miRNA-mediated inhibition of an actomyosin network in hippocampal pyramidal neurons restricts sociability in adult male mice

We recently reported that the loss of the microRNA cluster miR-379-410 leads to hypersocial behavior and anxiety in mice. With this study, we show that ablating miR-379-410 in excitatory neurons of the postnatal mouse hippocampus recapitulates hypersociability, but not anxiety. At the cellular level, miR-379-410 loss in excitatory neurons leads to increased excitatory synaptic transmission and upregulation of an actomyosin gene network. Re-expression of three cluster miRNAs, as well as pharmacological inhibition of the actomyosin activator ROCK, was sufficient to reinstate normal sociability in miR-379-410 knockout mice. Our results unveil a novel microRNA-actomyosin pathway involved in the control of sociability.