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1 Acta Neurobiologiae Experimentalis

1 2019

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Mice with a deletion of the mammal-specific microRNA 379‑410 cluster display altered ultrasonic communication

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Sungur A. O. , Lackinger M. , Stemmler L. , Grosse R. , Schwarting R. , Schratt G. , Wohr M.

nr Suppl.1

INTRODUCTION: microRNAs (miRNAs) represent a group of small, noncoding RNA molecules that play a major role in the posttranscriptional regulation of gene expression. Members of a large placental mammal‑specific miRNA cluster, miR379‑410 have been implicated in a variety of neurodevelopmental disorders. Recently, we have shown that deletion of this cluster in mice leads to hypersocial behavior and increased emission of ultrasonic vocalizations (USV), which is accompanied by altered excitatory synaptic transmission and exaggerated expression of ionotropic glutamate receptor complexes in the hippocampus. To further investigate the contribution of the miR379‑410 cluster to communication deficits present in neurodevelopmental disorders, here we performed a detailed analysis of acoustic features of isolation-induced pup USV and juvenile USV. AIM(S): We aimed to investigate mania-like elevated drive by studying effects of the psychostimulant d-amphetamine (AMPH) on locomotor activity. METHOD(S): To measure isolation-induced pup USV, mice were isolated from the mother and littermates for 10min on postnatal day (PND) 3, 6, 9, and 12. Juvenile reciprocal social interaction was tested on PND 23. Mania-like elevated drive was investigated by treating mice with 2.5mg/kg AMPH. RESULTS: In addition to increased call rate, mouse pups lacking the miR379‑410 cluster displayed increased peak amplitude and frequency modulation. Juvenile knockout pairs spent significantly more time interacting with each other and emitted more pro-social USV as compared to wildtype pairs. Mutant as well as wildtype mice reacted to AMPH treatment by a significant increase in locomotor activity, and no genotype differences were evident, indicating lack of mania-like behavior in miR379‑410 mutants. CONCLUSIONS: Taken together, the present study confirms and extends previous findings, showing that deletion of the miR379‑410 cluster leads to altered communication without affecting psychostimulant-induced hyperactivity.