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

Moult, P. R., Corrêa, S. A.L., Collingridge, G. L., Fitzjohn, S. M. and Bashir, Z. I. (2008) Co-activation of p38 mitogen-activated protein kinase and protein tyrosine phosphatase underlies metabotropic glutamate receptor-dependent long-term depression. Journal of Physiology, 586(10), pp. 2499-2510. (doi:10.1113/jphysiol.2008.153122) (PMID:18356198)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Moult, Dr Peter
Authors: Moult, P. R., Corrêa, S. A.L., Collingridge, G. L., Fitzjohn, S. M., and Bashir, Z. I.
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Journal of Physiology
Publisher:Wiley
ISSN:0022-3751
ISSN (Online):1469-7793
Published Online:20 March 2008

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