Drug addiction is a chronic, debilitating disease that devastates the lives of addicts and their loved ones, and has far-reaching economic and social consequences. Our goal is to understand the cells and circuits that underlie the transition to addiction. In addition, it is important to appreciate that the majority of people that try a drug do not become addicted. We are trying to identify the neurobiological mechanisms that render some individuals vulnerable to develop addiction and others resistant.
cortico-basal ganglia-thalamic circuit
A major goal of our research program is to identify the role of specific cells and projections within the cortico-basal ganglia-thalamic circuit in the development and maintenance of drug addiction, and relapse. We are particularly interested in determining the contributions of the direct ('go') and indirect ('brake') striatal pathways. It is our hypothesis that repeated drug use in vulnerable individuals fundamentally alters the balance in activity of these pathways, in part through changes in the activity of glutamatergic inputs into the striatum. As a result of this dysregulation, we believe that drugs and associated cues produce enhanced activity of the direct pathway and blunted activity of the indirect pathway, thereby driving drug-seeking behavior and relapse in addicts. We combine animals models of addiction (cocaine self-administration, psychomotor sensitization, conditioned place preference) with tools for cellular modulation (DREADDs, optogenetics) and monitoring (GCaMP, c-Fos) to tests these hypotheses and map the circuits of addiction.