NDLI: Acquisition of contextual discrimination involves the appearance of a RAS-GRF1/p38 mitogen-activated protein (MAP) kinase-mediated signaling pathway that promotes long term potentiation (LTP).

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Acquisition of contextual discrimination involves the appearance of a RAS-GRF1/p38 mitogen-activated protein (MAP) kinase-mediated signaling pathway that promotes long term potentiation (LTP).

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Acquisition of contextual discrimination involves the appearance of a RAS-GRF1/p38 mitogen-activated protein (MAP) kinase-mediated signaling pathway that promotes long term potentiation (LTP).

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Tian, Xuejun Jin, Shan-xue Feig, Larry A. Kumar-singh, Rajendra Arai, Junko
Description	Author Affiliation: Jin SX ( Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.)
Abstract	RAS-GRF1 is a guanine nucleotide exchange factor with the ability to activate RAS and RAC GTPases in response to elevated calcium levels. We previously showed that beginning at 1 month of age, RAS-GRF1 mediates NMDA-type glutamate receptor (NMDAR)-induction of long term depression in the CA1 region of the hippocampus of mice. Here we show that beginning at 2 months of age, when mice first acquire the ability to discriminate between closely related contexts, RAS-GRF1 begins to contribute to the induction of long term potentiation (LTP) in the CA1 hippocampus by mediating the action of calcium-permeable, AMPA-type glutamate receptors (CP-AMPARs). Surprisingly, LTP induction by CP-AMPARs through RAS-GRF1 occurs via activation of p38 MAP kinase rather than ERK MAP kinase, which has more frequently been linked to LTP. Moreover, contextual discrimination is blocked by knockdown of Ras-Grf1 expression specifically in the CA1 hippocampus, infusion of a p38 MAP kinase inhibitor into the CA1 hippocampus, or the injection of an inhibitor of CP-AMPARs. These findings implicate the CA1 hippocampus in the developmentally dependent capacity to distinguish closely related contexts through the appearance of a novel LTP-supporting signaling pathway.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	30
Volume Number	288
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2013-07-26
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discrimination (Psychology) Physiology Long-Term Potentiation Signal Transduction P38 Mitogen-Activated Protein Kinases Metabolism Ras-GRF1 Adamantane Analogs & Derivatives Pharmacology Animals Butadienes CA1 Region, Hippocampal Cytology Calcium Extracellular Signal-Regulated MAP Kinases Antagonists & Inhibitors Imidazoles Drug Effects Mice Mice, Inbred C57BL Mice, Knockout Neurons Nitriles Pyridines RNA Interference Receptors, AMPA Time Factors Genetics Research Support, N.I.H., Extramural Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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