretations lacked causal mechanisms. His collaboration with molecular biologist John Rubenstein proved pivotal, combining Puelles’ morphological expertise with gene expression data that other embryologists had dismissed as meaningless. The discussion addresses the relationship between structure and function in neuroscience, with Puelles arguing that understanding morphology requires understanding development, and that functional analysis must be consistent with the causal mechanisms operating in the embryo. Part of the Convergent Science Network podcast series from the BCBT Winter School.

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Both the triumphs of humanity and its most evil deeds have resulted from collaboration. In a time where humanity is required to aspire to the former and minimize the latter, the question arises of how collaboration arises and why it fails. Surprisingly, this phenomenon, so central to who we are, is not well understood. Hence, a collaborative effort is required to understand collaboration in its full biological, psychological, sociological, cultural, and economic complexity and to translate this understanding into operational impact. This series of podcasts is one step toward achieving these complementary goals. The Collaboration Podcast presents interviews with people who are central orchestrators of collaboration in various domains including business, government, science, art, health, sustainability, and the military. The discussions were conducted by Prof. Dr. Paul F.M.J. Verschure and members of the Program Advisory Committee of the Ernst Strungmann Forum on Collaboration (https://www.esforum.de/forums/ESF32_Collaboration.html) during 2021 and had the goal to sketch a map of opportunities, challenges, and obstacles in human collaboration. The forum took place in May 2022, and now we would like to share this series of interviews with a broader audience. The full report of the Forum will be published in 2023 by MIT Press. The podcast was produced by the Convergent Science Network (https://www.convergentsciencenetwork.org/). Context: The stability of social systems depends critically on realizing sustainable methods of “collaboration,” yet how and by which means collaboration is achieved is not clearly understood; neither are the conditions or processes that lead to its breakdown or failure. Collaboration can be understood as cooperation between agents toward mutually constructed goals. Part of the reason for our lack of understanding is that the phenomenon of collaboration is, by nature, a highly multidisciplinary problem, and effective research into its complexities has been difficult to achieve across the broad range of scientific and technical disciplines involved. The need for a fundamental understanding of collaboration, however, has become increasingly important. Not only does humankind demand answers as it attempts to address critical challenges at multiple scales (e.g., climate change, migration, enhanced automation, social and economic inequality), but ever-increasing technological and economic means of interconnecting people and societies are disrupting long-established, familiar patterns of how we interact. Radical technological changes that are ongoing have the potential to reshape collaboration in ways that are currently hard to predict or influence (e.g., by altering configurations in interaction, information creation, and modes of communication). On one hand, such changes could disrupt hitherto stable forms of collaboration by affecting critical communication channels and traditional roles, as can be observed in the rapidly changing patterns in governance, commerce, and social interaction. Conversely, technology could lead to the emergence of novel, successful forms of collaboration that deviate from traditional “hierarchical” architectures. Evidence of this can be seen in areas as diverse as highly automated manufacturing plants, the open science movement, collaborative software repositories, user-centered services, and the sharing of economy-based modes of organization. Without a fundamental understanding of the mechanisms, processes, and boundary conditions of collaboration, it is not possible to evaluate or predict which of these possible scenarios are sustainable or even plausible. The Forum “How Collaboration Arises and Why it Fails” (May 8–13, 2022, Location: Frankfurt am Main, Germany) Chairs: Andreas Roepstorff and Paul Verschure Program Advisory Committee: Jenna Bednar, Julia R. Lupp, Bhavani R. Rao , Andreas Roepstorff, Ferdinand von Siemens, and Paul Verschure

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  • fast_forward00:00:00 - So that was that, so not that one.
  • fast_forward00:00:04 - Because not that one, this is probably fatal, it's true, it's not certain,
  • fast_forward00:00:10 - not visceral. Ah, thank you.
  • fast_forward00:00:16 - Okay, I'm recording this with the camera and the microphone.
  • fast_forward00:00:21 - So, I hope my tripod holds out.
  • fast_forward00:00:27 - If you email me, I can send it to me at this class. You put it on something
  • fast_forward00:00:32 - there, if I can send it to you.
  • fast_forward00:00:34 - Anything that you don't find or whatever, then ask me, you know.
  • fast_forward00:00:40 - My address is quite easy. The name of Kool-Eyes and then O-M from the Russian
  • fast_forward00:00:46 - people here. All right. O-M, yes.
  • fast_forward00:00:49 - Oh, okay. Okay, so that's adequate DC.
  • fast_forward00:00:53 - Okay, good. So let's start.
  • fast_forward00:01:03 - So, welcome to our Convergent Science Network podcast, where I'm here together
  • fast_forward00:01:09 - with Tony Prescott and Luis Puelles from the University of Murcia. You pronounce Pueyes.
  • fast_forward00:01:16 - Pueyes. Pueyes. Pueyes. Pueyes. Pueyes. Okay. It's a good one. It's a good one.
  • fast_forward00:01:22 - Oh, but that's not in the text here. There's no yacht there.
  • fast_forward00:01:25 - Pueyes. We write it. We write it.
  • fast_forward00:01:28 - Okay. Okay. But, okay, now that we got that sorted.
  • fast_forward00:01:35 - And so, Luis, you're a great expert in neuroanatomy.
  • fast_forward00:01:39 - And in some sense, you also have a very idiosyncratic, to call it that,
  • fast_forward00:01:46 - view, in the sense that you've been fighting for a very specific view on neuroanatomy,
  • fast_forward00:01:51 - on comparative neuroanatomy, maybe for your whole career, you could say. Right?
  • fast_forward00:01:57 - And also very much more from, let's say, a molecular genetic perspective.
  • fast_forward00:02:01 - And what was really exciting in your presentation on many things,
  • fast_forward00:02:07 - on the one end, you give a very clear,
  • fast_forward00:02:10 - let's say anatomical perspective on how we can think about the brain as a system,
  • fast_forward00:02:16 - but in the end you also brought it together to a very functional system
  • fast_forward00:02:20 - level perspective which I thought was really an amazing bridge to build so let's
  • fast_forward00:02:28 - see of course us a little bit what are the challenges in that perspective and
  • fast_forward00:02:33 - what are the assumptions also and how solid and controversial is it really, right?
  • fast_forward00:02:39 - So, maybe you can sketch, you can give us a bit of sketch of the basic design
  • fast_forward00:02:48 - of just the anatomical structure of the brain. Hmm.
  • fast_forward00:02:54 - Well, I mean, I must say first that my interest in the brain started by being functional.
  • fast_forward00:03:01 - So when I started having an interest in the brain, I wanted to understand how
  • fast_forward00:03:05 - it works, how it loses the mind. That was my initial interest.
  • fast_forward00:03:09 - And only when I met psychology, I thought I should learn about that in psychology.
  • fast_forward00:03:16 - But for whatever reason, my teachers were pretty bad. So I didn't like what
  • fast_forward00:03:21 - I got in Spanish, the psychology.
  • fast_forward00:03:25 - And I decided, no, no, I won't, because they did a psychology completely separate from the brain.
  • fast_forward00:03:31 - So the only words and concepts and everything like that.
  • fast_forward00:03:33 - I thought it was too heavy. And I said, no, no, I want to see the brain.
  • fast_forward00:03:38 - This must be based on the brain. So I want to see how the mind comes out of
  • fast_forward00:03:42 - the brain. So that's why I became an anatomist.
  • fast_forward00:03:46 - But I always have kept... So
  • fast_forward00:03:48 - what time was that? When I started my medical studies, I started with 16.
  • fast_forward00:03:56 - So I wanted to understand how people thought and how they felt emotions and
  • fast_forward00:04:02 - things like that. My main initial interest.
  • fast_forward00:04:05 - And then I slowly did what they could. I entered the anatomy department.
  • fast_forward00:04:10 - Okay, what do you do here? So I adopted to whatever was being studied.
  • fast_forward00:04:14 - I was initially a visual system. So I started with the oculomotor,
  • fast_forward00:04:18 - oculi, control of the eyes, vision, and visual parts of the initial thing in
  • fast_forward00:04:25 - the brain, and then continued.
  • fast_forward00:04:27 - A bit by accident, I stumbled on the question of regionalization of the brain
  • fast_forward00:04:33 - and the spatial aspects of which directions of spatial.
  • fast_forward00:04:37 - The parts were oriented. So this point I raised today about longitudinal things or,
  • fast_forward00:04:44 - or sub-transversal boundaries, this idea, because initially nobody teaches anatomy in that way.
  • fast_forward00:04:54 - Like they don't tell you what this is topology of the brain,
  • fast_forward00:04:57 - they give you this is trans-exceptical, this is the encyclical and so on,
  • fast_forward00:05:00 - that they give it a name and you accept that it is like that.
  • fast_forward00:05:05 - But that's the only thing that I slowly discovered, that there was a way to
  • fast_forward00:05:10 - think a bit more theoretically of the morphology,
  • fast_forward00:05:13 - and of course, that was relative to how this form was the mechanism that usually
  • fast_forward00:05:21 - was not mentioned either in neuroanatomy or even in neurobiology.
  • fast_forward00:05:25 - So nobody ever explained anything in the textbooks I had of neurobiology. biology.
  • fast_forward00:05:30 - I used several of them, went updated, and they didn't explain anything.
  • fast_forward00:05:36 - Not before the era of molecular tritalist.
  • fast_forward00:05:40 - So I was always critical of this aspect and wanted to have more explanation.
  • fast_forward00:05:48 - So I entered into experimental biology.
  • fast_forward00:05:51 - I read a lot about that, did some myself and so on.
  • fast_forward00:05:55 - So I came here to try to commit us to the mechanism of induction,
  • fast_forward00:06:00 - of instruction or whatever of regulation that happens with development and so on.
  • fast_forward00:06:05 - And then that brought me nearer and nearer to the molecules in a way.
