Chapel Hill, NC--Researchers at the University of North Carolina (UNC) at Chapel Hill School of Medicine are using a combination of genetic engineering and laser technology called optogenetics to manipulate brain wiring responsible for reward-seeking behaviors, such as drug addiction. Conducted in rodent models, their work is the first to directly demonstrate the role of these specific connections in controlling behavior.
Published online on June 29, 2011 in the journal Nature, the UNC study uses optogenetics to tweak the microcircuitry of the brain and then assess how those changes impact behavior. The findings suggest that therapeutics targeting the path between two critical brain regions, namely the amygdala and the nucleus accumbens, represent potential treatments for addiction and other neuropsychiatric diseases. In the technique, scientists transfer light-sensitive proteins called opsins—derived from algae or bacteria that need light to grow—into the mammalian brain cells they wish to study. They then shine laser beams onto the genetically manipulated brain cells, either exciting or blocking their activity with millisecond precision.
In initial experiments, the target was the nerve cells connecting two separate brain regions associated with reward, the amygdala and the nucleus accumbens. The researchers used light to activate the connections between these regions, essentially "rewarding" the mice with laser stimulations for performing the mundane task of poking their nose into a hole in their cage. They found that the opsin treated mice quickly learned to "nosepoke" in order to receive stimulation of the neural pathway. In comparison, the genetically untouched control mice never caught on to the task.
Then the researchers wanted to see whether this brain wiring had a role in more natural behavioral processes. So they trained mice to associate a cue—a light bulb in the cage turning on—to a reward of sugar water. This time the opsin that the researchers transferred into the brains of their rodent subjects was one that would shut down the activity of neural connections in response to light. As they delivered the simple cue to the control mice, they also blocked the neuronal activity in the genetically altered mice. The control mice quickly began responding to the cue by licking the sugar-producing vessel in anticipation, whereas the treated mice did not give the same response.
The researchers are now exploring how changes to this segment of brain wiring can either make an animal sensitized to or oblivious to rewards. The researchers say that their approach presents an incredibly useful tool for studying basic brain function, and could one day provide a powerful alternative to electrical stimulation or pharmacotherapy for neuropsychiatric illnesses like Parkinson's disease.
The research was funded by NARSAD: The Brain & Behavior Research Fund; ABMRF/ The Foundation for Alcohol Research; The Foundation of Hope; and the National Institute on Drug Abuse, a component of NIH.
SOURCE: University of North Carolina at Chapel Hill School of Medicine; www.med.unc.edu/www/news/2011/june/scientists-use-optogenetics-to-control-reward-seeking-behavior
