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The Journal of Neuroscience, July 15, 2002, 22(14):6121-6128
Group I Metabotropic Glutamate Receptor (mGluR)-Dependent Long-Term Depression Mediated via p38 Mitogen-Activated Protein Kinase Is Inhibited by Previous High-Frequency Stimulation and Activation of mGluRs and Protein Kinase C in the Rat Dentate Gyrus In Vitro
Anthony M. Rush, Jianqun Wu, Michael J. Rowan, and Roger Anwyl Departments of Physiology and Pharmacology and Therapeutics, Trinity College, Dublin 2, Ireland
The induction of synaptic plasticity is known to be influenced by the previous history of the synapse, a process termed metaplasticity. Here we demonstrate a novel metaplasticity in which group I metabotropic glutamate receptor (mGluR)-dependent long-term depression (LTD) of synaptic transmission is regulated by previous mGluR activation. In these studies, the group I mGluR-dependent LTD induced by the selective agonist (RS)-3,5-dihydroxyphenylglycine (DHPG-LTD) was inhibited by previous preconditioning brief high-frequency stimulation (HFS), regardless of whether the preconditioning HFS induced long-term potentiation. Blockade of NMDA receptors during the preconditioning HFS did not alter the inhibition of DHPG-LTD by the HFS. However, antagonism of mGluRs during the preconditioning HFS did prevent the inhibition of DHPG-LTD by the HFS. In addition, blocking PKC stimulation during the preconditioning HFS also prevented the inhibitory effect of HFS on DHPG-LTD. The DHPG-LTD itself was not inhibited by blocking PKC stimulation but was inhibited by blocking the p38 mitogen-activated protein kinase (MAPK) pathway. Thus, whereas the DHPG-LTD is mediated via activation of the p38 MAPK pathway, the inhibitory effects of preconditioning HFS on DHPG-LTD are mediated via stimulation of group I/II mGluRs, activation of PKC, and subsequent blocking of the functioning of group I mGluR.
Key words: long-term potentiation (LTP); long-term depression (LTD); metabotropic glutamate receptor (mGluR); p38 MAPK; PKC; metaplasticity; preconditioning
Copyright © 2002 Society for Neuroscience 0270-6474/02/22146121-08$05.00/0
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