With their ability to regulate the proteomic composition of neuronal compartments, it stands to reason that miRNAs might play a role in shaping the functional properties of neurons. miRNAs and their precursors are present in synaptic fractions along with components of the miRNA machinery where together they are poised to regulate neurotransmission. MicroRNA-132 is a highly conserved miRNA that is induced by the neurotrophin BDNF in a CREB-dependent manner. In culture, upregulation of miR132 increases dendritic outgrowth in an activity-dependent fashion via suppression of a GTPase-activating protein. miR132 has also been shown to regulate cellular excitability in cultured cells, possibly via regulation of ion channels. We have recently demonstrated that miR132 is rapidly transcribed in the hippocampus in vivo following enhanced neuronal activity and contextual fear conditioning. Exposure to light also induces transcription of miR132 in the SCN in vivo,Ergosterol where it plays a role in regulating entrainment of the circadian clock. Because miR132 has been found to affect neuronal morphology and excitability, we investigated the effects of miR132 overexpression on synaptic transmission and short-term plasticity. Here we show that overexpression of miR132 increases the paired-pulse ratio and decreases synaptic depression without affecting initial presynaptic release probability or postsynaptic sensitivity to neurotransmitter. These data indicate that miR132 selectively influences short-term plasticity without altering basal synaptic transmission. Given that miR132 has been linked with dendritic outgrowth, a decrease in calcium sensitivity of release concomitant with an increase in synapse number in miR132 overexpressing neurons could Tenacissoside-G conceivably explain the results observed in the present study. To rule out the possibility that overexpression of miR132 modifies the calcium dependence of release, we varied the external calcium concentration and measured the corresponding changes in EPSC peak amplitudes in miR132 and EGFP infected neurons. MicroRNA-132 is a neurotrophin-induced miRNA that has been demonstrated to affect neuronal characteristics such as neurite outgrowth and cell excitability. Because of its documented ability to regulate cellular characteristics in an activity dependent manner, a role for miR132 in synaptic function was investigated. In the present study, we provide evidence that overexpression of miR132 in cultured hippocampal neurons leads to selective changes in short-term synaptic plasticity. Specifically, we observed an increase in the paired-pulse ratio and a decrease in the amount of synaptic depression in response to a train of stimuli. This phenotype was not accompanied by any evidence for changes in presynaptic vesicular release probability, nor was it caused by changes in the size or the rate of refilling of the readily releasable pool. Furthermore, it cannot be explained by miR132-induced changes in the calcium sensitivity of release or postsynaptic receptor desensitization. While changes in short-term plasticity are often correlated with changes in vesicular release probability, the dissociation of these two measurements observed in the present study is not without precedent. Synaptic depression is often considered a combination of reduced presynaptic glutamate release and altered properties of postsynaptic AMPARs following glutamate binding. In addition, upregulation of neuronal calcium sensor 1 has been shown to enhance neurotransmitter release during pairs of stimuli and stimulus trains without altering basal release probability. A gene ontology search of all the computationally predicted targets listed for miR132 in the mouse genome revealed the intriguing possibility that miR132 may negatively regulate the mRNA of the pore forming a1A subunit of the P/Q-type calcium channel.