Interestingly, a recent paper demonstrated increased paired-pulse facilitation and decreased synaptic depression with acute selective pharmacological blockade of Cav2.1, an identical phenotype to that shown here. While a reduction of P/Qtype calcium channels would also be predicted to decrease the probability of release, it is possible that levels of N-type calcium channels are increased in compensation, countering any change in basal release probability and yielding results similar to Scheuber et al. This possibility is supported by the fact that N-type channels are upregulated in Cav2.1 KO mice. A strong caveat to this candidate mechanism, however, comes from Ishikawa and colleagues who, using the aforementioned Cav2.1 KO mice to compare the basic properties of N-type and P/Q-type calcium currents in the calyx of Held, found that P/Q-type, but not Ntype, calcium currents undergo activity-dependent facilitation,Tenacissoside-I in conflict with the results of Scheuber et al.. Thus, while Cav2.1 is an intriguing computationally predicted target of miR132, its regulation by miR132 remains to be demonstrated and the expected phenotypic effect of such regulation is debated. The fact that we observed no change in either EPSC size or the frequency of spontaneous mEPSCs suggests that there was no change in the number of synapses made by miR132-overexpressing neurons. This result was slightly unexpected given that upregulation of miR132 was previously reported to increase neurite outgrowth. Indeed, two very recent studies did observe increases in spontaneous mEPSC frequency following either overexpression of miR132 or downregulation of p250GAP, a target of miR132. Together, these results suggest that the effects of miR132 on spontaneous release and neuronal morphology are complex, and likely influenced by undetermined variables. Increasingly, research shows that miRNAs play a role in regulating synaptic formation, maturation, and function. A growing body of evidence also implicates miRNAs in the regulation of long-term plasticity in the mature nervous system. However, to our knowledge, no previous study has demonstrated a role for miRNAs in short-term synaptic plasticity. Our findings suggest that miR132 can modulate the computational properties of hippocampal neurons by regulating short-term plasticity in ways that promote facilitation and/or reduce synaptic depression without affecting basal synaptic transmission. The molecular mechanism of this effect remains elusive, and future studies will be aimed at evaluating candidate mRNA targets of miRNA132 that might mediate this phenotype. Solutions were exchanged with a gravity-feed bath perfusion system. Immediately after achieving whole-cell configuration, spontaneous mEPSCs were recorded continuously over 10 sec periods. Peak amplitudes of Tenacissoside-X spontaneous mEPSCs were measured offline semi-automatically by using an adjustable amplitude threshold. All deflections from baseline greater than threshold were detected. Selected events were then visually examined, and any spurious events were manually rejected, and any missed events were flagged for inclusion in the mean amplitude and frequency calculations. mEPSC frequencies were calculated by dividing the total number of mEPSC events by the total time sampled. The size of the readily releasable pool of vesicles was measured with hypertonic solution by applying divalent-free extracellular solution containing 0.5 M sucrose to an isolated autaptic neuron using a puffer pipette controlled by a picospritzer. A vacuum pipette was used to clear the hypertonic solution rapidly.