Natural neural projection dynamics underlying social behavior (Sungmo Park)

AUTHORS: Lisa A. Gunaydin, Logan Grosenick, Joel C. Finkelstein, Isaac V. Kauvar, Lief E. Fenno, Avishek Adhikari, Stephan Lammel, Julie J. Mirzabekov, Raag D. Airan, Kelly A. Zalocusky, Kay M. Tye, Polina Anikeeva, Robert C. Malenka, and Karl Deisseroth

ABSTRACT: Social interaction is a complex behavior essential for many species, and is impaired in major neuropsychiatric disorders. Pharmacological studies have implicated certain neurotransmitter systems in social behavior, but circuit-level understanding of endogenous neural activity during social interaction is lacking. We therefore developed and applied a new methodology, termed fiber photometry, to optically record natural neural activity in genetically- and connectivity-defined projections to elucidate the real-time role of specified pathways in mammalian behavior. Fiber photometry revealed that activity dynamics of a ventral tegmental area (VTA)-to-nucleus accumbens (NAc) projection could encode and predict key features of social but not novel-object interaction. Consistent with this observation, optogenetic control of cells specifically contributing to this projection as sufficient to modulate social behavior, which was mediated by type-1 dopamine receptor signaling downstream in the NAc. Direct observation of projection-specific activity in this way captures a fundamental and previously inaccessible dimension of circuit dynamics.