back to indexDr. David Berson: Your Brain's Logic & Function | Huberman Lab Podcast #50
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Welcome to the Huberman Lab Podcast,
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where we discuss science and science-based tools
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for everyday life.
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I'm Andrew Huberman,
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and I'm a professor of neurobiology and ophthalmology
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at Stanford School of Medicine.
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Today, my guest is Dr. David Berson,
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professor of medical science, neurobiology,
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and ophthalmology at Brown University.
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Dr. Berson's laboratory is credited
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with discovering the cells in the eye
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that set your circadian rhythms.
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These are the so-called intrinsically
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photosensitive melanopsin cells,
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and while that's a mouthful,
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all you need to know for sake of this introduction
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is that those are the cells that inform your brain and body
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about the time of day.
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Dr. Berson's laboratory has also made
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a number of other important discoveries
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about how we convert our perceptions of the outside world
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into motor action.
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More personally, Dr. Berson has been my go-to resource
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for all things neuroscience for nearly two decades.
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I knew of his reputation as a spectacular researcher
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for a long period of time,
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and then many years ago, I cold-called him out of the blue.
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I basically corralled him into a long conversation
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over the phone, after which he invited me out to Brown,
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and we've been discussing neuroscience
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and how the brain works and the emerging new technologies
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and the emerging new concepts in neuroscience
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for a very long time now.
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You're going to realize today
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why Dr. Berson is my go-to source.
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He has an exceptionally clear and organized view
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of how the nervous system works.
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Now, there are many, many parts of the nervous system,
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different nuclei and connections and circuits and chemicals
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and so forth, but it takes a special kind of person
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to be able to organize that information
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into a structured and logical framework
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that can allow us to make sense of how we function
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in terms of what we feel, what we experience,
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how we move through the world.
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Dr. Berson is truly one of a kind
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in his ability to synthesize and organize
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and communicate that information.
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And I give him credit as one of my mentors
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and one of the people that I respect most
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in the field of science and medical science generally.
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Today, Dr. Berson takes us on a journey
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from the periphery of the nervous system,
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meaning from the outside, deep into the nervous system,
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layer by layer, structure by structure, circuit by circuit,
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making clear to us how each of these individual circuits
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work and how they work together as a whole.
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It's a really magnificent description
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that you simply cannot get from any textbook,
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from any popular book, and frankly, as far as I know,
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from any podcast that currently exists out there.
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So it's a real gift to have this opportunity
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to learn from Dr. Berson.
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Again, I consider him my mentor in the field
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of learning and teaching neuroscience,
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and I'm excited for you to learn from him.
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One thing is for certain, by the end of this podcast,
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you will know far more about how your nervous system works
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than the vast majority of people out there,
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including many expert biologists and neuroscientists.
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Before we begin, I'd like to emphasize that this podcast
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is separate from my teaching and research roles at Stanford.
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It is, however, part of my desire and effort
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to bring zero cost to consumer information about science
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and science-related tools to the general public.
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In keeping with that theme,
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I'd like to thank the sponsors of today's podcast.
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Our first sponsor is Athletic Greens.
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Athletic Greens is an all-in-one
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vitamin mineral probiotic drink.
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I've been taking Athletic Greens every day since 2012,
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so I'm delighted that they're sponsoring the podcast.
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The reason I started taking Athletic Greens
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and the reason I still take Athletic Greens
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Nowadays, there's a lot of data out there
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literally little microbes that live in our gut
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If you'd like to try Athletic Greens,
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So again, if you go to athleticgreens.com slash Huberman,
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Today's podcast is also brought to us by InsideTracker.
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Also, an interview I did with longevity research doctor
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and a link to that interview can be found
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in today's show notes.
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Today's episode is also brought to us by Magic Spoon.
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Magic Spoon is a zero-sugar,
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grain-free, keto-friendly cereal.
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I don't follow a ketogenic diet.
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The way that I eat is basically geared toward
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feeling alert when I want to be alert
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and feeling sleepy when I want to go to sleep,
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which for me means fasting until about 11 a.m. or noon,
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Then I eat low-carb during the day.
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So I'll have some meat or fish or chicken and some salad.
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I eat pastas and things primarily,
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and I throttle back on the protein,
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and that's what allows me to fall asleep at night.
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That's just what works for me.
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And now for my discussion with Dr. David Berson.
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Thank you, yeah, so nice to be here.
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Great to have you for more than 20 years.
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You've been my go-to source for all things,
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nervous system, how it works, how it's structured.
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So today I want to ask you some questions about that.
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I think people would gain a lot of insight
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into this machine that makes them think,
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and feel, and see, et cetera.
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If you would, could you tell us how we see?
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You know, a photon of light enters the eye, what happens?
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I mean, how is it that I look outside,
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I see a truck drive by, or I look on the wall,
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I see a photo of my dog, how does that work?
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Right, so this is an old question, obviously.
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And clearly in the end,
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the reason you have a visual experience
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is that your brain has got some pattern of activity
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that it associates with the input from the periphery.
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But you can have a visual experience
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with no input from the periphery as well.
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When you're dreaming, you're seeing things
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that aren't coming through your eyes.
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Are those memories?
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I would say in a sense,
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they may reflect your visual experience.
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They're not necessarily specific visual memories,
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but of course they can be.
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But the point is that the experience of seeing
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is actually a brain phenomenon.
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But of course, under normal circumstances,
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we see the world because we're looking at it,
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and we're using our eyes to look at it.
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And fundamentally, when we're looking at the exterior world,
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it's what the retina is telling the brain that matters.
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So there are cells called ganglion cells.
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These are neurons that are the key cells
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for communicating between eye and brain.
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The eye is like the camera.
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It's detecting the initial image,
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doing some initial processing,
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and then that signal gets sent back to the brain proper.
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And of course, it's there at the level of the cortex
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that we have this conscious visual experience.
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There are many other places in the brain
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that get visual input as well,
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doing other things with that kind of information.
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So I get a lot of questions about color vision.
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If you would, could you explain how is it
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that we can perceive reds and greens and blues
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and things of that sort?
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So the first thing to understand about light
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is that it's just a form of electromagnetic radiation.
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It's vibrating, it's oscillating.
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But when you say it's vibrating, it's oscillating,
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you mean that photons are actually moving?
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Well, in a sense, photons are,
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they're certainly moving through space.
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We think about photons as particles,
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and that's one way of thinking about light,
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but we can also think of it as a wave, like a radio wave.
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Either way is acceptable.
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And the radio waves have frequencies,
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like the frequencies on your radio dial.
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And certain frequencies in the electromagnetic spectrum
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can be detected by neurons in the retina.
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Those are the things we see.
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But there are still different wavelengths
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within the light that can be seen by the eye.
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And those different wavelengths are unpacked in a sense,
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or decoded by the nervous system
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to lead to our experience of color.
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Essentially, different wavelengths give us the sensation
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of different colors through the auspices
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of different neurons that are tuned
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to different wavelengths of light.
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So when a photon, so when a little bit of light hits my eye,
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it goes in, the photoreceptors convert
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that into electrical signal.
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How is it that a given photon of light
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gives me the perception, eventually leads to the perception
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of red versus green versus blue?
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So if you imagine that in the first layer of the retina,
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where this transformation occurs
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from electromagnetic radiation into neural signals,
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that you have different kinds of sensitive cells
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that are expressing, they're making different molecules
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within themselves for this express purpose
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of absorbing photons, which is the first step
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in the process of seeing.
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Now, it turns out that altogether,
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there are about five proteins like this
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that we need to think about in the typical retina.
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But for seeing color, really, it's three of them.
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So there are three different proteins.
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Each absorbs light with a different preferred frequency.
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And then the nervous system keeps track of those signals,
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compares and contrasts them to extract some understanding
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of the wavelength composition of light.
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So you can see just by looking at a landscape,
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oh, it must be late in the day
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because things are looking golden.
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That's all a function of our absorbing the light
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that's coming from the world
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and interpreting that with our brain
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because of the different composition
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of the light that's reaching our eyes.
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Is it fair to assume that my perception of red
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is the same as your perception of red?
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Well, that's a great question.
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And that mine is better.
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No, I'm just kidding, I'm just kidding.
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It's a great question.
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It's a deep philosophical question.
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It's a question that really probably can't even
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ultimately be answered
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by the usual empirical scientific processes
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because it's really about an individual's experience.
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What we can say is that the biological mechanisms
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that we think are important for seeing color, for example,
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seem to be very highly similar
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from one individual to the next,
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whether it be human beings or other animals.
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And so we think that the physiological process
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looks very similar on the front end,
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but once you're at the level of perception
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or understanding or experience,
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that's something that's a little bit tougher to nail down
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with the sorts of scientific approaches
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that we approach, biological vision, let's say.
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You mentioned that there are five different cone types,
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essentially, the cones being the cells
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that absorb light of different wavelengths.
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I often wondered when I had my dog,
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what he saw and how his vision differs from our vision.
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And certainly there are animals that can see things
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that we can't see.
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What are some of the more outrageous examples of that?
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Of seeing things that we can't?
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And in the extreme, you know,
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dogs, I'm guessing, see reds more as oranges, is that right?
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Because they don't have the same array of neurons
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that we have for seeing color.
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Right, so the first thing is
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it's not really five types of cones.
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There are really three types of cones.
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And if you look at the way
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that color vision is thought to work,
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you can sort of see
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that it has to be three different signals.
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There are a couple of other types of pigments.
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One is really mostly for dim light vision.
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When you're walking around in a moonless night
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and you're seeing things with very low light,
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that's the rod cell that uses its own pigment.
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And then there's another class of pigments
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we'll probably talk about a little bit later,
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this melanopsin pigment.
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I thought you were referring to like ultraviolet
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and infrared and things of that sort.
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Right, so in the case of a typical,
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well, let's put it this way, in human beings,
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most of us have three cone types
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and we can see colors that stem from that.
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In most mammals, including your dog or your cat,
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there really are only two cone types
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and that limits the kind of vision that they can have
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in the domain of wavelength or color, as you would say.
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So really a dog sees the world
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kind of like a particular kind of colorblind human
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might see the world,
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because instead of having three channels
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to compare and contrast, they only have two channels
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and that makes it much more difficult
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to figure out exactly which wavelength you're looking at.
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Do colorblind people suffer much
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as a consequence of being colorblind?
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Well, you know, it's like so many other disabilities,
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we are, you know, the world is built for people
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of the most common type.
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So in some cases, the expectation can be there
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that somebody can see something that they won't be able to
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if they're missing one of their cone types, let's say.
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So in those moments, that can be a real problem.
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You know, if there's a lack of contrast
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to their visual system, they will be blind to that.
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In general, it's a fairly modest
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visual limitation as things go.
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You know, for example, if not being able to see acutely
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can be much more damaging,
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not being able to read fine print, for example.
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Yeah, I suppose if I had to give up
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the ability to see certain colors
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or give up the ability to see clearly,
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I'd certainly trade out color for clarity.
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Right, of course, color is very meaningful
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to us as human beings, you know?
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So we would hate to give it up,
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but obviously dogs and cats and all kinds of other mammals
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do perfectly well in the world.
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Yeah, because we take care of them.
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I spent most of my time taking care of that dog.
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He took care of me too.
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Let's talk about that odd photo pigment.
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Photo pigment, of course, being the thing
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that absorbs light of a particular wavelength.
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And let's talk about these specialized ganglion cells
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that communicate certain types of information
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from eye to the brain
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that are so important for so many things.
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What I'm referring to here, of course,
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is your co-discovery of the so-called
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intrinsically photosensitive cells,
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the neurons in the eye that do so many of the things
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that don't actually have to do with perception,
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but have to do with important biological functions.
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What I would love for you to do
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is explain to me why once I heard you say
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we have a bit of fly eye in our eye.
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And you showed this slide of like a giant fly
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from a horror movie trying to attack this woman.
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And maybe it was an eye also.
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So what does it mean that we have a bit of a fly eye
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Yeah, so this last pigment is a really peculiar one.
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One can think about it as really
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the initial sensitive element in a system
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that's designed to tell your brain
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about how bright things are in your world.
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And the thing that's really peculiar about this pigment
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is that it's in the wrong place, in a sense.
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When you think about the structure of the retina,
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you think about a layer cake, essentially.
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You've got this thin membrane at the back of your eye,
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but it's actually a stack of thin layers.
