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  • Transcriber: Ivana Korom Reviewer: Krystian Aparta

  • I'm going to start by saying something you think you know to be true.

  • Your brain creates all facets of your mind.

  • So then why do we treat mental and physical illnesses

  • so differently,

  • if we think we know that the mind comes from the brain?

  • As a neuroscientist, I'm often told

  • that I'm not allowed to study how internal states

  • like anxiety or craving or loneliness

  • are represented by the brain,

  • and so I decided to set out and do exactly that.

  • My research program is designed to understand the mind

  • by investigating brain circuits.

  • Specifically, how does our brain give rise to emotion.

  • It's really hard to study feelings and emotions,

  • because you can't measure them.

  • Behavior is still the best and only window

  • into the emotional experience of another.

  • For both animals and people,

  • yes, self-report is a behavioral output.

  • Motivated behaviors fall into two general classes:

  • seeking pleasure and avoiding pain.

  • The ability to approach things that are good for you

  • and avoid things that are bad for you

  • is fundamental to survival.

  • And in our modern-day society,

  • trouble telling the difference can be labeled as a mental illness.

  • If I was having car trouble,

  • and I took my car to the mechanic,

  • the first thing they do is look under the hood.

  • But with mental health research,

  • you can't just pop open the hood with the press of a button.

  • So this is why we do experiments on animals.

  • Specifically, in my lab, mice.

  • To understand the brain, well, we need to study brains.

  • And for the first time, we actually can.

  • We can pop open the hood.

  • We can look inside

  • and do an experiment and see what comes out.

  • Technology has opened new windows into the black box that is our minds.

  • The development of optogenetic tools

  • has allowed us unprecedented control over specific neurons in the brain

  • and how they talk to each other by firing electrical signals.

  • We can genetically engineer neurons to be light sensitive

  • and then use light to control how neurons fire.

  • This can change an animal's behavior,

  • giving us insight into what that neural circuit can do.

  • Want to know how scientists figure this out?

  • Scientists developed optogenetic tools by borrowing knowledge

  • from other basic science fields.

  • Algae are single-celled organisms that have evolved to swim towards light.

  • And when blue light shines onto the eyespot of an algae cell,

  • a channel opens, sending an electrical signal

  • that makes little flagella flap

  • and propels the algae towards sunlight.

  • If we clone this light-sensitive part of the algae

  • and then add it to neurons through genetic modification,

  • we can make neurons light-sensitive, too.

  • Except, with neurons,

  • when we shine light down an optical fiber deep into the brain,

  • we change how they send electrical signals to other neurons in the brain

  • and thus change the animal's behavior.

  • With the help of my colleagues,

  • I pioneered the use of optogenetic tools

  • to selectively target neurons that are living in point A,

  • sending messages down wires aimed at point B,

  • leaving neighboring neurons going other places unaffected.

  • This approach allowed us to test the function of each wire

  • within the tangled mess that is our brain.

  • A brain region called the amygdala

  • has long been thought to be important for emotion,

  • and my laboratory discovered

  • that the amygdala resembles a fork in the road

  • where activating one path can drive positive emotion and approach,

  • and activating another path can drive negative emotion and avoidance.

  • I'm going to show you a couple of examples --

  • a taste of raw data --

  • of how we can use optogenetics to target specific neurons in the brain

  • and get very specific changes in behavior.

  • Anxiety patients have abnormal communication

  • between two parts of the amygdala,

  • but in people, it's hard to know if this abnormality is cause or effect

  • of the disease.

  • We can use optogenetics to target the same pathway in a mouse,

  • and see what happens.

  • So this is the elevated plus maze.

  • It's a widely used anxiety test

  • that measures the amount of time

  • that the mouse spends in the safety of the closed arms

  • relative to exploring the open arms.

  • Mice have evolved to prefer enclosed spaces,

  • like the safety of their burrows,

  • but to find food, water, mates,

  • they need to go out into the open

  • where they're more vulnerable to predatory threats.

  • So I'm sitting in the background here,

  • and I'm about to flip the switch.

  • And now, when I flip the switch and turn the light on,

  • you can see the mouse begins to explore the open arms of the maze more.

  • And in contrast to drug treatments for anxiety,

  • there's no sedation, no locomotor impairment,

  • just coordinated, natural-looking exploration.

  • So not only is the effect almost immediate,

  • but there are no detectable side effects.

  • Now, when I flip the switch off,

  • you can see that the mouse goes back to its normal brain function

  • and back to its corner.

  • When I was in the lab and I was taking these data,

  • I was all by myself, and I was so excited.

  • I was so excited, I did one of these quiet screams.

  • (Silently) Aah!

  • (Laughter)

  • Why was I so excited?

  • I mean, yeah, theoretically, I knew that the brain controlled the mind,

  • but to flip the switch with my hand

  • and see the mouse change its behavioral state

  • so rapidly and so reversibly,

  • it was really the first time that I truly believed it.

  • Since that first breakthrough,

  • there have been a number of other discoveries.

  • Finding specific neural circuits that can elicit dramatic changes

  • in animal behavior.

  • Here's another example: compulsive overeating.

