The prefrontal cortex (PFC) plays an important role in regulating social functions in mammals, and impairments in this region have been linked with social dysfunction in psychiatric disorders. The PFC plays a part in multiple brain-wide networks regulating behavior, and its long-range connections to different cortical and subcortical targets are thought to be involved in distinct behavioral functions. How is information about the multitude of cognitive/behavioral processes routed into and out of the PFC circuit? We are interested in understanding how PFC microcircuits process behavioral information, and how distinct PFC output neuron populations regulate learning, decision-making and social behavior.

I will first describe a set of experiments aimed at understanding the structure of synaptic connectivity among amygdala-projecting neurons in the mPFC. Using single-neuron two-photon optogenetic stimulation and imaging, we demonstrated that these neurons form unique connectivity modules in the deep and superficial layers of the mPFC. I will then describe our efforts to engineer new optogenetic tools for silencing of long-range axonal projections between brain regions. To efficiently suppress synaptic transmission, we engineered a new set of rhodopsin-based optogenetic tools that selectively couple to the Gi/o signaling pathway and strongly suppress synaptic release in vitro and in vivo.