Viral-Genetic Dissection of the Midbrain Dopamine System

Neuromodulators are signaling molecules that can rapidly broadcast messages to large populations of neurons and exert profound effects on behavior. The brain contains a variety of neuromodulators including the monoamines dopamine, serotonin, and norepinephrine as well as neuropeptides such as oxytocin, orexin, and neurotensin. Dysfunction in these neuromodulatory systems has been strongly implicated in many neurodevelopmental and neuropsychiatric disorders, including autism, mood disorders, and addictions. However, it is not clear for any of the brain's neuromodulatory systems how neurons releasing these neurotransmitters are controlled to promote specific behavioral outcomes in normal or pathological states, and how experience modulates their release. Concentrating on dopaminergic neurons in the ventral tegmental area, I will first discuss a novel viral-genetic method to unambiguously link the inputs to outputs of defined neuron classes, and detail the utility of such maps to generate and test hypotheses of neural circuit function. Secondly, I will describe the development and application of an unbiased method for identifying the neural circuit substrates of behavioral adaptation. Lastly, I will discuss how I plan to use these and related technologies to map and interrogate experience-driven changes in neuromodulatory systems.