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

Transcriber: Ivana Korom Reviewer: Krystian Aparta

Translator: sarela betanzos Reviewer: Mario Cal

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

Vou comezar con algo que todos pensades que é verdade:

Your brain creates all facets of your mind.

O cerebro crea todas as facetas da mente.

So then why do we treat mental and physical illnesses

Daquela, por que tratamos enfermidades mentais e físicas

so differently,

de xeito tan diferente,

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

se cremos saber que a mente ven do cerebro?

As a neuroscientist, I'm often told

Como neurocientífica, dinme a miúdo

that I'm not allowed to study how internal states

que non debo estudar de que modo estados internos

like anxiety or craving or loneliness

como a ansiedade, o desexo ou a soidade

are represented by the brain,

son representados polo cerebro,

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

así que eu decidín comezar por aí e facer exactamente iso.

My research program is designed to understand the mind

O meu programa de estudo está deseñado para entender a mente

by investigating brain circuits.

investigando os circuítos do cerebro.

Specifically, how does our brain give rise to emotion.

Concretamente, como o noso cerebro xera emocións.

It's really hard to study feelings and emotions,

É moi difícil estudar sentimentos e emocións,

because you can't measure them.

porque non se poden medir.

Behavior is still the best and only window

O comportamento segue sendo a mellor e única ventá

into the emotional experience of another.

cara á experiencia emocional do outro.

For both animals and people,

Tanto para animais como humanos,

yes, self-report is a behavioral output.

a autoavaliación é un resultado da conduta.

Motivated behaviors fall into two general classes:

Os comportamentos motivados pódense dividir en dúas clases xerais:

seeking pleasure and avoiding pain.

a busca do pracer e a evitación da dor.

The ability to approach things that are good for you

A capacidade de achegarse ás cousas boas

and avoid things that are bad for you

e afastarse daquelas que nos danan

is fundamental to survival.

é crucial para sobrevivir.

And in our modern-day society,

E hoxe en día

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

non ser quen de diferencialas pode considerarse unha enfermidade mental.

If I was having car trouble,

Se eu tivese un problema no coche

and I took my car to the mechanic,

e o levase ao mecánico,

the first thing they do is look under the hood.

a primeira cousa que farían, sería mirar debaixo do capó.

But with mental health research,

Pero na investigación de saúde mental

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

non podemos simplemente abrir o capó pulsando un botón.

So this is why we do experiments on animals.

Por iso facemos experimentos con animais.

Specifically, in my lab, mice.

No meu laboratorio, concretamente, ratos.

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

Para entender o cerebro, obviamente, temos que estudar cerebros.

And for the first time, we actually can.

E por primeira vez. podemos facelo.

We can pop open the hood.

Podemos abrir o capó,

We can look inside

mirar dentro,

and do an experiment and see what comes out.

e facer experimentos e observar que pasa.

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

A tecnoloxía abriunos ventás á caixa negra que é a nosa mente.

The development of optogenetic tools

O desenvolvemento de ferramentas optoxenéticas

has allowed us unprecedented control over specific neurons in the brain

permitiunos un control sen precedentes de neuronas específicas do cerebro

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

e de como se comunican entre elas por medio de sinais eléctricos.

We can genetically engineer neurons to be light sensitive

Podemos deseñar xeneticamente neuronas sensibles á luz

and then use light to control how neurons fire.

e logo usar luz para controlar a emisión de sinais.

This can change an animal's behavior,

Isto pode modificar o comportamento do animal

giving us insight into what that neural circuit can do.

mostrándonos o que fai ese circuíto neuronal.

Want to know how scientists figure this out?

Queredes saber como chegaron a isto os científicos?

Scientists developed optogenetic tools by borrowing knowledge

Desenvolveron as ferramentas optoxenéticas grazas á información

from other basic science fields.

tomada doutros campos básicos da ciencia.

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

As algas son organismos unicelulares que evolucionaron para nadar cara á luz.

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

E cando a luz azul incide sobre o ollo dunha célula de alga

a channel opens, sending an electrical signal

ábrese un canal que envía un sinal eléctrico

that makes little flagella flap

que fai que se movan os flaxelos

and propels the algae towards sunlight.

e que a alga se propulse cara á luz solar

If we clone this light-sensitive part of the algae

Se clonamos esta parte con sensibilidade á luz da alga

and then add it to neurons through genetic modification,

e a engadimos ás neuronas usando modificación xenética,

we can make neurons light-sensitive, too.

podemos facer as neuronas sensibles á luz.

