Research article summary (published 5 Nov 2007):

Mechanisms underlying dedepression of synaptic NMDA receptors in the hippocampus.

Full Abstract

N-Methyl-D-aspartate receptor (NMDAR)-mediated synaptic responses in hippocampal CA1 pyramidal cells are depressed during NMDAR-dependent long-term depression (LTD) due to mechanisms, in part, distinct from those underlying LTD of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated synaptic responses. The mechanisms underlying dedepression of synaptic NMDARs, however, are not known. We find that dedepression of NMDAR-mediated synaptic responses in the CA1 region of the rat hippocampus is input specific and does not require synaptic stimulation to be maintained. The induction of dedepression does not require activation of metabotropic glutamate receptors, L-type Ca(2+) channels, or release of Ca(2+) from intracellular stores. It does, however, rely on activation of NMDARs. In contrast to the dedepression of AMPAR-mediated synaptic responses, dedepression of NMDAR-mediated synaptic responses does not depend on activation of calcium/calmodulin-dependent protein kinase II, protein kinase C, cAMP-dependent protein kinase, or Src kinases. However, dedepression of synaptic NMDARs is significantly impaired by inhibitors of mitogen-activated protein kinase signaling. Specifically, inhibitors of extracellular signal-regulated kinase 1/2 prevented normal dedepression of synaptic NMDARs by a mechanism that did not require protein synthesis. These results provide further evidence that synaptic NMDARs can be bidirectionally modified by activity but by mechanisms distinct from those responsible for the activity-dependent, bidirectional modulation of synaptic AMPARs.

Author information

Author/s: Morishita, Wade (W); Malenka, Robert C (RC);

Affiliation: Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, USA.

Grants: 5 R37 MH-063394 (Agency:NIMH NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: Journal of neurophysiology (J Neurophysiol), published in United States. (Language: eng)

Reference: 2008-Jan; vol 99 (issue 1) : pp 254-63

Dates: Created 2008/01/15; Completed 2008/03/24;

PMID: 17989241, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Enzyme Inhibitors - pharmacology Excitatory Postsynaptic Potentials - drug effects; physiology Extracellular Signal-Regulated MAP Kinases - antagonists & inhibitors; metabolism Hippocampus - drug effects; metabolism; ultrastructure Inhibitory Postsynaptic Potentials - drug effects; physiology Long-Term Synaptic Depression - drug effects; physiology MAP Kinase Signaling System - drug effects; physiology Neural Inhibition - drug effects; physiology

Neural Pathways - drug effects; metabolism; ultrastructure Neurons - drug effects; metabolism; ultrastructure Nuclear Proteins - drug effects; metabolism Organ Culture Techniques Rats Rats, Sprague-Dawley Receptors, AMPA - drug effects; metabolism Synapses - drug effects; metabolism; ultrastructure Synaptic Transmission - drug effects; physiology

Associated Chemicals: Enzyme Inhibitors (0) ; NARG2 protein, mouse (0) ; Nuclear Proteins (0) ; Receptors, AMPA (0) ; Extracellular Signal-Regulated MAP Kinases (EC 2.7.1.37)

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