@ARTICLE{10.3389/fnmol.2018.00171, AUTHOR={Zampa, Federico and Bicker, Silvia and Schratt, Gerhard}, TITLE={Activity-Dependent Pre-miR-134 Dendritic Localization Is Required for Hippocampal Neuron Dendritogenesis}, JOURNAL={Frontiers in Molecular Neuroscience}, VOLUME={11}, YEAR={2018}, URL={https://www.frontiersin.org/articles/10.3389/fnmol.2018.00171}, DOI={10.3389/fnmol.2018.00171}, ISSN={1662-5099}, ABSTRACT={microRNAs (miRNAs) have emerged as critical regulators of neuronal dendrite development. Specific precursor (pre-)miRNAs are actively transported to dendrites, but whether this process is regulated by neuronal activity and involved in activity-dependent dendritogenesis is unknown. Here we show that BDNF, a neurotrophin that is released in response to increased neuronal activity, promotes dendritic accumulation of pre-miR-134. Dendritic accumulation, but not transcription of pre-miR-134, is abrogated by treatment of neurons with the NMDA receptor (NMDAR) antagonist APV. Furthermore, APV interferes with BDNF-mediated repression of the known miR-134 target Pumilio 2 (Pum2) in a miR-134 binding site-specific manner. At the functional level, both APV treatment and knockdown of the pre-miR-134 transport protein DHX36 antagonize BDNF-induced dendritogenesis. These effects are likely mediated by reduced dendritic miR-134 activity, since both transfection of a synthetic miR-134 duplex or of a dendritically targeted pre-miR-134-181a chimera rescues BDNF-dependent dendritogenesis in the presence of APV. In conclusion, we have identified a novel NMDAR-dependent mechanism involved in the activity-dependent control of miRNA function during neuronal development.} }