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The microRNA cluster miR-183/96/182 contributes to long-term memory in a protein phosphatase 1 dependent manner

ABSTRACT: Memory formation is a complex cognitive function regulated by coordinated synaptic and nuclear processes in neurons. In mammals, it is controlled by multiple molecular activators and suppressors, including the key signaling regulator protein phosphatase 1 (PP1). Here, we show that memory control by PP1 involves the miR-183/96/182 cluster, which is selectively regulated during memory formation. Inhibiting nuclear PP1 in mice brain or training in object recognition task similarly increases miR-183/96/182 expression in the hippocampus. Mimicking this increase by overexpressing miR-183/96/182 enhances object memory, while suppressing endogenous level of the cluster reduces it. This effect involves the modulation of many plasticity-related genes, and we identified HDAC9 as one of the functional targets. Further, PP1 controls miR-183/96/182 in a transcription-independent manner influencing processing of their precursors. These findings provide novel evidence for the role of miRNAs in memory formation and suggest the implication of PP1 in miRNAs processing in the adult brain.

ORGANISM(S): Mus musculus

PROVIDER: GSE83707 | GEO | 2016/09/20

SECONDARY ACCESSION(S): PRJNA326768

REPOSITORIES: GEO

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