Social memory deficit gated by dysregulation of the cerebellar vermis

Abstract Social recognition memory (SRM) is a key determinant of social behavior because it integrates past experiences into social interactions to distinguish familiar from novel conspecifics. The cerebellum is an important region for social functions; dysregulated cerebellar output is a common phenotype in various mouse models of autism. However, how the abnormal local activity in the cerebellum leads to social behavior deficits remains unknown. To this end, we selectively increased the excitability of molecular layer interneurons (MLIs) to suppress Purkinje cell (PC) firing with chemo- and optogenetic approaches in the mouse cerebellar vermis. Chemogenetic perturbation of MLIs impaired SRM without affecting sociability, anxiety levels, motor coordination or object recognition. Optogenetic interference of MLIs during distinct phases of a social recognition test highlighted cerebellar engagement in retrieval, but not encoding, of social information. Functional mapping with an immediate early gene product (c-Fos) following the social recognition test revealed that cerebellar manipulation significantly reduced brain-wide interregional correlations and shifted network structure from the medial prefrontal cortex (mPFC) and hippocampus- to amygdala-centered modules. Transsynaptic tracing showed hierarchical projections from the central cerebellum to the social brain network. Collectively, our results suggest that the cerebellum organizes the neural matrix required for SRM, providing a circuitry basis for social impairments in autism and other psychiatric disorders.