  • fast_forward00:06:10 - I went into neurochemistry, into immunochemistry of molecules in the brain.
  • fast_forward00:06:17 - So because I was a morphologist, I just wanted to see where the molecules were.
  • fast_forward00:06:23 - It was a position and time to classify somehow in a logical sense the positions.
  • fast_forward00:06:29 - And that prepared me mentally to speak to the moment the genes were suddenly
  • fast_forward00:06:34 - appeared in the picture.
  • fast_forward00:06:35 - You could map genes and these were the molecules that really had causal effects on the morphology.
  • fast_forward00:06:42 - And so the moment they appeared, the first people that mapped genes,
  • fast_forward00:06:47 - they did not understand anything about these genes because they had been thinking causally.
  • fast_forward00:06:52 - For the first time I saw a gene that mapped a boundary in the brain,
  • fast_forward00:06:56 - they all thought themselves had not realized what it meant.
  • fast_forward00:07:00 - But the moment I saw the photograph, in that moment, I was like a flash because
  • fast_forward00:07:05 - I had all the questions asking about that and suddenly there came a piece of
  • fast_forward00:07:09 - data that answered exactly my question that the way genes that coded for bondage in the brain.
  • fast_forward00:07:16 - So I immediately realized the importance of the genes and then I just jumped
  • fast_forward00:07:22 - to becoming interested in that direction.
  • fast_forward00:07:26 - Of course, for a time, me and my department, my university, all it was health
  • fast_forward00:07:32 - technology or know-how about how to work with genes or how to prepare gene pros or whatever.
  • fast_forward00:07:38 - So I needed like two, three, four years to slowly get where can I get this and
  • fast_forward00:07:45 - what should I read to learn about this and so on.
  • fast_forward00:07:48 - And then I was lucky that I met in a meeting in the States.
  • fast_forward00:07:52 - I met my colleague, John Rubenstein, who was a molecular biologist and he was
  • fast_forward00:07:58 - looking for a morphologist.
  • fast_forward00:08:00 - And I was looking for a molecular biologist, so we just met,
  • fast_forward00:08:03 - and automatically we realized that we could work together,
  • fast_forward00:08:07 - because he had found some genes that showed strange boundaries that nobody could
  • fast_forward00:08:14 - interpret with the normal models in the brain. They were meaningless, apparently.
  • fast_forward00:08:19 - And he was told by a series of American embryologists, he consulted many of
  • fast_forward00:08:24 - them, that his data were meaningless, his gene expression data.
  • fast_forward00:08:30 - And he just could not believe that a gene could be meaningless.
  • fast_forward00:08:34 - It had to be there to have some effect and to do something.
  • fast_forward00:08:39 - And nobody could tell me what was the meaning of that until I came around.
  • fast_forward00:08:43 - And then I thought, you know, the meaning of this, this, this,
  • fast_forward00:08:46 - and that. I explained to him with my own model.
  • fast_forward00:08:50 - So I could see that this gene could be explained according to my model easily.
  • fast_forward00:08:54 - This is putting this boundary there.
  • fast_forward00:08:59 - And he was amazed that I could so immediately resolve the problems we had.
  • fast_forward00:09:06 - So we decided, okay, let's collaborate.
  • fast_forward00:09:10 - It was difficult. So with your insight then, right, you said,
  • fast_forward00:09:13 - look, these molecular genetic markers help us to segment,
  • fast_forward00:09:17 - different neuromeres. I had already reached this conclusion that the brain was
  • fast_forward00:09:21 - segmented by other data, not molecular. And it was embryological.
  • fast_forward00:09:25 - People think that because I became thankful to see a gene that I started discovering
  • fast_forward00:09:29 - this, but it was not the molecule.
  • fast_forward00:09:32 - I started 10 years before with other sorts of morphological data that slowly
  • fast_forward00:09:37 - I integrated that the boundaries I saw, they were transversal,
  • fast_forward00:09:41 - that they were not in the...
  • fast_forward00:09:42 - Because the teachers say that they were longitudinal, and there were having
  • fast_forward00:09:46 - anti-divis against what the book said.
  • fast_forward00:09:49 - It was anatomy, but the functional anatomy of developing nervous systems.
  • fast_forward00:09:53 - Well, the function appears always later.
  • fast_forward00:09:55 - I wanted to see the function, but I was in a quarrel that had no function at
  • fast_forward00:10:00 - the moment when the brain stands having boundaries, genetic boundaries, the no.
  • fast_forward00:10:05 - But was it comparative? You may have functions of the genes in a molecular sense.
  • fast_forward00:10:11 - What does this mean do exactly in a molecular cell type of function,
  • fast_forward00:10:16 - but not in a neural function?
  • fast_forward00:10:18 - Isolated phenomenon?
  • fast_forward00:10:20 - So during most of my early career, I was not dealing with functions.
  • fast_forward00:10:25 - Of course, I was raised in both of neurophysiology.
  • fast_forward00:10:28 - I was trying to learn what was not done by physiologists all this time,
  • fast_forward00:10:32 - because I was interested in the functions. Yeah, but the main point here is
  • fast_forward00:10:36 - that, so what you're saying is that, just look at morphology, right?
  • fast_forward00:10:41 - You already had this hypothesis that the borders of two regions are transversal
  • fast_forward00:10:48 - in the tube, right? In the neural tube. It's not functional.
  • fast_forward00:10:52 - No, no, no, no, structure. It's a reality of how fish are.
  • fast_forward00:10:57 - No, but that was not necessarily accepted wisdom, right? No.
  • fast_forward00:11:01 - That was your hypothesis.
  • fast_forward00:11:03 - No, no, no. And then the molecular genetic revolution happened.
  • fast_forward00:11:07 - Happened, and that helped me, that represented for me good arguments in order
  • fast_forward00:11:14 - to prove my position to other people because it was the relevant instrument at that time.
  • fast_forward00:11:22 - So if you can prove your ideas, not without a method, but with genes in your
  • fast_forward00:11:26 - hands, then it had more weight.
  • fast_forward00:11:28 - But then let's look at this notion of transversal, right? But is that a universal
  • fast_forward00:11:33 - feature of a developing brain, that all segmentations are always transversal in the neural tube?
  • fast_forward00:11:40 - At the beginning, I mean, there is a set of the universal boundaries plus a
  • fast_forward00:11:43 - set of those developmental boundaries that you take across.
  • fast_forward00:11:46 - So there's boundaries like this and like that, defining quadrilateral of areas
  • fast_forward00:11:52 - that are differentially, expressing differential genes.
  • fast_forward00:11:57 - And that had been something, before I started, there had been a school sort
  • fast_forward00:12:02 - of proposing that sort of idea, but it was,
  • fast_forward00:12:06 - too far back, and the methodologies they used were two different tools in a way.
  • fast_forward00:12:13 - So they never achieved comprehension by the field and so on,
  • fast_forward00:12:16 - and they just disappeared from the literature.
  • fast_forward00:12:18 - When I started in neurobiology, nobody mentioned these people in the books or in the articles.
  • fast_forward00:12:26 - I discovered that they existed by looking back, as you say, looking back historically
  • fast_forward00:12:33 - at where the ideas came from.
  • fast_forward00:12:35 - Then I discovered that like 50 years before, there had been a school that had
  • fast_forward00:12:40 - proposed already these ideas of dividing into religion and all that.
  • fast_forward00:12:45 - It was a theory by some Swedish authors and so on that were completely forgotten
  • fast_forward00:12:51 - over the time when I read it.
  • fast_forward00:12:53 - What was the competing hypothesis at that time in the field?
  • fast_forward00:12:58 - Actually, it was a functional one. So there was somebody, an American that came
  • fast_forward00:13:03 - up saying, no, no, I'm not interested in mere morphological classification of
  • fast_forward00:13:09 - parts in the brain. I want to see function.
  • fast_forward00:13:11 - And since these divisions that somebody had already analyzed and they existed, has had no functional,
  • fast_forward00:13:20 - counterparts, so to speak, he became interested.
  • fast_forward00:13:23 - There was a time in the sort of turning of the 1900s, more or that there was
  • fast_forward00:13:31 - a period in which people discovered the analysis of the nerve components,
  • fast_forward00:13:35 - and there were sensory nerves, motor nerves,
  • fast_forward00:13:38 - sympathetic, parasympathetic, this and that, the only classification of all
  • fast_forward00:13:43 - the components of the nerves.
  • fast_forward00:13:44 - And that was analyzed in the brainstem and the spinal cord, and it was discovered
  • fast_forward00:13:49 - that there were discovered in the form of columns, which are arranged from dorsal to ventral.
  • fast_forward00:13:54 - So that was this model, the producer model of columnar analysis of the brain.
  • fast_forward00:14:00 - And while these American people that had rightly discovered the columnar arrangement
  • fast_forward00:14:06 - of this brain stem and spinal corpus of the brain.
  • fast_forward00:14:10 - He has postulated that all the rest of the brain, the forebrain,
  • fast_forward00:14:13 - is just a continuation of these columns extending into the telencephalus.
  • fast_forward00:14:17 - So this guy, Hedrick, was a very important guy and also a very interesting person.
  • fast_forward00:14:26 - He was a morphologist, a very good one, and very much interested in functional
  • fast_forward00:14:31 - conclusions. So he was the guy that most advanced.
  • fast_forward00:14:35 - He wrote like six or seven books about functional analysis of the neuroanatomy.
  • fast_forward00:14:40 - But from my point of view he
  • fast_forward00:14:43 - was producing ideas without having a
  • fast_forward00:14:46 - proper neurobiology behind him so he
  • fast_forward00:14:49 - produced two fancy ideas that
  • fast_forward00:14:52 - seemed interesting and so on and he drew all the interests of the field into
  • fast_forward00:14:58 - this and I was more governed by wishful ideas about how function could be in
  • fast_forward00:15:06 - theory if the conal structure of the brainstem was extended into the front of the brain.
