What investigating neural pathways can reveal about mental health Kay M. Tye
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)