Except, with neurons,

Só que no caso das neuronas,

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

cando iluminamos a través dunha fibra óptica o fondo do cerebro,

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

modificamos o envío de sinais eléctricos entre neuronas

and thus change the animal's behavior.

e, xa que logo, o comportamento do animal.

With the help of my colleagues,

Coa axuda dos meus colegas,

I pioneered the use of optogenetic tools

eu son pioneira no uso de ferramentas optoxenéticas

to selectively target neurons that are living in point A,

que apuntan selectivamente a neuronas dun punto A,

sending messages down wires aimed at point B,

que mandan sinais a un punto B

leaving neighboring neurons going other places unaffected.

deixando as neuronas veciñas inalteradas.

This approach allowed us to test the function of each wire

Isto permítenos examinar a función de cada fío

within the tangled mess that is our brain.

sen perdernos nos enredos do cerebro.

A brain region called the amygdala

Unha parte do cerebro chamada amígdala

has long been thought to be important for emotion,

estivo dende sempre relacionada coas emocións

and my laboratory discovered

e o meu laboratorio descubriu

that the amygdala resembles a fork in the road

que a amígdala aseméllase a unha bifurcación de rúas

where activating one path can drive positive emotion and approach,

onde activando un camiño é posible provocar emocións positivas e achegamento

and activating another path can drive negative emotion and avoidance.

mentres que activando outro é posible provocar emocións negativas e afastamento.

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

Vou mostrarvos un par de exemplos,

a taste of raw data --

con datos sen procesar,

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

de como podemos usar a optoxenética para apuntar a neuronas específicas

and get very specific changes in behavior.

e obter cambios moi significativos no comportamento.

Anxiety patients have abnormal communication

Pacientes con ansiedade teñen comunicacións anómalas

between two parts of the amygdala,

entre dúas partes da amígdala,

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

pero en persoas é difícil discernir se esta anormalidade é causa ou efecto

of the disease.

da enfermidade.

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

Podemos usar a optoxenética para apuntar a esta vía nos ratos,

and see what happens.

e observar que acontece.

So this is the elevated plus maze.

Aquí temos o "labirinto elevado en cruz".

It's a widely used anxiety test

É un test de ansiedade moi empregado

that measures the amount of time

que mide o tempo que o rato

that the mouse spends in the safety of the closed arms

permanece ao abeiro dos brazos pechados

relative to exploring the open arms.

en relación ao tempo que explora os brazos abertos.

Mice have evolved to prefer enclosed spaces,

Os ratos evolucionaron para preferir os espazos pechados,

like the safety of their burrows,

como a seguridade dos seus tobos,

but to find food, water, mates,

pero para obter comida, auga, aparearse,

they need to go out into the open

necesitan saír ao espazo aberto,

where they're more vulnerable to predatory threats.

onde son máis vulnerables ás ameazas de depredadores.

So I'm sitting in the background here,

Eu estou sentada detrás,

and I'm about to flip the switch.

e vou prender o interruptor.

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

E agora, cando lle dou á chave e acendo a luz,

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

podedes ver como o rato explora máis os brazos abertos.

And in contrast to drug treatments for anxiety,

E a diferenza dos tratamentos médicos para a ansiedade,

there's no sedation, no locomotor impairment,

non hai sedación ou torpeza motriz,

just coordinated, natural-looking exploration.

tan só exploración normal e coordinada.

So not only is the effect almost immediate,

Polo tanto, amais de ter efecto inmediato

but there are no detectable side effects.

non se observan efectos secundarios.

Now, when I flip the switch off,

Agora, se apago o interruptor,

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

podedes ver como o rato volve ao seu estado mental normal

and back to its corner.

e retorna á esquina.

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

Cando estaba no laboratorio, recopilando estes resultados,

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

estaba soa e moi emocionada.

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

Tan emocionada que botei un grito silencioso.

(Silently) Aah!

(Silencio) Ah!

(Laughter)

(Risas)

Why was I so excited?

Por que estaba tan feliz?

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

Obviamente, eu sabía que, en teoría, o cerebro controlaba a mente,

but to flip the switch with my hand

pero ao darlle eu mesma ao interruptor

and see the mouse change its behavioral state

e ver como o rato cambia o seu comportamento

so rapidly and so reversibly,

de xeito tan rápido e reversible,

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

foi cando de verdade o crin.