  • fast_forward00:15:12 - But it was wrong because he was forgetting about the bendings of the tube, about the notocorrel.
  • fast_forward00:15:19 - He was not thinking embryologically, he was just thinking about the adult brain
  • fast_forward00:15:24 - and whether the functions would be extended.
  • fast_forward00:15:26 - We thought thinking whether the morphology was really consistent with those ideas.
  • fast_forward00:15:32 - So there was a period in which anatomy turned to be very functional.
  • fast_forward00:15:37 - But in advance of the data and in advance of the theories.
  • fast_forward00:15:41 - So he wasn't really not explaining anything. Yeah, but was it also the challenge?
  • fast_forward00:15:45 - So when you started to get this molecular genetic data, and you had this idea
  • fast_forward00:15:50 - of a more embryological, developmental perspective on neuroanatomy… That is
  • fast_forward00:15:56 - explanation of what happens here. Right.
  • fast_forward00:15:58 - But what was, at that time, the pushback you received?
  • fast_forward00:16:02 - Because… Yeah, the push-over was, as I said, but for hundreds of years,
  • fast_forward00:16:06 - we have been knowing that, according to this American guy from hundreds of years
  • fast_forward00:16:10 - ago, this thing is not, as you say, this thing is longitudinal,
  • fast_forward00:16:14 - it's functional and so on, and the importance of an anatomy is to be functional, not to be causal.
  • fast_forward00:16:22 - Okay. And that was the reaction I got, and I said, okay, I'm interested in the
  • fast_forward00:16:26 - functions, but I want the function to be consistent with the biology and with
  • fast_forward00:16:30 - the mechanism that happens in the embryo. So I don't want the fancy functionality.
  • fast_forward00:16:35 - Yeah, but if you look now at the reference work, reference works in anatomy, like John Kass.
  • fast_forward00:16:40 - Yeah, no, no. The tall literature for 100 years since 1910, I started working in 1970s.
  • fast_forward00:16:48 - That's when I started my research.
  • fast_forward00:16:50 - So for 60 years when I started, all the books, all the articles,
  • fast_forward00:16:55 - everything was functional and based on this American guy's work,
  • fast_forward00:16:58 - based on the analysis of the network, that's correct. The eyes of the nurse was correct.
  • fast_forward00:17:03 - It was an extrapolation to the lost part of the brain that was wrong,
  • fast_forward00:17:07 - because it was completely uncidful.
  • fast_forward00:17:09 - Yeah, but also, when you built this story, this theory in 1970,
  • fast_forward00:17:15 - there was very dominant anatomy already, right?
  • fast_forward00:17:17 - I was starting with the visual system, which is entirely in the forebrain.
  • fast_forward00:17:21 - But also you're starting with embryology, because a lot of these classical models
  • fast_forward00:17:25 - were based on adult brains.
  • fast_forward00:17:28 - Yeah, what I saw in the books and so on was everything based on,
  • fast_forward00:17:32 - not only on memory, it was based on the other brain analysis and on imaginations
  • fast_forward00:17:38 - of how they thought that the functions could be.
  • fast_forward00:17:41 - Since they were so interested in functional analysis, they just accepted everything
  • fast_forward00:17:45 - this guy said without any proper proof or any proper analysis.
  • fast_forward00:17:50 - So it was, I think that still exists, so one half of the people nowadays,
  • fast_forward00:17:55 - they still believe that the structure of the brain, I mean the schema you use
  • fast_forward00:18:00 - and some other schema I have seen today,
  • fast_forward00:18:02 - they are this columnar schema that which are wrong, according to my data.
  • fast_forward00:18:06 - So that's the Larry Swanson scheme that our friend showed.
  • fast_forward00:18:10 - For instance. So what's wrong with those schemes?
  • fast_forward00:18:14 - It's wrong because it's not consistent with what you see in the embryology when
  • fast_forward00:18:18 - the things are happening, when some tissue is giving signal to,
  • fast_forward00:18:22 - so you are going to be floor, you are really ventral, and you are longitudinal, and you are roof.
  • fast_forward00:18:29 - I have interacted with Swanson through the internet, and I asked him,
  • fast_forward00:18:33 - okay, where do you think the roof plate ends, for instance?
  • fast_forward00:18:38 - And he could not explain to me where the roof plate ends, for instance,
  • fast_forward00:18:42 - because he had never thought of that sort of thing.
  • fast_forward00:18:45 - So for you to understand anatomy, we have to understand development.
  • fast_forward00:18:49 - Yeah, because morphology comes out of developmental phenomena.
  • fast_forward00:18:56 - So you have to start there, you have to build up more complicated phenomena,
  • fast_forward00:19:00 - And at a given point, once you produce the needle, the needle is connected,
  • fast_forward00:19:04 - the synapse and so on, suddenly you start to have neural functions,
  • fast_forward00:19:08 - and that's where the functions appear.
  • fast_forward00:19:11 - And all the rest, the structure is already prepared by the early phenomenon of development.
  • fast_forward00:19:15 - And the old school of the colonial people, they completely didn't look at the embryos.
  • fast_forward00:19:21 - They simply supposed that it was like a third art of analysis of the adult nerds.
  • fast_forward00:19:28 - So it was a very defective field in many ways.
  • fast_forward00:19:33 - But I was isolated in Spain. I could criticize myself.
  • fast_forward00:19:38 - I read in the books and articles that I couldn't do anything against it.
  • fast_forward00:19:43 - So the physiologists I contacted, they had no idea about it.
  • fast_forward00:19:47 - The physiologists at the time were not attending to morphology either,
  • fast_forward00:19:51 - so they were just putting the
  • fast_forward00:19:52 - electrode where they could and had no very primitive ideas of morphology.
  • fast_forward00:19:57 - So in my early years, I was not
  • fast_forward00:20:02 - very productive in terms of publication because I didn't know what to do.
  • fast_forward00:20:08 - But in a cartoon perspective, you would say, look, we have this developing neural
  • fast_forward00:20:13 - tube, which is resting on a nodal cord.
  • fast_forward00:20:16 - And this is an effect that I know starts here and ends there.
  • fast_forward00:20:21 - Right. I see the notary public. Exactly. So I know where it ends.
  • fast_forward00:20:24 - And that starts to demarcate. I started to get some answers precise enough to
  • fast_forward00:20:30 - be able to build some conclusions out of that.
  • fast_forward00:20:34 - And that's what NBRG needed, to start increasing the number of data that were
  • fast_forward00:20:39 - good enough to really serve as a basis for conclusions that would advance an
  • fast_forward00:20:46 - understanding of what's happening there.
  • fast_forward00:20:49 - That reason, and preparing the pathway to reach the moment in which you could analyze functions.
  • fast_forward00:20:55 - But the function was like several generations later, so to speak,
  • fast_forward00:20:59 - so for many good parts of my early career, I did not do anything functional. even now.
  • fast_forward00:21:05 - So I started my only paper speaking of function, I published like two years
  • fast_forward00:21:10 - ago, particularly at the end of my career.
  • fast_forward00:21:14 - But it's not, I was not interested in function, so only that I needed to feel
  • fast_forward00:21:19 - all the whole mental that existed before function appeared.
  • fast_forward00:21:25 - So we have to chew, then due to morphogene gradients, you get parcellation.
  • fast_forward00:21:32 - It's like investing in a building.
  • fast_forward00:21:33 - You first have to construct the building, and then you put things inside,
  • fast_forward00:21:39 - then you put people inside, and at the end, things happen with the people in this building.
  • fast_forward00:21:44 - So it's a later, a fundamental function is a later thing, also in the brain,
  • fast_forward00:21:49 - than merely producing neurons.
  • fast_forward00:21:51 - When the moment the neurons are born, they have no function, they are just there,
  • fast_forward00:21:55 - and they are developing, they are increasing, they are doing a number of things,
  • fast_forward00:22:00 - or they are moving along by migration, but they are not functioning as neurons,
  • fast_forward00:22:04 - there is no pathway there, no system, nothing.
  • fast_forward00:22:07 - So this slowly develops when the cells start connecting one to another and so
  • fast_forward00:22:11 - on, and they just start to get pathways that function and get perfected or whatever
  • fast_forward00:22:17 - in their connectivity. missing.
  • fast_forward00:22:19 - And that's something that I have always been interested in, I think,
  • fast_forward00:22:23 - when it happens and how it happens.
  • fast_forward00:22:25 - But my personal work has been more concentrated on understanding better the
  • fast_forward00:22:30 - morphological aspect of boundaries, where they are, how they form,
  • fast_forward00:22:35 - and how many boundaries, in which temporal order they appear, and so on.
  • fast_forward00:22:39 - Testing where the boundaries disappear, because there was a theory that some
  • fast_forward00:22:43 - early boundaries disappeared and were substituted by other boundaries and I
  • fast_forward00:22:48 - had to fight against them because I discovered that normally the boundaries are fixed.
  • fast_forward00:22:52 - Once you build a boundary in the early brain, it stays into that out.
  • fast_forward00:22:57 - So I never have found any boundary that disappears.
  • fast_forward00:23:00 - Once it is there, it stays. You can add new boundaries.
  • fast_forward00:23:04 - Yeah, but now, so we have the tube, we make the segmentation,
  • fast_forward00:23:09 - transversal, longitudinal, then the connectivity
  • fast_forward00:23:14 - has to develop but isn't there a risk in the way you sketch it that it is purely
  • fast_forward00:23:22 - in sort of a feed forward causal chain because at some point the activity of
  • fast_forward00:23:28 - the neurons might not be functional in terms of generating behavior but activity matters.
  • fast_forward00:23:34 - Yeah but of course but when it exists if there is no activity What are you saying
  • fast_forward00:23:40 - about functions when there are no needles there?