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And the outermost of those layers
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is where these photoreceptors
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you were talking about earlier are sitting.
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That's where the film of your camera is, essentially.
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That's where the photons do their magic
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with the photopigments and turn it into a neural signal.
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I've never really thought of the photoreceptors
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as the film of the camera, but that makes sense.
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Yeah, or like the sensitive CCD chip in your cell phone.
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It's the surface on which the light pattern is imaged
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by the optics of the eye.
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And now you've got an array of sensors
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that's capturing that information
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and creating a bitmap, essentially.
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But now it's in neural signals
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distributed across the surface of the retina.
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So all of that was known to be going on 150 years ago.
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A couple of types of photoreceptors, cones and rods.
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If you look a little bit more closely, three types of cones.
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That's where the transformation
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from electromagnetic radiation to neural signals
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was thought to take place.
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But it turns out that this last photopigment
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is in the other end of the retina,
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the innermost part of the retina.
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That's where the so-called ganglion cells are.
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Those are the cells that talk to the brain,
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the ones that actually can communicate directly
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what information comes to them from the photoreceptors.
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And here you've got a case where actually
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some of the output neurons
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that we didn't think had any business being directly
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sensitive to light were actually making this photopigment,
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absorbing light and converting that to neural signals
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and sending it to the brain.
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So that made it pretty surprising and unexpected,
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but there are many surprising things about these cells.
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So, and what is the relationship to the fly eye?
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Right, so the link there is that if you ask
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how the photopigment now communicates
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downstream from the initial absorption event
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to get to the electrical signal,
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that's a complex cellular process,
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involves many chemical steps.
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And if you look at how photoreceptors in our eyes work,
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you can see what that cascade is, how that chain works.
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If you look in the eyes of flies or other insects
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or other invertebrates,
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there's a very similar kind of chain,
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but the specifics of how the signals get
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from the absorption event by the pigment
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to the electrical response
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that the nervous system can understand
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are characteristically different
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between fuzzy furry creatures like us
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and insects, for example, like the fly, I say.
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So these funny extra photoreceptors
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that are in the wrong layer
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doing something completely different
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are actually using a chemical cascade
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that looks much more like what you would see
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in a fly photoreceptor
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than what you would see in a human photoreceptor,
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a rod or a cone, for example.
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So it sounds like it's a very primitive part of,
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a primitive aspect of biology that we maintain.
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Exactly right, exactly right.
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And despite the fact that dogs
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can't see as many colors as we can,
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and cats can't see as many colors as we can,
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we have all this extravagant stuff for seeing color.
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And then you've got this other pigment
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sitting in the wrong, not wrong,
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but in a different part of the eye,
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sending, processing light very differently
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and sending that information into the brain.
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So what do these cells do?
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I mean, presumably they're there for a reason.
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They are, and the interesting thing
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is that one cell type like this
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carrying one kind of signal,
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which I would call a brightness signal essentially,
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can do many things in the brain.
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When you say brightness signal,
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you mean that it, like right now,
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I have these cells, do I have these cells?
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You do. Of course not.
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I'm joking, I hope I have these cells in my eye.
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And they're paying attention to how bright it is overall,
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but they're not paying attention, for instance,
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to the edge of your ear
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or what else is going on in the room.
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Right, so it's the difference
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between knowing what the objects are on the table
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and knowing whether it's bright enough
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to be daylight right now.
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So why does your nervous system
link |
need to know whether it's daylight right now?
link |
Well, one thing that needs to know,
link |
that is your circadian clock.
link |
If you travel across time zones to Europe,
link |
now your internal clock thinks it's California time,
link |
but the rotation of the earth
link |
is for a different part of the planet.
link |
The rising and setting of the sun
link |
is not at all what your body is anticipating.
link |
So you've got an internal representation
link |
of the rotation of the earth in your own brain.
link |
That's your circadian system.
link |
It's keeping time.
link |
But now you've played a trick on your nervous system.
link |
You put yourself in a different place
link |
where the sun is rising at the, quote, wrong time.
link |
Well, that's not good for you, right?
link |
So you've got to get back on track.
link |
One of the things this system does is sends a,
link |
oh, it's daylight now signal to the brain,
link |
which compares with its internal clock.
link |
And if that's not right,
link |
it tweaks the clock gradually
link |
until you get over your jet lag
link |
and you feel back on track again.
link |
So the jet lag case makes a lot of sense to me,
link |
but presumably these elements didn't evolve for jet lag.
link |
So what are they doing on a day-to-day basis?
link |
Right, well, one way to think about this
link |
is that the clock that you have in not just your brain,
link |
in all the cells, or almost all of the cells of your body,
link |
they're all oscillating.
link |
They're all, you know-
link |
They got little clocks in them.
link |
They got little clocks in them themselves.
link |
They're all clocks.
link |
You know, they need to be synchronized appropriately.
link |
And the whole thing has to be built in biological machinery.
link |
This is actually a beautiful story
link |
about how gene expression can control gene expression.
link |
And if you set it up right,
link |
you can set up a little thing that just sort of hums along
link |
at a particular frequency.
link |
In our case, it's humming along at 24 hours,
link |
because that's how our earth rotates
link |
and it's all built into our biology.
link |
but the reality is that the clock can only be so good.
link |
I mean, we're talking about biology here.
link |
It's not precision engineering.
link |
And so it can be a little bit off.
link |
Well, also it doesn't, it's in our brain,
link |
so it doesn't have access to any regular unerring signal.
link |
Well, if in the absence of the rising
link |
and setting of the sun, it doesn't,
link |
if you put someone in a cave,
link |
their biological clock will keep time
link |
to within a handful of minutes of 24 hours.
link |
That's no problem for one day.
link |
But if this went on without any correction,
link |
eventually you'd be out of phase.
link |
And this is actually one of the things
link |
that blind patients often complain about.
link |
They've got retinal blindness, is insomnia, and-
link |
Because their brains are awake in the middle of the night.
link |
Exactly, they're not synchronized.
link |
Their clock is there, but they're drifting out of phase
link |
because their clock's only good to 24.2 hours
link |
Little by little, they're drifting.
link |
So you need a synchronization signal.
link |
So even if you never cross time zones,
link |
and of course we didn't back on the savanna,
link |
we stayed within walking distance of where we were,
link |
you still need a synchronizer
link |
because otherwise you have nothing to actually confirm
link |
when the rising and the setting of the sun is.
link |
That's what you're trying to synchronize yourself to.
link |
I'm fascinated by the circadian clock
link |
and the fact that all the cells of our body
link |
have essentially a 24-hour-ish clock in them.
link |
We hear a lot about these circadian rhythms
link |
and circadian clocks,
link |
the fact that we need light input from these special neurons
link |
in order to set the clock,
link |
but I've never really heard it described
link |
how the clock itself works
link |
and how the clock signals to all the rest of the body
link |
when the liver should be doing one thing
link |
and when the stomach should be doing another.
link |
I know you've done some work on the clock.
link |
So if you would just maybe briefly describe
link |
where the clock is, what it does,
link |
and some of the top contour
link |
of how it tells the cells of the body what to do.
link |
So the first thing to say is that, as you said,
link |
the clock is all over the place.
link |
Most of the tissues in your body have clocks.
link |
We probably have, what, millions of clocks in our body.
link |
Yeah, I would say that's probably fair.
link |
You have millions of cell types,
link |
you probably have millions of clocks.
link |
That the role of the central pacemaker
link |
for the circadian system is to coordinate all of these.
link |
And there's a little nucleus,
link |
a little collection of nerve cells in your brain.
link |
It's called the suprachiasmatic nucleus, the SCN,
link |
and it is sitting in a funny place
link |
for the rest of the structures in the nervous system
link |
that get direct retinal input.
link |
It's sitting in the hypothalamus,
link |
which you can think about as sort of the great coordinator
link |
of drives and- The source of all our pleasures
link |
and all our problems. Right.
link |
Or most our problems.
link |
Yes, it really is.
link |
But it's sort of deep in your brain,
link |
things that drive you to do things.
link |
If you're freezing cold, you put on a coat, you shivery,
link |
all these things are coordinated by the hypothalamus.
link |
So this pathway that we're talking about from the retina
link |
and from these peculiar cells
link |
that are encoding light intensity
link |
are sending signals directly into a center
link |
that's surrounded by all of these centers
link |
that control autonomic nervous system
link |
and your hormonal systems.
link |
So this is a part of your visual system
link |
that doesn't really reach the level of consciousness.
link |
It's not something you think about.
link |
It's happening under the radar kind of all the time.
link |
And the signal is working its way
link |
into this central clock coordinating center.
link |
Now, what happens then is not that well understood,
link |
but it's clear that this is a neural center
link |
that has the same ability to communicate
link |
with other parts of your brain as any other neural center.
link |
And clearly there are circuits
link |
that involve connections between neurons
link |
that are conventional.
link |
But in addition, it's quite clear
link |
that there are also sort of humoral effects
link |
that things are oozing out of the cells in the center
link |
and maybe into the circulation
link |
or just diffusing through the brain to some extent
link |
that can also affect neurons all square.
link |
But the hypothalamus uses everything
link |
to control the rest of the bodies.
link |
And that's true of the suprachiasmatic nucleus,
link |
this circadian center as well.
link |
It can get its fingers into the autonomic nervous system,
link |
the humoral system,
link |
and of course up to the centers of the brain
link |
that organize coordinated rational behavior.
link |
So if I understand correctly,
link |
we have this group of cells, the suprachiasmatic nucleus,
link |
it's got a 24 hour rhythm.
link |
That rhythm is more or less matched
link |
to what's going on in our external world
link |
by the specialized set of neurons in our eye.
link |
But then the master clock itself, the SCN,
link |
releases things in the blood, humoral signals,
link |
that go out various places in the body.
link |
And then you said to the autonomic system,
link |
which is regulating more or less how alert or calm we are,
link |
as well as our thinking and our cognition.
link |
So I'd love to talk to you about the autonomic part.
link |
Presumably that's through melatonin,
link |
it's through adrenaline.
link |
How is it that this clock is impacting
link |
how the autonomic system, how alert or calm we feel?
link |
Right, so there are pathways
link |
by which the suprachiasmatic nucleus can access
link |
both the parasympathetic and sympathetic nervous system.
link |
Just so people know, the sympathetic nervous system
link |
is the one that tends to make us more alert,
link |
and the parasympathetic nervous system
link |
is the portion of the autonomic nervous system
link |
makes us feel more calm in broad context.
link |
To first approximation, right.
link |
So this is, both of these systems
link |
are within the grasp of the circadian system
link |
through hypothalamic circuits.
link |
One of the circuits that will be,
link |
I think, of particular interest to some of your listeners,
link |
is a pathway that involves this sympathetic branch
link |
of the autonomic nervous system, the fight or flight system,
link |
that is actually through a very circuitous route,
link |
innervating the pineal gland,
link |
which is sitting in the middle of your brain.
link |
The so-called third eye.
link |
Right, so this is the-
link |
We'll have to get back to why it's called the third eye,
link |
That's an interesting history.
link |
You can't call something the third eye and not,
link |
and just, you know.
link |
Just leave it there.
link |
Just leave it there.
link |
Anyway, this is the major source of melatonin in your body.
link |
So light comes into my eye.
link |
Passed off to the suprachiasmatic nucleus,
link |
essentially not the light itself,
link |
but the signal representing the light.
link |
Then the SCN, the suprachiasmatic nucleus,
link |
can impact the melatonin system
link |
Right, the way this is seen is that
link |
if you were to measure your melatonin level
link |
over the course of the day,
link |
if you could do this, you know, hour by hour,
link |
you'd see that it's really low during the day,
link |
very high at night.
link |
But if you get up in the middle of the night
link |
and go to the bathroom
link |
and turn on the bright fluorescent light,
link |
your melatonin level is slammed to the floor.
link |
Light is directly impacting your hormonal levels
link |
through this mechanism that we just described.
link |
So this is one of the routes by which light can act
link |
on your hormonal status through pathways
link |
that are completely beyond
link |
what you normally would think about, right?
link |
You're thinking about the things in the bathroom.
link |
Oh, there's the toothbrush.
link |
You know, there's the tube of toothpaste.
link |
But meanwhile, this other system is just counting photons
link |
and saying, oh, wow, there's a lot of photons right now.
link |
Let's shut down the melatonin release.