  • We can eat for two reasons.

  • Seeking pleasure, like tasty food,

  • or avoiding pain, like being hungry.

  • How can we find a treatment for compulsive overeating

  • without messing up the hunger-driven feeding

  • that we need to survive?

  • The first step is to understand

  • how the brain gives rise to feeding behavior.

  • This fully-fed mouse is just exploring a space

  • completely devoid of any food.

  • Here we're using optogenetics to target neurons living in the hypothalamus,

  • sending messages down wires aimed at the midbrain.

  • When I turn the light on, right here,

  • you can see that the mouse immediately begins licking the floor.

  • (Laughter)

  • This seemingly frenzied behavior

  • is about to escalate into something I find really incredible.

  • It's kind of trippy, actually.

  • Ready?

  • It's right here.

  • See, he picks up his hands as if he is eating a piece of food,

  • but there's nothing there, he's not holding anything.

  • So this circuit is sufficient to drive feeding behavior

  • in the absence of hunger,

  • even in the absence of food.

  • I can't know for sure how this mouse is feeling,

  • but I speculate these neurons drive craving

  • based on the behaviors we elicit when we target this pathway.

  • Turn the light back off --

  • animal's back to normal.

  • When we silence this pathway,

  • we can suppress and reduce compulsive overeating

  • without altering hunger-driven feeding.

  • What did you take away from these two videos

  • that I just showed you?

  • That making a very specific change to neural circuits in the brain

  • can have specific changes to behavior.

  • That every conscious experience that we have

  • is governed by cells in our brain.

  • I am the daughter of a physicist and a biologist,

  • who literally met on the boat coming to America

  • in pursuit of an education.

  • So naturally,

  • since there was "no pressure" to be a scientist ...

  • (Laughter)

  • as a college student,

  • I had to decide whether I wanted to focus on psychology, the study of the mind,

  • or neuroscience, the study of the brain.

  • And I chose neuroscience,

  • because I wanted to understand how the mind is born

  • out of biological tissue.

  • But really, I've come full circle to do both.

  • And now my research program

  • bridges the gap between the mind and the brain.

  • Research from my laboratory

  • suggests that we can begin to tie specific neural circuits

  • to emotional states.

  • And we have found a number of circuits

  • that control anxiety-related behavior,

  • compulsive overeating,

  • social interaction, avoidance

  • and many other types of motivated behaviors

  • that may reflect internal emotional states.

  • We used to think of functions of the mind as being defined by brain regions.

  • But my work shows that within a given brain region,

  • there are many different neurons doing different things.

  • And these functions are partly defined by the paths they take.

  • Here's a metaphor to help illustrate

  • how these discoveries change the way that we think about the brain.

  • Let's say that the brain is analogous to the world

  • and that neurons are analogous to people.

  • And we want to understand how information is transmitted across the planet.

  • Sure, it's useful to know

  • where a given person is located when recording what they're saying.

  • But I would argue that it's equally important

  • to know who this person is talking to,

  • who is listening

  • and how the people listening respond to the information that they receive.

  • The current state of mental health treatment

  • is essentially a strategy of trial and error.

  • And it is not working.

  • The development of new drug therapies for mental health disorders

  • has hit a brick wall,

  • with scarcely any real progress since the 1950s.

  • So what does the future hold?

  • In the near future,

  • I expect to see a mental health treatment revolution,

  • where we focus on specific neural circuits in the brain.

  • Diagnoses will be made based on both behavioral symptoms

  • and measurable brain activity.

  • Further in the future,

  • by combining our ability to make acute changes to the brain

  • and get acute changes to behavior

  • with our knowledge of synaptic plasticity to make more permanent changes,

  • we could push the brain into a state of fixing itself

  • by reprogramming neural circuits.

  • Exposure therapy at the circuit level.

  • Once we switch the brain into a state of self-healing,

  • this could potentially have long-lasting effects

  • with no side effects.

  • I can envision a future where neural circuit reprogramming

  • represents a potential cure, not just a treatment.

  • OK, but what about right now?

  • If from this very moment forward,

  • each and every one of you left this talk

  • and truly believed that the mind comes entirely from cells in your brain,

  • then we could immediately get rid of negative perceptions and stigmas

  • that prevent so many people

  • from getting the mental health support that they need.

  • Mental health professionals,

  • we're always thinking about what's the next new treatment.

  • But before we can apply new treatments,

  • we need people to feel comfortable seeking them.

  • Imagine how dramatically we could reduce the rates of suicides

  • and school shootings

  • if everyone who needed mental health support actually got it.

  • When we truly understand exactly how the mind comes from the brain,

  • we will improve the lives of everyone

  • who will have a mental illness in their lifetime --

  • half the population --

  • as well as everyone else with whom they share the world.

  • Thank you.

  • (Applause)

Transcriber: Ivana Korom Reviewer: Krystian Aparta

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神経経路を調べることで、メンタルヘルスについて何がわかるのか|ケイ・M・タイ (What investigating neural pathways can reveal about mental health | Kay M. Tye)

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    林宜悉 に公開 2021 年 01 月 14 日
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