miR-135a Regulates Synaptic Transmission and Anxiety-Like Behavior in Amygdala

Cecilia Mannironi, Antonio Biundo, Samyutha Rajendran, Francesca de Vito, Luana Saba, Silvia Caioli, Cristina Zona, Teresa Ciotti, Silvana Caristi, Emerald Perlas, Giorgia Del Vecchio, Irene Bozzoni, Arianna Rinaldi, Andrea Mele, Carlo Presutti

Research output: Contribution to journalArticle

Abstract

MicroRNAs are a class of non-coding RNAs with a growing relevance in the regulation of gene expression related to brain function and plasticity. They have the potential to orchestrate complex phenomena, such as the neuronal response to homeostatic challenges. We previously demonstrated the involvement of miR-135a in the regulation of early stress response. In the present study, we examine the role of miR-135a in stress-related behavior. We show that the knockdown (KD) of miR-135a in the mouse amygdala induces an increase in anxiety-like behavior. Consistently with behavioral studies, electrophysiological experiments in acute brain slices indicate an increase of amygdala spontaneous excitatory postsynaptic currents, as a result of miR-135a KD. Furthermore, we presented direct evidences, by in vitro assays and in vivo miRNA overexpression in the amygdala, that two key regulators of synaptic vesicle fusion, complexin-1 and complexin-2, are direct targets of miR-135a. In vitro analysis of miniature excitatory postsynaptic currents on miR-135a KD primary neurons indicates unpaired quantal excitatory neurotransmission. Finally, increased levels of complexin-1 and complexin-2 proteins were detected in the mouse amygdala after acute stress, accordingly to the previously observed stress-induced miR-135a downregulation. Overall, our results unravel a previously unknown miRNA-dependent mechanism in the amygdala for regulating anxiety-like behavior, providing evidences of a physiological role of miR-135a in the modulation of presynaptic mechanisms of glutamatergic neurotransmission.

Original languageEnglish
Pages (from-to)1-15
Number of pages15
JournalMolecular Neurobiology
DOIs
Publication statusAccepted/In press - May 9 2017

Keywords

  • Amygdala
  • microRNAs
  • miR-135a
  • Post-transcriptional regulation
  • Stress-related disease
  • Synaptic activity
  • Synaptic transmission

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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    Mannironi, C., Biundo, A., Rajendran, S., de Vito, F., Saba, L., Caioli, S., Zona, C., Ciotti, T., Caristi, S., Perlas, E., Del Vecchio, G., Bozzoni, I., Rinaldi, A., Mele, A., & Presutti, C. (Accepted/In press). miR-135a Regulates Synaptic Transmission and Anxiety-Like Behavior in Amygdala. Molecular Neurobiology, 1-15. https://doi.org/10.1007/s12035-017-0564-9