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This Article Full Text Full Text (PDF) All Versions of this Article: 586/10/2499    most recent jphysiol.2008.153122v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Moult, P. R. Articles by Bashir, Z. I. Search for Related Content PubMed PubMed Citation Articles by Moult, P. R. Articles by Bashir, Z. I. Related Collections Neuroscience

¹ MRC Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, Bristol BS8 1TD, UK

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.

(Received 25 February 2008; accepted after revision 13 March 2008; first published online 20 March 2008)
Corresponding author P. R. Moult: Neurosciences Institute, Division of Pathology & Neuroscience, Ninewells Hospital & Medical School, University of Dundee, Dundee DD1 9SY, UK. Email: p.r.moult{at}dundee.ac.uk

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