Since that first breakthrough,

Dende ese primeiro avance,

there have been a number of other discoveries.

houbo varios descubrimentos máis,

Finding specific neural circuits that can elicit dramatic changes

buscando circuítos neuronais específicos que poidan provocar cambios

in animal behavior.

na conduta animal.

Here's another example: compulsive overeating.

Póñovos outro exemplo: comer compulsivamente.

We can eat for two reasons.

Podemos comer por dous motivos:

Seeking pleasure, like tasty food,

Buscar o pracer, como a comida gustosa,

or avoiding pain, like being hungry.

ou evitar a dor, como ter fame.

How can we find a treatment for compulsive overeating

Como atopar un tratamento para o comer compulsivo

without messing up the hunger-driven feeding

sen danar o instinto de comer por fame,

that we need to survive?

que necesitamos para sobrevivir?

The first step is to understand

O primeiro paso é entender

how the brain gives rise to feeding behavior.

como o cerebro xera a conduta de alimentación.

This fully-fed mouse is just exploring a space

Este rato farto explora un lugar

completely devoid of any food.

baleiro de todo de comida.

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

Aquí, usamos a optoxenética para apuntar a neuronas do hipotálamo,

sending messages down wires aimed at the midbrain.

que envían sinais cara ao mesencéfalo.

When I turn the light on, right here,

Cando prendo a luz, xusto agora,

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

podedes ver como o rato comeza decontado a lamber o chan.

(Laughter)

(Risas)

This seemingly frenzied behavior

Este comportamento aparentemente frenético

is about to escalate into something I find really incredible.

está a piques de pasar a algo que me parece impresionante.

It's kind of trippy, actually.

De feito, é algo delirante.

Ready?

Listos?

It's right here.

Aquí o tedes.

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

Mirade, colle coas súas patas como se tivese unha peza de comida

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

pero non hai nada, non ten nada nas mans.

So this circuit is sufficient to drive feeding behavior

Así, este circuíto acciona a conduta alimentaria

in the absence of hunger,

en ausencia de fame,

even in the absence of food.

mesmo en ausencia de comida.

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

Non podo saber exactamente como se sente este rato

but I speculate these neurons drive craving

pero especulo que estas neuronas accionan as ansias de comer

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

baseándome nos comportamentos que xeran cando apuntamos a esta vía.

Turn the light back off --

Apagamos as luces,

animal's back to normal.

o animal volve á normalidade.

When we silence this pathway,

Cando silenciamos esta vía

we can suppress and reduce compulsive overeating

podemos eliminar e reducir o comer compulsivo

without altering hunger-driven feeding.

sen alterar a alimentación por fame.

What did you take away from these two videos

Que se deduce destes dous vídeos

that I just showed you?

que vos acabo de ensinar?

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

Que facer un cambio moi específico en vías neuronais do cerebro

can have specific changes to behavior.

pode xerar cambios específicos na conduta.

That every conscious experience that we have

Que cada experiencia consciente que temos

is governed by cells in our brain.

está dirixida por células no noso cerebro.

I am the daughter of a physicist and a biologist,

Eu son filla dun físico e unha bióloga,

who literally met on the boat coming to America

que se coñeceron no barco de camiño aos EE. UU.

in pursuit of an education.

buscando unha educación.

So naturally,

Así que,

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

"sen presión ningunha" para ser científica...

(Laughter)

(Risas)

as a college student,

como universitaria,

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

tiven que elixir se centrarme en psicoloxía, o estudo da mente

or neuroscience, the study of the brain.

ou neurociencia, o estudo do cerebro.

And I chose neuroscience,

E escollín neurociencia,

because I wanted to understand how the mind is born

porque quería entender como a mente nace

out of biological tissue.

de tecido biolóxico.

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

Pero a verdade, rematei facendo as dúas.

And now my research program

Agora o meu programa de pescuda

bridges the gap between the mind and the brain.

salva a fenda entre a mente e o cerebro.

Research from my laboratory

Pescudas do meu laboratorio

suggests that we can begin to tie specific neural circuits

suxiren que podemos comezar a asociar vías neuronais concretas

to emotional states.

a estados emocionais.

And we have found a number of circuits

E atopamos varios circuítos

that control anxiety-related behavior,

que controlan condutas ansiosas,

compulsive overeating,

comer compulsivamente,

social interaction, avoidance

interacción social, evitación

and many other types of motivated behaviors

e outras moitas condutas dirixidas

that may reflect internal emotional states.

que quizais reflictan estados emocionais.