link |
This is one of the main reasons why I've encouraged people
link |
to avoid bright light exposure in the middle of the night,
link |
not just blue light, but bright light of any wavelength.
link |
Because there's this myth out there that blue light,
link |
because it's the optimal signal for activating this pathway
link |
and shutting down melatonin,
link |
is the only wavelength of light that can shut it down.
link |
But am I correct in thinking that if a light
link |
is bright enough, it doesn't matter if it's blue light,
link |
green light, purple light, even red light,
link |
you're going to slam melatonin down to the ground,
link |
which is not a good thing to happen
link |
in the middle of the night, correct?
link |
I mean, any light will affect the system to some extent.
link |
The blue light is somewhat more effective,
link |
but don't fool yourself into thinking
link |
that if you use red light,
link |
that means you're avoiding the effect.
link |
It's certainly still there.
link |
And certainly if it's very bright,
link |
it'll be more effective in driving the system
link |
than dim blue light would be.
link |
A lot of people wear blue blockers.
link |
And in a kind of odd twist of misinformation out there,
link |
a lot of people wear blue blockers
link |
during the middle of the day,
link |
which basically makes no sense
link |
because during the middle of the day
link |
is when you want to get a lot of bright light
link |
and including blue light into your eyes, correct?
link |
And not just for the reasons we've been talking about
link |
in terms of circadian effects.
link |
There are major effects of light on mood.
link |
And seasonal affective disorder
link |
apparently is essentially a reflection
link |
of this same system in reverse.
link |
If you're living in the Northern climes
link |
and you're not getting that much light
link |
during the middle of the winter in Stockholm,
link |
you might be prone to depression
link |
and phototherapy might be just the ticket for you.
link |
And that's because there's a direct effect of light on mood.
link |
There's an example where if you don't have enough light,
link |
So I think you're exactly right.
link |
It's not about, is light good or bad for you?
link |
It's about what kind of light and when
link |
that makes the difference.
link |
Yeah, the general rule of thumb that I've been living by
link |
is to get as much bright light in my eyes,
link |
ideally from sunlight, anytime I want to be alert
link |
and doing exactly the opposite when I want to be asleep
link |
or getting drowsy.
link |
And there are aspects of this that spin out
link |
way beyond the conversation we're having now
link |
to things like this.
link |
It turns out that the incidence of myopia,
link |
Nearsightedness, right, is strongly related
link |
to the amount of time that kids spend outdoors.
link |
In what direction of effect?
link |
The more they spend time outdoors,
link |
the less nearsightedness they have.
link |
So this is all about-
link |
And is that because they're viewing things at a distance
link |
or because they're getting a lot of blue light, sunlight?
link |
It's a great question.
link |
It is not fully resolved what the epidemiological,
link |
what the basis of that epidemiological finding is.
link |
One possibility is the amount of light,
link |
which would make me think about this
link |
melanopsin system again,
link |
but it might very well be a question of accommodation.
link |
That is the process by which you focus
link |
on near or far things.
link |
If you're never outdoors, everything is nearby.
link |
If you're outdoors, you're focusing far.
link |
So this is- Unless you're on your phone.
link |
There's a tremendous amount of interest these days
link |
in watches and things that count steps.
link |
I'm beginning to realize that we should probably have
link |
a device that can count photons during the day.
link |
And can also count photons at night and tell us,
link |
hey, you're getting too many photons.
link |
You're going to shut down your melatonin at night
link |
or you're not getting enough photons.
link |
Today you didn't get enough bright light,
link |
whether or not it's from artificial light or from sunlight.
link |
I guess the, where would you put it?
link |
I guess you put it on the top of your head or something.
link |
You'd probably want it someplace outward facing.
link |
Right, probably what you need is as many photons
link |
over as much of the retina as possible
link |
to recruit as much of this system as possible.
link |
In thinking about other effects
link |
of this non-image forming pathway
link |
that involves these special cells in the eye and the SCN,
link |
you had a paper a few years ago
link |
looking at retinal input to an area of the brain,
link |
which has a fancy name, the perihabenula,
link |
but names don't necessarily matter,
link |
that had some important effects on mood
link |
and other aspects of light.
link |
Maybe you could tell us a little bit about
link |
what is the perihabenula.
link |
Oh, wow, so that's a fancy term,
link |
but I think the way to think about this
link |
is as a chunk of the brain
link |
that is sitting as part of a bigger chunk
link |
that's really the linker between peripheral sensory input
link |
of all kinds, virtually all kinds,
link |
whether it's auditory input or tactile input
link |
or visual input to the region of your brain,
link |
the cortex that allows you to think about these things
link |
and make plans around them
link |
and to integrate them and that kind of thing.
link |
So, we've known about a pathway
link |
that gets from the retina
link |
through this sort of linker center,
link |
it's called the thalamus, and then on up to the cortex.
link |
Exactly, but you wanna arrive at the destination, right?
link |
Now you're at Grand Central
link |
and now you can do your thing as you're up at the cortex.
link |
So, this is the standard pattern.
link |
You have the sensory input coming from the periphery.
link |
You've got these peripheral elements
link |
that are doing the initial stages of-
link |
The eye, the ear, the nose.
link |
The skin of your fingertips, right?
link |
You know, the taste buds on your tongue.
link |
They're taking this raw information in
link |
and they're doing some pre-processing maybe,
link |
or the early circuits are,
link |
but eventually most of these signals
link |
have to pass through the gateway to the cortex,
link |
which is the thalamus.
link |
And we've known for years, for decades, many decades,
link |
what the major throughput pathway
link |
from the retina to the cortex is,
link |
and where it ends up.
link |
It ends up in the visual cortex.
link |
You know, you pat the back of your head.
link |
That's where the receiving center is
link |
for the main pathway from retina to cortex.
link |
But wait a minute, there's more.
link |
There's this little side pathway
link |
that goes through a different part
link |
of that linking thalamus center,
link |
the gateway to the cortex.
link |
It's like a local train
link |
from Grand Central to-
link |
It's in a weird part of the neighborhood, right?
link |
It's a completely different,
link |
it's like a little trunk line that branches off
link |
and goes out into the hinterlands.
link |
And it's going to the part of this linker center
link |
that's talking to a completely different part of cortex,
link |
way up front, frontal lobe,
link |
which is much more involved in things like planning
link |
Self-image, literally how one thinks about-
link |
You know, do you feel good about yourself?
link |
Or, you know, what's your plan for next Thursday?
link |
You know, it's a very high level center
link |
in the highest level of your nervous system.
link |
And this is the region that is getting input
link |
from this pathway,
link |
which is mostly worked out in its function
link |
by Samir Hatara's lab.
link |
I know you had him on the podcast.
link |
We didn't talk about this pathway.
link |
This pathway at all, right.
link |
So, Diego Fernandez and Samir
link |
and the folks that work with them
link |
were able to show that this pathway doesn't just exist
link |
and get you to a weird place.
link |
But if you activate it at kind of the wrong time of day,
link |
animals can become depressed.
link |
And if you silence it under the right circumstances,
link |
then weird lighting cycles that would normally
link |
make them act sort of depressed
link |
no longer have that effect.
link |
So, it sounds to me like there's this pathway
link |
from I to this unusual train route
link |
through the structure we call the thalamus,
link |
then up to the front of the brain
link |
that relates to things of self-perception,
link |
kind of higher level functions.
link |
I find that really interesting
link |
because most of what I think about
link |
when I think about these fancy,
link |
well, or these primitive, rather,
link |
neurons that don't pay attention to the shapes of things,
link |
but instead to brightness,
link |
I think of, well, it regulates melatonin,
link |
circadian clock, mood, hunger,
link |
the really kind of vegetative stuff, if you will.
link |
And this is interesting
link |
because I think a lot of people experience depression,
link |
not just people that live in Scandinavia
link |
in the middle of winter.
link |
And we are very much divorced
link |
from our normal interactions with light.
link |
It also makes me realize
link |
that these intrinsically photosensitive cells
link |
that set the clock, et cetera,
link |
are involved in a lot of things.
link |
I mean, they seem to regulate
link |
a dozen or more different basic functions.
link |
I want to ask you about
link |
a different aspect of the visual system now,
link |
which is the one that relates to our sense of balance.
link |
So I love boats, but I hate being on them.
link |
I love the ocean from shore
link |
because I get incredibly seasick.
link |
It's awful, I think I'm going to get seasick
link |
if I think about it too much.
link |
And once I went on a boat trip,
link |
I came back and I actually got motion sick
link |
or wasn't seasick because I went rafting.
link |
So there's a system that somehow gets messed up.
link |
They always tell us if you're feeling sick
link |
to look at the horizon, et cetera, et cetera.
link |
So what is the link between our visual system
link |
and our balance system?
link |
And why does it make us nauseous sometimes
link |
when the world is moving in a way
link |
that we're not accustomed to?
link |
I realize this is a big question
link |
because it involves eye movement, et cetera,
link |
but let's maybe just walk in at the simplest layers
link |
of vision, vestibular, so-called balance system,
link |
and then maybe we can piece the system together for people
link |
so that they can understand.
link |
And then also we should give them some tools
link |
for adjusting their nausea
link |
when their vestibular system is out of whack.
link |
Cool, so I mean, the first thing to think about
link |
is that the vestibular system is designed
link |
to allow you to see how your, or detect, sense,
link |
how you're moving in the world, through the world.
link |
It's a funny one because it's about your movement
link |
in relationship to the world in a sense,
link |
and yet it's sort of interoceptive in the sense
link |
that it is really in the end sensing
link |
the movement of your own body.
link |
Okay, so interoception we should probably delineate
link |
for people is when you're focusing on your internal state
link |
as opposed to something outside you.
link |
But it's a gravity sensing system.
link |
Well, it's partly a gravity sensing system
link |
in the sense that gravity is a force that's acting on you
link |
as if you were moving through the world
link |
in the opposite direction.
link |
All right, now you got to explain that one to me.
link |
Okay, so basically the idea is that
link |
if we leave gravity aside,
link |
we're just sitting in a car in the passenger seat
link |
and the driver hits the accelerator
link |
and you start moving forward, you sense that.
link |
If your eyes were closed, you'd sense it.
link |
If your ears were plugged and your eyes were closed,
link |
you'd still know it.
link |
Yeah, many people take off on the plane like this,
link |
they're dreading the flight
link |
and they know when the plane is taking off.
link |
Sure, that's your vestibular system talking
link |
because anything that jostles you
link |
out of the current position you're in right now
link |
will be detected by the vestibular system, pretty much.
link |
So this is a complicated system,
link |
but it's basically in your inner ear,
link |
very close to where you're hearing.
link |
I can put it there.
link |
And I don't know who they is.
link |
I don't really know, they're starting to ride.
link |
To steal our friend Russ Van Gelder's explanation,
link |
we weren't consulted the design phase and no one-
link |
That's a great line.
link |
That's a great line.
link |
But it's interesting, it's in the ear.
link |
Yeah, it's deep in there
link |
and it's served by the same nerve, actually,
link |
that serves the hearing system.
link |
One way to think about it is both the hearing system
link |
and the vestibular self-motion sensing system
link |
are really detecting the signal in the same way.
link |
They're hairy cells and they're excited.
link |
Yeah, sort of, they got little cilia
link |
sticking up off the surfaces.
link |
And depending on which way you bend those,
link |
the cells will either be inhibited or excited.
link |
They're not even neurons, but then they talk to neurons
link |
with a neuron-like process and off you go.
link |
Now you've got an auditory signal
link |
if you're sensing things bouncing around in your cochlea,
link |
which is- Sound waves.
link |
Sympathetically, the bouncing of your eardrum,
link |
which is sympathetically the sound waves in the world.
link |
But in the case of the vestibular apparatus,
link |
evolution has built a system that detects the motion
link |
of say fluid going by those hairs.
link |
And if you put a sensor like that in a tube
link |
that's fluid-filled, now you've got a sensor
link |
that will be activated when you rotate that tube
link |
around the axis that passes through the middle of it.
link |
Those, you know, we're just listening,
link |
won't be able to visualize that.
link |
No, I think that makes sense.
link |
I was thinking of it as three hula hoops.
link |
Right, three hula hoops.
link |
One standing up, one lying down on the ground.
link |
Right, one the other way.
link |
The people who fly will talk about roll, pitch, and yaw,
link |
that kind of thing.
link |
So the three axes of encoding,
link |
just like in the cones of the retina.