  • fast_forward00:23:42 - Now let's just think about the retinal way. When the needle has to immature,
  • fast_forward00:23:45 - they don't even connect.
  • fast_forward00:23:47 - No, but what I'm saying is to think about retinal waves, right?
  • fast_forward00:23:49 - Retinal waves are pretty relevant
  • fast_forward00:23:51 - in the development of the thalmocortical projections, for instance, right?
  • fast_forward00:23:56 - So we have activity in one part of the system that is functional because it
  • fast_forward00:24:00 - drives the development in another part of the system, right?
  • fast_forward00:24:04 - It's a story that happens later than the moment when the eyes are formed.
  • fast_forward00:24:10 - Sure, no, no, absolutely. One thing is to decide what is going to be an eye.
  • fast_forward00:24:14 - And the eye will have a pigmented retina, a neural retina. It divides the primordial
  • fast_forward00:24:20 - into a number of eyes that needs boundaries.
  • fast_forward00:24:22 - You see what I mean? So those are
  • fast_forward00:24:24 - the early questions that need to be resolved. How do I put an eye here?
  • fast_forward00:24:28 - And how I separate what is going to be the stalk? What is the vesicle and this and that and so on?
  • fast_forward00:24:34 - And now, when do my first neuron are born in the retina? And you have to find this data.
  • fast_forward00:24:40 - I work on all these questions. I published on the LDV ganglionic cells,
  • fast_forward00:24:45 - LDM, my client cells, and so on.
  • fast_forward00:24:47 - I studied the visual pathway in every aspect.
  • fast_forward00:24:51 - When the neurons are born, when they extend the axons, when the axons reach
  • fast_forward00:24:55 - the target, when they do synaptogenesis.
  • fast_forward00:24:58 - So I did step-by-step analysis of this point, and this is going forward in time.
  • fast_forward00:25:03 - And then the time comes when the things start to function. So the argument is
  • fast_forward00:25:09 - that these early developmental tribunals are.
  • fast_forward00:25:15 - Largely genetically determined by with regulatory genes, and then later interactions
  • fast_forward00:25:20 - with other nearby cells are affecting the fate.
  • fast_forward00:25:25 - Yeah, but when you go to later phenomena, you normally have other sort of genes.
  • fast_forward00:25:30 - Some of the early cells can continue working, but usually when you have these
  • fast_forward00:25:34 - cascades of genes, this gene activates 10 other genes, these 10 other genes
  • fast_forward00:25:40 - activate 30 other ones, So you reach 500 genes,
  • fast_forward00:25:44 - which result from the first activation of one gene very early in the groundwater, Mala said.
  • fast_forward00:25:50 - So when you reach the neurons, you have activated 500 genes in a specific spot on the brain.
  • fast_forward00:25:57 - That is what the genetic analysis can do more complex and more complex.
  • fast_forward00:26:02 - But do those genes do more than the specified coordinate system?
  • fast_forward00:26:06 - Yeah, because it's not enough to say this is a neuron. Now you have to say this
  • fast_forward00:26:10 - neuron is inhibitory or is excitatory, or is it going to connect with this or with that?
  • fast_forward00:26:16 - And then this depends on molecules in the cell membrane, and these molecules are coded by genes.
  • fast_forward00:26:23 - And also, there's the interaction of that cell and of the other cells,
  • fast_forward00:26:27 - where it sort of migrates to the position of the brain, and based on genes,
  • fast_forward00:26:31 - it says on the cell. Everything is based on genes.
  • fast_forward00:26:34 - But also it's based on the interactions but not always
  • fast_forward00:26:38 - the same genes in time the the set
  • fast_forward00:26:40 - of these changes no but but everything is a it's a
  • fast_forward00:26:43 - little bit an overstatement right at some point there's also a transition that
  • fast_forward00:26:47 - environment and dynamics comes in right so so yeah of course i think that's
  • fast_forward00:26:52 - also what tony is is after right yeah but but that did but i mean that there
  • fast_forward00:26:57 - is no no stick boundary because the brain is telegineous and not everything
  • fast_forward00:27:01 - goes at the same velocity, so to speak.
  • fast_forward00:27:04 - So you may have, in a given part, one part where it's already starting to function,
  • fast_forward00:27:08 - but in another one it's not yet there.
  • fast_forward00:27:11 - So the things go a bit like, because everything does not go,
  • fast_forward00:27:15 - it's not chronically organized.
  • fast_forward00:27:18 - I showed examples of advanced domains and retarded domains in the brain.
  • fast_forward00:27:23 - So the similar phenomenon may go a bit out of phase in adjacent and part of
  • fast_forward00:27:28 - the brain through a path of analysis to get analyzing what is the discrepancy
  • fast_forward00:27:34 - within what happens here,
  • fast_forward00:27:36 - what happens in the adjacent piece of the main, to understand what is the pattern.
  • fast_forward00:27:40 - When I started in this sort of thing, there was this theory that neurogenesis
  • fast_forward00:27:45 - or any other important phenomenon starts in a point that spreads out like a
  • fast_forward00:27:50 - wave into the rest of the one of the brain. That's what they call the books.
  • fast_forward00:27:55 - If you have the fact here, you're not going to be at the same,
  • fast_forward00:27:59 - then that's like a wave spreading.
  • fast_forward00:28:01 - And that has come out to my observation, show and demonstrate that it's not true.
  • fast_forward00:28:07 - You have this quadratic therapy that is in advance, and then here you have a
  • fast_forward00:28:13 - tablet one, and you have the next advanced one in that corner over there.
  • fast_forward00:28:17 - So that means that they were regulated independently, the places where things
  • fast_forward00:28:22 - advanced more quickly, they were regulated not in relation one to another in a wave-like thing.
  • fast_forward00:28:27 - It was here, and now there, and now there, and now here, and now there.
  • fast_forward00:28:31 - That's the pattern in how the world of the brain produces its neural,
  • fast_forward00:28:35 - and the neural is mature, and so on, at different velocities and different quadrangular
  • fast_forward00:28:40 - pieces, limited by longitudinal boundaries and transversal boundaries.
  • fast_forward00:28:45 - So that is what really means the shape which I saw.
  • fast_forward00:28:49 - I take the photograph and I show that this is for your billion,
  • fast_forward00:28:53 - and at the same time, there is only very few neurons. I showed you the photograph today.
  • fast_forward00:28:58 - So, that was me when that is. But does this development speed,
  • fast_forward00:29:04 - if you want, in any way relate to the final function?
  • fast_forward00:29:09 - In the sense that you know that if this is an advance of the other field,
  • fast_forward00:29:12 - and these cells will stop to function before the other ones are leaving.
  • fast_forward00:29:17 - But that also means that the later cells will depend in their function on the
  • fast_forward00:29:22 - preceding cells? Not necessarily.
  • fast_forward00:29:24 - No? But, I mean, because it's a very interesting brain. There are so many different domains.
  • fast_forward00:29:31 - Our conclusion is that you can divide into more than 1,000 areas, the entire brain.
  • fast_forward00:29:37 - And then our conclusion is that we need at least 1,250 different areas in order
  • fast_forward00:29:44 - to produce the number of cell types that are supposed to exist.
  • fast_forward00:29:48 - And that's on molecular genetic grounds. Yeah, on these grounds.
  • fast_forward00:29:52 - So the people, just because of a group of high-level laboratories in the States,
  • fast_forward00:29:57 - they did such pectones and so on, and they concluded all together,
  • fast_forward00:30:00 - like 10 or 12 high-level laboratories, There are 5,300 or 400 cell types in
  • fast_forward00:30:08 - the entire brain, and if you say, okay,
  • fast_forward00:30:12 - an improgenital domain only can put five,
  • fast_forward00:30:15 - if you divide, then you get how many.
  • fast_forward00:30:18 - But how many of these cell types and expression patterns are really unique for the brain?
  • fast_forward00:30:23 - Let's say if we put a threshold of 80% unique. Well, we are speaking of the
  • fast_forward00:30:28 - cell type, we are speaking of a combinatorial pattern of genes.
  • fast_forward00:30:32 - It's not about this. Sure, well, of course.
  • fast_forward00:30:35 - Meaning that the median neuron expresses, let's say, 700, 800 genes that are
  • fast_forward00:30:42 - relevant for its function.
  • fast_forward00:30:44 - And this is a combination of 20,000 genes of the genome taken by 700 and 700.
  • fast_forward00:30:52 - How many combinations can you make? Yeah, but how many of those are then unique
  • fast_forward00:30:56 - for the function of the neurons?
  • fast_forward00:31:00 - Many, many of them, because… If you have to make a guess for this… …on those
  • fast_forward00:31:04 - that call for chanelins in the insulin brain, or for receptors of neurotransmitters,
  • fast_forward00:31:08 - or for, like, CBT proteins that attach one axon to a dentide or whatever, sure.
  • fast_forward00:31:14 - So there are families, entire families of molecules, which are dozens of molecules,
  • fast_forward00:31:19 - and that means hundreds.
  • fast_forward00:31:22 - Although, with this also, many of them are… But what I'm trying to get to,
  • fast_forward00:31:26 - if you say we need 1,500 separate regions based on molecular grounds, but then,
  • fast_forward00:31:34 - of course, you can say many of these neurons have shared expression patterns
  • fast_forward00:31:40 - with many other neurons.
  • fast_forward00:31:42 - So if we strip out that component, that's just for ATP and so on, right?
  • fast_forward00:31:47 - If you take that out, what's left? How many regions we got then?
  • fast_forward00:31:50 - Well, we don't have a complete picture. No, I want you to guess, okay? Just guess.
  • fast_forward00:31:55 - Speculate. I mean, for the classical functional analysis, look into sensory
  • fast_forward00:32:00 - pathways and autopilot and so on, tells you more or less the sort of order of things,
  • fast_forward00:32:06 - plus maybe some unknown pathways and some unknown systems.
