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Activity-induced protein synthesis is critical for long-lasting synaptic plasticity and subject to tight controls. MicroRNAs (miRNAs) are negative regulators of mRNA translation, but their role during synaptic plasticity is not clear. In this study, we have investigated how induction of long-term potentiation (LTP) and long-term depression (LTD) regulates the expression of miRNAs. Using miRNA arrays, we determined the temporal expression profiles of 62 hippocampal miRNAs following induction of chemical LTP (C-LTP) and metabotropic glutamate receptor-dependent LTD (mGluR-LTD). Several striking features were observed. First, C-LTP or mGluR-LTD induction changed the expression levels of most hippocampal miRNAs. Second, the majority of miRNAs regulated by C-LTP or mGluR-LTD induction followed a similar temporal expression profile. Third, most miRNAs were regulated by both C-LTP and mGluR …