link |
Sort of the yes, the no, and then I always say it's,
link |
and then the puppy head tilt.
link |
Yeah, the puppy head tilt.
link |
That's the other one.
link |
So the point is that your brain is eventually going
link |
to be able to unpack what these sensors are telling you
link |
about how you just rotated your head in very much the way
link |
that the three types of cones we were talking about before
link |
are reading the incoming photons
link |
in the wavelength domain differently.
link |
Red, green, and blue.
link |
Yeah, you can compare and trust, you get red, green, and blue.
link |
So it's the same basic idea.
link |
If you have three sensors and you array them properly,
link |
now you can tell if you're rotating your head left or right,
link |
That's the sensory signal coming back into your brain,
link |
confirming that you've just made a movement that you will.
link |
But what about on the plane?
link |
Because when I'm on the plane, I'm completely stationary.
link |
The plane's moving, but my head hasn't moved.
link |
So I'm just moving forward, gravity is constant.
link |
How do I know I'm accelerating?
link |
So what's happening now is your brain is sensing the motion
link |
and the brain is smart enough also to ask itself,
link |
did I will that movement or did that come from the outside?
link |
So now in terms of sort of understanding
link |
what the distributor signal means,
link |
it's gotta be embedded in the context
link |
of what you tried to do
link |
or what your other sensory systems are telling you
link |
about what's happening right now.
link |
So it's very interesting, but it's not conscious.
link |
Or at least if it's conscious, it's not conscious,
link |
it's definitely very fast, right?
link |
The moment that plane starts moving,
link |
I know that I didn't get up out of my chair
link |
But I'm not really thinking about getting up out of my chair
link |
I guess the way I think about it is that
link |
the nervous system is quote, aware at many levels.
link |
When it gets all the way up to the cortex
link |
and we're thinking about it, you're talking about it.
link |
You know, that's cortical,
link |
but the lower levels of the brain
link |
that don't require you to actually actively think about it,
link |
they're just doing their thing, are also made aware, right?
link |
A lot of this is happening under the surface
link |
of what you're thinking.
link |
These are reflexes.
link |
So we've got this gravity sensing system.
link |
I'm nodding for those that are listening
link |
for a yes movement of the head, a no movement of the head,
link |
or the tilting of the head from side to side.
link |
And then you said that knowledge about whether or not
link |
activation of that system comes from my own movements
link |
or something acting upon me, like the plane moving,
link |
has to be combined with other signals.
link |
And so how is the visual information
link |
or information about the visual world
link |
combined with balance information?
link |
So, yeah, I mean, I guess maybe the best way
link |
to think about how these two systems work together
link |
is to think about what happens
link |
when you suddenly rotate your head to the left.
link |
When you suddenly rotate your head to the left,
link |
your eyes are actually rotating to the right automatically.
link |
You do this in complete darkness.
link |
If you had an infrared camera and watched yourself
link |
in complete darkness, you can't see anything.
link |
Rotating your head to the left,
link |
your eyes would rotate to the right.
link |
That's your vestibular system saying,
link |
it's, I'm going to try to compensate for the head rotation,
link |
so my eyes are still looking in the same place.
link |
Why is that useful?
link |
Well, if it's always doing that,
link |
then the image of the world on your retina
link |
will be pretty stable most of the time.
link |
And that actually helps vision.
link |
Have they built this into cameras for image stabilization?
link |
Because when I move, when I take a picture with my phone,
link |
it's blurry, it's not clear.
link |
Well, actually, you might want to get a better phone
link |
because now what they have is software in the better abs
link |
that will do a kind of image stabilization post hoc
link |
by doing a registration of the images
link |
that are bouncing around.
link |
They say the edge of the house was here,
link |
so let's get that aligned in each of your images.
link |
So you may not be aware if you're using a good new phone,
link |
that if you walk around a landscape and hold your phone,
link |
that there's all this image stabilization going on.
link |
But it's built into standard cinematic technology now,
link |
because if you tried to do a handheld camera,
link |
things would be bouncing around, things would be unwatchable,
link |
you wouldn't be able to really understand
link |
what's going on in the scene.
link |
So the brain works really hard to mostly stabilize
link |
the image of the world on your retina.
link |
Now, of course, you're moving through the world,
link |
so you can't stabilize everything.
link |
But the more you can stabilize most of the time,
link |
the better you can see.
link |
And that's why when we're scanning a scene,
link |
looking around at things,
link |
we're making very rapid eye movements
link |
for very short periods of time, and then we just rest.
link |
But we're not the only ones that do that.
link |
If you ever watch a hummingbird,
link |
it does exactly the same thing in a feeder, right?
link |
But it's with its body, it's gonna make a quick movement,
link |
and then it's gonna be stable.
link |
And when you watch a pigeon walking on the sidewalk,
link |
it does this funny head bobbing thing.
link |
But what it's really doing is racking its head back
link |
on its neck while its body goes forward,
link |
so that the image of the visual world stays static.
link |
Is that why they're doing it?
link |
And you've seen the funny chicken videos on YouTube, right?
link |
You take a chicken, move it up and down,
link |
the head stays in one place.
link |
It's all the same thing.
link |
All of these animals are trying hard
link |
to keep the image of the world stable on their retina
link |
as much of the time as they possibly can.
link |
And then when they've gotta move, make it fast,
link |
make it quick, and then stabilize again.
link |
So are the pigeons have their head back?
link |
I think I just need to pause there for a second
link |
In case people aren't, well, there's no reason
link |
why people would know what we're doing here,
link |
but essentially what we're doing is we're building up
link |
from sensory, light onto the eye, color,
link |
to what the brain does with that, the integration of that,
link |
circadian clock, melatonin, et cetera.
link |
And now what we're doing is we're talking about
link |
multi-sensory or multimodal, combining one sense, vision,
link |
with another sense, balance.
link |
And it turns out that pigeons know more about this
link |
than I do because pigeons know to keep their head back
link |
as they walk forward.
link |
All right, so that gets us to this issue of motion sickness.
link |
And you don't have to go out on a boat.
link |
Anytime I go to New York, I sit in an Uber
link |
or in a cab in the back, and if I'm looking at my phone
link |
while the car is driving, I feel nauseous
link |
by time I arrive at my destination.
link |
I always try and look out the front of the windshield
link |
because I'm told that helps, but it's a little tiny window.
link |
And I end up feeling slightly less sick if I do that.
link |
So what's going on with the vision and the balance system
link |
that causes a kind of a nausea?
link |
And actually, if I keep talking about this,
link |
I probably will get sick.
link |
I don't throw up easily, but for some reason,
link |
motion sickness is a real thing for me.
link |
It's a problem for a lot of people.
link |
I mean, I think the fundamental problem typically
link |
when you get motion sick is what they call
link |
visual vestibular conflict.
link |
That is, you have two sensory systems
link |
that are talking to your brain
link |
about how you're moving through the world.
link |
And as long as they agree, you're fine.
link |
So if you're driving, your body senses
link |
that you're moving forward.
link |
Your vestibular systems is picking up this acceleration
link |
of the car, and your visual system is seeing the consequences
link |
of forward motion in the sweeping of the scene past you.
link |
Everything is honky-dory, right?
link |
But when you are headed forward,
link |
but you're looking at your cell phone,
link |
what is your retina seeing?
link |
Your retina is seeing the stable image of the screen.
link |
There's absolutely no motion in that screen.
link |
Or the motion is, or some other motion,
link |
like a movie or, yeah. Or it's a motion
link |
you're watching if you're playing a game
link |
or you're watching a video, a football game.
link |
Or the motion is uncoupled
link |
with what's actually happening to your body.
link |
Your brain doesn't like that.
link |
Your brain likes everything to be aligned.
link |
And if it's not, it's going to complain to you.
link |
By making me feel nauseous.
link |
By making you feel nauseous,
link |
and maybe you'll change your behavior.
link |
So you're getting-
link |
I'm getting punished.
link |
Yeah, for setting it up
link |
so you're a signal second flick, right.
link |
By the vestibular visuals in time.
link |
I love the idea of reward signals.
link |
And we've done a lot of discussion about this
link |
on this podcast of things like dopamine reward and things,
link |
but also punishment signals.
link |
And I love this example.
link |
Well, maybe marching a little bit further
link |
along this pathway,
link |
visual input is combined with balance input.
link |
Where does that occur?
link |
And maybe, because I have some hint of where it occurs,
link |
you could tell us a little bit about this
link |
kind of mysterious little mini brain
link |
that they call the cerebellum.
link |
So, you know, the way I tried to describe the cerebellum
link |
to my students is that it serves sort of like
link |
the air traffic control system functions in air travel.
link |
So that it's a system that's very complicated
link |
and it's really dependent on great information.
link |
So it's taking in the information
link |
about everything that's happening everywhere,
link |
not only through your sensory systems,
link |
but it's listening into all the little centers
link |
elsewhere in your brain that are computing
link |
what you're gonna be doing next and so forth.
link |
So it's just ravenous for that kind of information.
link |
So it really is like a little mini brain.
link |
It is, it's got access to all of the signals
link |
and it really has an important role
link |
in coordinating and shaping movements.
link |
But, you know, if you suddenly eliminated the air traffic
link |
control system, planes could still take off and land,
link |
but you might have some unhappy accidents in the process.
link |
So the cerebellum is kind of like that.
link |
It's not that you would be paralyzed
link |
if your cerebellum was gone
link |
because you still have motor neurons,
link |
you still have ways to talk to your muscles,
link |
you still have reflex centers,
link |
and it's not like you would have any sensory loss
link |
because you still have your cortex
link |
getting all of those beautiful signals
link |
that you can think about,
link |
but you wouldn't be coordinating things so well anymore.
link |
The timing between input and output might be off.
link |
Or if you were trying to practice a new athletic move,
link |
like an overhead serve in tennis,
link |
you'd be just terrible at learning.
link |
But all of the sequences of muscle movements
link |
and the feedback from your sensory apparatus
link |
that would let you really get that ball
link |
exactly where you want it to after the nth rep, right now,
link |
the thousandth rep or something, you get much better at it.
link |
So the cerebellum is all involved in things like
link |
motor learning and refining the precisions of movement
link |
so that they get you where you want to go.
link |
If you reach for a glass of champagne
link |
that you don't knock it over or stop short.
link |
You know, that's what it's good at.
link |
People who have selective damage to the cerebellum.
link |
And what I come familiar with,
link |
well, Korsakoff's is different, right?
link |
Isn't that a B vitamin deficiency from,
link |
in chronic alcoholics?
link |
And they have a, they tend to walk kind of bow-legged
link |
and they can't coordinate their movements.
link |
Is that, that has some that-
link |
Not sure about the cerebellar.
link |
Mammary bodies, but also cerebellum.
link |
I'm not sure about the cerebellar involvement there,
link |
but you know, the typical thing would be
link |
a patient who has a cerebellar stroke or a tumor,
link |
for example, might be not that steady on their feet.
link |
You know, if the, you know, dynamics of the situation
link |
is standing on a street car with no pole to hold onto,
link |
they might not be as good at adjusting
link |
all of the little movements of the car.
link |
You know, there's a kind of tremor that can occur
link |
as they're reaching for things
link |
because they reach a little too far
link |
and then they over-correct and come back, things like that.
link |
So it's very common neurological phenomenon, actually.
link |
Cerebellar ataxia, this is what the neurologists call it.
link |
And it can happen not just with cerebellar damage,
link |
but damage to the tracks that feed the information
link |
into the cerebellum.
link |
Right, just to provide the structure.
link |
Exactly, or output from the cerebellum.
link |
And so the cerebellum is where a lot of visual
link |
and balance information is combined.
link |
In a very key place in the cerebellum,
link |
which is, it's really one of the oldest parts
link |
in terms of evolution.
link |
Talking about the flocculus.
link |
The flocculus, right.
link |
This is a, it's a critical place in the cerebellum
link |
where visual and vestibular information comes together
link |
recording just the kinds of movements
link |
we were talking about, this image stabilizing network.
link |
It's all happening there.
link |
And there's learning happening there as well.
link |
So that if your vestibular apparatus
link |
is a little bit damaged somehow,
link |
your visual system is actually talking to your cerebellum
link |
saying there's a problem here, there's an error.
link |
And your cerebellum is learning to do better
link |
by increasing the output of the vestibular system
link |
to compensate for whatever that loss was.
link |
So it's a little error correction system.
