David Anderson: Your brain is more than a bag of chemicals

164,113 views ใƒป 2013-03-12

TED


ืื ื ืœื—ืฅ ืคืขืžื™ื™ื ืขืœ ื”ื›ืชื•ื‘ื™ื•ืช ื‘ืื ื’ืœื™ืช ืœืžื˜ื” ื›ื“ื™ ืœื”ืคืขื™ืœ ืืช ื”ืกืจื˜ื•ืŸ.

00:00
Translator: Joseph Geni Reviewer: Morton Bast
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ืžืชืจื’ื: Zeeva Livshitz ืžื‘ืงืจ: Or Hazan
00:15
So raise your hand if you know someone
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ืชืจื™ืžื• ืืช ื™ื“ื›ื ืื ืืชื ืžื›ื™ืจื™ื ืžื™ืฉื”ื•
00:19
in your immediate family or circle of friends
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ื‘ืžืฉืคื—ื” ื”ืงืจื•ื‘ื” ืื• ื‘ืžืขื’ืœ ื”ื—ื‘ืจื™ื ืฉืœื›ื
00:21
who suffers from some form of mental illness.
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ืฉืกื•ื‘ืœ ืžืžื—ืœืช ื ืคืฉ ื›ืœืฉื”ื™.
00:25
Yeah. I thought so. Not surprised.
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ื›ืŸ. ื›ืš ื—ืฉื‘ืชื™. ืœื ืžืชืคืœื.
00:28
And raise your hand if you think that
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ื•ื”ืจื™ืžื• ืืช ื™ื“ื›ื ืื ืืชื ื—ื•ืฉื‘ื™ื
00:30
basic research on fruit flies has anything to do
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ืฉืœืžื—ืงืจ ื‘ืกื™ืกื™ ืขืœ ื–ื‘ื•ื‘ื™ ืคื™ืจื•ืช ื™ืฉ ืงืฉืจ ื›ืœืฉื”ื•
00:33
with understanding mental illness in humans.
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ืœื”ื‘ื ื” ืฉืœ ืžื—ืœื•ืช ื ืคืฉ ืืฆืœ ื‘ื ื™ ืื“ื.
00:37
Yeah. I thought so. I'm also not surprised.
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ื›ืŸ. ื›ืš ื—ืฉื‘ืชื™. ืื ื™ ื’ื ืœื ืžื•ืคืชืข.
00:40
I can see I've got my work cut out for me here.
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ืื ื™ ื™ื›ื•ืœ ืœืจืื•ืช ืฉืžืฆืคื” ืœื™ ื›ืืŸ ืขื‘ื•ื“ื” ืจื‘ื”.
00:43
As we heard from Dr. Insel this morning,
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ื›ืคื™ ืฉืฉืžืขื ื• ืžื“"ืจ ืื™ื ืกืœ ื”ื‘ื•ืงืจ,
00:46
psychiatric disorders like autism, depression and schizophrenia
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ื”ืคืจืขื•ืช ืคืกื™ื›ื™ืื˜ืจื™ื•ืช ื›ืžื• ืื•ื˜ื™ื–ื, ื“ื™ื›ืื•ืŸ ื•ืกื›ื™ื–ื•ืคืจื ื™ื”
00:50
take a terrible toll on human suffering.
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ื’ื•ืจืžื™ื ืœืกื‘ืœ ืื ื•ืฉื™ ื ื•ืจื.
00:53
We know much less about their treatment
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ืื ื—ื ื• ื™ื•ื“ืขื™ื ื”ืจื‘ื” ืคื—ื•ืช ืขืœ ื”ื˜ื™ืคื•ืœ ื‘ื”ื
00:56
and the understanding of their basic mechanisms
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ื•ื”ื”ื‘ื ื” ืฉืœ ื”ืžื ื’ื ื•ื ื™ื ื”ื‘ืกื™ืกื™ื™ื ืฉืœื”ื
00:59
than we do about diseases of the body.
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ืžืžื” ืฉืื ื• ื™ื•ื“ืขื™ื ืขืœ ืžื—ืœื•ืช ืฉืœ ื”ื’ื•ืฃ.
01:01
Think about it: In 2013,
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ื—ืฉื‘ื• ืขืœ ื–ื”: ื‘-2013,
01:04
the second decade of the millennium,
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ื”ืขืฉื•ืจ ื”ืฉื ื™ ืฉืœ ื”ืžื™ืœื ื™ื•ื,
01:06
if you're concerned about a cancer diagnosis
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ืื ืืชื ืžื•ื“ืื’ื™ื ืœื’ื‘ื™ ืื‘ื—ื•ืŸ ืกืจื˜ืŸ
01:08
and you go to your doctor, you get bone scans,
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ืืชื ื”ื•ืœื›ื™ื ืœืจื•ืคื, ืขื•ืฉื™ื ืœื›ื ืกืจื™ืงื•ืช ืขืฆื,
01:11
biopsies and blood tests.
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ื‘ื™ื•ืคืกื™ื•ืช ื•ื‘ื“ื™ืงื•ืช ื“ื.
01:14
In 2013, if you're concerned about a depression diagnosis,
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ื‘-2013, ืื ืืชื ืžื•ื“ืื’ื™ื ืœื’ื‘ื™ ืื‘ื—ื•ืŸ ื“ื™ื›ืื•ืŸ,
01:18
you go to your doctor, and what do you get?
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ืืชื ื”ื•ืœื›ื™ื ืœืจื•ืคื, ื•ืžื” ืืชื ืžืงื‘ืœื™ื?
01:20
A questionnaire.
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ืฉืืœื•ืŸ.
01:22
Now, part of the reason for this is that we have
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ืขื›ืฉื™ื•, ื—ืœืง ืžื”ืกื™ื‘ื” ืœื›ืš ื”ื™ื ืฉื™ืฉ ืœื ื•
01:24
an oversimplified and increasingly outmoded view
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ื”ืฉืงืคื” ืคืฉื˜ื ื™ืช ื•ืžื™ื•ืฉื ืช
01:28
of the biological basis of psychiatric disorders.
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ืขืœ ื”ื‘ืกื™ืก ื”ื‘ื™ื•ืœื•ื’ื™ ืฉืœ ื”ืคืจืขื•ืช ืคืกื™ื›ื™ืื˜ืจื™ื•ืช.
01:32
We tend to view them --
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ืื ื• ื ื•ื˜ื™ื ืœืจืื•ืช ืื•ืชืŸ -
01:33
and the popular press aids and abets this view --
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ื•ื”ืชืงืฉื•ืจืช ืชื•ืจืžืช ืœืชืคื™ืกื” ื–ื• -
01:36
as chemical imbalances in the brain,
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ื›ื—ื•ืกืจ ืื™ื–ื•ืŸ ื›ื™ืžื™ ื‘ืžื•ื—,
01:39
as if the brain were some kind of bag of chemical soup
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ื›ืื™ืœื• ื”ืžื•ื— ื”ื•ื ืฉืงื™ืช ืฉืœ ืžืจืง ื›ื™ืžื™
01:42
full of dopamine, serotonin and norepinephrine.
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ืžืœื ื‘ื“ื•ืคืžื™ืŸ, ืกืจื•ื˜ื•ื ื™ืŸ, ื•ื ื•ืจืื“ืจื ืœื™ืŸ.
01:47
This view is conditioned by the fact
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ื”ืฉืงืคื” ื–ื• ืžื•ืชื ื™ืช ื‘ืขื•ื‘ื“ื”
01:49
that many of the drugs that are prescribed to treat these disorders,
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ืฉืจื‘ื•ืช ืžื”ืชืจื•ืคื•ืช ื”ื ื™ืชื ื•ืช ืœื˜ื™ืคื•ืœ ื‘ื”ืคืจืขื•ืช ืืœื”,
01:52
like Prozac, act by globally changing brain chemistry,
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ื›ืžื• ืคืจื•ื–ืง, ืคื•ืขืœื•ืช ืข"ื™ ืฉื™ื ื•ื™ ื”ื›ื™ืžื™ื” ื‘ืžื•ื— ื‘ืื•ืคืŸ ื’ืœื•ื‘ืœื™,
01:57
as if the brain were indeed a bag of chemical soup.
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ื›ืื™ืœื• ื”ืžื•ื— ืื›ืŸ ื”ื™ื ื• ืฉืงื™ืช ืฉืœ ืžืจืง ื›ื™ืžื™.
02:01
But that can't be the answer,
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ืื‘ืœ ื–ื• ืœื ื™ื›ื•ืœื” ืœื”ื™ื•ืช ื”ืชืฉื•ื‘ื”,
02:03
because these drugs actually don't work all that well.
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ื›ื™ ืชืจื•ืคื•ืช ืืœื• ืื™ื ืŸ ืคื•ืขืœื•ืช ื›ืœ ื›ืš ื˜ื•ื‘.
02:06
A lot of people won't take them, or stop taking them,
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ื”ืจื‘ื” ืื ืฉื™ื ืœื ื ื•ื˜ืœื™ื ืื•ืชืŸ, ืื• ืžืคืกื™ืงื™ื ืœืงื—ืช ืื•ืชืŸ,
02:09
because of their unpleasant side effects.
