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CEMO Seminar - Wednesday October, 11th at 12:00

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Woluwé-St-Lambert
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The CEMO Division is pleased to invite you to the next CEMO seminar that will take place on Wednesday Octobre, 11 th from 12:00 to 2:00 pm in the room Gerty Cori.

Speaker: Farah ISSA - Laboratory of Cell Physiology

Background: Group I metabotropic glutamate receptors (mGluR) are involved in various forms of synaptic plasticity that are believed to underlie declarative memory by inducing long-term depression (mGluR-LTD). This 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 channels containing TRPC1, an isoform of the canonical family of Transient Receptor Potential channels that is highly expressed in CA1-3 regions of the hippocampus.

Methods: 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 genetic 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.

Results: Acute deletion of Trpc1 was able to almost abolish the mGluR-LTD observed in these FX mice (FX Cre), and results in a maintained surface AMPARs that did not undergo endocytosis. Furthermore, memory extinction seen in these mice 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.

Discussion: 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.

  • Mercredi, 11 octobre 2023, 08h00
    Mercredi, 11 octobre 2023, 17h00