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Abstract:
Long-range synaptic transmission between brain regions allows synchrony and coordination between neural circuits and is the foundation for complex information processing and behavior. For example, outputs from the prefrontal cortex to diverse subcortical circuits are crucial for regulation of learning, decision-making, and social behavior. Optogenetics has allowed unprecedented advances in understanding the causal roles of distinct neural populations in behavior. However, while optogenetic tools have been widely used for the excitation of neuronal cell bodies and axons, optogenetic silencing of long-range transmission has posed significant challenges. I will present our work developing several novel optogenetic tools for spatiotemporally-precise silencing of long-range axonal projections. To efficiently suppress synaptic transmission, we designed a new set of inhibitory bistable rhodopsins that couple to the Gi/o signaling pathway and can be used to suppress synaptic release in vitro and in vivo, in a spatially and temporally precise manner. New tools within this family allow spectral multiplexing for combined imaging and optogenetic silencing, opening up new avenues for the functional interrogation of long-range connectivity in neural circuits.