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ื‘ื’ืœืœ ืชื•ืคืขื•ืช ื”ืœื•ื•ืื™ ื”ื‘ืœืชื™ ื ืขื™ืžื•ืช ืฉืœื”ืŸ.
02:12
These drugs have so many side effects
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ืœืชืจื•ืคื•ืช ืืœื• ื™ืฉ ื›ืœ ื›ืš ื”ืจื‘ื” ืชื•ืคืขื•ืช ืœื•ื•ืื™
02:14
because using them to treat a complex psychiatric disorder
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ืžืคื ื™ ืฉื”ืฉื™ืžื•ืฉ ื‘ื”ืŸ ืœื˜ื™ืคื•ืœ ื‘ื”ืคืจืขื” ื ืคืฉื™ืช ืžื•ืจื›ื‘ืช
02:18
is a bit like trying to change your engine oil
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ื“ื•ืžื” ืœื ืกื™ื•ืŸ ืœื”ื—ืœื™ืฃ ืืช ืฉืžืŸ ื”ืžื ื•ืข ืฉืœื›ื
02:21
by opening a can and pouring it all over the engine block.
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ืขืœ-ื™ื“ื™ ืคืชื™ื—ืช ืคื—ื™ืช ื•ืฉืคื™ื›ืชื” ืขืœ ื›ืœ ืžืขืจื›ืช ื”ืžื ื•ืข.
02:25
Some of it will dribble into the right place,
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ื—ืœืง ืžืžื ื” ื™ื˜ืคื˜ืฃ ืœืชื•ืš ื”ืžืงื•ื ื”ื ื›ื•ืŸ,
02:27
but a lot of it will do more harm than good.
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ืื‘ืœ ื”ืจื‘ื” ืžื–ื” ื™ื’ืจื•ื ืœื™ื•ืชืจ ื ื–ืง ืžืชื•ืขืœืช.
02:30
Now, an emerging view
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ื›ืขืช, ื”ืฉืงืคื” ื—ื“ืฉื”
02:32
that you also heard about from Dr. Insel this morning,
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ืฉื’ื ืขืœื™ื” ืฉืžืขืชื ื”ื‘ื•ืงืจ ืžืคื™ ื“"ืจ ืื™ื ืกืœ,
02:35
is that psychiatric disorders are actually
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ื”ื™ื ืฉื”ืคืจืขื•ืช ืคืกื™ื›ื™ืื˜ืจื™ื•ืช ื”ืŸ ืœืžืขืฉื”
02:38
disturbances of neural circuits that mediate
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ื”ืคืจืขื•ืช ืฉืœ ื”ืžืขื’ืœื™ื ื”ืขืฆื‘ื™ื™ื ืฉืžืชื•ื•ื›ื™ื
02:41
emotion, mood and affect.
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ืจื’ืฉ, ืžืฆื‘ ืจื•ื— ื•ืจื’ืฉื•ืช.
02:45
When we think about cognition,
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ื›ืืฉืจ ืื ื• ื—ื•ืฉื‘ื™ื ืขืœ ื—ืฉื™ื‘ื”,
02:47
we analogize the brain to a computer. That's no problem.
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ืื ื• ืžืฉื•ื•ื™ื ืืช ื”ืžื•ื— ืœืžื—ืฉื‘. ื–ื• ืื™ื ื” ื‘ืขื™ื”.
02:50
Well it turns out that the computer analogy
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ื•ื‘ื›ืŸ ืžืกืชื‘ืจ ืฉืื ืœื•ื’ื™ื™ืช ื”ืžื—ืฉื‘
02:53
is just as valid for emotion.
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ืชืงืคื” ื‘ืื•ืชื” ืžื™ื“ื” ืœืจื’ืฉื•ืช.
02:55
It's just that we don't tend to think about it that way.
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ืื‘ืœ ืื™ื ื ื• ื ื•ื˜ื™ื ืœื—ืฉื•ื‘ ืขืœ ื–ื” ื›ืš.
02:58
But we know much less about the circuit basis
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ืื‘ืœ ืื ื—ื ื• ื™ื•ื“ืขื™ื ื”ืจื‘ื” ืคื—ื•ืช ืขืœ ื”ืžืกืœื•ืœื™ื ื”ืขืฆื‘ื™ื™ื
03:01
of psychiatric disorders
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ืฉืœ ื”ืคืจืขื•ืช ืคืกื™ื›ื™ืื˜ืจื™ื•ืช
03:03
because of the overwhelming dominance
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ื‘ื’ืœืœ ื”ื“ื•ืžื™ื ื ื˜ื™ื•ืช ื”ืžื•ื—ืฆืช
03:05
of this chemical imbalance hypothesis.
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ืฉืœ ื”ื”ืฉืขืจื” ืขืœ ื—ื•ืกืจ ืื™ื–ื•ืŸ ื›ื™ืžื™.
03:09
Now, it's not that chemicals are not important
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ื›ืขืช, ื–ื” ืœื ืฉื›ื™ืžื™ืงืœื™ื ืื™ื ื ื—ืฉื•ื‘ื™ื
03:12
in psychiatric disorders.
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ื‘ื”ืคืจืขื•ืช ืคืกื™ื›ื™ืื˜ืจื™ื•ืช.
03:14
It's just that they don't bathe the brain like soup.
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ืื‘ืœ ื”ื ืœื ืžืฆื™ืคื™ื ืืช ื”ืžื•ื— ื›ืžื• ืžืจืง.
03:18
Rather, they're released in very specific locations
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ืืœื ื”ื ืžืฉืชื—ืจืจื™ื ื‘ืžื™ืงื•ืžื™ื ืกืคืฆื™ืคื™ื™ื ืžืื•ื“
03:22
and they act on specific synapses
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ื•ืคื•ืขืœื™ื ืขืœ ืกื™ื ืคืกื•ืช (ืžื™ืกื ืคื™ื) ืกืคืฆื™ืคื™ื•ืช
03:24
to change the flow of information in the brain.
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ื›ื“ื™ ืœืฉื ื•ืช ืืช ื–ืจื™ืžืช ื”ืžื™ื“ืข ื‘ืžื•ื—.
03:28
So if we ever really want to understand
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ืื– ืื ืื ื—ื ื• ื‘ืืžืช ืจื•ืฆื™ื ืื™ ืคืขื ืœื”ื‘ื™ืŸ
03:30
the biological basis of psychiatric disorders,
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ืืช ื”ื‘ืกื™ืก ื”ื‘ื™ื•ืœื•ื’ื™ ืฉืœ ื”ืคืจืขื•ืช ืคืกื™ื›ื™ืื˜ืจื™ื•ืช,
03:33
we need to pinpoint these locations in the brain
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ืื ื—ื ื• ืฆืจื™ื›ื™ื ืœืืชืจ ืžื™ืงื•ืžื™ื ืืœื” ื‘ืžื•ื—
03:36
where these chemicals act.
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ื”ื™ื›ืŸ ืฉื›ื™ืžื™ืงืœื™ื ืืœื” ืคื•ืขืœื™ื.
03:38
Otherwise, we're going to keep pouring oil all over our mental engines
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ืื—ืจืช, ื ืžืฉื™ืš ืœืฉืคื•ืš ืฉืžืŸ ืขืœ ื›ืœ ืžื ื•ืขื™ ื”ื ืคืฉ ืฉืœื ื•
03:41
and suffering the consequences.
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ื•ืœืกื‘ื•ืœ ืžืŸ ื”ื”ืฉืœื›ื•ืช.
03:44
Now to begin to overcome our ignorance
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ื›ื“ื™ ืœื”ืชื—ื™ืœ ืœื”ืชื’ื‘ืจ ืขืœ ื”ื‘ื•ืจื•ืช ืฉืœื ื•
03:47
of the role of brain chemistry in brain circuitry,
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ืœื’ื‘ื™ ืชืคืงื™ื“ ื›ื™ืžื™ื™ืช ื”ืžื•ื— ื‘ืžืขื’ืœื™ ื”ืžื•ื—,
03:51
it's helpful to work on what we biologists call
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ื›ื“ืื™ ืœืขื‘ื•ื“ ืขืœ ืžื” ืฉืื ื—ื ื• ื”ื‘ื™ื•ืœื•ื’ื™ื ืงื•ืจืื™ื ืœื•
03:54
"model organisms,"
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"ืื•ืจื’ื ื™ื–ื ืžื•ื“ืœ,"
03:55
animals like fruit flies and laboratory mice,
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ื‘ืขืœื™ ื—ื™ื™ื ื›ืžื• ื–ื‘ื•ื‘ื™ ืคื™ืจื•ืช ื•ืขื›ื‘ืจื™ ืžืขื‘ื“ื”,
03:58
in which we can apply powerful genetic techniques
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ืฉื‘ื”ื ื ื•ื›ืœ ืœื™ื™ืฉื ื˜ื›ื ื™ืงื•ืช ื’ื ื˜ื™ื•ืช ื—ื–ืงื•ืช
04:02
to molecularly identify and pinpoint
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ื›ื“ื™ ืœื–ื”ื•ืช ืžื‘ื—ื™ื ื” ืžื•ืœืงื•ืœืจื™ืช ื•ืœืืชืจ ื‘ืžื“ื•ื™ืง
04:06
specific classes of neurons,
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ืกื•ื’ื™ื ืกืคืฆื™ืคื™ื™ื ืฉืœ ื ื•ื™ืจื•ื ื™ื,
04:07
as you heard about in Allan Jones's talk this morning.