  • fast_forward00:32:11 - Yeah, but for the 1500, what will be left? Do you think a thousand, 500, a hundred?
  • fast_forward00:32:15 - I would say that we are near a hundred different systems.
  • fast_forward00:32:21 - At least. That will be on the low side.
  • fast_forward00:32:25 - But it sounds more manageable then, right? Yeah, I mean, we can't reach a point
  • fast_forward00:32:29 - where we understand really how many functional C things in the brain.
  • fast_forward00:32:33 - But the problem is that the C things get mixed in a complex way because it's
  • fast_forward00:32:40 - not any longer, you cannot say this is a column, so because it's a column,
  • fast_forward00:32:45 - all these neighbors will share a particular function.
  • fast_forward00:32:49 - It happens at a given level, like the geminal sensory canal,
  • fast_forward00:32:53 - or nucleosolitarium, or whatever.
  • fast_forward00:32:56 - You can say, this is somatosensory from the head, or this is visceral sensory
  • fast_forward00:33:00 - for all the visceral, and so on.
  • fast_forward00:33:02 - But that just tells you that a number of units, adjacent units,
  • fast_forward00:33:06 - they share a likeness for getting signals from this particular function,
  • fast_forward00:33:14 - this particular function.
  • fast_forward00:33:15 - Even so, each one of them will analyze the data in a bit different way.
  • fast_forward00:33:19 - We have certain villages that last lots of ones.
  • fast_forward00:33:22 - More compressing, like memory, or things happening in the cellulose,
  • fast_forward00:33:26 - then usually you have a center in the telomose, another center in the telomose,
  • fast_forward00:33:31 - another center in the hypotelomose, another in the brainstem,
  • fast_forward00:33:34 - and then your pathways are arranged around the entire brain.
  • fast_forward00:33:37 - Even the spinal cord is needed. But an answer is for, let's say,
  • fast_forward00:33:42 - standard parasolidations, right?
  • fast_forward00:33:43 - We start with Brogna. I mean, farm shields are not organized into close,
  • fast_forward00:33:48 - tightly, and nicely localizable subsystems.
  • fast_forward00:33:53 - They are distributed in a complex way, and in many cases, they are not yet well
  • fast_forward00:33:58 - enough mapped, because people are prepared to select.
  • fast_forward00:34:05 - Which is the main component in the visual pathway?
  • fast_forward00:34:08 - That's the natural engine nicolator. So a lot of authors have just focused on
  • fast_forward00:34:12 - the natural-indiculate with just one point in a distributed patchwork of many areas.
  • fast_forward00:34:18 - So if you don't look at the other ones, then you have Apache knowledge of the
  • fast_forward00:34:22 - visual system that right now happens.
  • fast_forward00:34:25 - I have interacted with visual experts in Bethesda, the city of the working on
  • fast_forward00:34:30 - the visual pathway, and they were amazed when they saw my map and so on,
  • fast_forward00:34:34 - because most of these things, we didn't even know they existed.
  • fast_forward00:34:40 - So these are areas where you get an equinotropic map, so you're so responsive to them.
  • fast_forward00:34:46 - But they're also responsive to other things? That happens with practically any other thing.
  • fast_forward00:34:51 - You look into how do I focus my eyes, and you have a center in the cortex,
  • fast_forward00:34:55 - another center here, and I'm in the pretentium, and I'm there,
  • fast_forward00:34:59 - and you have like several eyes.
  • fast_forward00:35:01 - Or how do we regulate my eye's diameter to get more light got less light into my eyes.
  • fast_forward00:35:08 - And again, it's distributed over a number of windows.
  • fast_forward00:35:11 - And they are not adjacent. They are one here in the tencephalus,
  • fast_forward00:35:15 - and two of them in the brainstems and so on, and then something in the tencephalus,
  • fast_forward00:35:21 - something in the tencephalus.
  • fast_forward00:35:22 - So it's distributed like that. For anything you look, functionally,
  • fast_forward00:35:26 - it's a distributed system that uses neuromeric structure or a center,
  • fast_forward00:35:31 - because you saw that my centers, there were several of them inside of the same neuromere.
  • fast_forward00:35:37 - So a neuromere is like a mini-brain. This is an important idea that we can deduce
  • fast_forward00:35:42 - functionally one neuromere works like a mini-brain, a minimal unit of a brain,
  • fast_forward00:35:48 - because it has, in the dorsal part,
  • fast_forward00:35:51 - the sensory analysis part, where it has neurons, different centers,
  • fast_forward00:35:55 - analyzing given parts of enough information sensory that needs to be integrated
  • fast_forward00:36:02 - for some purpose, for a general purpose,
  • fast_forward00:36:05 - and then this part can have reflex connection with the corresponding vasal portion
  • fast_forward00:36:11 - that contains particular minglons or bottom or whatever that lead to a output
  • fast_forward00:36:16 - and sort of behavioral output.
  • fast_forward00:36:19 - So every needlemaid in a way is complete so it can work by itself only to produce some reflex activity.
  • fast_forward00:36:28 - Normally all of them are functional So the brain uses sets of these neuromeres
  • fast_forward00:36:34 - for given things, for some particular point of view, this, this, this, and that.
  • fast_forward00:36:39 - For you, a neuromere is really like a structure that cuts across various segments.
  • fast_forward00:36:46 - Yeah, but in a functional way.
  • fast_forward00:36:49 - In some way to always have some effect, if you keep my signal to this other
  • fast_forward00:36:53 - plate, I can give you from this puzzle plate some answer.
  • fast_forward00:36:57 - Is it going to be useful? Well, it depends what another neurobeer does.
  • fast_forward00:37:01 - And there are 20 neurobeers in the brain, discounted in the sparracore,
  • fast_forward00:37:06 - the forgettable sparracore.
  • fast_forward00:37:07 - In the rest of the brain, we have 20 neurobeers.
  • fast_forward00:37:10 - So can you define the neuromere more precise? So, in the heart brain and forebrain,
  • fast_forward00:37:16 - if you take what we call brain, so to speak, that is divided into 20, into 20 with this.
  • fast_forward00:37:23 - All of them are mini-brains, have an anal part, an analytic part,
  • fast_forward00:37:27 - and are answering both parts.
  • fast_forward00:37:30 - But they will all loop through cortex, basal ganglia, hippocampus, amygdala thalamus.
  • fast_forward00:37:36 - Some of them more directly and others more indirectly, because in the brain
  • fast_forward00:37:40 - you have analytic portions that connect with the thalamus, and this is a different
  • fast_forward00:37:44 - neuromere, and from the thalamus they go to the copter, which is a different neuromere.
  • fast_forward00:37:49 - On this pathway, they are jumping from one neuromere to another,
  • fast_forward00:37:53 - but not going by adjacent neuromeres.
  • fast_forward00:37:55 - They are jumping from this neuromere to that, jumping from another.
  • fast_forward00:37:59 - This is almost true that a neuromere is like a functional unit.
  • fast_forward00:38:02 - In a way, it's an ethical function that even when it does go into the cortex,
  • fast_forward00:38:08 - it is maybe it's irrelevant, but it can produce as a phylic.
  • fast_forward00:38:11 - So you can have only both options, and then you'll make them produce already
  • fast_forward00:38:16 - some sort of solution from its own point of view.
  • fast_forward00:38:20 - So if the only data available is my data, then I will do this.
  • fast_forward00:38:25 - Against this signal, I will do that. I will do more extension or more flexion
  • fast_forward00:38:30 - or more increase in my heart rate or do some... There's also a metaphor that you're saying.
  • fast_forward00:38:35 - The brain has 20 experts. They can all do something.
  • fast_forward00:38:39 - But they work together. They can also talk to each other.
  • fast_forward00:38:42 - And then some centers will stop to tell the listeners a lot.
  • fast_forward00:38:46 - Stop. We are not interested in what you are in your conclusion.
  • fast_forward00:38:49 - I am more interested in what this other guy is saying. But what does the cortex
  • fast_forward00:38:54 - can do? The cortex can select.
  • fast_forward00:38:57 - Like a keyboard, which gives you the content you want to play.
  • fast_forward00:39:04 - But the 20-Duramers are like a keyboard. And many of the adjacent kids can do
  • fast_forward00:39:09 - very similar things with the next, but the cortex always chooses,
  • fast_forward00:39:14 - okay, do respiration, do this and that. But what are the names?
  • fast_forward00:39:19 - What names would you give to 20-Duramers?
  • fast_forward00:39:22 - Well, then they have... You would get them functionally. No,
  • fast_forward00:39:23 - it's not, but I have nine for them, the embryological ones.
  • fast_forward00:39:27 - I have a classification by alphanumeric classification. Okay.
  • fast_forward00:39:33 - Yeah, but isn't it now a contradiction is slipping in? Because you started out
  • fast_forward00:39:37 - by saying, I just want to classify looking at embryological data.
  • fast_forward00:39:41 - Yeah, and the neurons out there, exactly as they were in the embryo, only they are adult now.
  • fast_forward00:39:46 - Now they have neurons that are connected, and they are some genetically functional.
  • fast_forward00:39:50 - Now, they're getting the trophic fractals and dying or not dying,
  • fast_forward00:39:54 - and they are getting signals from the afferent nerves, and they are putting
  • fast_forward00:39:58 - out responses by the muscle nerves.
  • fast_forward00:40:00 - So all that is now funny. But the funny thing is, didn't you exactly now create
  • fast_forward00:40:05 - the antithesis of the original position that said, anatomy follows function?
  • fast_forward00:40:11 - Well, you say function follows anatomy. No, function follows anatomy.
  • fast_forward00:40:15 - Yeah, that doesn't mean that. Anatomy is always tough, but you start with anatomy
  • fast_forward00:40:18 - without function. and then that is a world of building development into functional anatomy.
