MiR-980 Is a Memory Suppressor MicroRNA that Regulates the Autism-Susceptibility Gene A2bp1

•Drosophila miR-980 inhibition enhances olfactory memory; miR-980 overexpression impairs olfactory memory•miR-980 inhibition in multiple areas of the adult brain enhances memory•miR-980 modulates odor-induced calcium responses and excitability in the adult brain•miR-980 represses A2bp1 expression in the adult brain; reducing A2bp1 expression reverses the memory enhancement due to miR-980 inhibition

SummaryMicroRNAs have been associated with many different biological functions, but little is known about their roles in conditioned behavior. We demonstrate that Drosophila miR-980 is a memory suppressor gene functioning in multiple regions of the adult brain. Memory acquisition and stability were both increased by miR-980 inhibition. Whole cell recordings and functional imaging experiments indicated that miR-980 regulates neuronal excitability. We identified the autism susceptibility gene, A2bp1, as an mRNA target for miR-980. A2bp1 levels varied inversely with miR-980 expression; memory performance was directly related to A2bp1 levels. In addition, A2bp1 knockdown reversed the memory gains produced by miR-980 inhibition, consistent with A2bp1 being a downstream target of miR-980 responsible for the memory phenotypes. Our results indicate that miR-980 represses A2bp1 expression to tune the excitable state of neurons, and the overall state of excitability translates to memory impairment or improvement.

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