Viral-Mediated Gene Transfer to Study the Behavioral Correlates of CREB Function in the Nucleus Accumbens of Rats

There is an enormous initiative to establish causal relationships between brain biology (including patterns of gene expression) and behavior. Unfortunately, genetic intervention is not accomplished easily in the brain. One strategy is to engineer and deliver to the brain specialized viral vectors that carry a gene (or genes) of interest, thereby exploiting the natural ability of viruses to insert genetic material into cells. When delivered to the brain, these vectors cause infected cells to increase expression of the genes of interest. Viral vectors are particularly useful when the goal is to manipulate expression of a single gene (1) in a specific brain region (2) at a specific time (3) in animals that developed normally. As such, this technology has the potential to offer new insights into the etiology of a wide variety of neuropsychiatric disorders; ultimately it may usher in a new generation of “smart” pharmacotherapies that are designed to negate or reverse alterations in the molecular structure of the brain that lead to pathophysiological changes in behavior.