Activity‐dependent changes in gene‐expression are believed to underlie the molecular representation of memory. In this study, we report that in vivo activation of neurons rapidly induces the CREB‐regulated microRNA miR‐132. To determine if production of miR‐132 is regulated by neuronal activity its expression in mouse brain was monitored by quantitative RT‐PCR (RT‐qPCR). Pilocarpine‐induced seizures led to a robust, rapid, and transient increase in the primary transcript of miR‐132 (pri‐miR‐132) followed by a subsequent rise in mature microRNA (miR‐132). Activation of neurons in the hippocampus, olfactory bulb, and striatum by contextual fear conditioning, odor‐exposure, and cocaine‐injection, respectively, also increased pri‐miR‐132. Induction kinetics of pri‐miR‐132 were monitored and found to parallel those of immediate early genes, peaking at 45 min and returning to basal levels within 2 h of stimulation. Expression levels of primary and mature‐miR‐132 increased significantly between postnatal Days 10 and 24. We conclude that miR‐132 is an activity‐dependent microRNA in vivo, and may contribute to the long‐lasting proteomic changes required for experience‐dependent neuronal plasticity. © 2009 Wiley‐Liss, Inc.