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ื›ืคื™ ืฉืฉืžืขืชื ื‘ืฉื™ื—ืชื• ืฉืœ ืืœืŸ ื’'ื•ื ืก ื”ื‘ื•ืงืจ.
04:10
Moreover, once we can do that,
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ื™ืชืจ ืขืœ ื›ืŸ, ื‘ืจื’ืข ืฉื ื•ื›ืœ ืœืขืฉื•ืช ื–ืืช,
04:12
we can actually activate specific neurons
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ื ื•ื›ืœ ืœื”ืคืขื™ืœ ื ื•ื™ืจื•ื ื™ื ืกืคืฆื™ืคื™ื™ื
04:15
or we can destroy or inhibit the activity of those neurons.
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ืื• ืœื”ืจื•ืก ืื• ืœืขื›ื‘ ืืช ืคืขื™ืœื•ืชื ืฉืœ ื ื•ื™ืจื•ื ื™ื ืืœื”.
04:19
So if we inhibit a particular type of neuron,
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ืื– ืื ืื ื—ื ื• ืžืขื›ื‘ื™ื ืกื•ื’ ืžืกื•ื™ื ืฉืœ ื ื•ื™ืจื•ืŸ,
04:22
and we find that a behavior is blocked,
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ื•ืื ื• ืžื•ืฆืื™ื ืฉื”ืชื ื”ื’ื•ืช ื ื—ืกืžืช,
04:25
we can conclude that those neurons
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ืื ื• ื™ื›ื•ืœื™ื ืœื”ืกื™ืง ืฉื ื•ื™ืจื•ื ื™ื ืืœื”
04:27
are necessary for that behavior.
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ื ื—ื•ืฆื™ื ืขื‘ื•ืจ ื”ืชื ื”ื’ื•ืช ื–ื•.
04:30
On the other hand, if we activate a group of neurons
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ืœืขื•ืžืช ื–ืืช, ืื ืื ื• ืžืคืขื™ืœื™ื ืงื‘ื•ืฆื” ืฉืœ ื ื•ื™ืจื•ื ื™ื
04:32
and we find that that produces the behavior,
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ื•ืžื•ืฆืื™ื ืฉื”ื™ื ืžื™ื™ืฆืจืช ืืช ื”ื”ืชื ื”ื’ื•ืช,
04:35
we can conclude that those neurons are sufficient for the behavior.
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ื ื•ื›ืœ ืœื”ืกื™ืง ื›ื™ ื ื•ื™ืจื•ื ื™ื ืืœื” ืžืกืคื™ืงื™ื ืœื”ืชื ื”ื’ื•ืช.
04:39
So in this way, by doing this kind of test,
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ืื– ื‘ื“ืจืš ื–ื•, ืขืœ ื™ื“ื™ ื‘ื“ื™ืงื” ื›ื–ื•,
04:42
we can draw cause and effect relationships
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ืื ื• ื™ื›ื•ืœื™ื ืœื”ืกื™ืง ืงืฉืจื™ ืกื™ื‘ื” ื•ืชื•ืฆืื”
04:46
between the activity of specific neurons
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ื‘ื™ืŸ ื”ืคืขื™ืœื•ืช ืฉืœ ื ื•ื™ืจื•ื ื™ื ืกืคืฆื™ืคื™ื™ื
04:48
in particular circuits and particular behaviors,
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ื‘ืžืขื’ืœื™ื ืžืกื•ื™ืžื™ื ืœื‘ื™ืŸ ื”ืชื ื”ื’ื•ื™ื•ืช ืžืกื•ื™ืžื•ืช,
04:51
something that is extremely difficult, if not impossible,
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ื“ื‘ืจ ืฉื”ื•ื ืžืื•ื“ ืงืฉื”, ืื ืœื ื‘ืœืชื™ ืืคืฉืจื™,
04:53
to do right now in humans.
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ืœืขืฉื•ืชื• ืขื›ืฉื™ื• ื‘ื‘ื ื™ ืื“ื.
04:58
But can an organism like a fruit fly, which is --
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ืืš ื”ืื ื™ืฉ ื‘ืืคืฉืจื•ืชื• ืฉืœ ืื•ืจื’ื ื™ื–ื ื›ืžื• ื–ื‘ื•ื‘ ื”ืคื™ืจื•ืช --
05:01
it's a great model organism
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ื”ื•ื ืื•ืจื’ื ื™ื–ื ืžื•ื“ืœ ื ื”ื“ืจ
05:03
because it's got a small brain,
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ืžืฉื•ื ืฉื™ืฉ ืœื• ืžื•ื— ืงื˜ืŸ,
05:06
it's capable of complex and sophisticated behaviors,
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ื”ื•ื ืžืกื•ื’ืœ ืœื”ืชื ื”ื’ื•ื™ื•ืช ืžื•ืจื›ื‘ื•ืช ื•ืžืชื•ื—ื›ืžื•ืช,
05:10
it breeds quickly, and it's cheap.
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ื”ื•ื ืžืชืจื‘ื” ื‘ืžื”ื™ืจื•ืช, ื•ื”ื•ื ื–ื•ืœ.
05:13
But can an organism like this
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ืืš ื”ืื ืื•ืจื’ื ื™ื–ื ื›ืžื• ื–ื”
05:15
teach us anything about emotion-like states?
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ื™ื›ื•ืœ ืœืœืžื“ ืื•ืชื ื• ืžืฉื”ื• ืขืœ ืžืฆื‘ื™ื ื“ืžื•ื™ื™ ืจื’ืฉ?
05:18
Do these organisms even have emotion-like states,
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ื”ืื ื‘ื›ืœืœ ื™ืฉ ืœืื•ืจื’ื ื™ื–ืžื™ื ืืœื” ืžืฆื‘ื™ื ื“ืžื•ื™ื™-ืจื’ืฉ,
05:22
or are they just little digital robots?
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ืื• ืฉื”ื ืจืง ืจื•ื‘ื•ื˜ื™ื ื“ื™ื’ื™ื˜ืœื™ื™ื ืงื˜ื ื™ื?
05:25
Charles Darwin believed that insects have emotion
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ืฆ'ืืจืœืก ื“ืจื•ื•ื™ืŸ ื”ืืžื™ืŸ ืฉืœื—ืจืงื™ื ื™ืฉ ืจื’ืฉ
05:28
and express them in their behaviors, as he wrote
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ื•ื”ื ืžื‘ื˜ืื™ื ืื•ืชื• ื‘ื”ืชื ื”ื’ื•ืช ืฉืœื”ื, ื›ืคื™ ืฉื”ื•ื ื›ืชื‘
05:31
in his 1872 monograph on the expression of the emotions in man and animals.
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ื‘ืžื•ื ื•ื’ืจืคื™ื” ืฉืœื• ื‘- 1872 ืขืœ ื”ื‘ืขืช ื”ืจื’ืฉื•ืช ื‘ืื“ื ื•ื‘ื‘ืขืœื™ ื—ื™ื™ื.
05:36
And my eponymous colleague, Seymour Benzer, believed it as well.
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ื•ืขืžื™ืชื™ ื”ืืคื•ื ื™ืžื™, ืกื™ืžื•ืจ ื‘ื ื–ืจ ื”ืืžื™ืŸ ื‘ื–ืืช ื’ื ื›ืŸ.
05:40
Seymour is the man that introduced the use of drosophila
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ืกื™ืžื•ืจ ื”ื•ื ื”ืื™ืฉ ืืฉืจ ื”ืฆื™ื’ ืœืจืืฉื•ื ื” ืืช ื”ืฉื™ืžื•ืฉ ื‘ื“ืจื•ื–ื•ืคื™ืœื” (ื–ื‘ื•ื‘ ื”ืคื™ืจื•ืช)
05:43
here at CalTech in the '60s as a model organism
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ื›ืืŸ ื‘ืงืืœื˜ืง ื‘ืฉื ื•ืช ื”ืฉื™ืฉื™ื ื›ืื•ืจื’ื ื™ื–ื ืžื•ื“ืœ
05:47
to study the connection between genes and behavior.
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ืœื—ืงืจ ื”ื—ื™ื‘ื•ืจ ื‘ื™ืŸ ื’ื ื™ื ืœื‘ื™ืŸ ื”ืชื ื”ื’ื•ืช.
05:50
Seymour recruited me to CalTech in the late 1980s.
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ืกื™ืžื•ืจ ื’ื™ื™ืก ืื•ืชื™ ืœืงืืœื˜ืง ื‘ืฉืœื”ื™ ืฉื ื•ืช ื”ืฉืžื•ื ื™ื.