  • fast_forward00:40:23 - Yeah, but so now the question is, you still also said, but they have to work together.
  • fast_forward00:40:28 - Like a child evolving into an adult person, but you cannot expect from the child to do everything.
  • fast_forward00:40:35 - You cannot expect the early brain to do everything.
  • fast_forward00:40:39 - What's the data that would support the idea that neuromeres can autonomously
  • fast_forward00:40:44 - contribute to adaptive behaviors?
  • fast_forward00:40:48 - Autonomous because we know that they have the connections there,
  • fast_forward00:40:52 - that these neurons here, and these nuclei in the other portion,
  • fast_forward00:40:56 - which we know are noise in this signal, in this signal, in this signal,
  • fast_forward00:40:59 - they are connecting with these particular neurons in the basal plane,
  • fast_forward00:41:03 - and this is connecting with even motor neurons in these nerves, and so on.
  • fast_forward00:41:07 - Yes, so there is a path, right? So we know there is an afference,
  • fast_forward00:41:10 - a computation, and an answering signal, that is a simple sort of output of a response.
  • fast_forward00:41:20 - But does it work every time? No, because they don't work at all.
  • fast_forward00:41:24 - So, do you want people to abandon their existing way of segmenting them? No, no.
  • fast_forward00:41:30 - I want them to complicate the simplistic analysis of the brain.
  • fast_forward00:41:34 - In only choosing this and that, Over there, to analyze this research analysis,
  • fast_forward00:41:39 - what the Nazis completed the ontology of how many functional sensors exist in the brain.
  • fast_forward00:41:45 - And there are many more than the facilities are analyzing and the algorithmic
  • fast_forward00:41:50 - textbook are explaining. There are many more.
  • fast_forward00:41:52 - But say I'm interested in the superior calculus, likewise with the… That's one
  • fast_forward00:41:59 - of my main places of study.
  • fast_forward00:42:00 - So that's one neuromere. And that is part of one neuromere.
  • fast_forward00:42:06 - In the same neuromere where you have the super colliculus, you have the inferior
  • fast_forward00:42:10 - colliculus and a third central ortho-visual, it's called tectal gray,
  • fast_forward00:42:15 - that you have never heard of. The peri-active rectal gray? No, no.
  • fast_forward00:42:18 - That is a stratum. But that's also in there. That is there, but it's a deep
  • fast_forward00:42:22 - stratum peri-ventricular.
  • fast_forward00:42:25 - So it belongs to this area, but people classify it as it is not a part of the
  • fast_forward00:42:30 - superior colliculus and so on, but actually they are passed deep to the supercritical
  • fast_forward00:42:36 - and they are legitimately corresponding to it.
  • fast_forward00:42:39 - You cannot separate fully the pale and water grave from the rest of the story.
  • fast_forward00:42:44 - This never really corresponds to what people traditionally called the membranes.
  • fast_forward00:42:47 - If you put everything together, you fill up the boundary.
  • fast_forward00:42:52 - But together with Shigeru, you need two other centers of analysis which analyze
  • fast_forward00:42:56 - different information.
  • fast_forward00:42:58 - So, in Collegios, it's not a law.
  • fast_forward00:43:01 - So, in the Lumière Normandy, divide in the analysis portion into different parts.
  • fast_forward00:43:07 - I show them with the gradient of this use, and divide the structure into four
  • fast_forward00:43:12 - or five different territories. That is the reason why an alert territory of
  • fast_forward00:43:18 - a general mayor is divided in different adult centers.
  • fast_forward00:43:22 - So that is in the center for vision, they use the supercurriculars,
  • fast_forward00:43:26 - but for audition, they use the inferior curriculars.
  • fast_forward00:43:29 - And for instance, the supercurriculars is used mainly for jumping with the eye,
  • fast_forward00:43:35 - the center of the ocular motion into new areas of interest.
  • fast_forward00:43:40 - So you see a movement in your eyes, that is a function of the supercaligus,
  • fast_forward00:43:44 - to compute where you need to jump, too, with your eyes in a coordinated way.
  • fast_forward00:43:49 - But the other area that nobody knows, the tetrae in front of the supercaligus,
  • fast_forward00:43:54 - that is, I was from a Japanese facilitator who told me that the alien is in
  • fast_forward00:44:00 - this area, and he found that it was for fixing the gaze, not for jumping, but for fixing.
  • fast_forward00:44:07 - When you want to look along and
  • fast_forward00:44:09 - not jump to any place, they just continue looking at this paper mirror.
  • fast_forward00:44:12 - Then one point, these mirrors were activated. And there were also retinotopic inputs and so on.
  • fast_forward00:44:17 - They had a copy of the signals from the retina, but they used for a computation
  • fast_forward00:44:21 - leading to fixing the gaze, not for jumping.
  • fast_forward00:44:25 - So there you see a functional difference, but this was inside the same mirror
  • fast_forward00:44:30 - mirror. One person in the public center for fixing and another for jumping.
  • fast_forward00:44:35 - And then a self-center for auditions.
  • fast_forward00:44:39 - Yeah, but functionally, could you then say that every neuromere has a sensory
  • fast_forward00:44:44 - component, a memory processing component, and then a motor component?
  • fast_forward00:44:50 - Yeah, it's like a mini-brain. But they all have this. Yeah, the lozen has this issue.
  • fast_forward00:44:55 - Yeah, okay. So that means that it's a basic function that each neuromere already has by existing.
  • fast_forward00:45:00 - And now this combines with that by-connective connectivity, so that given pathway
  • fast_forward00:45:05 - goes here, here, here, here, and there. And other pathways maybe go through
  • fast_forward00:45:10 - the same neural mirror, but selecting other groups of neural, not the same.
  • fast_forward00:45:15 - So it's a complicated picture. But can you select or bias the use of neuromeres,
  • fast_forward00:45:21 - for instance, to neuromodulation?
  • fast_forward00:45:23 - I was thinking about Gray's idea about how serotonin is sort of configuring the neural axis, right?
  • fast_forward00:45:29 - So would you think about also that that selection across neuromeres is performed
  • fast_forward00:45:34 - in that way? The second part of plasticity, which normally does not introduce new pathways.
  • fast_forward00:45:39 - What it does is modulate by learning. No, it's sensitive, I see.
  • fast_forward00:45:44 - The idea would be that it sort of brings radiance. It makes an existing pathway
  • fast_forward00:45:48 - work better or more precisely for some purpose or whatever.
  • fast_forward00:45:53 - But it does not introduce a new pathway.
  • fast_forward00:45:56 - No, no, my question is, if you have these 20 neuromeres that all have different
  • fast_forward00:46:01 - functional contributions to make, that you need some meta-neuromere that sort
  • fast_forward00:46:05 - of balances how they interact, right? Otherwise, there will be chaos in the brain.
  • fast_forward00:46:09 - Apparently, they are given parts of the structure that, for some functions, moderate the rest.
  • fast_forward00:46:17 - Probably because either they have better connection or appropriate connections
  • fast_forward00:46:21 - to be guiding the overall function. But how do you imagine that?
  • fast_forward00:46:25 - That's more incompetence. Hypothalamus governance visceral work.
  • fast_forward00:46:33 - The cortex is not so important, viscerally, because it's the hypoteloma that you have.
  • fast_forward00:46:38 - And that can't even use the cortex for a given thing, because the hypoteloma
  • fast_forward00:46:42 - is connected with the cortex, and they say, ah, it cuts back hypoteloma,
  • fast_forward00:46:45 - but it's the hypoteloma that controls the brain centers and so on.
  • fast_forward00:46:49 - So for given things, it may be hypoteloma. For some other things,
  • fast_forward00:46:53 - it's a clear colloquial.
  • fast_forward00:46:54 - But basically, the elaptomy also shows some conversion centers,
  • fast_forward00:46:59 - so the blue ring path field typically is pointed to. Yeah, the basal ganglia.
  • fast_forward00:47:03 - For example, we know that the physiologists have identified centers for working and running.
  • fast_forward00:47:10 - So there are multiple centers that exist in some particular places that they
  • fast_forward00:47:14 - are not doing anything by themselves.
  • fast_forward00:47:17 - They are not weaponing and other things ending in the sparacord that control
  • fast_forward00:47:21 - your movements, working, and they control from your past working to trotting
  • fast_forward00:47:25 - and from trotting to running. And that is controlled by something which is a
  • fast_forward00:47:30 - group of nanos in the deep brain, for instance.
  • fast_forward00:47:32 - But I was thinking more specifically of the Basel-Bandria nuclei,
  • fast_forward00:47:37 - which appeared to have compared to Japan from cortex and from sub cortex.
  • fast_forward00:47:42 - That is actually part of the sensory analyzer stories of people who always have
  • fast_forward00:47:49 - thought, We thought we were not really covering the way that the Basagandia are not a motor center.
  • fast_forward00:47:56 - They are not most of them, they are everything.
  • fast_forward00:47:58 - So if you count all the parts of the Basagandia, it's just a circuit that is
  • fast_forward00:48:04 - acting the goddess in everything that the court is like. But it's a center structure.
  • fast_forward00:48:08 - But how does it mesh in the neuromir story, right? That's your answer point.
  • fast_forward00:48:12 - In Java, the telencephrine is just an hypertrophic analytical part of one neuromia,
  • fast_forward00:48:19 - the entire telencephrine, with vasodanglia, with cordon, with amygdala,
  • fast_forward00:48:23 - with septum, everything you have in a telencephrine, is part differentiated
  • fast_forward00:48:27 - part of the single neuromia.
  • fast_forward00:48:29 - So, for many, since this is an hypertrophic part of the brain,
  • fast_forward00:48:34 - it will have many important functions there.
  • fast_forward00:48:36 - That's why it has hypertrophic, because evolution has shown that the more you
  • fast_forward00:48:40 - have on those populations, the more efficiently you can survive.