link |
That's sort of typical of a cerebellar function.
link |
And it can happen in many, many different domains.
link |
This is just one of the domains
link |
of sensory motor integration that takes place there.
link |
So I should stay off my phone in the Ubers.
link |
If I'm on a boat, I should essentially look
link |
and as much as possible act as if I'm driving the machine.
link |
That'd be weird if I was in the passenger seat
link |
pretending I was driving the machine,
link |
but I do always feel better
link |
if I'm sitting in the front seat passenger.
link |
The more of the visual world that you can see
link |
as if you were actually the one doing the motion,
link |
Let's stay in the inner ear for a minute
link |
as we continue to march around the nervous system.
link |
When you take off in the plane or when you land
link |
or sometimes in the middle of there,
link |
your ears get clogged, or at least my ears get clogged.
link |
That's because of pressure buildup
link |
in the various tubes of the inner ear, et cetera.
link |
We'll get into this.
link |
But years ago, our good friend, Harvey Carton,
link |
who's another world-class neuroanatomist,
link |
gave a lecture and it talked about
link |
how plugging your nose and blowing out
link |
versus plugging your nose and sucking in
link |
can, should be done at different times
link |
depending on whether or not you're taking off or landing.
link |
And I always see people trying to un-pop their ears.
link |
And when you do scuba diving,
link |
you learn how to do this without necessarily,
link |
I can do it by just kind of moving my jaw now
link |
because I've done a little bit of diving.
link |
But what's the story there?
link |
We don't have to get into all the differences
link |
in atmospheric pressure, et cetera.
link |
But if I'm taking off and my ears are plugged,
link |
or I've recently ascended, plane took off,
link |
my ears are plugged.
link |
Do I plug my nose and blow out
link |
or do I plug my nose and suck in?
link |
Right, so the basic idea is that if your ears feel bad
link |
because you're going into an area of higher pressure,
link |
so if they pressurize the cabin more than the pressure
link |
that you have on the surface of the planet,
link |
your eardrums will be bending in and they don't like that.
link |
If you push them more, they'll hurt even more.
link |
That's a good description that the pressure goes up,
link |
then they're gonna bend in.
link |
Bend in, and then the reverse would be true
link |
if you go into an area of low pressure.
link |
So if you started to drive up the mountainside,
link |
the pressure is getting lower and lower outside.
link |
Now the air behind your eardrum is blooming out, right?
link |
So it's just a question of are you trying to get
link |
more pressure or less pressure behind the eardrum?
link |
And there's a little tube that does that
link |
and comes down into the back of your throat there.
link |
And if you force pressure up that tube,
link |
you're gonna be putting more air pressure
link |
into the compartment to counter it, if it's not enough.
link |
And if you're sucking, you're going the other way.
link |
In reality, I think as long as you open the passageway,
link |
I think the pressure differential
link |
is gonna solve your problem.
link |
So I think you could actually blow in
link |
when you're not, quote, supposed to.
link |
Okay, so you could just hold your nose and blow air out
link |
or hold your nose and suck in the effect.
link |
Either way is fine.
link |
Excellent, I just won $100 from Harvey Carton.
link |
Thank you very much.
link |
Harvey and I used to teach in our anatomy together.
link |
And I'll say, I don't think it matters, but thank you.
link |
I'll split that with you.
link |
This is important stuff, but it's true.
link |
You hear this, so it doesn't matter either way.
link |
Yeah, I'm no expert in this area.
link |
Don't worry. Don't quote me.
link |
He's not gonna, well, I'm going to quote you, but okay.
link |
So we've talked about the inner ear
link |
and we've talked about the cerebellum.
link |
I want to talk about an area of the brain
link |
that is rarely discussed, which is the midbrain.
link |
And for those that don't know,
link |
the midbrain is an area beneath the cortex.
link |
I guess we never really defined cortex.
link |
It was just kind of the outer layers
link |
or the outer layers of the least mammalian brain
link |
But the midbrain is super interesting
link |
because it controls a lot of unconscious stuff,
link |
reflexes, et cetera.
link |
And then there's this phenomenon even called blindsight.
link |
So could you please tell us about the midbrain,
link |
about what it does and what in the world is blindsight?
link |
Yeah, so there's a lot of pieces there.
link |
I think the first thing to say is if you imagine
link |
the nervous system in your mind's eye,
link |
you see this big honking brain
link |
and then there's this little wand that dangles down
link |
into your vertebral column, the spinal cord,
link |
and that's kind of your visual impression.
link |
What you have to imagine is starting in the spinal cord
link |
and working your way up into this big, magnificent brain.
link |
And what you would do as you enter the skull
link |
is get into a little place where the spinal cord
link |
kind of thickens out.
link |
It still has that sort of long, skinny, trunk-like feeling.
link |
Sort of like a paddle or a spoon shape.
link |
Right, it starts to spread out a little bit
link |
and that's because your evolution has packed
link |
more interesting goodies in there
link |
for processing information and generating movement.
link |
So beyond that is this tween brain.
link |
You were talking about this link, this linker brain.
link |
Diencephalon really means the between brain.
link |
Oh, I thought you said tween.
link |
No, no, between, between.
link |
Sorry, I thought you said tween.
link |
Yeah, it's the between, it's the between brain
link |
is what the name means.
link |
It's the linker from the spinal cord in the periphery
link |
up to these grand centers of the cortex.
link |
But this midbrain you're talking about
link |
is the last bit of this enlarged sort of spinal cord-y thing
link |
in your skull, which is really the brainstem
link |
is what we call it.
link |
The last bit of that before you get to this relay
link |
up to the cortex is the midbrain.
link |
And there's a really important visual center there.
link |
It's called the superior colliculus.
link |
There's a similar center in the brains
link |
of other vertebrate animals.
link |
A frog, for example, or a lizard would have this.
link |
It's called the optic tectum there.
link |
But it's a center that in these non-mammalian vertebrates
link |
is really the main visual center.
link |
They don't really have what we would call a visual cortex,
link |
although there's something sort of like that.
link |
But this is where most of the action is
link |
in terms of interpreting visual input
link |
and organizing behavior around that.
link |
You can sort of think about this region of the brainstem
link |
as a reflex center that can reorient the animal's gaze
link |
or body, or maybe even attention,
link |
or maybe even attention to particular regions of space
link |
out there around the animal.
link |
And that could be for all kinds of reasons.
link |
I mean, it might be a predator just showed up
link |
in one corner of the forest and you pick that up
link |
and you're trying to avoid it.
link |
Or just any movement.
link |
Many movement, right?
link |
It might be that suddenly something splats on the page
link |
when you're reading a novel
link |
and your eye reflexly looks at it.
link |
You don't have to think about that.
link |
What if you throw me a ball, but I'm not expecting it,
link |
and I just reach up and try and grab it, catch it or not?
link |
Is that handled by the midbrain?
link |
Well, that's probably not the midbrain,
link |
although, I mean, by itself,
link |
because it's going to involve all these limb movements,
link |
this movement of your arm and body.
link |
What about ducking if something's suddenly thrown at my head?
link |
Things like that will certainly have a brainstem component,
link |
a midbrain component.
link |
Something looms and you duck.
link |
It may not be the superior colliculus we're talking about.
link |
Now, it might be another part of the visual midbrain,
link |
but these are centers that emerged early
link |
in the evolution of brains like ours
link |
to handle complicated visual events
link |
that have significance for the animal.
link |
In terms of space, where is it in space?
link |
And in fact, this same center actually gets input
link |
from all kinds of other sensory systems
link |
that take information from the external world,
link |
from particular locations,
link |
and where you might want to either avoid
link |
or approach things according to their significance to you.
link |
So, you get input from the touch system.
link |
You get input from the auditory system.
link |
I worked for a while in rattlesnakes.
link |
They get input from a part of their warm sensors
link |
They're in these little pits on the face.
link |
They used to work on baby rattlesnakes, right?
link |
Well, they were adults, actually.
link |
Oh, I wasn't trying to diminish the danger.
link |
I thought for some reason they were little ones.
link |
Why in the world would you work on rattlesnakes?
link |
Well, because they have a version
link |
of an extra receptive sensory system.
link |
That is, they're looking out into the world
link |
using a completely different set of sensors.
link |
They're using the same sensors
link |
that would feel the warmth on your face
link |
if you stood in front of a bonfire,
link |
except evolution has given them
link |
this very nice specialized system
link |
that lets them image where the heat's coming from.
link |
You can sort of do that anyway, right?
link |
If you walk around the fire,
link |
you can feel where the fire is from the heat coming in.
link |
It's hitting your face.
link |
Is that the primary way in which they detect prey?
link |
It's one of the major ways.
link |
And in fact, they use vision as well.
link |
And they bring these two systems together
link |
in the same place, in this tectum region,
link |
this brain stem, midbrain region.
link |
What's all the tongue jutting about when the snakes?
link |
That I don't know.
link |
That may be olfactory.
link |
They're sniffing the air with their tongue?
link |
Yeah, there may be-
link |
Early air in our drive,
link |
you told me that flies actually taste things
link |
Yeah, they have taste receptors in lots of funny places.
link |
I want to pause here just for one second
link |
before we get back into the midbrain.
link |
I think what's so interesting in all seriousness
link |
about taste receptors on feet, heat sensors,
link |
tongues jutting out of snakes,
link |
and vision and all this integration
link |
is that it really speaks to the fact
link |
that all these sensory neurons
link |
are trying to gather information
link |
and stuff it into a system
link |
that can make meaningful decisions and actions.
link |
And that it really doesn't matter
link |
whether or not it's coming from eyes or ears or nose
link |
or bottoms of feet,
link |
because in the end it's just electricity flowing in.
link |
And so it sounds like it's placed on each animal.
link |
It's always feels weird to call fly an animal,
link |
but they are creatures.
link |
It's placed in different locations on different animals,
link |
depending on the particular needs of that animal.
link |
Right, but how much more powerful
link |
if the nervous systems can also cross-correlate
link |
across sensory systems?
link |
So if you've got a weak signal from one sensory system,
link |
you're not quite sure there's something there.
link |
And a weak signal from another sensory system
link |
that's telling you the same locations
link |
is a little bit interesting.
link |
There might be something there.
link |
If you've got those two together, you've got corroboration.
link |
Your brain now says it's much more likely
link |
that that's gonna be something
link |
worth paying attention to.
link |
Right, so maybe I'm feeling some heat
link |
on one side of my face
link |
and I also smell something baking in the oven.
link |
So now neither is particularly strong,
link |
but as you said, there's some corroboration
link |
and that corroboration is occurring in the midbrain.
link |
Right, and then if you throw things into conflict,
link |
now the brain is confused
link |
and that may be where your motion sickness comes from.
link |
So it's great to have, as a brain,
link |
it's great to have as many sources of information
link |
as you can have, just like if you're a spy
link |
or a journalist, you don't want as much information
link |
as you can get about what's out there.
link |
But if things conflict, that's problematic, right?
link |
Your sources are giving you different information
link |
about what's going on.
link |
Now you've got a problem on your hands.
link |
What do you publish?
link |
The midbrain is so fascinating.
link |
I don't wanna eject us from the midbrain
link |
and go back to the vestibular system,
link |
but I do have a question that I forgot to ask
link |
about the vestibular system,
link |
which is why is it that for many people, including me,
link |
there's despite my motion sickness in cabs,
link |
that there's a sense of pleasure in moving through space
link |
and getting tilted relative
link |
to the gravitational pull of the earth.
link |
For me growing up, it was skateboarding,
link |
but people like to corner in cars, corner on bikes.
link |
It may be for some people it's done running or dance,
link |
but what is it about moving through space
link |
and getting tilted, a lot of surfers around here,
link |
getting tilted that can tap into some of the pleasure centers?
link |
Do we have any idea why that would feel good?
link |
Is there a dopaminergic input to this system?
link |
Well, the dopaminergic system gets a lot of places.
link |
It's pretty much, to some extent,
link |
everywhere in the cortex,
link |
a lot more in the frontal lobe, of course,
link |
but that's just for starters.
link |
I mean, there's basically dopaminergic innervation
link |
in most places in the central nervous system,
link |
so there's the potential for dopaminergic involvement,
link |
but I really have no clue about the tilting phenomenon.
link |
People pay money to go on roller coasters.
link |
Well, I think that may be as much about the thrill
link |
Sure, and the falling reflex is very robust in all of us.
