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  • Reward-seeking behavior regulated with optogenetics

Sep 2011
Compiled by BioPhotonics staff

CHAPEL HILL, N.C. – Scientists have used optogenetics to control reward-seeking behaviors such as drug addiction in rodents, demonstrating the roles of specific connections in the brain that control behavior.

Through combining genetic engineering and laser technology, scientists at the University of North Carolina tweaked the microcircuitry of the brain so that they could assess how those changes affect behavior. Their findings, which appeared in the June 29 issue of Nature (doi: 10.1038/nature 10194), suggest that therapeutics that target the path between two critical brain regions – the amygdala and the nucleus accumbens, the regions that are associated with reward – could act as treatments for neuropsychiatric diseases and addiction.

Nerve cells in the nucleus accumbens (red) receive input from amygdala fibers (green). Optogenetic stimulation of these nerve fibers produces a rewarding effect in mice. Courtesy of Stuber Lab, UNC-Chapel Hill.

These regions are important for assessing clinical disorders, but until now there were no proper tools to directly study the connections between them.

Using the new technique, scientists transferred light-sensitive proteins called “opsins” – derived from algae or bacteria that need light to grow – into mammalian brain cells they wished to study. Shining a laser beam directly onto the genetically manipulated brain cells, they could either excite or block the activity with millisecond precision.

Initial experiments targeted the nerve cells that connect the amygdala and the nucleus accumbens. Using light to activate the connection between the regions, the scientists “rewarded” the mice with laser stimulations for performing mundane tasks, such as poking their nose into a hole in their cage. The mice treated with opsins quickly learned how to obtain stimulation of the neural pathway, while the genetically untouched mice in their experiment never caught on to the task.

To study whether this brain wiring plays a role in more natural behavioral processes, the scientists trained the mice to associate a cue – in this case, a light bulb turning on in the cage – with a reward of sugar water. This time, the opsin that was transferred into the brains of the mice was one that shut down the activity of neural connections in response to light. While delivering the cue to the control mice, they blocked the neuronal activity in the genetically altered mice, and they observed that the control mice responded quickly to the cue by licking the sugar-producing vessel, while the treated mice did not exhibit the same response.

The researchers are exploring how changes to this segment of brain wiring could render animals either sensitized or oblivious to rewards. Proving a useful tool for studying brain function, the technique could one day provide an alternative to electrical stimulation or pharmacotherapy for neuropsychiatric illnesses like Parkinson’s disease.

A discipline that combines optics and genetics to enable the use of light to stimulate and control cells in living tissue, typically neurons, which have been genetically modified to respond to light. Only the cells that have been modified to include light-sensitive proteins will be under control of the light. The ability to selectively target cells gives researchers precise control. Using light to control the excitation, inhibition and signaling pathways of specific cells or groups of cells...
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