05:54
He was my Jedi and my rabbi while he was here,
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ื”ื•ื ื”ื™ื” ื”ื’'ื“ื™ื™ ื•ื”ืจื‘ ืฉืœื™ ื‘ื–ืžืŸ ืฉื”ื•ื ื”ื™ื” ื›ืืŸ,
05:58
and Seymour taught me both to love flies
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ืกื™ืžื•ืจ ืœื™ืžื“ ืื•ืชื™ ื’ื ืœืื”ื•ื‘ ื–ื‘ื•ื‘ื™ื
06:01
and also to play with science.
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ื•ื’ื ืœืฉื—ืง ืขื ืžื“ืข.
06:04
So how do we ask this question?
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ืื– ืื™ืš ืฉื•ืืœื™ื ืฉืืœื” ื–ื•?
06:07
It's one thing to believe that flies have emotion-like states,
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ื–ื” ื“ื‘ืจ ืื—ื“ ืœื”ืืžื™ืŸ ืฉื™ืฉ ืœื–ื‘ื•ื‘ื™ื ืžืฆื‘ื™ื ื“ืžื•ื™ื™-ืจื’ืฉ,
06:11
but how do we actually find out whether that's true or not?
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ืืš ื›ื™ืฆื“ ืื ื• ืžื‘ืจืจื™ื ืื ื–ื” ื ื›ื•ืŸ ืื• ืœื?
06:14
Now, in humans we often infer emotional states,
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ืืฆืœ ื‘ื ื™ ืื“ื ืื ื• ืœืขืชื™ื ืžืกื™ืงื™ื ืฉื™ืฉ ืžืฆื‘ื™ื ืจื’ืฉื™ื™ื,
06:18
as you'll hear later today, from facial expressions.
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ื›ืคื™ ืฉืชืฉืžืขื• ืžืื•ื—ืจ ื™ื•ืชืจ ื”ื™ื•ื, ืžื”ื‘ืขื•ืช ืคื ื™ื.
06:22
However, it's a little difficult to do that in fruit flies.
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ืื‘ืœ ื–ื” ืงืฆืช ืงืฉื” ืœืขืฉื•ืช ื–ืืช ื‘ื–ื‘ื•ื‘ื™ ืคื™ืจื•ืช.
06:26
(Laughter)
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(ืฆื—ื•ืง)
06:29
It's kind of like landing on Mars
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ื–ื” ื›ืžื• ืœื ื—ื•ืช ืขืœ ืžืื“ื™ื
06:32
and looking out the window of your spaceship
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ื•ืœื”ื‘ื™ื˜ ืžื”ื—ืœื•ืŸ ืฉืœ ื”ื—ืœืœื™ืช ืฉืœื›ื
06:35
at all the little green men who are surrounding it
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ืขืœ ื›ืœ ื”ื™ืฆื•ืจื™ื ื”ืงื˜ื ื™ื ื”ื™ืจื•ืงื™ื ืฉืžืงื™ืคื™ื ืื•ืชื”
06:37
and trying to figure out, "How do I find out
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ื•ืœื ืกื•ืช ืœื”ื‘ื™ืŸ "ื›ื™ืฆื“ ื ื™ืชืŸ ืœื‘ืจืจ
06:40
if they have emotions or not?"
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ืื ื™ืฉ ืœื”ื ืจื’ืฉื•ืช ืื• ืœื?"
06:42
What can we do? It's not so easy.
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ืžื” ืืคืฉืจ ืœืขืฉื•ืช? ื–ื” ืœื ืงืœ ื›ืœ ื›ืš.
06:45
Well, one of the ways that we can start
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ื•ื‘ื›ืŸ, ืื—ืช ื”ื“ืจื›ื™ื ืฉื‘ื”ืŸ ื ื•ื›ืœ ืœื”ืชื—ื™ืœ
06:48
is to try to come up with some general characteristics
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ื”ื™ื ืœื ืกื•ืช ืœื—ืฉื•ื‘ ืขืœ ื›ืžื” ืžืืคื™ื™ื ื™ื ื›ืœืœื™ื™ื
06:52
or properties of emotion-like states
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ืื• ืชื›ื•ื ื•ืช ืฉืœ ืžืฆื‘ื™ื ื“ืžื•ื™ื™-ืจื’ืฉ
06:56
such as arousal, and see if we can identify
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ื›ื’ื•ืŸ ืขื•ืจืจื•ืช, ื•ืœืจืื•ืช ืื ืื ื—ื ื• ื™ื›ื•ืœื™ื ืœื–ื”ื•ืช
06:59
any fly behaviors that might exhibit some of those properties.
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ื›ืœ ื”ืชื ื”ื’ื•ืช ื–ื‘ื•ื‘ื™ืช ืฉืžืฆื™ื’ื” ื›ืžื” ืžืชื›ื•ื ื•ืช ืืœื”.
07:04
So three important ones that I can think of
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ืื– ืฉืœื•ืฉื” ื—ืฉื•ื‘ื™ื ืฉืื ื™ ื™ื›ื•ืœ ืœื—ืฉื•ื‘ ืขืœื™ื”ื
07:07
are persistence, gradations in intensity, and valence.
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ื”ื ื”ืชืžื“ื”, ื”ื“ืจื’ืชื™ื•ืช ื‘ืขื•ืฆืžื”, ื•ืขืจื›ื™ื•ืช.
07:12
Persistence means long-lasting.
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ื”ืชืžื“ื” ืคื™ืจื•ืฉื” ืœื˜ื•ื•ื— ืืจื•ืš.
07:14
We all know that the stimulus that triggers an emotion
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ื›ื•ืœื ื• ื™ื•ื“ืขื™ื ืฉื”ื’ื™ืจื•ื™ ืฉืžืขื•ืจืจ ืจื’ืฉ
07:18
causes that emotion to last long after the stimulus is gone.
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ื’ื•ืจื ืœืจื’ืฉ ืœื”ื™ืžืฉืš ื–ืžืŸ ืจื‘ ืœืื—ืจ ืฉื”ื’ื™ืจื•ื™ ื ืขืœื.
07:23
Gradations of intensity means what it sounds like.
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ื”ื“ืจื’ืชื™ื•ืช ื‘ืขื•ืฆืžื” ืคื™ืจื•ืฉื” ื”ื•ื ื›ืžื• ืฉื—ื•ืฉื‘ื™ื.
07:26
You can dial up the intensity or dial down the intensity of an emotion.
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ืืคืฉืจ ืœื”ื’ื‘ื™ืจ ืื• ืœื”ื—ืœื™ืฉ ืืช ืขื•ืฆืžืช ื”ืจื’ืฉ.
07:31
If you're a little bit unhappy, the corners of your mouth
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ืื ืืชื ืงืฆืช ืขืฆื•ื‘ื™ื, ื–ื•ื•ื™ื•ืช ื”ืคื” ืฉืœื›ื
07:33
turn down and you sniffle,
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ื ื•ื˜ื•ืช ืžื˜ื” ื•ืืชื ืžืื ืคืคื™ื,
07:35
and if you're very unhappy, tears pour down your face
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ืื ืืชื ืžืื•ื“ ืื•ืžืœืœื™ื, ื“ืžืขื•ืช ื–ื•ืœื’ื•ืช ืขืœ ืœื—ื™ื™ื›ื
07:38
and you might sob.
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ื•ืืชื ืขืœื•ืœื™ื ืœื™ื™ื‘ื‘.
07:40
Valence means good or bad, positive or negative.
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ืขืจื›ื™ื•ืช ืคื™ืจื•ืฉื” ื˜ื•ื‘ ืื• ืจืข, ื—ื™ื•ื‘ื™ ืื• ืฉืœื™ืœื™.
07:44
So we decided to see if flies could be provoked into showing
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ืื– ื”ื—ืœื˜ื ื• ืœื‘ื“ื•ืง ืื ื ื™ืชืŸ ืœื’ืจื•ืช ื–ื‘ื•ื‘ื™ื ืœื”ืฆื™ื’
07:49
the kind of behavior that you see
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ื”ืชื ื”ื’ื•ืช ืฉืจื•ืื™ื
07:51
by the proverbial wasp at the picnic table,
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ืืฆืœ ื”ืฆืจืขื” ืฉืžืกืชื•ื‘ื‘ืช ืœื™ื“ ืฉื•ืœื—ืŸ ื”ืคื™ืงื ื™ืง,
07:54
you know, the one that keeps coming back to your hamburger
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ืืชื ื™ื•ื“ืขื™ื, ื–ื• ืฉืชืžื™ื“ ื—ื•ื–ืจืช ืœื”ืžื‘ื•ืจื’ืจ ืฉืœื›ื
07:57
the more vigorously you try to swat it away,
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ื›ื›ืœ ืฉืชื ืกื• ื™ื•ืชืจ ืœื ืคื ืฃ ืื•ืชื” ืžืฉื ื‘ื ืžืจืฆื•ืช,
07:59
and it seems to keep getting irritated.
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ื•ื”ื™ื ื ื“ืžื™ืช ื›ืžืจื•ื’ื–ืช ืžื›ืš.
