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Mechanisms underlying dedepression of synaptic NMDA receptors in the hippocampus.
J Neurophysiol. 2008 Jan; 99(1):254-63.JN

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.

Authors+Show Affiliations

Morishita W
Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, USA.
Malenka RC
No affiliation info available

MeSH

AnimalsEnzyme InhibitorsExcitatory Postsynaptic PotentialsExtracellular Signal-Regulated MAP KinasesHippocampusInhibitory Postsynaptic PotentialsLong-Term Synaptic DepressionMAP Kinase Signaling SystemNeural InhibitionNeural PathwaysNeuronsNuclear ProteinsOrgan Culture TechniquesRatsRats, Sprague-DawleyReceptors, AMPASynapsesSynaptic Transmission

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17989241

Citation

Morishita, Wade, and Robert C. Malenka. "Mechanisms Underlying Dedepression of Synaptic NMDA Receptors in the Hippocampus." Journal of Neurophysiology, vol. 99, no. 1, 2008, pp. 254-63.
Morishita W, Malenka RC. Mechanisms underlying dedepression of synaptic NMDA receptors in the hippocampus. J Neurophysiol. 2008;99(1):254-63.
Morishita, W., & Malenka, R. C. (2008). Mechanisms underlying dedepression of synaptic NMDA receptors in the hippocampus. Journal of Neurophysiology, 99(1), 254-63.
Morishita W, Malenka RC. Mechanisms Underlying Dedepression of Synaptic NMDA Receptors in the Hippocampus. J Neurophysiol. 2008;99(1):254-63. PubMed PMID: 17989241.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanisms underlying dedepression of synaptic NMDA receptors in the hippocampus. AU - Morishita,Wade, AU - Malenka,Robert C, Y1 - 2007/11/07/ PY - 2007/11/9/pubmed PY - 2008/3/25/medline PY - 2007/11/9/entrez SP - 254 EP - 63 JF - Journal of neurophysiology JO - J Neurophysiol VL - 99 IS - 1 N2 - 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. SN - 0022-3077 UR - https://www.unboundmedicine.com/medline/citation/17989241/Mechanisms_underlying_dedepression_of_synaptic_NMDA_receptors_in_the_hippocampus_ DB - PRIME DP - Unbound Medicine ER -