Many psychiatric disorders involve dysfunction of the limbic system that is manifested in a reduced ability to experience pleasure and learning and memory impairment.Dopamine is important in the limbic system, which includes structures such as the nucleus accumbens, ventral tegmental area and prefrontal cortex. Drugs such as opiates and cocaine, but also antidepressant agents, and deep brain stimulation can possibly recruit certain types of interneurons, whose function is to regulate the firing and integration of information in local circuits. Functional study of local inhibitory interneurons of two classes, parvalbumin and somatostatin interneurons, using optogenetics and mouse genetics are the main focus of this proposal. It is of great interest to better understand the function of distinct neuronal classes during reward-related behaviors, and to identify how dopamine neurtransmission in specific neuronal classes regulate behavior. I propose to apply optogenetics to study the functional impact of GABAergic interneurons during reward-related behaviors. Functional studies of the limbic system have previously been limited to pharmacological approaches or lesion studies that provide poor cell-type specificity and low temporal resolution. Expression and control of light-activated channels using genetic methods in mice allows us to dissect the function of each neuronal class during awake behavior with millisecond resolution. The proposed research can provide important information on the function of discrete neuronal classes and their specific receptors, thereby providing the foundation for rational design of novel therapeutics targeting the limbic system.