08:02
So we built a device, which we call a puff-o-mat,
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ืื– ื‘ื ื™ื ื• ืžืชืงืŸ, ืฉืื ื• ืžื›ื ื™ื ื ืฉื™ืคื•ืžื˜,
08:05
in which we could deliver little brief air puffs to fruit flies
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ืฉื‘ื• ื ื•ื›ืœ ืœื”ืขื‘ื™ืจ ื ืฉื™ืคื•ืช ืื•ื•ื™ืจ ืงื˜ื ื•ืช ืœื–ื‘ื•ื‘ื™ ืคื™ืจื•ืช
08:10
in these plastic tubes in our laboratory bench
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ื‘ืฆื™ื ื•ืจื•ืช ืคืœืกื˜ื™ืง ืืœื” ืขืœ ืฉื•ืœื—ืŸ ื”ืžืขื‘ื“ื” ืฉืœื ื•
08:12
and blow them away.
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ื•ืœื”ืขื™ืฃ ืื•ืชื.
08:14
And what we found is that if we gave these flies
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ืžืฆืื ื• ืฉืื ื ืชื ื• ืœื–ื‘ื•ื‘ื™ื ืืœื”
08:17
in the puff-o-mat several puffs in a row,
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ื‘ื ืฉื™ืคื•ืžื˜ ืžืกืคืจ ื ืฉื™ืคื•ืช ื‘ื–ื• ืื—ืจ ื–ื•,
08:20
they became somewhat hyperactive
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ื”ื ื ืขืฉื• ืžืขื˜ ื”ื™ืคืจืืงื˜ื™ื‘ื™ื™ื
08:23
and continued to run around for some time after the air puffs actually stopped
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ื•ื”ืžืฉื™ื›ื• ืœื”ืชืจื•ืฆืฅ ื’ื ืœืื—ืจ ืฉื”ื ืฉื™ืคื•ืช ื”ืคืกื™ืงื•
08:27
and took a while to calm down.
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ื•ืœืงื— ืœื”ื ื–ืžืŸ ืžื” ื›ื“ื™ ืœื”ื™ืจื’ืข.
08:30
So we quantified this behavior
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ืื– ื›ื™ืžืชื ื• ื”ืชื ื”ื’ื•ืช ื–ื•
08:32
using custom locomotor tracking software
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ื‘ืืžืฆืขื•ืช ืชื•ื›ื ืช ืžืขืงื‘ ืชื ื•ืขืชื™ืช
08:35
developed with my collaborator Pietro Perona,
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ืฉืคื•ืชื—ื” ืขื ืฉื•ืชืคื™ ืœืžื—ืงืจ ืคื™ื™ื˜ืจื• ืคืจื•ื ื”,
08:38
who's in the electrical engineering division here at CalTech.
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ืฉื”ื•ื ื‘ื—ื˜ื™ื‘ืช ื”ื ื“ืกืช ื—ืฉืžืœ ื›ืืŸ ื‘ืงืืœื˜ืง.
08:42
And what this quantification showed us is that,
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ื•ืžื” ืฉื›ื™ืžื•ืช ื–ื” ื”ืจืื” ืœื ื• ื”ื•ื
08:45
upon experiencing a train of these air puffs,
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ืฉืœืื—ืจ ืกื“ืจืช ื ืฉื™ืคื•ืช ืื•ื•ื™ืจ ืืœื•,
08:48
the flies appear to enter a kind of state of hyperactivity
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ื ืจืื” ืฉื”ื–ื‘ื•ื‘ื™ื ื ื›ื ืกื™ื ืœืžืขื™ืŸ ืžืฆื‘ ืฉืœ ื”ื™ืคืจืืงื˜ื™ื‘ื™ื•ืช
08:52
which is persistent, long-lasting,
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ืฉื”ื•ื ืžืชืžื™ื“, ืืจื•ืš ื˜ื•ื•ื—,
08:55
and also appears to be graded.
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ื•ื’ื ื ืจืื” ืฉื”ื•ื ืžื“ื•ืจื’,
08:57
More puffs, or more intense puffs,
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ื™ื•ืชืจ ื ืฉื™ืคื•ืช, ืื• ื ืฉื™ืคื•ืช ื™ื•ืชืจ ื—ื–ืงื•ืช,
09:00
make the state last for a longer period of time.
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ื’ื•ืจืžื•ืช ืœืžืฆื‘ ืœื”ื™ืžืฉืš ื™ื•ืชืจ ื–ืžืŸ.
09:04
So now we wanted to try to understand something
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ืื– ืจืฆื™ื ื• ืœื ืกื•ืช ืœื”ื‘ื™ืŸ
09:06
about what controls the duration of this state.
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ืžื” ืžืฉืคื™ืข ืขืœ ืžืฉืš ื”ื–ืžืŸ ืฉืœ ืžืฆื‘ ื–ื”.
09:10
So we decided to use our puff-o-mat
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ืื– ื”ื—ืœื˜ื ื• ืœื”ืฉืชืžืฉ ื‘ื ืฉื™ืคื•ืžื˜ ืฉืœื ื•
09:13
and our automated tracking software
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ื•ื‘ืชื•ื›ื ืช ื”ืžืขืงื‘ ื”ืื•ื˜ื•ืžื˜ื™ืช ืฉืœื ื•
09:15
to screen through hundreds of lines of mutant fruit flies
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ื›ื“ื™ ืœื‘ื—ื•ืŸ ืžืื•ืช ืกื•ื’ื™ื ืฉืœ ื–ื‘ื•ื‘ื™ ืคื™ืจื•ืช ืžื•ื˜ื ื˜ื™ื
09:19
to see if we could find any that showed abnormal responses to the air puffs.
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ื›ื“ื™ ืœื—ืคืฉ ื›ืืœื” ืฉื”ืจืื• ืชื’ื•ื‘ื•ืช ื—ืจื™ื’ื•ืช ืœื ืฉื™ืคื•ืช ื”ืื•ื•ื™ืจ.
09:24
And this is one of the great things about fruit flies.
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ื•ื–ื” ืื—ื“ ื”ื“ื‘ืจื™ื ื”ื˜ื•ื‘ื™ื ื‘ื–ื‘ื•ื‘ื™ ืคื™ืจื•ืช.
09:26
There are repositories where you can just pick up the phone
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ืืคืฉืจ ืคืฉื•ื˜ ืœื”ืชืงืฉืจ
09:29
and order hundreds of vials of flies of different mutants
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ื•ืœื”ื–ืžื™ืŸ ืžืื•ืช ืžื‘ื—ื ื•ืช ืฉืœ ื–ื‘ื•ื‘ื™ื ืžืžื•ื˜ืฆื™ื•ืช ืฉื•ื ื•ืช
09:32
and screen them in your assay and then find out
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ืœื‘ื“ื•ืง ืื•ืชื ื•ืื– ืœื’ืœื•ืช
09:35
what gene is affected in the mutation.
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ืื™ื–ื” ื’ืŸ ืžืขื•ืจื‘ ื‘ืžื•ื˜ืฆื™ื”.
09:38
So doing the screen, we discovered one mutant
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ื•ื›ืš ื‘ืžื”ืœืš ื”ื‘ื“ื™ืงื” ื’ื™ืœื™ื ื• ืžื•ื˜ื ื˜
09:41
that took much longer than normal to calm down
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ืฉื“ืจืฉ ื”ืจื‘ื” ื™ื•ืชืจ ื–ืžืŸ ืžื”ืจื’ื™ืœ ื›ื“ื™ ืœื”ื™ืจื’ืข
09:45
after the air puffs,
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ืœืื—ืจ ื ืฉื™ืคื•ืช ื”ืื•ื•ื™ืจ,
09:47
and when we examined the gene that was affected in this mutation,
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ื•ื›ืืฉืจ ื‘ื—ื ื• ืืช ื”ื’ืŸ ืฉื”ื™ื” ืžืขื•ืจื‘ ื‘ืžื•ื˜ืฆื™ื” ื–ื•,
09:51
it turned out to encode a dopamine receptor.
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ื”ืชื‘ืจืจ ืฉื”ื•ื ืžืงื•ื“ื“ ืงื•ืœื˜ืŸ ื“ื•ืคืžื™ืŸ.
09:55
That's right -- flies, like people, have dopamine,
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ื ื›ื•ืŸ - ืœื–ื‘ื•ื‘ื™ื, ื›ืžื• ืœืื ืฉื™ื, ื™ืฉ ื“ื•ืคืžื™ืŸ,
09:58
and it acts on their brains and on their synapses
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ื•ื”ื•ื ืคื•ืขืœ ืขืœ ืžื•ื—ื, ื•ืขืœ ื”ืกื™ื ืคืกื•ืช ืฉืœื”ื
10:00
through the same dopamine receptor molecules
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ื‘ืืžืฆืขื•ืช ืื•ืชืŸ ืžื•ืœืงื•ืœื•ืช ืฉืœ ืงื•ืœื˜ื ื™ ื“ื•ืคืžื™ืŸ
10:03
that you and I have.
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ืฉื™ืฉ ืœื›ื ื•ืœื™.
