Co-activation of p38 mitogen-activated protein kinase and protein tyrosine phosphatase underlies metabotropic glutamate receptor-dependent long-term depression

Peter R. Moult, Sônia A. L. Corrêa, Graham L. Collingridge, Stephen M. Fitzjohn, Zafar I. Bashir

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Long-term potentiation (LTP) and long-term depression (LTD) are forms of synaptic plasticity thought to contribute to learning and memory. Much is known about the mechanisms of NMDA receptor-dependent LTD in the CA1 region of rat hippocampus but there is still considerable uncertainty about the mechanisms of LTD induced by mGluR activation (mGluR-LTD). Furthermore, data on mGluR-LTD derives largely from studies using pharmacologically induced LTD. To investigate mGluR-LTD that is more physiologically relevant we have examined, in CA1 of adult rat hippocampus, mechanisms of synaptically induced mGluR-LTD. We provide the first demonstration that activation of protein tyrosine phosphatase (PTP) is essential for the induction of synaptically induced mGluR-LTD. In addition, we show that activation of p38 MAPK is also required for this form of LTD. Furthermore, LTD can be mimicked and occluded by activation of p38 MAPK, provided that protein tyrosine kinases (PTKs) are inhibited. These data therefore demonstrate that a novel combination of signalling cascades, requiring both activation of p38 MAPK and tyrosine de-phosphorylation, underlies the induction of synaptically induced mGluR-LTD.
Original languageEnglish
Pages (from-to)2499-2510
Number of pages12
JournalThe Journal of Physiology
Volume587
Issue number10
DOIs
Publication statusPublished - May 2008

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