On and off once a mouse is genetically engineered to produce light-activated proteins in brain cells, the right wavelength of light can turn
neurons on or off. blue light causes the protein channelrhodopsin- 2 (green) to change shape, allowing positive ions to flow into the cell. Halorhodopsin
(red) changes shape with yellow light, allowing negative ions to flow in. positive ions can activate a cell; negative ions can turn the cell off.
addiction. As the virus spreads, it infects
other cells in the region the researchers
are looking at.
Shining a blue light on the nucleus
accumbens activated connections to
the amygdala, rewarding the mice. Mice
trained to poke their noses into a hole
to trigger a pulse of light on the nucleus
accumbens kept going back again and
again for another flash, indicating
that the light flashes caused a reward
response. But mice that got a flash of light
to stimulate connections between the
nucleus accumbens and the prefrontal
cortex didn’t seem to have a rewarding
experience, Stuber reported at the neuroscience meeting. That suggests that
the connections between the prefrontal
cortex and nucleus accumbens are not
involved in this reward circuitry.
Optogenetics can also help scientists
learn more about circuitry associated
with normal brain functions, says Michael
Häusser of University College London.
He and his colleagues are investigating
a long-standing debate in neuroscience
about how the brain recalls memories.
Learning is thought to activate networks of neurons, and scientists think
activating subsets of the cells in the
networks may reactivate a memory.
Before optogenetics, there was no way
to directly test that hypothesis.
Häusser’s group presented preliminary, unpublished evidence supporting
the idea at the neuroscience meeting.
The team injected a piece of DNA into
the hippocampus of mice that would
produce channelrhodopsin- 2 wherever
neuronal remodeling associated with
learning occurred. The hippocampus is
an area of the brain known to be important in learning and memory.
The next day, the mice were trained
to fear a shock on the foot. Mice that
learned to connect an audio tone and
the shock froze, a known response to
fear, when they heard the tone, even if
no shock followed.
Light shining into the hippocampus
could also activate the cells that made
the mice freeze, indicating that those
cells were involved in learning to fear
the shock. The researchers also tested
whether activating any cells in the hippocampus could cause the fear response.
Only those cells involved in the initial
learning could make mice freeze. The
researchers further found that activating
just 100 to 200 cells is enough to reproduce the behavior, suggesting that the
reactivation theory could be correct.
Miesenböck thinks optogenetics may
help settle this reactivation debate and
answer other basic questions about brain
biology, such as whether the precise timing of each spike of electricity a neuron
sends out is important, or neighboring
cells listen only to the average pattern
of activity. Optogenetics isn’t yet precise
enough to answer that question and has
some other limitations, Miesenböck says.
He outlined the technique’s strengths and
weaknesses in the Oct. 16 Science.
“Optogenetic technology, despite all of
its refinement, is not able to control activity of individual members of a group of
neurons,” he says.
And for all its power, it’s not intended to
be a therapeutic tool; that would require
gene therapy and brain surgery. But optogenetics is helping scientists discover
things about the brain and nervous system that no one ever knew before. And,
for that reason, it is good. s
youtube video of a mouse whose s
behavior is being altered through
January 30, 2010 | SCIENCE NEWS | 21