10:05
Dopamine plays a number of important functions in the brain,
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ื“ื•ืคืžื™ืŸ ืžืžืœื ืžืกืคืจ ืชืคืงื™ื“ื™ื ื—ืฉื•ื‘ื™ื ื‘ืžื•ื—,
10:09
including in attention, arousal, reward,
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ืœืจื‘ื•ืช ืงืฉื‘, ืขื•ืจืจื•ืช, ืชื’ืžื•ืœ,
10:12
and disorders of the dopamine system have been linked
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ื•ื”ืคืจืขื•ืช ืฉืœ ืžืขืจื›ืช ื”ื“ื•ืคืžื™ืŸ ื ืงืฉืจื•
10:15
to a number of mental disorders including drug abuse,
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ืœืžืกืคืจ ื”ืคืจืขื•ืช ื ืคืฉื™ื•ืช ื›ื•ืœืœ ื”ืชืžื›ืจื•ืช ืœืกืžื™ื,
10:19
Parkinson's disease, and ADHD.
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ืžื—ืœืช ืคืจืงื™ื ืกื•ืŸ, ื•-ADHD (ื”ืคืจืขืช ืงืฉื‘ ื•ืจื™ื›ื•ื–).
10:23
Now, in genetics, it's a little counterintuitive.
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ื›ืขืช, ื‘ื’ื ื˜ื™ืงื”, ื–ื” ืงืฆืช ืžื ื•ื’ื“ ืœืื™ื ื˜ื•ืื™ืฆื™ื”.
10:26
We tend to infer the normal function of something
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ืื ื• ื ื•ื˜ื™ื ืœื”ืกื™ืง ืืช ื”ืชืคืงื•ื“ ื”ืชืงื™ืŸ ืฉืœ ืžืฉื”ื•
10:29
by what doesn't happen when we take it away,
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ืขืœ-ื™ื“ื™ ืžื” ืฉืœื ืงื•ืจื” ื›ืฉืžื•ืฆื™ืื™ื ืื•ืชื•,
10:33
by the opposite of what we see when we take it away.
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ืขืœ-ื™ื“ื™ ื”ื”ื™ืคืš ืžืžื” ืฉืจื•ืื™ื ื›ืฉืžื•ืฆื™ืื™ื ืื•ืชื•.
10:36
So when we take away the dopamine receptor
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ืœื›ืŸ, ื›ืฉืžื•ืฆื™ืื™ื ืงื•ืœื˜ืŸ ื“ื•ืคืžื™ืŸ
10:39
and the flies take longer to calm down,
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ื•ืœื–ื‘ื•ื‘ื™ื ืœื•ืงื— ื–ืžืŸ ืจื‘ ื™ื•ืชืจ ื›ื“ื™ ืœื”ื™ืจื’ืข,
10:41
from that we infer that the normal function of this receptor and dopamine
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ืื ื• ืžืกื™ืงื™ื ืฉืชืคืงื•ื“ ืชืงื™ืŸ ืฉืœ ืงื•ืœื˜ืŸ ื–ื” ื•ื“ื•ืคืžื™ืŸ
10:45
is to cause the flies to calm down faster after the puff.
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ื”ื•ื ืœื’ืจื•ื ืœื–ื‘ื•ื‘ื™ื ืœื”ื™ืจื’ืข ืžื”ืจ ื™ื•ืชืจ ืœืื—ืจ ื”ื ืฉื™ืคื”.
10:49
And that's a bit reminiscent of ADHD,
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ื•ื–ื” ืžื–ื›ื™ืจ ืงืฆืช ADHD,
10:52
which has been linked to disorders of the dopamine system in humans.
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ืฉื ืงืฉืจ ืœื”ืคืจืขื•ืช ื‘ืžืขืจื›ืช ื”ื“ื•ืคืžื™ืŸ ื‘ื‘ื ื™ ืื“ื.
10:56
Indeed, if we increase the levels of dopamine in normal flies
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ื•ืื›ืŸ, ืื ื ื’ื“ื™ืœ ืืช ืจืžื•ืช ื”ื“ื•ืคืžื™ืŸ ื‘ื–ื‘ื•ื‘ื™ื ืจื’ื™ืœื™ื
11:01
by feeding them cocaine
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ืขืœ ื™ื“ื™ ื”ืื›ืœืชื ื‘ืงื•ืงืื™ืŸ,
11:03
after getting the appropriate DEA license
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ืœืื—ืจ ืงื‘ืœืช ื”ืจืฉื™ื•ืŸ ื”ืžืชืื™ื ืžื”ื™ื—ื™ื“ื” ืœืœื•ื—ืžื” ื‘ืกืžื™ื,
11:06
โ€” oh my God -- (Laughter) โ€”
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โ€” ื”ื• ืืœื•ื”ื™ื-- (ืฆื—ื•ืง) โ€”
11:10
we find indeed that these cocaine-fed flies
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ืื ื• ืื›ืŸ ืžื•ืฆืื™ื ืฉื–ื‘ื•ื‘ื™ื ืฉืงื™ื‘ืœื• ืงื•ืงืื™ืŸ
11:13
calm down faster than normal flies do,
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ื ืจื’ืขื™ื ืžื”ืจ ื™ื•ืชืจ ืžื”ืจื’ื™ืœ,
11:16
and that's also reminiscent of ADHD,
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ื•ื–ื” ื’ื ืžื–ื›ื™ืจ ADHD,
11:19
which is often treated with drugs like Ritalin
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ืืฉืจ ืœืขืชื™ื ืงืจื•ื‘ื•ืช ืžื˜ื•ืคืœ ื‘ืชืจื•ืคื•ืช ื›ืžื• ืจื™ื˜ืœื™ืŸ
11:21
that act similarly to cocaine.
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ืฉืคื•ืขืœื•ืช ื‘ื“ื•ืžื” ืœืงื•ืงืื™ืŸ.
11:24
So slowly I began to realize that what started out
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ืื– ื”ืชื—ืœืชื™ ืœื”ื‘ื™ืŸ ืฉืžื” ืฉื”ืชื—ื™ืœ
11:27
as a rather playful attempt to try to annoy fruit flies
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ื›ื ื™ืกื™ื•ืŸ ืฉื•ื‘ื‘ ืœื”ืจื’ื™ื– ื–ื‘ื•ื‘ื™ ืคื™ืจื•ืช
11:31
might actually have some relevance to a human psychiatric disorder.
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ืขืฉื•ื™ ืœื”ื™ื•ืช ืจืœื•ื•ื ื˜ื™ ืœื”ืคืจืขื” ืคืกื™ื›ื™ืื˜ืจื™ืช ืื ื•ืฉื™ืช.
11:35
Now, how far does this analogy go?
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ืขื›ืฉื™ื•, ื›ืžื” ืจื—ื•ืง ืืคืฉืจ ืœืงื—ืช ืืช ื”ืื ืœื•ื’ื™ื” ื”ื–ื•?
11:37
As many of you know, individuals afflicted with ADHD
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ื›ืคื™ ืฉืจื‘ื™ื ืžื›ื ื™ื•ื“ืขื™ื, ืื ืฉื™ื ืฉืกื•ื‘ืœื™ื ืž-ADHD
11:40
also have learning disabilities.
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ืกื•ื‘ืœื™ื ื’ื ืžืœื™ืงื•ื™ื™ ืœืžื™ื“ื”.
11:43
Is that true of our dopamine receptor mutant flies?
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ื”ืื ื–ื” ื ื›ื•ืŸ ื’ื ืœื’ื‘ื™ ื”ื–ื‘ื•ื‘ื™ื ื”ืžื•ื˜ื ื˜ื™ื ืฉืœื ื• ื‘ืงื•ืœื˜ืŸ ื”ื“ื•ืคืžื™ืŸ?
11:46
Remarkably, the answer is yes.
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ืœืžืจื‘ื” ื”ืคืœื, ื”ืชืฉื•ื‘ื” ื”ื™ื ื›ืŸ.
11:49
As Seymour showed back in the 1970s,
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ื›ืคื™ ืฉืกื™ืžื•ืจ ื”ืจืื” ืขื•ื“ ื‘ืฉื ื•ืช ื”-70,
11:52
flies, like songbirds, as you just heard,
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ื–ื‘ื•ื‘ื™ื, ื›ืžื• ืฆื™ืคื•ืจื™ ืฉื™ืจ, ื›ืคื™ ืฉืฉืžืขืชื,
11:54
are capable of learning.
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ื”ื ื‘ืขืœื™ ื™ื›ื•ืœืช ืœืžื™ื“ื”.
11:56
You can train a fly to avoid an odor, shown here in blue,
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ื ื™ืชืŸ ืœืืžืŸ ื–ื‘ื•ื‘ ืœื”ื™ืžื ืข ืžืจื™ื—, ืžื•ืฆื’ ื›ืืŸ ื‘ื›ื—ื•ืœ,
12:00
if you pair that odor with a shock.
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ืื ืžืฉื™ื™ื›ื™ื ืืช ื”ืจื™ื— ืœืžื›ืช ื—ืฉืžืœ.
