Metabotropic glutamate receptor-mediated depression of the slow afterhyperpolarization is gated by tyrosine phosphatases in hippocampal CA1 pyramidal neurons

Journal of Neurophysiology
David R IrelandWickliffe C Abraham

Abstract

Group I metabotropic glutamate receptor (mGluR) agonists increase the excitability of hippocampal CAl pyramidal neurons via depression of the postspike afterhyperpolarization. In adult rats, this is mediated by both mGluR1 and -5, but the signal transduction processes involved are unknown. In this study, we investigated whether altered levels of tyrosine phosphorylation of proteins are involved in the depression of the slow-duration afterhyperpolarization (sAHP) by the Group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) in CA1 pyramidal neurons of rat hippocampal slices. Preincubation with the tyrosine kinase inhibitors lavendustin A or genistein, or the Src-specific inhibitor 3-(4-chlorophenyl) 1-(1,1-dimethylethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (PP2), did not inhibit the DHPG-mediated depression of the sAHP. However, preincubation with the tyrosine phosphatase inhibitor orthovanadate reduced the effects of DHPG. This effect of orthovanadate was prevented by simultaneous inhibition of tyrosine kinases with lavendustin A. Selective activation of either mGluR1 or -5 by application of DHPG plus either the mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP) or the mGluR1 antagonist (S)-(+)-alpha-amino-4-carb...Continue Reading

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Citations

Apr 11, 2008·Nature Reviews. Neuroscience·Wickliffe C Abraham
Jun 8, 2007·The European Journal of Neuroscience·Katja NaieDenise Manahan-Vaughan
Mar 28, 2008·The European Journal of Neuroscience·Sergey Neyman, Denise Manahan-Vaughan
May 27, 2015·Biochemical Society Transactions·Aidan Kaar, Mark G Rae
Dec 2, 2006·The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry·Geoffrey G MurphyAlcino J Silva
Dec 30, 2008·Pharmacological Reviews·Francesco FerragutiFerdinando Nicoletti
Aug 24, 2019·Neurobiology of Learning and Memory·Amy R Dunn, Catherine C Kaczorowski

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