Emotional behavior is regulated by a host of chemicals, including neurotransmitters and neuromodulators, acting on specific circuits within the brain. There is strong evidence for the existence of both endogenous stress and anti-stress systems. Chronic exposure to drugs of abuse and stress are hypothesized to modulate the relative balance of activity of these systems within key circuitry in the brain leading to dysregulated emotional behavior. One of the primary focuses of the Kash lab is to understand how chronic drugs of abuse and stress alter neuronal function, focusing on these stress and anti-stress systems in brain circuitry important for anxiety-like behavior. In particular, we are interested in defining alterations in synaptic function, modulation and plasticity using a combination of whole-cell patch-clamp physiology, biochemistry and mouse models. Current projects are focused on the role of a unique population of dopamine neurons in alcoholism and anxiety.