Genetic analyses have linked MicroRNA-137 ( MIR137 ) to neuropsychiatric disorders, including schizophrenia and autism spectrum disorder (ASD). MiR-137 plays important roles in neurogenesis and neuronal maturation, but the impact of miR-137 loss of function in vivo remains unclear. Here we show the complete loss of miR-137 in the mouse germline (gKO) or nervous system (cKO) leads to postnatal lethality, while heterozygous gKO and cKO mice remain viable. Partial loss of miR-137 in heterozygous cKO mice results in dysregulated synaptic plasticity, repetitive behavior, and impaired learning and social behavior. Transcriptomic and proteomic analyses revealed that the miR-137 mRNA target, Phosphodiesterase 10a (Pde10a), is elevated in heterozygous KO mice. Treatment with the PDE10A inhibitor papaverine or knockdown of Pde10a ameliorates the deficits observed in the heterozygous cKO mice. Collectively, our results suggest that MIR137 plays essential roles in postnatal neurodevelopment, and that dysregulation of miR-137 potentially contributes to neuropsychiatric disorders in humans.

Acid taste, evoked mainly by protons (H+), is a core taste modality for many organisms. The hedonic valence of acid taste is bidirectional: animals prefer slightly but avoid highly acidic foods. However, how animals discriminate low from high acidity remains poorly understood. To explore the taste perception of acid, we use the fruit fly as a model organism. We find that flies employ two competing taste sensory pathways to detect low and high acidity, and the relative degree of activation of each determines either attractive or aversive responses. Moreover, we establish one member of the fly Otopetrin family, Otopetrin-like a (OtopLa), as a proton channel dedicated to the gustatory detection of acid. OtopLa defines a unique subset of gustatory receptor neurons and is selectively required for attractive rather than aversive taste responses. Loss of otopla causes flies to reject normally attractive low-acid foods. Therefore, the identification of OtopLa as a low-acid sensor firmly supports our competition model of acid taste sensation. Altogether, we have discovered a binary acid-sensing mechanism that may be evolutionarily conserved between insects and mammals.