imreti@jhmi.edu

Evidence linking neuronal immediate early genes to enduring forms of neuronal plasticity has heightened interest in their role in mediating behavioral alterations induced by drugs of abuse and other forms of brain stimulation. As these genes are rapidly induced by neuronal stimulation, they represent a mechanism by which drug administration could elicit long-term adaptations in neuronal function that underlie their reinforcing properties. We have focused on one of these immediate early genes, Narp, which clusters AMPA receptors and is expressed selectively in limbic brain regions regulating behavior. A series of studies we have conducted suggest Narp signaling pathways may represent a potential therapeutic target for drug addiction and possibly other motivated behaviors.

Electroconvulsive therapy is the most effective available therapy for treating depression however little is known about its mechanism of action. Mice genetically engineered to lack key genes which are inducible by eletroconvulsive stimulation and which regulate synaptic plasticity may yield clues to how it works. Although ECT is highly effective, it is not without side-effects and so there has been keen interest in developing alternate forms of therapeutic brain stimulation for depression, such as transcranial magnetic stimulation and deep brain stimulation, that are more focal and do not involve anesthesia. We are setting up clinical trials using these techniques which may also lead us to an improved understanding of mood and how it is regulated.