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

Adoitabamos crer en funcións da mente definidas por rexións cerebrais.

But my work shows that within a given brain region,

Pero o meu traballo mostra que nunha zona cerebral

there are many different neurons doing different things.

hai moitas neuronas diferentes facendo cousas diferentes.

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

E estas funcións están definidas en parte polas vías que toman.

Here's a metaphor to help illustrate

Vouvos mostrar cunha metáfora

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

como estes descubrimentos cambian o xeito no que pensamos sobre o cerebro.

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

Supoñamos que o cerebro é unha analoxía do mundo

and that neurons are analogous to people.

e que as neuronas son persoas.

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

E queremos entender como a información se transmite dun lado a outro do planeta.

Sure, it's useful to know

Por suposto, é útil saber

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

onde está unha determinada persoa cando gravamos o que está dicindo

But I would argue that it's equally important

Pero eu diría que é igualmente importante

to know who this person is talking to,

saber a quen lle fala esta persoa,

who is listening

quen escoita

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

e como as persoas que escoitan responden á información que reciben.

The current state of mental health treatment

Actualmente o tratamento na saúde mental

is essentially a strategy of trial and error.

baséase nunha estratexia de ensaio e erro.

And it is not working.

E non funciona.

The development of new drug therapies for mental health disorders

O desenvolvemento de novos fármacos para trastornos de saúde mental

has hit a brick wall,

topou cun muro,

with scarcely any real progress since the 1950s.

con escaso progreso real dende os anos 50.

So what does the future hold?

Daquela, que nos depara o futuro?

In the near future,

Nun futuro próximo,

I expect to see a mental health treatment revolution,

eu espero ver unha revolución no tratamento de saúde mental

where we focus on specific neural circuits in the brain.

onde nos centremos en vías específicas do cerebro.

Diagnoses will be made based on both behavioral symptoms

As diagnoses faranse tanto en base a síntomas comportamentais

and measurable brain activity.

como á actividade cerebral medible.

Further in the future,

Máis adiante,

by combining our ability to make acute changes to the brain

combinando a nosa capacidade para provocar cambios profundos no cerebro

and get acute changes to behavior

e obter cambios no comportamento,

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

co que sabemos da plasticidade sináptica para provocar cambios máis permanentes,

we could push the brain into a state of fixing itself

poderiamos forzar o cerebro a arranxarse el mesmo

by reprogramming neural circuits.

reprogramando circuítos neuronais.

Exposure therapy at the circuit level.

Terapia de exposición a nivel das vías.

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

Unha vez que tornamos o cerebro a un estado de autocuración,

this could potentially have long-lasting effects

isto podería ter resultados a longo prazo

with no side effects.

sen efectos secundarios.

I can envision a future where neural circuit reprogramming

Podo visualizar un futuro no cal a reprogramación de vías neuronais

represents a potential cure, not just a treatment.

represente unha cura potencial, non tan só un tratamento.

OK, but what about right now?

Ben, pero que temos agora?

If from this very moment forward,

Se de aquí en diante,

each and every one of you left this talk

cada un de vós marcha desta charla

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

convencido de que a mente procede enteiramente do cerebro,

then we could immediately get rid of negative perceptions and stigmas

entón poderiamos deixar atrás percepcións negativas e estigmas

that prevent so many people

que impiden que moita xente

from getting the mental health support that they need.

obteña a axuda en saúde mental que precisan.

Mental health professionals,

Os profesionais da saúde mental

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

sempre pensamos no próximo tratamento.

But before we can apply new treatments,

Pero antes de que poidamos usar novos tratamentos

we need people to feel comfortable seeking them.

necesitamos que a xente se sinta cómoda pedíndoos.

Imagine how dramatically we could reduce the rates of suicides

Imaxinade canto poderiamos reducir as cifras de suicidios

and school shootings

e tiroteos nas escolas

if everyone who needed mental health support actually got it.

se todos os que necesitasen atención de saúde mental a obtivesen.

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

Cando comprendamos exactamente como a mente vén do cerebro,

we will improve the lives of everyone

poderemos mellorar a vida de todos aqueles

who will have a mental illness in their lifetime --

que terán un trastorno mental na súa vida

half the population --

--a metade da poboación--

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

así como a de todos aqueles cos que comparten o mundo.

Thank you.

Grazas.

(Applause)

(Aplausos)