  • fast_forward00:48:45 - That's the reason that the N-libacter brain practically did not have any Terencephoron.
  • fast_forward00:48:51 - That's really the cell group that became bigger.
  • fast_forward00:48:54 - The bigger it goes… Okay. But that would mean that from these 19 neuromeres
  • fast_forward00:48:58 - that are not an telencephalo, some of them might just be evolutionary remnants.
  • fast_forward00:49:05 - No, because all of them are alive. The neurons are alive because they are doing something.
  • fast_forward00:49:09 - Maybe they play a role just in a little developmental moment to bootstrap the telencephalo.
  • fast_forward00:49:16 - I cannot know because Fischer-Oleus has not yet studied every corner of the brain.
  • fast_forward00:49:21 - So there are many dark corners in the brain. If you have to speculate, how would you see it?
  • fast_forward00:49:25 - I tend to think that they are going to do something. Every one of them that
  • fast_forward00:49:29 - is alive is going to be participating in some function that is required that
  • fast_forward00:49:35 - it is there doing its job.
  • fast_forward00:49:36 - Even if it's in a minor hospital, like for example, regulating your iris,
  • fast_forward00:49:40 - I can't look without the lighted iris, I can also see.
  • fast_forward00:49:44 - I don't need my reflex for iris console, no?
  • fast_forward00:49:48 - But you have an entire circuit just working for the iris reflex.
  • fast_forward00:49:52 - Okay. It's not only a nucleus, it's a sequence going through several neuromeres,
  • fast_forward00:49:57 - all of them regulating your mass brain is entering.
  • fast_forward00:50:01 - But then, so there's one telencephalic neuromere, which is a pretty important
  • fast_forward00:50:07 - one for the human brain, right?
  • fast_forward00:50:08 - The more we have of that, the better is our intelligence and our capacity to
  • fast_forward00:50:13 - restore problems and to survive.
  • fast_forward00:50:15 - But you've also proposed a very specific functional model of that, right?
  • fast_forward00:50:19 - So you were thinking about the cortical analyzer surrounded by an limbic cortical
  • fast_forward00:50:25 - system interface to a… So it has to be a lot of functions and there's no other nanomeres.
  • fast_forward00:50:31 - So can you explain a bit more how you see that structure and organization?
  • fast_forward00:50:35 - Well, I think that within the tertarism, which is itself a complex analyzer,
  • fast_forward00:50:43 - the most analytic portion of that complex is the cortex, because it has the
  • fast_forward00:50:49 - properties of being divided into areas and so on.
  • fast_forward00:50:54 - So it has properties that are low through division of areas and specialization and so on.
  • fast_forward00:50:59 - So that increases, and we know through evolution, that lower mammals,
  • fast_forward00:51:03 - for instance, have less areas in the cortex than higher mammals.
  • fast_forward00:51:07 - So we have like 180 areas in our cortex, whereas the mouse only has about 50.
  • fast_forward00:51:13 - So in the evolution of 30 million years between rodents and primates,
  • fast_forward00:51:19 - we have multiplied by, well, divided by six, more or less.
  • fast_forward00:51:25 - So six, seven is the proportion. How we have incremented the differentiation,
  • fast_forward00:51:31 - functional differentiation for our cortex relative to what the rodder does.
  • fast_forward00:51:35 - But the rodder, in a simplified cortex relative to ours, can do a bit of everything we do.
  • fast_forward00:51:41 - Or it cannot speak, it cannot think about in the future, it cannot think about into the past.
  • fast_forward00:51:46 - So it's limited in the complexity of the function we can do,
  • fast_forward00:51:51 - but he analyzes the region, he analyzes somatosensory, he does motor analysis.
  • fast_forward00:51:56 - So if he does a lot of the basic stuff that we do, the U is also. What is it?
  • fast_forward00:52:00 - We can be de-filosified more, we can be more perfect, and we can be deeper in
  • fast_forward00:52:05 - how much we can prolongate into the past or into the future or calculations.
  • fast_forward00:52:11 - We can predict even what our grandchildren are going to do, nevertheless.
  • fast_forward00:52:17 - Well, the predictions might be off, but we can't predict. Not only,
  • fast_forward00:52:21 - at least we try to predict.
  • fast_forward00:52:22 - We can't think about resolving the problem of our families, one or two generations.
  • fast_forward00:52:28 - Yeah, but so in the mouse brain, on which you would base this work… In the mouse
  • fast_forward00:52:31 - brain, you cannot do that. No.
  • fast_forward00:52:33 - Well, in the mouse brain, you have, let's say, a cortical analyzer,
  • fast_forward00:52:37 - then you get a limbic cortex around it, then you have the… You have the mouse
  • fast_forward00:52:41 - arcanga, which is a mechanism to perfect sequences, So to introduce a memory
  • fast_forward00:52:46 - of sequences of responses that you already learn,
  • fast_forward00:52:50 - and have quick sequences that are pre-calculated, so to speak, by training a force,
  • fast_forward00:52:57 - and that's why you have to learn to go, and you have to learn to run,
  • fast_forward00:53:00 - and you have to learn to every motor action, you have to learn,
  • fast_forward00:53:04 - and you have to learn to play the piano, and so on, so on.
  • fast_forward00:53:07 - But if you learn, then you have at your service things that you can automatize
  • fast_forward00:53:14 - to the point that you don't need to do wrong and think about the progress involved.
  • fast_forward00:53:18 - How do I pass my big finger when I do the piano on a scale?
  • fast_forward00:53:22 - I have to regulate this movement every time my fingers.
  • fast_forward00:53:26 - I come to the last finger, I have to do something like that to move my heart.
  • fast_forward00:53:30 - Pianists do it automatically without thinking at all. That means that through
  • fast_forward00:53:34 - the steatons, there's a pathway that I'm doing a scale and that goes on automatically
  • fast_forward00:53:38 - restored because you train for it.
  • fast_forward00:53:41 - Right. And that is the function of the basal ganglia not only for the motor
  • fast_forward00:53:45 - progress but also for But in the diagram you showed us the basal ganglia didn't
  • fast_forward00:53:49 - have a big look but I understand,
  • fast_forward00:53:51 - They are a big spot because they are divided into numbers of areas.
  • fast_forward00:53:55 - Again, the more they have evolved, the more areas they have adopted.
  • fast_forward00:54:00 - My calculation presently in the month already, only in the month,
  • fast_forward00:54:03 - is that we have 60 different subdivisions of the Basal Gambia, 60.
  • fast_forward00:54:09 - You classify, okay, in this sense of space, this divides into five.
  • fast_forward00:54:13 - In the other sense of space, now once I add my five territories like that,
  • fast_forward00:54:18 - now I divide like this, and then I get into four.
  • fast_forward00:54:21 - 2 of 5 multiplied by 4 is already 20, and now each one of the four angularers
  • fast_forward00:54:27 - I defined like this divides into three SATA.
  • fast_forward00:54:30 - So I multiply by 3, and 20, and multiply by 36.
  • fast_forward00:54:34 - There is 60 different groups of neurons, each one of them, with its particular
  • fast_forward00:54:38 - input and its particular output,
  • fast_forward00:54:41 - and participating in a differentiated way in the solutions that need to be to
  • fast_forward00:54:48 - the task planned by the cortex.
  • fast_forward00:54:50 - So, the Kota Jav is dependent on thoughts, or for memory acts,
  • fast_forward00:54:55 - or for emotional reactions.
  • fast_forward00:54:57 - For movement, it's often combined, because in most of our arts,
  • fast_forward00:55:02 - we are doing both at the same time the emotional thing, the intellectual thing,
  • fast_forward00:55:07 - and the mental thing. We are reacting with everything we have.
  • fast_forward00:55:10 - That is the role of the Blossom Gambia for me.
  • fast_forward00:55:14 - It's an accessory, sort of a free accessory to the thoughts in the analysis
  • fast_forward00:55:20 - of the cortex in order to, okay, what can we do about this?
  • fast_forward00:55:24 - The cortex only needs to say, I want to go to a work, and then the mechanism
  • fast_forward00:55:29 - will automatically, if it's not new for you, but it's something that you have
  • fast_forward00:55:33 - done often, then you will have an automatized way of going for a work.
  • fast_forward00:55:38 - You want for ascending a stairs or for sitting but you also in your presentation
  • fast_forward00:55:42 - seem to suggest that foundational to that whole layout is in the end the hypothalamus,
  • fast_forward00:55:50 - Is that a fair...? Because foundation in the sense that it was the first part
  • fast_forward00:55:54 - of the brain that evolved.
  • fast_forward00:55:55 - So I have just always a paper postulating a new theory about how the brain starts
  • fast_forward00:56:01 - in evolution, and starting in invertebrates, not invertebrates.
  • fast_forward00:56:05 - So before the vertebrates exist, before these are not occurred,
  • fast_forward00:56:08 - and you have vertebrae and so on, they are animal without a curve and so on,
  • fast_forward00:56:13 - that they already have the beginning of the brain, and that's hypotaragos.
  • fast_forward00:56:16 - So, the first part of the rain that is induced by signal-resolved… How long
  • fast_forward00:56:20 - ago was that an evolution?
  • fast_forward00:56:23 - More or less? That was 700 million years.
  • fast_forward00:56:27 - Oh, that's before the Cambrian, or early Cambrian, before the Cambrian.
  • fast_forward00:56:31 - Yeah, the first sort of tissue.
  • fast_forward00:56:34 - There were, and it's about among the, how do you say, I don't remember,
  • fast_forward00:56:41 - I miss my age, I forget the use of human words.
  • fast_forward00:56:44 - But when the animal started having a secondary mouse, you know,
  • fast_forward00:56:48 - at the beginning, the annus was both the mouse and the annus.
