[Murg] [>Htech] scienceblog: genetically modifying flies to make them easier to control remotely (fwd from alito@organicrobot.com)

[Eugen Leitl]

----- Forwarded message from Alejandro Dubrovsky <alito at organicrobot.com> -----

From: Alejandro Dubrovsky <alito at organicrobot.com>
Date: Fri, 08 Apr 2005 05:50:33 +1000
To: transhumantech <transhumantech at yahoogroups.com>
Subject: [>Htech] scienceblog: genetically modifying flies to make them easier to
	control remotely
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Reply-To: transhumantech at yahoogroups.com


(
http://www.scienceblog.com/cms/node/7484
)

Remote control flies? Fly behavior controlled by laser light

Yale University School of Medicine researchers have found a way to
exercise a little mind control over fruit flies, making the flies jump,
beat their wings, and fly on command by triggering genetic "remote
controls" that the scientists designed and installed in the insects'
central nervous systems, according to a new report in the 8 April issue
of the journal Cell.

Susana Lima and Gero Miesenböck hope that the remote control system will
provide a valuable way to study how nerve-cell activity and connections
are related to specific behaviors, from simple movements to more complex
behaviors like learning, aggression, and even abstract thought.

The ability to control specific groups of neurons without implanting
electrodes in the brain or using similarly invasive techniques "would
represent a significant step in moving neuroscience from passive
observation???to active and predictive manipulation of behavior," the Cell
authors write.

Miesenböck also says "one could use this method to restore neural
signals that have been lost" due to injury or disease, such as in spinal
cord trauma, although he notes that the possibility is "far-fetched" at
the moment.

The remote control is based on the idea that specific nerve cells could
be equipped with molecular "receivers" that allow them to recognize an
outside signal like a laser light pulse and translate that signal into
the electrical signals characteristic of nerve-cell activity.

To accomplish this, Miesenböck and Lima devised a triggered molecular
lock and key system, where the "lock" was the receiver genetically
encoded to be expressed in the target neurons, the "key" was the
molecule that would bind to and activate the lock, and laser light was
the trigger that brought the key to the lock.

For the lock, the researchers used an ion channel, or a pore-forming
protein that allows charged particles to pass through a cell membrane.
The small molecule ATP activates the ion channel chosen by the
researchers, so ATP became the key. To keep the ATP from binding to the
ion channel and jump-starting the nerve cell's activity before the
proper moment, Lima and Miesenböck caged the ATP with other chemical
compounds that could be removed by the laser light.

Miesenböck says one of the most difficult parts of the experiment was
deciding which particular nerve cells to target with the remote control
system. "To ascertain that the system actually worked, it wasn't clear
how we could measure activation in the neurons in moving, freely
behaving organisms," he explains.

The breakthrough, he says, came when they decided to target a small set
of nerve cells in the fly called the giant fiber system. The giant fiber
system controls very specific, stereotypical movements such as escape
movements, jumping, and the beginnings of flight. If the flies engaged
in these behaviors after the giant fiber neurons had been outfitted and
"operated" with the remote control, Miesenböck and Lima reasoned, they
could be sure that their system was working.

After genetically engineering the flies to express the ion channel in
the giant fiber system cells and using the tiniest of injections to
place the caged ATP inside the flies, the researchers shone a
ultraviolet-wavelength laser in brief, millisecond pulses at the flies
trapped inside a glass-domed arena. On command, the flies began a series
of escape movements--extending their legs, jumping, and opening and
rapidly flapping their wings.

The laser-triggered remote controls in the giant fiber system worked
about 63 percent of the time, while remote controls placed in other
nerve cells that were targets of the giant fiber system worked 82
percent of the time, the researchers concluded. Lima and Misenböck also
equipped another set of nerve cells called dopaminergic neurons with the
remote controls, boosting the flies' activity levels and changing their
flight paths.

Misenböck says the triggered behaviors can last seconds or continue for
minutes, depending on whether the neural circuit activated by the remote
control has feedback loops that keep the circuit. "In the case of the
flight circuits," he says, "it is like pushing a swing. One initial kick
and it keeps swinging back and forth for a while."

>From Cell Press



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