English subtitles

← What investigating neural pathways can reveal about mental health

Get Embed Code
31 Languages

Showing Revision 6 created 03/05/2020 by marialadias.

  1. I'm going to start by saying something
    you think you know to be true.
  2. Your brain creates
    all facets of your mind.
  3. So then why do we treat
    mental and physical illnesses
  4. so differently,
  5. if we think we know
    that the mind comes from the brain?
  6. As a neuroscientist, I'm often told
  7. that I'm not allowed to study
    how internal states
  8. like anxiety or craving or loneliness
  9. are represented by the brain,
  10. and so I decided to set out
    and do exactly that.
  11. My research program is designed
    to understand the mind

  12. by investigating brain circuits.
  13. Specifically, how does our brain
    give rise to emotion.
  14. It's really hard to study
    feelings and emotions,
  15. because you can't measure them.
  16. Behavior is still the best and only window
  17. into the emotional experience of another.
  18. For both animals and people,
  19. yes, self-report is a behavioral output.
  20. Motivated behaviors
    fall into two general classes:

  21. seeking pleasure and avoiding pain.
  22. The ability to approach things
    that are good for you
  23. and avoid things that are bad for you
  24. is fundamental to survival.
  25. And in our modern-day society,
  26. trouble telling the difference
    can be labeled as a mental illness.
  27. If I was having car trouble,

  28. and I took my car to the mechanic,
  29. the first thing they do
    is look under the hood.
  30. But with mental health research,
  31. you can't just pop open the hood
    with the press of a button.
  32. So this is why we do
    experiments on animals.
  33. Specifically, in my lab, mice.
  34. To understand the brain, well,
    we need to study brains.
  35. And for the first time, we actually can.
  36. We can pop open the hood.
  37. We can look inside
  38. and do an experiment
    and see what comes out.
  39. Technology has opened new windows
    into the black box that is our minds.

  40. The development of optogenetic tools
  41. has allowed us unprecedented control
    over specific neurons in the brain
  42. and how they talk to each other
    by firing electrical signals.
  43. We can genetically engineer neurons
    to be light sensitive
  44. and then use light to control
    how neurons fire.
  45. This can change an animal's behavior,
  46. giving us insight
    into what that neural circuit can do.
  47. Want to know how scientists
    figure this out?
  48. Scientists developed optogenetic tools
    by borrowing knowledge

  49. from other basic science fields.
  50. Algae are single-celled organisms
    that have evolved to swim towards light.
  51. And when blue light shines
    onto the eyespot of an algae cell,
  52. a channel opens,
    sending an electrical signal
  53. that makes little flagella flap
  54. and propels the algae towards sunlight.
  55. If we clone this light-sensitive
    part of the algae
  56. and then add it to neurons
    through genetic modification,
  57. we can make neurons light-sensitive, too.
  58. Except, with neurons,
  59. when we shine light down
    an optical fiber deep into the brain,
  60. we change how they send electrical signals
    to other neurons in the brain
  61. and thus change the animal's behavior.
  62. With the help of my colleagues,

  63. I pioneered the use of optogenetic tools
  64. to selectively target neurons
    that are living in point A,
  65. sending messages down wires
    aimed at point B,
  66. leaving neighboring neurons
    going other places unaffected.
  67. This approach allowed us to test
    the function of each wire
  68. within the tangled mess that is our brain.
  69. A brain region called the amygdala

  70. has long been thought
    to be important for emotion,
  71. and my laboratory discovered
  72. that the amygdala
    resembles a fork in the road
  73. where activating one path
    can drive positive emotion and approach,
  74. and activating another path
    can drive negative emotion and avoidance.
  75. I'm going to show you
    a couple of examples --

  76. a taste of raw data --
  77. of how we can use optogenetics
    to target specific neurons in the brain
  78. and get very specific changes in behavior.
  79. Anxiety patients
    have abnormal communication
  80. between two parts of the amygdala,
  81. but in people, it's hard to know
    if this abnormality is cause or effect
  82. of the disease.
  83. We can use optogenetics
    to target the same pathway in a mouse,
  84. and see what happens.
  85. So this is the elevated plus maze.

  86. It's a widely used anxiety test
  87. that measures the amount of time
  88. that the mouse spends in the safety
    of the closed arms
  89. relative to exploring the open arms.
  90. Mice have evolved to prefer
    enclosed spaces,
  91. like the safety of their burrows,
  92. but to find food, water, mates,
  93. they need to go out into the open
  94. where they're more vulnerable
    to predatory threats.
  95. So I'm sitting in the background here,
  96. and I'm about to flip the switch.
  97. And now, when I flip the switch
    and turn the light on,
  98. you can see the mouse begins to explore
    the open arms of the maze more.
  99. And in contrast
    to drug treatments for anxiety,
  100. there's no sedation,
    no locomotor impairment,
  101. just coordinated,
    natural-looking exploration.
  102. So not only is the effect
    almost immediate,
  103. but there are no detectable side effects.
  104. Now, when I flip the switch off,

  105. you can see that the mouse goes back
    to its normal brain function
  106. and back to its corner.
  107. When I was in the lab
    and I was taking these data,
  108. I was all by myself, and I was so excited.
  109. I was so excited,
    I did one of these quiet screams.
  110. (Silently) Aah!

  111. (Laughter)

  112. Why was I so excited?

  113. I mean, yeah, theoretically,
    I knew that the brain controlled the mind,
  114. but to flip the switch with my hand
  115. and see the mouse
    change its behavioral state
  116. so rapidly and so reversibly,
  117. it was really the first time
    that I truly believed it.
  118. Since that first breakthrough,

  119. there have been a number
    of other discoveries.
  120. Finding specific neural circuits
    that can elicit dramatic changes
  121. in animal behavior.
  122. Here's another example:
    compulsive overeating.

