Science News - January 30, 2010

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Häusser’s group presented preliminary, unpublished evidence supporting the idea at the neuroscience meeting.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