Behavioral inhibition is a normal process that allows individuals to interrupt a pre-planned action in order to function optimally in a dynamic world. Deficits in behavioral inhibition are prominent among psychiatric disorders, including obsessive-compulsive disorder, schizophrenia, attention deficit/hyperactivity disorder (ADHD) and addiction. Impairments in behavioral inhibition lead to many of the shared symptoms of these disorders, such as compulsivity and impulsivity. These deficits can be modeled in animals using operant learning tasks, such as the stop-signal task, the go/no-go task and delay-discounting. (Click here to see a movie showing these learning tasks.) Studies investigating the neural mechanisms of behavioral inhibition have identified the cortex and the striatum as key structures for regulating normal response inhibition, and deficits in cortical and striatal functioning have been linked to impairments in behavioral inhibition. Dr. Susan Ferguson’s laboratory employs a novel chemical-genetic approach that uses viral vectors to express artificial, engineered G-protein coupled receptors (known as DREADD receptors) in discrete neuronal cell populations in rodents (e.g. striatonigral ‘direct’ pathway neurons, striatopallidal ‘indirect’ pathway neurons, populations of cortical neurons) in combination with rodent operant learning tasks in order to study the role of the cortex and the striatum in behavioral inhibition. Activation of DREADD receptors by the otherwise inert synthetic ligand clozapine-N-oxide will lead to transient alterations in neuronal signaling (either increasing or decreasing cell signaling depending on which G-protein coupled DREADD receptor is expressed) of the targeted cell populations.