  123. We can eat for two reasons.
  124. Seeking pleasure, like tasty food,
  125. or avoiding pain, like being hungry.
  126. How can we find a treatment
    for compulsive overeating
  127. without messing up
    the hunger-driven feeding
  128. that we need to survive?
  129. The first step is to understand
  130. how the brain gives rise
    to feeding behavior.
  131. This fully-fed mouse
    is just exploring a space
  132. completely devoid of any food.
  133. Here we're using optogenetics to target
    neurons living in the hypothalamus,
  134. sending messages down wires
    aimed at the midbrain.
  135. When I turn the light on, right here,
  136. you can see that the mouse
    immediately begins licking the floor.
  137. (Laughter)

  138. This seemingly frenzied behavior

  139. is about to escalate into something
    I find really incredible.
  140. It's kind of trippy, actually.
  141. Ready?
  142. It's right here.
  143. See, he picks up his hands
    as if he is eating a piece of food,
  144. but there's nothing there,
    he's not holding anything.
  145. So this circuit is sufficient
    to drive feeding behavior
  146. in the absence of hunger,
  147. even in the absence of food.
  148. I can't know for sure
    how this mouse is feeling,
  149. but I speculate
    these neurons drive craving
  150. based on the behaviors we elicit
    when we target this pathway.
  151. Turn the light back off --
  152. animal's back to normal.
  153. When we silence this pathway,
  154. we can suppress and reduce
    compulsive overeating
  155. without altering hunger-driven feeding.
  156. What did you take away
    from these two videos

  157. that I just showed you?
  158. That making a very specific change
    to neural circuits in the brain
  159. can have specific changes to behavior.
  160. That every conscious
    experience that we have
  161. is governed by cells in our brain.
  162. I am the daughter
    of a physicist and a biologist,

  163. who literally met on the boat
    coming to America
  164. in pursuit of an education.
  165. So naturally,
  166. since there was "no pressure"
    to be a scientist ...
  167. (Laughter)

  168. as a college student,

  169. I had to decide whether I wanted to focus
    on psychology, the study of the mind,
  170. or neuroscience, the study of the brain.
  171. And I chose neuroscience,
  172. because I wanted to understand
    how the mind is born
  173. out of biological tissue.
  174. But really, I've come
    full circle to do both.
  175. And now my research program
  176. bridges the gap between
    the mind and the brain.
  177. Research from my laboratory

  178. suggests that we can begin
    to tie specific neural circuits
  179. to emotional states.
  180. And we have found a number of circuits
  181. that control anxiety-related behavior,
  182. compulsive overeating,
  183. social interaction, avoidance
  184. and many other types
    of motivated behaviors
  185. that may reflect internal
    emotional states.
  186. We used to think of functions of the mind
    as being defined by brain regions.

  187. But my work shows
    that within a given brain region,
  188. there are many different neurons
    doing different things.
  189. And these functions
    are partly defined by the paths they take.
  190. Here's a metaphor to help illustrate

  191. how these discoveries change the way
    that we think about the brain.
  192. Let's say that the brain
    is analogous to the world
  193. and that neurons are analogous to people.
  194. And we want to understand how information
    is transmitted across the planet.
  195. Sure, it's useful to know
  196. where a given person is located
    when recording what they're saying.
  197. But I would argue
    that it's equally important
  198. to know who this person is talking to,
  199. who is listening
  200. and how the people listening respond
    to the information that they receive.
  201. The current state
    of mental health treatment

  202. is essentially a strategy
    of trial and error.
  203. And it is not working.
  204. The development of new drug therapies
    for mental health disorders
  205. has hit a brick wall,
  206. with scarcely any real progress
    since the 1950s.
  207. So what does the future hold?
  208. In the near future,

  209. I expect to see a mental health
    treatment revolution,
  210. where we focus on specific
    neural circuits in the brain.
  211. Diagnoses will be made
    based on both behavioral symptoms
  212. and measurable brain activity.
  213. Further in the future,
  214. by combining our ability
    to make acute changes to the brain
  215. and get acute changes to behavior
  216. with our knowledge of synaptic plasticity
    to make more permanent changes,
  217. we could push the brain
    into a state of fixing itself
  218. by reprogramming neural circuits.
  219. Exposure therapy at the circuit level.
  220. Once we switch the brain
    into a state of self-healing,

  221. this could potentially have
    long-lasting effects
  222. with no side effects.
  223. I can envision a future
    where neural circuit reprogramming
  224. represents a potential cure,
    not just a treatment.
  225. OK, but what about right now?

  226. If from this very moment forward,
  227. each and every one of you left this talk
  228. and truly believed that the mind
    comes entirely from cells in your brain,
  229. then we could immediately get rid
    of negative perceptions and stigmas
  230. that prevent so many people
  231. from getting the mental health
    support that they need.
  232. Mental health professionals,

  233. we're always thinking
    about what's the next new treatment.
  234. But before we can apply new treatments,
  235. we need people to feel
    comfortable seeking them.
  236. Imagine how dramatically
    we could reduce the rates of suicides
  237. and school shootings
  238. if everyone who needed
    mental health support actually got it.
  239. When we truly understand
    exactly how the mind comes from the brain,
  240. we will improve the lives of everyone
  241. who will have a mental illness
    in their lifetime --
  242. half the population --
  243. as well as everyone else
    with whom they share the world.
  244. Thank you.

  245. (Applause)