  • fast_forward00:56:51 - When the animal made the jump to produce a secondary mouth, that created a new organ with the pharynx.
  • fast_forward00:56:59 - You see endodermal part of the digestive tube.
  • fast_forward00:57:03 - Before, there was just a sack ending. There was no interaction with the endoderm.
  • fast_forward00:57:07 - Suddenly, when you open the mouth, you start having interaction.
  • fast_forward00:57:11 - That's why the mouth opens, because the endoderm starts giving signals with
  • fast_forward00:57:16 - the nearby endoderm. and they say, okay, let's add here and let's degenerate and make a mouth here.
  • fast_forward00:57:22 - Once you have a mouth, you start inhibiting food coming through there and you
  • fast_forward00:57:27 - start having new reactions. You produce the ginslits on the sides.
  • fast_forward00:57:31 - You produce the tiroids on the bottom.
  • fast_forward00:57:34 - And you produce the pecora plate that touches the brain and then the neck to
  • fast_forward00:57:39 - them, which was on the skin, and you change the neck to them into the neuro to them.
  • fast_forward00:57:44 - So the beginning of the brain is the pharynx, producing dorsally,
  • fast_forward00:57:47 - apart of all the other effects it's doing on the sides, it's producing dorsally
  • fast_forward00:57:51 - and important contact with the egg to there, and where it contacts,
  • fast_forward00:57:56 - you produce an hypotermal.
  • fast_forward00:57:57 - That's where the hypothesis is going to be.
  • fast_forward00:58:00 - So exactly where we have the hypothesis, that's where the signal first,
  • fast_forward00:58:04 - and that appears first in animals, we thought, not occurred.
  • fast_forward00:58:09 - That is the first thing of having a vector brain brain.
  • fast_forward00:58:13 - These animals are called abicordates, they are worms.
  • fast_forward00:58:17 - Yeah, exactly. Because they have their worms living at the bottom of the sea,
  • fast_forward00:58:22 - they just open their mouth and they eat what enters in their mouth.
  • fast_forward00:58:25 - They don't swim, they do anything, they remove and prove that it seems to be,
  • fast_forward00:58:30 - they just open their mouth and whatever falls into their mouth is what they
  • fast_forward00:58:34 - eat. So it's very primitive animals.
  • fast_forward00:58:36 - But they already have a hippopotamus, and then by evolution.
  • fast_forward00:58:41 - Things continue changing and the nautochordal appears, then this fulcine mordium
  • fast_forward00:58:45 - of a forebrain was extended also into the caudal part with the appearance of the nautochord.
  • fast_forward00:58:50 - So the nautochord complemented the missing parts of the brain.
  • fast_forward00:58:53 - And also, the forebrain at the beginning was incomplete, and if you go from
  • fast_forward00:58:58 - there to the fulcine to the fulcine to the fulcine, if you progress into lamprest,
  • fast_forward00:59:03 - you also make more complete the forebrain.
  • fast_forward00:59:05 - At the beginning, it was only hypotalamus, then you get the eyes,
  • fast_forward00:59:09 - and you get the transcephaline, you get the diencephaline, you get the midbrain.
  • fast_forward00:59:12 - All this is a series in time.
  • fast_forward00:59:15 - So that means the phobia does not be like that, the entire phobia.
  • fast_forward00:59:18 - You begin with hypotalamus, so the oldest part of the brain of the entire brain is the hypotalamus.
  • fast_forward00:59:24 - So that gives you a reason why it has some governing functional roles in the
  • fast_forward00:59:29 - entire physiology of the brain, because it was there from the very beginning.
  • fast_forward00:59:33 - But in your model, you have the hypothymosis at the tip of the neural tube.
  • fast_forward00:59:43 - So the animals only had this tip.
  • fast_forward00:59:46 - So first there was one signal, and it was hypothymosis, and then the other signals emerged.
  • fast_forward00:59:53 - Yeah, because there was more signal to grow a bit more, and it grew a bit more,
  • fast_forward01:00:00 - then it was at a distance of the end signals, and then if you have an area which
  • fast_forward01:00:04 - gets different in the radian of the signal,
  • fast_forward01:00:07 - then it gets transformed into a second dimension,
  • fast_forward01:00:10 - because it no longer cannot be equal as the first, which gets higher levels of the signal.
  • fast_forward01:00:15 - The more you grow quarterly, the less signal you get, and that makes that part
  • fast_forward01:00:20 - of the range you produce is slightly different.
  • fast_forward01:00:23 - But you are pulling us in a pretty rich universe on brain in that way and function.
  • fast_forward01:00:30 - But that is what really happened.
  • fast_forward01:00:32 - Because we have animals that are taught at a particular level of the story.
  • fast_forward01:00:36 - We have the living animals for 700 years have maintained their single hypothalamus
  • fast_forward01:00:43 - as the only part of the brain they have. And they are still living today. Right.
  • fast_forward01:00:47 - But then, so if we look forward, right? It's because there's lots of data behind this.
  • fast_forward01:00:54 - And now in the end, we also look at some speculation about overall functional organization.
  • fast_forward01:00:59 - Yeah, missing parts of the story, things that haven't been investigated yet.
  • fast_forward01:01:03 - Sure, they are. Yeah, but then to close up the whole dialogue,
  • fast_forward01:01:08 - if in three years from now, Tony and I go visit you in Moorsia to have a really
  • fast_forward01:01:14 - nice lunch, because the food is great, what is the prediction you would like to have seen.
  • fast_forward01:01:20 - Verified in three years' time that is really central to your thinking?
  • fast_forward01:01:25 - Right now, I am concentrated on the limbic system because I think that there's
  • fast_forward01:01:30 - one area that has been behind in terms of development in the functional field.
  • fast_forward01:01:36 - And I am also becoming more functional than I ever was before.
  • fast_forward01:01:40 - So now I am wanting to produce something that increases the functional analysis
  • fast_forward01:01:47 - of the brain because it's the end of my personal study, and I want to finish
  • fast_forward01:01:52 - as I began interested in that sort of thing.
  • fast_forward01:01:55 - So I hope that in three years I can build up a much better schema.
  • fast_forward01:02:00 - What will you show, right? So what's a testable thing you have shown there?
  • fast_forward01:02:04 - Well, I am already showing, as I showed you in the last images I showed today.
  • fast_forward01:02:09 - Where is the link resistance? Nobody had answered that question before,
  • fast_forward01:02:13 - with strong data before, and now my data is wrong.
  • fast_forward01:02:17 - To have 85 years selectively living in the system that is very strong,
  • fast_forward01:02:23 - particularly because many of these molecules we already know what they are and what they do.
  • fast_forward01:02:28 - So now I can type what tech physiology is to help me in analyzing what is the algorithm,
  • fast_forward01:02:37 - the neuronal algorithm that is being represented by this combination of multiple molecules.
  • fast_forward01:02:44 - So what is happening with a neuron that has this receptor, this receptor,
  • fast_forward01:02:48 - and this channel, and this channel, and this channel, and not these other ones and so on?
  • fast_forward01:02:52 - So what is happening within you when you enter this?
  • fast_forward01:02:56 - And there are also differences in the sort of interneurons that are present.
  • fast_forward01:03:00 - There are groups of interneurons, like the paracombin ones, that practically
  • fast_forward01:03:04 - don't exist in the limbic cortex.
  • fast_forward01:03:06 - So the antagonists of interneurons, practically in these points I discovered,
  • fast_forward01:03:11 - there are very few of them. That's exciting, yeah. Sometimes it's also interesting.
  • fast_forward01:03:16 - So, Luis, my very last question.
  • fast_forward01:03:18 - So you are almost 60 years in this business, almost, right?
  • fast_forward01:03:23 - So that's a really long experience. And also, if you want working on controversial
  • fast_forward01:03:28 - issues, this is stuff that people did not just accept.
  • fast_forward01:03:31 - But we have also a connection between Amit Dala and other centers.
  • fast_forward01:03:35 - No, sure. But wait, but now that's why I'm looking at it. I know.
  • fast_forward01:03:39 - But that's why I want, if you would give advice to younger researchers,
  • fast_forward01:03:46 - what's your advice? What is Louisa's rule?
  • fast_forward01:03:49 - To use the door as open and to enter into the space that's behind the door and
  • fast_forward01:03:55 - to start looking at many questions that need to be analyzed.
  • fast_forward01:03:59 - So enter Lewis's universe.
  • fast_forward01:04:01 - Yeah, because that's the only door that is trying to open into that.
  • fast_forward01:04:05 - People just say the big system is the emotions, and that's all.
  • fast_forward01:04:10 - Nobody centers the discussion into more operable things that you can register
  • fast_forward01:04:16 - and test hypotheses, experimentalities, and that. that, but my genes are a concrete thing that you can test.
  • fast_forward01:04:23 - What's the role of this channel in this function? You can produce a mutant mouse
  • fast_forward01:04:28 - that lacks this particular channel or whatever.
  • fast_forward01:04:31 - So you can do things with the method now available. You can do things with my list of 85.
  • fast_forward01:04:37 - In half a year, we'll have 150. That's great. Well, Luis, thank you very much
  • fast_forward01:04:41 - for this conversation. That was great. Thank you.
  • fast_forward01:04:45 - So I am very happy that I finally could turn my function up because I just wanted
  • fast_forward01:04:51 - to do it all my life and I could do it when I retired.
  • fast_forward01:04:56 - Now you came a long way, it's really amazing, but it's a very challenging story
  • fast_forward01:05:02 - you're telling us, right? There's really something we have to chew on carefully.
  • fast_forward01:05:06 - And it's not anti-anything that already exists, it's just enriching whatever
  • fast_forward01:05:10 - possibilities is the existence before.
  • fast_forward01:05:13 - What I have opened is just possibility to do more. Yeah, no,
  • fast_forward01:05:18 - that's really great. Be more precise, no? So thank you.

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