12:03
Then when you give those trained flies the chance to choose
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ืœืื—ืจ ืžื›ืŸ ื›ืฉื ื•ืชื ื™ื ืœื–ื‘ื•ื‘ื™ื ืžืื•ืžื ื™ื ืืœื” ื”ื–ื“ืžื ื•ืช ืœื‘ื—ื•ืจ
12:06
between a tube with the shock-paired odor and another odor,
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ื‘ื™ืŸ ืฆื™ื ื•ืจ ืขื ืจื™ื— ื”ืงืฉื•ืจ ืœืฉื•ืง, ืœื‘ื™ืŸ ืจื™ื— ืื—ืจ,
12:09
it avoids the tube containing the blue odor that was paired with shock.
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ื”ื•ื ื™ืชื—ืžืง ืžื”ืฆื™ื ื•ืจ ื”ืžื›ื™ืœ ืืช ื”ืจื™ื— ื”ื›ื—ื•ืœ ืฉืงื•ืฉืจ ืœืฉื•ืง.
12:13
Well, if you do this test on dopamine receptor mutant flies,
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ื•ื‘ื›ืŸ, ืื ืขื•ืฉื™ื ื‘ื“ื™ืงื” ื–ื• ื‘ื–ื‘ื•ื‘ื™ื ืžื•ื˜ื ื˜ื™ื ืœืงื•ืœื˜ืŸ ื“ื•ืคืžื™ืŸ,
12:17
they don't learn. Their learning score is zero.
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ื”ื ืœื ืœื•ืžื“ื™ื. ืฆื™ื•ืŸ ื”ืœืžื™ื“ื” ืฉืœื”ื ื”ื•ื ืืคืก.
12:19
They flunk out of CalTech.
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ืžืขื™ืคื™ื ืื•ืชื ืžืงืืœื˜ืง.
12:23
So that means that these flies have two abnormalities,
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ืื– ืœื–ื‘ื•ื‘ื™ื ืืœื” ื™ืฉ ืฉืชื™ ื—ืจื™ื’ื•ืช,
12:28
or phenotypes, as we geneticists call them,
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ืื• ืคื ื•ื˜ื™ืคื™ื, ื›ืคื™ ืฉืื ื• ื”ื’ื ื˜ื™ืงืื™ื ืงื•ืจืื™ื ืœื”ื,
12:31
that one finds in ADHD: hyperactivity and learning disability.
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ืฉืžื•ืฆืื™ื ื‘- ADHD: ื”ื™ืคืจืืงื˜ื™ื‘ื™ื•ืช, ื•ืœืงื•ืช ืœืžื™ื“ื”.
12:36
Now what's the causal relationship, if anything, between these phenotypes?
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ืขื›ืฉื™ื• ืžื” ื”ื™ื—ืก ื”ืกื™ื‘ืชื™, ืื ื‘ื›ืœืœ, ื‘ื™ืŸ ืคื ื•ื˜ื™ืคื™ื ืืœื”?
12:41
In ADHD, it's often assumed that the hyperactivity
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ื‘- ADHD, ืœืขืชื™ื ืงืจื•ื‘ื•ืช ืžื ื™ื—ื™ื ืฉื”ื”ื™ืคืจืืงื˜ื™ื‘ื™ื•ืช
12:45
causes the learning disability.
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ื’ื•ืจืžืช ืœืœืงื•ืช ื”ืœืžื™ื“ื”.
12:47
The kids can't sit still long enough to focus, so they don't learn.
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ื”ื™ืœื“ื™ื ืœื ื™ื›ื•ืœื™ื ืœืฉื‘ืช ื‘ืฉืงื˜ ืžืกืคื™ืง ื–ืžืŸ ื›ื“ื™ ืœื”ืชืจื›ื–, ื•ืœื›ืŸ ืื™ื ื ืœื•ืžื“ื™ื.
12:50
But it could equally be the case that it's the learning disabilities
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ืื‘ืœ ื‘ืื•ืชื” ืžื™ื“ื” ื™ื›ื•ืœ ืœื”ื™ื•ืช ืฉืœืงื•ื™ื•ืช ื”ืœืžื™ื“ื”
12:54
that cause the hyperactivity.
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ื”ืŸ ืฉื’ื•ืจืžื•ืช ืœื”ื™ืคืจืืงื˜ื™ื‘ื™ื•ืช.
12:55
Because the kids can't learn, they look for other things to distract their attention.
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ืžื›ื™ื•ื•ืŸ ืฉื”ื™ืœื“ื™ื ืœื ื™ื›ื•ืœื™ื ืœืœืžื•ื“, ื”ื ืžื—ืคืฉื™ื ื“ื‘ืจื™ื ืื—ืจื™ื ืœื”ืกื™ื— ืืช ืชืฉื•ืžืช ื”ืœื‘ ืฉืœื”ื.
13:00
And a final possibility is that there's no relationship at all
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ื•ืืคืฉืจื•ืช ืื—ืจื•ื ื” ื”ื™ื ืฉืื™ืŸ ืงืฉืจ ื‘ื›ืœืœ
13:03
between learning disabilities and hyperactivity,
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ื‘ื™ืŸ ืœืงื•ื™ื•ืช ืœืžื™ื“ื”, ืœื”ื™ืคืจืืงื˜ื™ื‘ื™ื•ืช,
13:05
but that they are caused by a common underlying mechanism in ADHD.
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ืืœื ืฉื”ืŸ ื ื’ืจืžื•ืช ืขืœ ื™ื“ื™ ืžื ื’ื ื•ืŸ ืžืฉื•ืชืฃ ื”ืงื™ื™ื ื‘- ADHD.
13:10
Now people have been wondering about this for a long time
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ืื ืฉื™ื ื›ื‘ืจ ืชื•ื”ื™ื ืขืœ ื›ืš ื–ื” ื–ืžืŸ ืจื‘
13:13
in humans, but in flies we can actually test this.
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ื‘ืงืฉืจ ืœื‘ื ื™ ืื“ื, ืื‘ืœ ื‘ื–ื‘ื•ื‘ื™ื ืื ื• ื™ื›ื•ืœื™ื ืœื‘ื“ื•ืง ื–ืืช.
13:16
And the way that we do this is to delve deeply into the mind
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ื•ื”ื“ืจืš ืฉืื ื• ืขื•ืฉื™ื ื–ืืช ื”ื™ื ืœื”ืชืขืžืง ื‘ืžื•ื—
13:19
of the fly and begin to untangle its circuitry using genetics.
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ืฉืœ ื”ื–ื‘ื•ื‘ ื•ืœื”ืชื™ืจ ืืช ื”ืžืขื’ืœื™ื ื”ื—ืฉืžืœื™ื™ื ืฉืœื• ื‘ืืžืฆืขื•ืช ื’ื ื˜ื™ืงื”.
13:23
We take our dopamine receptor mutant flies
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ืื ื—ื ื• ืœื•ืงื—ื™ื ืืช ื”ื–ื‘ื•ื‘ื™ื ื”ืžื•ื˜ื ื˜ื™ื ืœืงื•ืœื˜ืŸ ื”ื“ื•ืคืžื™ืŸ
13:26
and we genetically restore, or cure, the dopamine receptor
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ื•ืื ื—ื ื• ืžืฉื—ื–ืจื™ื ื’ื ื˜ื™ืช, ืื• ืžืจืคืื™ื, ืืช ืงื•ืœื˜ืŸ ื”ื“ื•ืคืžื™ืŸ
13:30
by putting a good copy of the dopamine receptor gene
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ืขืœ ื™ื“ื™ ื”ื—ื“ืจืช ืขื•ืชืง ื˜ื•ื‘ ืฉืœ ื”ื’ืŸ ืฉืœ ืงื•ืœื˜ืŸ ื”ื“ื•ืคืžื™ืŸ
13:34
back into the fly brain.
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ืœืชื•ืš ืžื•ื—ื• ืฉืœ ื”ื–ื‘ื•ื‘.
13:36
But in each fly, we put it back only into certain neurons
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ืื‘ืœ ืœืชื•ืš ื›ืœ ื–ื‘ื•ื‘, ืื ื• ืžื—ื–ื™ืจื™ื ืื•ืชื• ืจืง ืœื ื•ื™ืจื•ื ื™ื ืžืกื•ื™ืžื™ื
13:40
and not in others, and then we test each of these flies
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ื•ืœื ืœืื—ืจื™ื, ื•ืœืื—ืจ ืžื›ืŸ ืื ื• ื‘ื•ื—ื ื™ื ืืฆืœ ื›ืœ ืื—ื“ ืžื”ื
13:43
for their ability to learn and for hyperactivity.
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ืืช ื”ื™ื›ื•ืœืช ืฉืœื”ื ืœืœืžื•ื“ ื•ืืช ื”ื”ื™ืคืจืืงื˜ื™ื‘ื™ื•ืช.
13:47
Remarkably, we find we can completely dissociate these two abnormalities.
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ืœื”ืคืชืขืชื ื•, ื’ื™ืœื™ื ื• ืฉื ื™ืชืŸ ืœื”ืคืจื™ื“ ืœื’ืžืจื™ ื‘ื™ืŸ ืฉืชื™ ื”ืœืงื•ื™ื•ืช ื”ืœืœื•.