link |
When the visual world's going up very fast,
link |
it usually means that we're falling,
link |
but in some people like that, some people don't.
link |
Right, and kids tolerate a lot more
link |
sort of vestibular craziness spinning around
link |
Well, I've friends, it always, you know,
link |
worries me a little bit that they throw their kids.
link |
I'm not recommending anyone do this.
link |
When they're little kids, you know,
link |
like throwing the kids really far back and forth,
link |
some kids seem to love it.
link |
Yeah, our son loved being shaken up and down
link |
very, very vigorously.
link |
That's the only thing that would calm him down sometimes.
link |
Yeah, so I'm guessing, we can guess
link |
that maybe there's some activation of the reward systems
link |
from moving through space.
link |
Well, I mean, if you think about, you know,
link |
how rewarding it is to be able to move through space
link |
and how unhappy people are who are used to that,
link |
who suddenly aren't able to do that,
link |
there is a sense of agency, right?
link |
If you can choose to move through the world and to tilt,
link |
that's not only you're moving through the world,
link |
but you're doing it with a certain amount of finesse.
link |
Maybe that's what it is.
link |
You can feel like you're the master of your own movement
link |
in a way that you wouldn't if you're going straight.
link |
I'm just blowing smoke here, right?
link |
Yeah, well, we can speculate.
link |
I couldn't help but ask the question.
link |
Okay, so if we move ourselves, pun intended,
link |
back into the midbrain,
link |
the midbrain's combining all these different signals
link |
for reflexive action.
link |
At what point does this become deliberate action?
link |
Because if I look at something I want
link |
and I want to pursue it, I'm going to go toward it.
link |
And many times that's a deliberate decision.
link |
So this gets very slippery, I think,
link |
because what you have to try to imagine
link |
is all these different parts of the brain
link |
working on the problem of staying alive
link |
and surviving in the world.
link |
They're working on the problem simultaneously.
link |
And there's not one right answer to how to do that.
link |
But one way to think about it is that
link |
you have high levels of your nervous system
link |
that are very well designed to override
link |
an otherwise automatic movement if it's inappropriate.
link |
So if you've imagined,
link |
you've been invited to tea with the queen
link |
and she hands you a very fancy Wedgwood tea cup, very thin.
link |
Yes, with very hot tea in it
link |
and you're burning your hand,
link |
you probably will try to find a way
link |
to put that back down on the saucer
link |
rather than just dropping it on the floor
link |
because you're with the queen.
link |
You're trying to be appropriate to that.
link |
So you have ways of reining in automatic behaviors
link |
if they're gonna be maladaptive.
link |
But you also want the reflex to work quickly
link |
if it's the only thing that's gonna save you,
link |
the looming object coming at your head.
link |
You don't have time to think about that.
link |
So this is the interplay
link |
in these hierarchically organized centers
link |
of the nervous system.
link |
At the lowest level, you've got the automatic sensors
link |
and centers and reflex arcs that will keep you safe
link |
even if you don't have time to think about it.
link |
And then you've got the higher center saying,
link |
well, maybe we could do this as well
link |
or maybe we shouldn't do that at all, right?
link |
So you have all of these different levels
link |
operating simultaneously
link |
and you need bi-directional communication
link |
between high level cognitive centers,
link |
decision-making on the one hand
link |
and these low level, very helpful reflexive centers,
link |
but they're a little bit rigid, a little hardwired,
link |
so they need some nuance.
link |
So both of these things are operating in tandem,
link |
in real time, all the time in our brains.
link |
And sometimes we listen more to one than the other.
link |
You've heard people in sports talking about
link |
messing up at the plate because they overthought it,
link |
thinking too hard about it.
link |
That's partly, you've already trained your cerebellum
link |
how to hit a fastball right down the middle.
link |
Right, and if you start looking for something new
link |
or different, you're going to mess up your reflexive swing.
link |
Right, if you're trying to think about the physics
link |
of the ball as it's coming at you,
link |
you've already missed, right?
link |
Because you're not using your,
link |
all those reps have built a kind of knowledge
link |
is what you want to rely on
link |
when you don't have enough time to contemplate.
link |
This is important and a great segue
link |
for what I'd like to discuss next,
link |
which is the basal ganglia.
link |
This really interesting area of the brain
link |
that's involved in go type commands and behaviors,
link |
instructing us to do things and no go,
link |
preventing us from doing things.
link |
Because so much of motor learning and skill execution
link |
and not saying the wrong thing or sitting still in class
link |
or as you used with the, you know,
link |
tea with the queen example,
link |
feeling discomfort involves suppressing behavior.
link |
And sometimes it's activating behavior.
link |
A tremendous amount of online attention
link |
is devoted to trying to get people motivated.
link |
You know, this isn't the main focus of our podcast.
link |
We touch on some of the underlying neural circuits
link |
of motivation, dopamine, and so forth.
link |
But so much of what people struggle with out there
link |
are elements around failure to pay attention
link |
or challenges in paying attention,
link |
which is essentially like putting the blinders on there,
link |
you know, getting a soda straw view of the world
link |
and maintaining that for a bout of work
link |
or something of that sort and trying to get into action.
link |
So of course, this is carried out by many neural circuits,
link |
not just the basal ganglia,
link |
but what are the basal ganglia
link |
and what are their primary roles
link |
in controlling go type behavior and no go type behavior?
link |
Yeah, so I mean, the basal ganglia are sitting deep
link |
in what you would call the forebrain.
link |
So the highest levels of the brain,
link |
they're sort of cousins to the cerebral cortex,
link |
which we talked about is sort of the highest level
link |
of your brain, the thing you're thinking with.
link |
Cerebral cortex being the refined cousins,
link |
and then you've got the, you know, the brutes.
link |
Yeah, I mean, that's probably totally unfair,
link |
but that's all right.
link |
I like the basal ganglia.
link |
I can relate to the brutish parts of the brain.
link |
A little bit of hypothalamus,
link |
a little bit of basal ganglia, sure.
link |
We need it all, we need it all.
link |
And, you know, this area of the brain
link |
has gotten a lot bigger as the cortex has gotten bigger,
link |
and it's deeply intertwined with cortical function.
link |
The cortex can't really do what it needs to do
link |
without the help of the basal ganglia and vice versa.
link |
So they're really intertwined.
link |
And in a way, you can think about this logically
link |
as saying, you know, if you have the ability
link |
to withhold behavior or to execute it,
link |
how do you decide which to do?
link |
Well, the cortex is gonna have to do that thinking for you.
link |
You have to be looking at all the contingencies
link |
of your situation to decide, is this a crazy move?
link |
Or is this a really smart investment right now?
link |
Or, you know, what?
link |
I don't wanna go out for a run in the morning,
link |
but I'm gonna make myself go out for a run.
link |
Or I'm having a great time out on a run,
link |
and I know I need to get back,
link |
but I kind of wanna go another mile.
link |
I mean, another great example is that, you know,
link |
the marshmallow test for the little kids, you know,
link |
they can get two marshmallows if they hold off, you know,
link |
just 30 seconds initially, you know.
link |
They can have one right away,
link |
but if they can wait 30 seconds, they got two, you know.
link |
So that's the no-go because their cortex is saying,
link |
you know, I would really like to have two
link |
more than having one,
link |
but they're not gonna get the two
link |
unless they can not reach for the one.
link |
So they've got to hold off the action,
link |
and that has to result from a cognitive process.
link |
So the cortex is involved in this in a major way.
link |
Yeah, as I recall in that experiment,
link |
the kids used a variety of tools to,
link |
some would distract themselves.
link |
I particularly related to the kid
link |
that would just put himself right next to the marshmallows,
link |
and then some of the kids covered their eyes.
link |
Some of them would count or sing.
link |
Yeah, so that's all very cortical, right?
link |
Coming up with a novel strategy.
link |
Simple example that we're using here,
link |
but of course, this is at play.
link |
Anytime someone decides they wanna go watch
link |
a motivational speech or something,
link |
just, you know, a Steve Jobs commencement speech
link |
just to get motivated to engage in their day.
link |
Should I take this new job?
link |
You know, it's got great benefits,
link |
but it's in a lousy part of the country.
link |
Why do you think that some people have a harder time
link |
running these go-no-go circuits,
link |
and other people seem to have
link |
very low activation energy, we would say.
link |
They can just, you know, they have a task,
link |
they just lean into the task.
link |
Whereas some people getting into task completion
link |
or things of that sort is very challenging for them.
link |
Yeah, I mean, I think it's really just another,
link |
it's a special case of a very general phenomenon,
link |
which is brains are complicated.
link |
And brains, you know, the brains we have
link |
are the result of genetics and experience.
link |
And my genes are different from your genes,
link |
and my experiences are different from your experiences.
link |
So the things that will be easy or hard for us
link |
won't necessarily be aligned.
link |
They might just happen to be just because they are.
link |
But the point is that you're dealt a certain set of cards,
link |
you have a certain set of genes, you are handed a brain.
link |
You don't choose your brain, it's handed to you.
link |
But then there's all this stuff you can do with it.
link |
You know, you can learn to have new skills
link |
or to act differently or to show more restraint,
link |
which is kind of relevant to what we're talking about here.
link |
Or maybe show less restraint if your problem is
link |
you're so buttoned down, you never have any fun in life
link |
and you should loosen up a little bit.
link |
I appreciate the insult.
link |
David's always encouraged me
link |
to have a little more fun in life.
link |
So basal ganglia are, they're kind of the disciplinarian
link |
or they're sort of the instructor or conductor of sorts.
link |
Go, no go, you know, you be quiet, you start now.
link |
I wish I knew more about the basal ganglia than I do.
link |
My sense is that it, you know, this system is key
link |
for implementing the plans that get cooked up
link |
in the cortex, but they also influence the plans
link |
that the cortex is dishing out
link |
because this is a major source of information
link |
So it becomes almost impossible to figure out
link |
where the computation begins and where it ends
link |
and who's doing what because these things
link |
are all interacting in a complex network.
link |
And it's all of it, it's the whole network.
link |
It's not, you know, one is the leader
link |
and the other is the follower.
link |
Yeah, these are, all the structures that we're discussing
link |
are working in parallel.
link |
And there's a lot of changing crosstalk.
link |
I have this somewhat sick habit, David,
link |
every day I try and do 21 no-gos.
link |
So if I want to reach for my phone, I try and not do it
link |
just to see if I can prevent myself
link |
from engaging in that behavior.
link |
If it was reflexive, if it's something I want to do,
link |
a deliberate choice, then I certainly allow myself
link |
I don't tend to have too much trouble with motivation,
link |
with go-type functions, mostly because I'm so busy
link |
that I wish I had more time for more go's, so to speak.
link |
But do you think these circuits
link |
have genuine plasticity in them?
link |
Absolutely, I mean, everybody knows
link |
how they've learned over time
link |
to wait for the two marshmallows, right?
link |
You know, you don't have to have
link |
instant gratification all the time.
link |
You're willing to do a job sometimes
link |
that isn't your favorite job
link |
because it comes with the territory
link |
and you want the salary that comes at the end of the week
link |
or the end of the month, right?
link |
So we can defer gratification.
link |
You know, we can choose not to say the thing
link |
that we know is gonna inflame our partner
link |
and create a meltdown for the next week.
link |
You know, we learn this control,
link |
but I think these are skills like any other.
link |
You can get better at them if you practice them.
link |
So I think you're choosing to do that spontaneously.
link |
It's kind of a, you know, it's a mental practice.
link |
It's a discipline.
link |
It's a way of building a skill that you wanna have.
link |
Yeah, I find it to be something
link |
that when I engage in a no-go type situation,
link |
then the next time and the next time
link |
that I find myself about to move reflexively,
link |
there's a little gap in consciousness
link |
that I can make a decision
link |
whether or not this is really the best use of my time.
link |
Because I sometimes wonder whether or not
link |
all this business around attention,
link |
certainly there's the case of ADHD
link |
and clinical diagnosed ADHD,
link |
but all these, the issue around focus and attention
link |
is really that people just have not really learned
link |
how to short circuit a reflex.
link |
And so much of what makes us different than rattlesnakes
link |
or, well, actually they could be deliberate,
link |
but from the other animals
link |
and is our ability to suppress reflex.
link |
Yeah, well, that's the cortex.
link |
Let's just say the forebrain.
