Post-transcriptional regulation of gene expression plays an important role in activity-dependent regulation of synaptic function and plasticity. One of the important class of regulators are microRNAs which pair in a sequence-specific manner to target mRNAs. The mature miRNA recruits Arogonaute 2 (Ago2) and other proteins of the RNA-induced silencing complex (RISC), resulting in translational silencing of target mRNAs. At active synapses, derepression of microRNAs could function in protein synthesis-dependent plasticity. However, very little is known about the regulation of microRNA-RISC proteins during the cycle of miRNA function, especially in in-vivo models. Here, we sought to identify changes in the composition of the miRNA-RISC following induction of Long term potentiation (LTP) in the dentate gyrus of intact adult rats. Induction of LTP is done unilaterally in the left dentate gyrus (LDG) of adult anesthetized rats, stimulating the medial perfront path by high frequency stimulation (HFS) and recording of evoked potentials in the hilar region of dentate gyrus. Following LTP induction, the dentate gyrus is dissected and subjected to co-immunoprecipitation with anti-Ago2 antibody, to isolate the RISC. A combination of immunoblotting and proteomic approaches is being used to identify and quantify possible changes in the miRNA-RISC during LTP. Co-immunoprecipitation of RISC with anti-Ago2 identified several RISC proteins, including Dicer, Mov10 and DDX6. The levels of Ago2 protein vary at various time points of High Frequency stimulation (HFS). Analysis of modulation of the miRNA RISC could thus provide insight into how miRNAs along with its protein partners mediate long term potentiation, in-vivo.