13:52
If we put a good copy of the dopamine receptor back
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ืื ืžื›ื ื™ืกื™ื ืขื•ืชืง ื˜ื•ื‘ ืฉืœ ืงื•ืœื˜ืŸ ื“ื•ืคืžื™ืŸ
13:54
in this elliptical structure called the central complex,
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ืœืžื‘ื ื” ืืœื™ืคื˜ื™ ื–ื” ืฉื ืงืจื ืกื ื˜ืจืœ ืงื•ืžืคืœืงืก,
13:57
the flies are no longer hyperactive, but they still can't learn.
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ื”ื–ื‘ื•ื‘ื™ื ืื™ื ื ืขื•ื“ ื”ื™ืคืจืืงื˜ื™ื‘ื™ื™ื, ืืš ื”ื ืขื“ื™ื™ืŸ ืœื ื™ื›ื•ืœื™ื ืœืœืžื•ื“.
14:01
On the other hand, if we put the receptor back in a different structure
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ืœืขื•ืžืช ื–ืืช, ืื ืื ื• ืžื—ื–ื™ืจื™ื ืืช ื”ืงื•ืœื˜ืŸ ืœืžื‘ื ื” ืฉื•ื ื”
14:04
called the mushroom body,
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ื‘ืฉื ื’ื•ืฃ ื”ืคื˜ืจื™ื”,
14:06
the learning deficit is rescued, the flies learn well,
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ื”ืœืžื™ื“ื” ื ื™ืฆืœืช, ื”ื–ื‘ื•ื‘ื™ื ืœื•ืžื“ื™ื ื”ื™ื˜ื‘,
14:09
but they're still hyperactive.
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ืื‘ืœ ื”ื ืขื“ื™ื™ืŸ ื”ื™ืคืจืืงื˜ื™ื‘ื™ื™ื.
14:11
What that tells us is that dopamine
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ืžื” ืฉืื•ืžืจ ืœื ื• ืฉื“ื•ืคืžื™ืŸ
14:13
is not bathing the brain of these flies like soup.
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ืื™ื ื• ืžืฆื™ืฃ ืืช ืžื•ื—ื ืฉืœ ื–ื‘ื•ื‘ื™ื ืืœื” ื›ืžื• ืžืจืง.
14:16
Rather, it's acting to control two different functions
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ืืœื ื”ื•ื ืฉื•ืœื˜ ืขืœ ืฉื ื™ ืชืคืงื™ื“ื™ื ืฉื•ื ื™ื
14:19
on two different circuits,
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ืขืœ ืฉื ื™ ืžืขื’ืœื™ื ืฉื•ื ื™ื,
14:21
so the reason there are two things wrong with our dopamine receptor flies
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ืื– ื”ืกื™ื‘ื” ืฉื™ืฉ ืœื–ื‘ื•ื‘ื™ื ื”ืœืœื• ืฉืชื™ ื‘ืขื™ื•ืช
14:25
is that the same receptor is controlling two different functions
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ื”ื™ื ืฉืื•ืชื• ืงื•ืœื˜ืŸ ืฉื ื™ ืชืคืงื™ื“ื™ื ืฉื•ื ื™ื
14:29
in two different regions of the brain.
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ื‘ืฉื ื™ ืื–ื•ืจื™ื ืฉื•ื ื™ื ืฉืœ ื”ืžื•ื—.
14:32
Whether the same thing is true in ADHD in humans
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ืื•ืชื• ื“ื‘ืจ ื ื›ื•ืŸ ื‘- ADHD ืืฆืœ ื‘ื ื™ ืื“ื
14:35
we don't know, but these kinds of results
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ืื ื—ื ื• ืœื ื™ื•ื“ืขื™ื, ืื‘ืœ ืชื•ืฆืื•ืช ื›ืืœื”
14:37
should at least cause us to consider that possibility.
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ืฆืจื™ื›ื•ืช ืœื’ืจื•ื ืœื ื• ืœืฉืงื•ืœ ืืช ื”ืืคืฉืจื•ืช ื”ื–ืืช.
14:41
So these results make me and my colleagues more convinced than ever
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ืื– ื”ืชื•ืฆืื•ืช ื”ืืœื” ื’ื•ืจืžื•ืช ืœื™ ื•ืœืขืžื™ืชื™ื™ ืœื”ื™ื•ืช ืžืฉื•ื›ื ืขื™ื ื™ื•ืชืจ ืžืชืžื™ื“
14:45
that the brain is not a bag of chemical soup,
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ืฉื”ืžื•ื— ืื™ื ื• ืฉืงื™ืช ืฉืœ ืžืจืง ื›ื™ืžื™,
14:48
and it's a mistake to try to treat complex psychiatric disorders
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ื•ื–ื• ื˜ืขื•ืช ืœื ืกื•ืช ืœื˜ืคืœ ื‘ื”ืคืจืขื•ืช ืคืกื™ื›ื™ืื˜ืจื™ื•ืช ืžื•ืจื›ื‘ื•ืช
14:52
just by changing the flavor of the soup.
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ืจืง ืขืœ-ื™ื“ื™ ืฉื™ื ื•ื™ ื˜ืขืžื• ืฉืœ ื”ืžืจืง.
14:55
What we need to do is to use our ingenuity and our scientific knowledge
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ืžื” ืฉืื ื—ื ื• ืฆืจื™ื›ื™ื ืœืขืฉื•ืช ื”ื•ื ืœื”ืฉืชืžืฉ ื‘ื›ื•ืฉืจ ื”ื”ืžืฆืื” ื•ื‘ื™ื“ืข ื”ืžื“ืขื™ ืฉืœื ื•
14:59
to try to design a new generation of treatments
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ื›ื“ื™ ืœื ืกื•ืช ืœืขืฆื‘ ื“ื•ืจ ื—ื“ืฉ ืฉืœ ื˜ื™ืคื•ืœื™ื
15:01
that are targeted to specific neurons and specific regions of the brain
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ืฉืžื›ื•ื•ื ื™ื ืœื ื•ื™ืจื•ื ื™ื ื•ืœืื–ื•ืจื™ื ืžืกื•ื™ืžื™ื ื‘ืžื•ื—
15:06
that are affected in particular psychiatric disorders.
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ืฉืžื•ืฉืคืขื™ื ื‘ืžื™ื•ื—ื“ ื‘ื”ืคืจืขื•ืช ืคืกื™ื›ื™ืื˜ืจื™ื•ืช.
15:09
If we can do that, we may be able to cure these disorders
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ืื ื ื•ื›ืœ ืœืขืฉื•ืช ื–ืืช, ืื•ืœื™ ื ืฆืœื™ื— ืœืจืคื ืืช ื”ื”ืคืจืขื•ืช ื”ืœืœื•
15:12
without the unpleasant side effects,
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ืœืœื ืชื•ืคืขื•ืช ืœื•ื•ืื™ ื‘ืœืชื™-ื ืขื™ืžื•ืช,
15:14
putting the oil back in our mental engines,
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ืœืฉื•ื‘ ื•ืœืฉืžืŸ ืืช ืžื ื•ืขื™ ื”ื ืคืฉ ืฉืœื ื•,
15:17
just where it's needed. Thank you very much.
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ื‘ื“ื™ื•ืง ื”ื™ื›ืŸ ืฉื ื—ื•ืฅ. ืชื•ื“ื” ืจื‘ื”.
ืขืœ ืืชืจ ื–ื”

ืืชืจ ื–ื” ื™ืฆื™ื’ ื‘ืคื ื™ื›ื ืกืจื˜ื•ื ื™ YouTube ื”ืžื•ืขื™ืœื™ื ืœืœื™ืžื•ื“ ืื ื’ืœื™ืช. ืชื•ื›ืœื• ืœืจืื•ืช ืฉื™ืขื•ืจื™ ืื ื’ืœื™ืช ื”ืžื•ืขื‘ืจื™ื ืขืœ ื™ื“ื™ ืžื•ืจื™ื ืžื”ืฉื•ืจื” ื”ืจืืฉื•ื ื” ืžืจื—ื‘ื™ ื”ืขื•ืœื. ืœื—ืฅ ืคืขืžื™ื™ื ืขืœ ื”ื›ืชื•ื‘ื™ื•ืช ื‘ืื ื’ืœื™ืช ื”ืžื•ืฆื’ื•ืช ื‘ื›ืœ ื“ืฃ ื•ื™ื“ืื• ื›ื“ื™ ืœื”ืคืขื™ืœ ืืช ื”ืกืจื˜ื•ืŸ ืžืฉื. ื”ื›ืชื•ื‘ื™ื•ืช ื’ื•ืœืœื•ืช ื‘ืกื ื›ืจื•ืŸ ืขื ื”ืคืขืœืช ื”ื•ื•ื™ื“ืื•. ืื ื™ืฉ ืœืš ื”ืขืจื•ืช ืื• ื‘ืงืฉื•ืช, ืื ื ืฆื•ืจ ืื™ืชื ื• ืงืฉืจ ื‘ืืžืฆืขื•ืช ื˜ื•ืคืก ื™ืฆื™ืจืช ืงืฉืจ ื–ื”.

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