link |
Cortex and basal ganglia are working together,
link |
sitting on top of this lizard brain
link |
that's giving you all these great adaptive reflexes
link |
that help you survive.
link |
You just hope you don't get the surprising case
link |
where the thing that your reflex is telling you
link |
is actually exactly the wrong thing
link |
and you make a mistake, right?
link |
Right, so that's what the cortex is for.
link |
It's adding nuance and context and experience,
link |
past association and in human beings,
link |
obviously learning from others through communication.
link |
Well, I was, you went right to it
link |
and it was where I was gonna go.
link |
So let's talk about the cortex.
link |
We've worked our way up the so-called neuroaxis
link |
as the aficionados will know.
link |
So we're in the cortex.
link |
This is the seat of our higher consciousness,
link |
self-image, planning and action.
link |
But as you mentioned, the cortex isn't just about that.
link |
It's got other regions that are involved in other things.
link |
So maybe we should, staying with vision,
link |
let's talk a little bit about visual cortex.
link |
You told me a story, an amazing story about visual cortex.
link |
And it was somewhat of a sad story, unfortunately,
link |
about someone who had a stroke to visual cortex.
link |
Maybe if you would share that story,
link |
because I think it illustrates many important principles
link |
about what the cortex does.
link |
Right, so the visual cortex is,
link |
you could say the projection screen,
link |
the first place where this information streaming
link |
from the retina through this thalamus,
link |
connecting linker gets played out
link |
for the highest level of your brain to see.
link |
I mean, it's a representation.
link |
It's a map of things going on in the visual world
link |
that's in your brain.
link |
And when we describe a scene to a friend,
link |
we're using this chunk of our brain
link |
to be able to put words,
link |
which are coming from a different part of our cortex,
link |
to the objects and movements and colors
link |
that we see in the world.
link |
So, you know, that's a key part of your visual experience.
link |
When you can describe the things you're seeing,
link |
you're looking at your visual cortex.
link |
Could I just ask a quick question?
link |
So right now, because I'm looking at your face.
link |
As we're talking, there are neurons
link |
in my brain, more or less in the configuration
link |
of your face that are active as you move about.
link |
And what if I were to close my eyes and just imagine,
link |
I do this all the time, by the way, David,
link |
I close my eyes and I imagine David Berson's face.
link |
I don't tend to do that as often, maybe I should,
link |
but you get the point.
link |
I'm now using visualization of what you look like
link |
If we were to image the neurons in my brain,
link |
would the activity of neurons resemble the activity
link |
of neurons that's present when I open my eyes
link |
and look at your actual face?
link |
This is a deep question.
link |
We don't really have a full accounting yet.
link |
Seems like an easy experiment to do.
link |
Yes, except, you know, you're talking about looking
link |
in detail at the activity of neurons in a human brain,
link |
and that's not as easy to do as it would be
link |
in some kind of animal model.
link |
But, you know, the bottom line is that you have
link |
a spatial representation of the visual world,
link |
laid as a map of the visual world,
link |
laid out on the surface of your cortex.
link |
The thing that's surprising is that it's not one map.
link |
It's actually dozens of maps.
link |
What do each of those maps do?
link |
Well, we don't really have a full accounting there either,
link |
but it looks a little bit like the diversification
link |
of the output neurons of the retina,
link |
the ganglion cells we were talking about before.
link |
There are different types of ganglion cells
link |
that are encoding different kinds of information
link |
about the visual world.
link |
We talk about the ones that were encoding the brightness,
link |
but other ones are encoding motion or color,
link |
these kinds of things.
link |
The same kinds of specializations
link |
in different representations of the visual world
link |
in the cortex seem to be true.
link |
It's a complex story.
link |
We don't have the whole picture yet,
link |
but it does look as if some parts of the brain
link |
are much more important for things like reaching
link |
for things in the space around you,
link |
and other parts of the cortex are really important
link |
for making associations between particular visual things
link |
you're looking at now and their significance.
link |
What is that object?
link |
What can it do for me?
link |
What about the really specialized areas of cortex,
link |
like the neurons that respond to particular faces
link |
or neurons that, I don't know,
link |
can help me understand where I am
link |
relative to some other specific object?
link |
Right, so these are properties of neurons
link |
that are extracted from, detected by,
link |
recording the activity of single neurons
link |
in some experimental system.
link |
What's going on when you actually perceive
link |
your grandmother's face is a much more complicated question.
link |
It clearly involves hundreds and thousands
link |
and probably millions of neurons acting in a cooperative way.
link |
So you can pick out any one little element
link |
in this very complicated system
link |
and see that it's responding differentially
link |
to certain kinds of visual patterns,
link |
and you think you're seeing a glimpse
link |
of some part of the process
link |
by which you recognize your grandmother's face.
link |
But that's a long way from a complete description,
link |
and it certainly isn't gonna be at the level
link |
of a magic single neuron that has the special stuff
link |
to recognize your grandmother.
link |
It's gonna be in some pattern of activity
link |
across many, many cells,
link |
resonating in some kind of special way
link |
that will represent the internal memory of your mother.
link |
She's really incredible.
link |
I mean, every time we do this deep dive,
link |
which we do from time to time,
link |
you and I, we kind of like march into the nervous system
link |
and explore how different aspects of our life experiences
link |
is handled there and how it's organized.
link |
After so many decades of doing this,
link |
it still boggles my mind that the collection of neurons
link |
one through seven active in a particular sequence
link |
gives the memory of a particular face
link |
and run backwards seven through to one.
link |
It gives you a complete, you know,
link |
could be rattlesnake, pit viper, heat-sensing organs-
link |
As we were talking about earlier.
link |
So it sounds, is it true that there's a lot
link |
of multi-purposing of the circuitry?
link |
Like we can't say one area of the brain does A
link |
and another area of the brain does B,
link |
so, you know, areas can multitask or have multiple jobs.
link |
They can moonlight.
link |
But I think in my career,
link |
the hard problem has been to square that
link |
with the fact that, you know, things are specialized,
link |
that there are specific genes expressed in specific neurons
link |
that make them make synaptic connections
link |
with only certain other neurons.
link |
And that particular synaptic arrangement
link |
actually results in the processing of information
link |
that's useful to the animal to survive, right?
link |
So it's not as if it's either
link |
a big undifferentiated network of cells
link |
and looking at any one is never gonna tell you anything.
link |
That's too extreme on the one hand,
link |
nor is it the case that everything is hardwired
link |
and every neuron has one function
link |
and this all happens in one place in the brain.
link |
It's way more complicated and interactive
link |
and interconnected than that.
link |
So we're not hardwired or softwired.
link |
We're sort of, I don't know what the analogy should be.
link |
What substance would work best, David?
link |
No idea there, but you know,
link |
the idea is that it's always network activity.
link |
There's always many, many neurons involved
link |
and yet there's tremendous specificity in the neurons
link |
that might or might not be participating
link |
in any distributed function like that, right?
link |
So you have to get your mind around the fact
link |
that it's both very specific and very nonspecific
link |
It's a little tricky to do,
link |
but I think that's kind of where the truth lies.
link |
Yeah, and so this example that you mentioned to me once
link |
before about a woman who had a stroke and visual cortex,
link |
I think speaks to some of this.
link |
Could you share with us that story?
link |
Sure, so the point is that you all,
link |
those of us who see have representations
link |
of the visual world and our visual cortex.
link |
What happens to somebody when they become blind
link |
because of problems in the eye, the retina, perhaps?
link |
You have a big chunk of the cortex,
link |
this really valuable real estate for neural processing
link |
that has come to expect input from the visual system
link |
and there isn't any anymore.
link |
So you might think about that as fallow land, right?
link |
It's just, it's unused by the nervous system
link |
and that would be a pity,
link |
but it turns out that it is in fact used.
link |
And the case that you're talking about
link |
is of a woman who was blind from very early in her life
link |
and who had risen through the ranks
link |
to a very high level executive secretarial position
link |
in a major corporation.
link |
And she was extremely good at braille reading
link |
and she had a braille typewriter
link |
and that's how everything was done.
link |
And apparently she had a stroke
link |
and was discovered at work, collapsed,
link |
and they brought her to the hospital.
link |
And apparently the neurologist who saw her
link |
when she finally came to said,
link |
I've got good news and bad news.
link |
Bad news is you've had a stroke.
link |
The good news is that it was in an area of your brain
link |
you're not even using, it's your visual cortex.
link |
And I know you're blind from birth,
link |
so there shouldn't be any issue here.
link |
The problem was she lost her ability to read braille.
link |
So what appears to have been the case,
link |
and this has been confirmed in other ways
link |
by imaging experiments in humans,
link |
is that in people who are blind from very early in birth,
link |
the visual cortex gets repurposed
link |
as a center for processing tactile information.
link |
And especially if you drain to be a good braille reader,
link |
you're actually reallocating somehow
link |
that real estate to your fingertips,
link |
a part of the cortex that should be listening to the eyes.
link |
So that's an extreme level of plasticity,
link |
but what it shows is the visual cortex
link |
is kind of a general purpose processing machine.
link |
It's good at spatial information
link |
and the skin of your fingers
link |
is just another spatial sense
link |
and deprived of any other input.
link |
The brain seems smart enough,
link |
if you want to put it that way,
link |
to rewire itself to use that real estate
link |
for something useful, in this case, reading braille.
link |
Incredible, somewhat tragic, but incredible.
link |
At least in that case, tragic.
link |
And of course it can go the other way too,
link |
where people can gain function in particular modalities
link |
like improved hearing or tactile function
link |
in the absence of vision.
link |
Tell us about connectomes.
link |
We hear about genomes, proteomes,
link |
microbiomes, ohms, ohms, ohms these days.
link |
What's a connectome and why is it valuable?
link |
Yeah, so connectome actually now has two meanings.
link |
So I'll only refer to the one that is my passion right now.
link |
And that is really trying to understand
link |
the structure of nervous tissue at a scale
link |
that's very, very fine.
link |
Smaller than a millimeter.
link |
Way smaller than a millimeter, a nanometer or less.
link |
That's a thousand times smaller.
link |
Or it's actually, you know, a million times smaller.
link |
So really, really tiny on the scale of individual synapses
link |
between individual neurons or even smaller,
link |
like the individual synaptic vesicles
link |
containing little packets of neurotransmitter
link |
that are going to get released to one neuron
link |
to communicate to the next.
link |
So very, very fine, but the notion here is that
link |
you're doing this section after section at very fine scale.
link |
So in theory, what you have is a complete description
link |
of a chunk of nervous tissue that is so complete
link |
that if you took enough time to identify
link |
where the boundaries of all the cells are,
link |
you could come up with a complete description
link |
of the synaptic wiring of that chunk of nervous tissue
link |
because you have a complete description
link |
of where all the cells are and where all the synapses
link |
So you have a complete description
link |
of where all the cells are and where all the synapses
link |
begin where all the cells are.
link |
So now you essentially have a wiring diagram
link |
of this complicated piece of tissue.
link |
So the omics part is the exhaustiveness of it.
link |
Rather than looking at a couple of synapses
link |
that are interesting to you from two different cell types,
link |
you're looking at all the synapses of all of the cell types,
link |
which of course is this massive avalanche of data, right?
link |
So in genetics, you have genetics and then you have genomics,
link |
which is the idea of getting the whole genome.
link |
And we don't really have an analogous word for genetics,
link |
but it would be connectivity and kinomics.
link |
Excuse me, connectomics, connectivity and connectomics.
link |
Right, so it's wanting it all.
link |
And of course it's crazy ambitious,
link |
but that's where it gets fun.
link |
Really it's a use of electron microscopy,
link |
a very high resolution microscopic imaging system
link |
on a new scale with way more payoff in terms
link |
of understanding the connectivity of the nervous system.
link |
And it's just emerging,
link |
but I really think it's gonna revolutionize the field
link |
because we're gonna be able to query these circuits.
link |
How did they actually do it?
link |
Look at the hardware in a way
link |
that's never been possible before.
link |
The way that I describe this to people is
link |
if you were to take a chunk of kind of cooked
link |
but cold spaghetti and slice it up very thin,
link |
you're trying to connect up each image
link |
of each slice of the edge of the spaghetti
link |
as figure out which ropes of spaghetti belong to which.
link |
And have a complete description
link |
of where this piece of spaghetti touches
link |
that piece of spaghetti
link |
and is there something special there?
