Role of the TRPC1 Channel in Hippocampal Long-Term Depression and in Spatial Memory Extinction

International Journal of Molecular Sciences
Xavier YernaPhilippe Gailly

Abstract

Group I metabotropic glutamate receptors (mGluR) are involved in various forms of synaptic plasticity that are believed to underlie declarative memory. We previously showed that mGluR5 specifically activates channels containing TRPC1, an isoform of the canonical family of Transient Receptor Potential channels highly expressed in the CA1-3 regions of the hippocampus. Using a tamoxifen-inducible conditional knockout model, we show here that the acute deletion of the Trpc1 gene alters the extinction of spatial reference memory. mGluR-induced long-term depression, which is partially responsible for memory extinction, was impaired in these mice. Similar results were obtained in vitro and in vivo by inhibiting the channel by its most specific inhibitor, Pico145. Among the numerous known postsynaptic pathways activated by type I mGluR, we observed that the deletion of Trpc1 impaired the activation of ERK1/2 and the subsequent expression of Arc, an immediate early gene that plays a key role in AMPA receptors endocytosis and subsequent long-term depression.

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Citations

Jun 4, 2020·International Journal of Molecular Sciences·Roberta Gualdani, Philippe Gailly
Sep 3, 2020·Cells·Xingjuan ChenAlexander G Obukhov

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Methods Mentioned

BETA
GTPase
PCR
genotyping

Software Mentioned

WinLTP

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