Group I metabotropic glutamate receptors (mGluR) are involved in various forms of synaptic plasticity that underlie declarative memory by inducing long-term depression (mGluR-LTD). mGLUR-LTD results from an endocytosis of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) underlying synaptic depression. The lab has previously shown that mGluR5 specifically activates TRPC1 channel, a Transient Receptor Potential channel that is highly expressed in CA1-3 regions of the hippocampus.To investigate the role of mGluR-TRPC1 in synaptic plasticity, and to decipher its downstream pathway, we induced an acute deletion of Trpc1 gene, using the Cre-tamoxifen conditional system, in a murine model of Fragile X Syndrome (FX). FX is a genetical disorder characterized by an enhanced activation of mGluR5, an accelerated memory extinction, and an exaggerated mGluR-LTD that persists even in the presence of anisomycin, a protein synthesis inhibitor.Acute deletion of Trpc1 almost abolished the mGluR-LTD observed in FX mice (FX Cre), and results in a maintained surface AMPARs that did not undergo endocytosis. Furthermore, memory extinction was reduced in both Morris Water Maze and Passive Avoidance tests after inhibiting Trpc1. Finally, in hippocampal brain slices that lack Trpc1, activation of mGluR5 by its agonist, DHPG, failed to increase Arc, an activity regulated cytoskeleton associated protein and failed to phosphorylate ERK, the extracellular signal-regulated kinases, both essentials for mGluR-LTD.Here we show that TRPC1 is involved in maintaining a normal mGluR-LTD, and is required for memory extinction, an important process in synaptic plasticity. Deciphering its pathway remains under-investigation through different candidates and transcription-factors implicated in synaptic-plasticity.