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

Abstract

SUMMARY 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.

Genomic Analysis of Genotype-by-Social Environment Interaction for Drosophila melanogaster Aggressive Behavior

“…Three of the genes associated with GSEI were osa, which is believed to be involved in neurogenesis (Neumüller et al 2011); Ten-a, which has shown to affect synaptic growth (Mosca et al 2012); and trv, which has shown to regulate dendritic morphogenesis (Honjo et al 2016). In addition, two of the associated genes have previously been associated with sleep (CG13868 and DNaseII (Thimgan et al 2015)), and two have been found to influence memory (Rbfox1 (Guven-Ozkan et al 2016) and Syn (Michels et al 2011)). tow was found associated with GSEI.…”

Mushroom body-specific profiling of gene expression identifies regulators of long-term memory inDrosophila

“…Interestingly while both genes regulated neuronal excitability, the molecular mechanisms that regulate learning and memory appear distinct. The autism susceptibility gene, A2bp1 was identified as target of mir-980 causing memory enhancement, while mir-276a interferes with memory formation by regulating Dopamine receptor expression (Li et al 2013; Guven-Ozkan et al 2016). While the role for mir-282 in learning and memory formation was unknown, a recent study identified the adenylyl cyclase rutabaga as target gene of mir-282 (Vilmos et al 2013).…”

Ex vivo Whole-cell Recordings in Adult Drosophila Brain

“…Although the process is invasive and may cause damage to the brain, intact neurons and functional circuits can be persevered and maintained for up to one hour after skillful dissection. Labs have used whole brain dissection and whole-cell recordings to characterize the electrical properties of circadian neurons (Sheeba et al , 2008b), uncover the electrical cellular mechanisms responsible for sleep and arousal (Sheeba et al , 2008a), discover a new light-sensing pathway in the brain (Ni et al , 2017), determine the mechanism of action for a common pesticide (Qiao et al , 2014), find a memory suppressor miRNA that regulates an autism susceptibility gene (Guven-Ozkan et al , 2016), and describe synaptic dysfunction in a model of Parkinson’s Disease (Sun et al , 2016). …”