MicroRNA as modulators of neuronal responses

Neuronal activity controls the correct establishment and refinement of neuronal circuits by regulating key aspects such as dendritogenesis and spine development. Both transcriptional and post-transcriptional gene expression programs induced by neuronal activity have to be coordinated in a tight spatio-temporal manner in order for proper functioning of the neuron. In this context microRNAs (miRNAs), which are implicated in post-transcriptional gene regulation, are good candidates to control dendritic and spine development. In a recent study we have demonstrated that neuronal activity induces myocyte enhancing factor 2 (Mef2) dependent transcription of a large cluster of brain-specific miRNAs (miR379-410). Expression of at least three microRNAs (miR-329,-134 and -381) from this cluster is essential for activity-dependent dendritic outgrowth of hippocampal neurons. One of these three miRNAs, miR-134, promotes dendritic outgrowth by inhibiting translation of the mRNA encoding the translational regulator Pumilio2 (Pum2). In brief, our results suggest a novel role for Mef2 in promoting activity-dependent dendritogenesis by inducing the transcription of the miR379-410 cluster.