Premium
Long‐Term Depression in the Hippocampus In Vivo Is Associated with Protein Phosphatase‐Dependent Alterations in Extracellular Signal‐Regulated Kinase
Author(s) -
Norman Eric D.,
Thiels Edda,
Barrionuevo German,
Klann Eric
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0740192.x
Subject(s) - phosphatase , mapk/erk pathway , okadaic acid , kinase , long term potentiation , hippocampal formation , protein kinase a , dusp6 , biology , extracellular , microbiology and biotechnology , hippocampus , protein phosphatase 1 , phosphorylation , medicine , endocrinology , protein phosphatase 2 , biochemistry , receptor
There is growing evidence that activation of either protein kinases or protein phosphatases determines the type of plasticity observed after different patterns of hippocampal stimulation. Because activation of the extracellular signal‐regulated kinase (ERK) has been shown to be necessary for long‐term potentiation, we investigated the regulation of ERK in long‐term depression (LTD) in the adult hippocampus in vivo. We found that ERK immunoreactivity was decreased following the induction of LTD and that this decrease required NMDA receptor activation. The LTD‐associated decrease in ERK immunoreactivity could be simulated in vitro via incubation of either purified ERK2 or hippocampal homogenates with either protein phosphatase 1 or protein phosphatase 2A. The protein phosphatase‐dependent decrease in ERK immunoreactivity was inhibited by microcystin. Intrahippocampal administration of the protein phosphatase inhibitor okadaic acid blocked the LTD‐associated decrease in ERK2, but not ERK1, immunoreactivity. Collectively, these data demonstrate that protein phosphatases can decrease ERK immunoreactivity and that such a decrease occurs with ERK2 during LTD. These observations provide the first demonstration of a biochemical alteration of ERK in LTD.