Abstract
MicroRNAs 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.
Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Animals, Genetically Modified
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Autism Spectrum Disorder / genetics
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Autism Spectrum Disorder / metabolism
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Autism Spectrum Disorder / pathology
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Base Sequence
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Brain / growth & development
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Brain / metabolism*
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Conditioning, Classical / physiology
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Disease Models, Animal
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Drosophila Proteins / antagonists & inhibitors
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Drosophila Proteins / genetics*
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Drosophila Proteins / metabolism
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Drosophila melanogaster / genetics*
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Drosophila melanogaster / metabolism
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Gene Expression Regulation, Developmental
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Genetic Predisposition to Disease
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Humans
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Memory / physiology*
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MicroRNAs / genetics*
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MicroRNAs / metabolism
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Molecular Sequence Data
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Olfactory Receptor Neurons / cytology
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Olfactory Receptor Neurons / metabolism*
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Protein Binding
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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RNA-Binding Proteins / antagonists & inhibitors
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RNA-Binding Proteins / genetics*
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RNA-Binding Proteins / metabolism
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Signal Transduction
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Transcription Factors / genetics
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Transcription Factors / metabolism
Substances
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Drosophila Proteins
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GAL4 protein, Drosophila
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MicroRNAs
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RNA, Small Interfering
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RNA-Binding Proteins
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Rbfox1 protein, Drosophila
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Transcription Factors