link |
Where the meat sauce is and all the other cell types
link |
and the pesto, where it all is around the spaghetti
link |
because those are the other cells,
link |
the blood vessels and the glial cells.
link |
So what's it good for?
link |
I mean, maps are great.
link |
I always think of connectomics and genomics
link |
and proteomics, et cetera, as necessary, but not sufficient.
link |
So, I mean, in many cases,
link |
what you do is you go out and probe the function
link |
and you understand how the brain does the function
link |
by finding neurons that seem to be firing
link |
in association with this function that you're observing.
link |
And little by little, you're working your way in
link |
and now you wanna know what the connectivity is.
link |
Maybe the anatomy could help you.
link |
But this connectomics approach,
link |
or at least the serial electron microscopy reconstruction
link |
of neurons approach really is allowing us
link |
to frame questions starting from the anatomy
link |
and saying, I see a synaptic circuit here.
link |
My prediction would be that these cell types
link |
would interact in a particular way.
link |
And then you can go and probe the physiology
link |
and you might be right or you might be wrong,
link |
but more often than not,
link |
it looks like the structure is pointing us
link |
in the right direction.
link |
So in my case, I'm using this to try to understand a circuit
link |
that is involved in this image stabilization network
link |
we're talking about, keeping things stable on the retina.
link |
And this thing will only respond
link |
at certain speeds of motion.
link |
These cells in the circuit, like slow motion,
link |
they won't respond to fast motion.
link |
How does that come about?
link |
Well, I was able to probe the circuitry.
link |
I knew what my cells looked like.
link |
I could see which other cells were talking to it.
link |
I could categorize all the cells
link |
that might be the players here
link |
that are involved in this mechanism
link |
of tuning the thing for slow speeds.
link |
And then we said, it looks like it's that cell type.
link |
And we went and looked and the data bore that up.
link |
But the anatomy drove the search
link |
for the particular cell type
link |
because we could see it connected
link |
in the right place to the right cells.
link |
So that creates the hypothesis
link |
that lets you go query the physiology,
link |
but it can go the other way as well.
link |
So it's always the synergy
link |
between these functional and structural approaches
link |
that gives you the most lift.
link |
But in many cases,
link |
the anatomy has been a little bit the weak sister in this,
link |
the structure, trying to work out the diagram
link |
because we haven't had the methods.
link |
Now the methods exist.
link |
And this whole field is expanding very quickly
link |
because people want these circuit diagrams
link |
for the particular part of the nervous system
link |
that they're working on.
link |
If you don't know the cell types and the connections,
link |
how do you really understand how the machine works?
link |
Yeah, what I love about it is
link |
we don't know what we don't know.
link |
And as scientists, we don't ask questions.
link |
We pose hypotheses, hypotheses being, of course,
link |
some prediction that you wager your time on basically.
link |
And it either turns out to be true or not true.
link |
But if you don't know that a particular cell type is there,
link |
you could never in any configuration of life
link |
or a career or exploration of a nervous system
link |
wager a hypothesis because you didn't know it was there.
link |
So this allows you to say,
link |
ah, there's a little interesting little connection
link |
between this cell that I know is interesting
link |
and another cell that's a little mysterious,
link |
but interesting, I'm going to hypothesize
link |
that it's doing blank, blank, and blank and go test that.
link |
And in the absence of these connectomes,
link |
you would never know that that cell
link |
was lurking there in the shadows.
link |
Yeah, and if you're just trying to understand
link |
how information flows through this biological machine,
link |
you want to know where things are.
link |
Neuro-transmitters are dumped out of the terminals
link |
of one cell and they diffuse across the space
link |
between the two cells, which is kind of a liquidy space,
link |
and they hit some receptors on the post-synaptic cell
link |
and they have some impact.
link |
Sometimes that's not through a regular synapse.
link |
Sometimes it's through a neuromodulator,
link |
like you often talk about on your podcast
link |
that are sort of oozing dopamine, exactly,
link |
oozing into the space between the cells,
link |
and it may be acting at some distance
link |
far from where it was released, right?
link |
But if you don't know where the release is happening
link |
and where other things are that might respond
link |
to that release, you're groping around in the dark.
link |
Well, I love that you are doing this,
link |
and I have to share with the listeners
link |
that the first time I ever met David,
link |
and every time I've ever met with him in person,
link |
at least at his laboratory at Brown,
link |
he was in his office, door closed,
link |
drawing neurons and their connections.
link |
And this is somewhat unusual for somebody
link |
who's a, you know, endowed full professor,
link |
chairman of the department, et cetera, for many years,
link |
to be doing the hands-on work.
link |
Typically that's the stuff that's done by technicians
link |
or graduate students or post-docs,
link |
but I think it's fair to say that you really love
link |
looking at nervous systems and drawing
link |
the accurate renditions of how those nervous systems
link |
are organized and thinking about how they work.
link |
Yeah, it's pure joy for me.
link |
I mean, I'm a very visual person.
link |
My wife is an artist.
link |
We look at a lot of art together.
link |
Just the forms of things are gorgeous in their own right,
link |
but to know that the form is, in a sense, the function,
link |
that the architecture of the connectivity
link |
is how the computation happens in the brain at some level,
link |
even though we don't fully understand that in most contexts,
link |
gives me great joy, because I'm working on something
link |
that's both visually beautiful, but also deeply beautiful
link |
and it's sort of a higher sort of knowledge context.
link |
You know, what is it all about?
link |
Well, as a final question, I get asked very often
link |
about how people should learn about neuroscience
link |
or how they should go about pursuing
link |
maybe an education in neuroscience
link |
if they're at that stage of their life
link |
or that's appropriate for their current trajectory.
link |
Do you have any advice to young people, old people,
link |
and anything in between about how to learn
link |
about the nervous system, maybe in a more formal way?
link |
I mean, obviously we have our podcast.
link |
There are other sources
link |
of neuroscience information out there,
link |
but for the young person who thinks
link |
they want to understand the brain,
link |
they want to learn about the brain,
link |
what should we tell them?
link |
Well, that's a great question.
link |
And there's so many sources out there.
link |
It's almost a question of, you know,
link |
how do you deal with this avalanche
link |
of information out there?
link |
I mean, I think our podcast is a great way
link |
for people to learn more about the nervous system
link |
in an accessible way.
link |
But there's so much stuff out there.
link |
And it's not just that.
link |
I mean, the resources are becoming more and more available
link |
for average folks to participate
link |
in neuroscience research on some level.
link |
There's this famous eye wire project
link |
of Sebastian Sommer.
link |
Oh yeah, maybe tell us about eye wire.
link |
Yeah, so that's connectomics.
link |
And that's a situation where a very clever scientist realized
link |
that the physical work of doing all this reconstruction
link |
of neurons from these electron micrographs,
link |
there's a lot of time involved.
link |
Many, many person hours have to go into that
link |
to come up with the map that you want of where the cells are.
link |
And he was very clever about setting up a context
link |
in which he could crowdsource this.
link |
And people who were interested
link |
in getting a little experience looking at nervous tissue
link |
and participating in a research project
link |
could learn how to do this and do a little bit.
link |
From their living room.
link |
From their living room, their laptop.
link |
We'll put a link to eye wire.
link |
It also is a great bridge
link |
between what we were just talking about, connectomics
link |
and actually participating in research.
link |
And you don't need a graduate mentor or anything like that.
link |
Right, so more of this is coming.
link |
And I'm actually interested in building more of this
link |
so that people who are interested,
link |
wanna participate at some level,
link |
don't necessarily have the time or resources
link |
to get involved in laboratory research
link |
and can get exposed to it
link |
and participate and actually contribute.
link |
So I think that's one thing.
link |
I mean, just asking questions of the people around you
link |
who know a little bit more
link |
and have them point you in the right direction.
link |
Here's a book you might like to read.
link |
There's lots of great popular books out there
link |
that are accessible that will give you some more sense
link |
of the full range of what's out there in the neurosciences
link |
We can put some links to a few of those that we like
link |
on basic neuroscience.
link |
My good friend, Dick Masland,
link |
the late Richard, people will call him Dick,
link |
Dick Masland had a good book.
link |
I forget the title at the moment.
link |
It's sitting behind me somewhere over there on the shelf,
link |
but about vision and how nervous systems work.
link |
A pretty accessible book for the general public.
link |
So that, and there's so many sources out there.
link |
I mean, Wikipedia is a great way.
link |
If you had a particular question about visual function,
link |
I would say, by all means,
link |
head to Wikipedia and get the first look
link |
and follow the references from there
link |
or go to your library or, you know,
link |
there's so many ways to get into it.
link |
It's such an exciting field now.
link |
There's so many, I mean,
link |
any particular realm that's special to you,
link |
your experience, your, you know,
link |
your strengths, your passions,
link |
there's a field of neuroscience devoted to that.
link |
You know, if you've got,
link |
if you know somebody who's got a neurological problem
link |
or a psychiatric problem,
link |
there's a branch of neuroscience that is devoted
link |
to trying to understand that and to solve
link |
these kinds of problems down the line.
link |
So feel the, feel the buzz.
link |
It's an exciting time to get involved.
link |
Great, those are great resources
link |
that people can access from anywhere,
link |
zero cost as you need an internet connection.
link |
But aside from that, we'll put the links to some.
link |
And I'm remembering Dick's book is called
link |
We Know It When We See It.
link |
Right, one of my heroes.
link |
Yeah, a wonderful colleague who unfortunately
link |
we lost a few years ago.
link |
But listen, David, this has been wonderful.
link |
It's been a blast.
link |
We really appreciate you taking the time to do this.
link |
As people probably realize by now,
link |
you're an incredible wealth of knowledge
link |
about the entire nervous system.
link |
Today, we just hit this top contour
link |
of a number of different areas to give a flavor
link |
of the different ways that the nervous system works
link |
and is organized and how that's put together,
link |
how these areas are talking to one another.
link |
What I love about you is that you're
link |
such an incredible educator and I've taught so many students
link |
over the years, but also for me personally as friends,
link |
but also anytime that I want to touch into the beauty
link |
of the nervous system, I rarely lose touch with it.
link |
But anytime I want to touch into it and start thinking
link |
about new problems and ways that the nervous system
link |
is doing things that I hadn't thought about, I call you.
link |
So please forgive me for the calls past, present,
link |
and future, unless you change your number.
link |
And even if you do, I'll be calling.
link |
It's been such a blast, Andy.
link |
This has been a great session
link |
and it's always fun talking to you.
link |
It always gets my brain racing.
link |
Thank you for joining me today
link |
for my discussion with Dr. David Berson.
link |
By now, you should have a much clearer understanding
link |
of how the brain is organized and how it works
link |
to do all the incredible things that it does.
link |
If you're enjoying and or learning from this podcast,
link |
please subscribe to our YouTube channel.
link |
That's a terrific zero cost way to support us.
link |
In addition, please subscribe to our podcast
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link |
And on Apple, you have the opportunity to leave us
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As well, if you'd like to make suggestions
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link |
or future podcast episode guests,
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please put those in the comment section
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Please also check out our sponsors mentioned
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at the beginning of each podcast.
link |
That's the best way to support us.
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And we have a Patreon.
link |
It's patreon.com slash Andrew Huberman.
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There, you can support us at any level that you like.
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While today's discussion did not focus on supplements,
link |
many previous podcast episodes include discussions
link |
about supplements.
link |
And while supplements aren't necessary for everybody,
link |
many people derive benefit from them for things like sleep
link |
or focus or anxiety relief and so on.
link |
One issue with the supplement industry, however,
link |
is that oftentimes the quality
link |
will really vary across brands.
link |
That's why we partnered with Thorne, T-H-O-R-I-N-E,
link |
because Thorne supplements are
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of the absolute highest standards
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in terms of the quality of the ingredients they include
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of the ingredients they include.
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In other words, what's listed on the bottle
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is what's actually found in the bottle,
link |
which is not true of many supplements out there
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that have been tested.
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If you'd like to see the supplements that I take,
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you can go to thorne.com slash the letter U slash Huberman.
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And there you can see the supplements that I take
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and you can get 20% off any of those supplements.
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And if you navigate deeper into the Thorne site
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through that portal,
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thorne.com slash the letter U slash Huberman,
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If you're not already following Huberman Lab
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Both places I regularly post short video posts
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And most of the time that information is not overlapping
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Again, it's just Huberman Lab on Instagram and Twitter.
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And last but not least,
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thank you for your interest in science.