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 Posted: Fri Oct 16, 2009 3:16 pm |
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http://www.scientificamerican.com/article.cfm?id=flies-get-fright-from-false-me&sc=CAT_BS_20091016
October 15, 2009 | 0 comments
Flies get fright from false memories
Scientists use light activation to pinpoint where learning happens in fruit
flies.
The seemingly complex phenomenon by which fruit flies (Drosophila) learn
from bad experiences has been reduced to the actions of a mere 12 neurons,
according to research by a team of UK- and US-based scientists. Manipulating
this cluster of cells with a laser, the scientists were able to trick the
flies into having associative memories of events they had not actually
experienced.
Flies learn from smells and other signals in their environment. Conditioning
by, for example, electric shocks, can teach them to avoid certain odours.
Previous experiments had shown that a structure in the fly brain called the
mushroom body was essential for storing those memories, but the mechanism by
which those memories get stored has not been well understood.
To examine the mechanism, a team led by the University of Oxford's Gero
Miesenb?took advantage of "optogenetics", a technique in which they use
light to activate particular cell types that have been genetically
engineered to express a light-responsive protein. When laser pulses hit the
brain, cells expressing the light-sensitive protein activate. "It's
like sending a radio signal to a city but only those houses with a radios
set to the right frequency will get the signal," says Miesenb?
Light work
Previous research showed that dopamine was involved in making negative
associations, for example with smells to be avoided, so Miesenb?apos;s team
made different clusters of dopaminergic cells light-sensitive. Then the
flies were trained: when they crossed into a certain gas stream
methylcyclohexanol (MCH) a laser was flipped on and the dopaminergic cells
were activated.
The experiment was as effective as electric shock treatment the flies
learned to avoid MCH. The memory was written directly into the brain without
the sensory input. Although it is impossible to know, Miesenb?doubts the
flies experience pain, like a shock. "I think it's probably more
abstract than that," he says.
The surprise, reported today in Cell1, came when they cut open the fly
brains and found in all of the several dozen flies analyzed that only 12
neurons were responsible for the training effect. "These 12 neurons point to
presumed memory storage sites in the mushroom body," says Miesenb?
"It's a landmark study, and very clever," says Ann-Shyn Chiang, a
Drosophila neuroscientist at National Tsing Hua University in Hsinchu,
Taiwan. "We have known that dopaminergic cells act as stimuli for forming
memories, but we have been waiting for a long time to know which ones."
What's more, some of those neurons point directly to the central
complex, a brain region implicated in visual memory. Miesenb?says the same
group of neurons might account for the formation of negative visual
associations too. "It would make sense. When your brain tells you that
you're doing something wrong, that you should change your actions, it
shouldn't matter which sense it uses to get that information."
Love it or hate it
Miesenb?apos;s next target is to find out what lies upstream from that
message, to see how that signal gets to the 12 neurons. This pathway could
be used by researchers to make predictions of impending reward or
punishment.
Chiang agrees that that is the next step, and he says better imaging
techniques could get there. Figures in the Cell paper show how the neurons
cluster around the mushroom body, but it's not possible to see
individual neurons, says Chiang. "What I'd really like to know is which
of these neurons is involved. It might be a smaller subset of the 12.
I'd also like to see the specific morphology of the connections where
the dendrites go," he says. This kind of precision, says Chiang, would help
in efforts to reconstruct the whole circuit of how memories are formed.
Miesenb?says it is unlikely that this degree of resolution will be possible
in mice or other animals because the brains of larger animals have more
neurons and the genetics of the Drosophila brain has been mapped in greater
detail. "Numerically the odds are stacked against you," he says.
But the study does parallel a report earlier this year in which scientists
used optogenetic techniques to train mice. Mice, unlike fruit flies, respond
positively to released dopamine, so instead of teaching them to dislike
something (negative reinforcement), as with the flies, the mice were taught
to prefer something (positive reinforcement) in this case, a certain
location.
Despite the differences, Miesenb?says many aspects of the basic pathway are
probably conserved evolutionarily so that the fly studies will teach us much
about how the human brain learns.
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