NMDA receptor phosphorylation at a site affected in schizophrenia controls synaptic and behavioral plasticity.

Full Abstract

Phosphorylation of the NR1 subunit of NMDA receptors (NMDARs) at serine (S) 897 is markedly reduced in schizophrenia patients. However, the role of NR1 S897 phosphorylation in normal synaptic function and adaptive behaviors are unknown. To address these questions, we generated mice in which the NR1 S897 is replaced with alanine (A). This knock-in mutation causes severe impairment in NMDAR synaptic incorporation and NMDAR-mediated synaptic transmission. Furthermore, the phosphomutant animals have reduced AMPA receptor (AMPAR)-mediated synaptic transmission, decreased AMPAR GluR1 subunit in the synapse, and impaired long-term potentiation. Finally, the mutant mice exhibit behavioral deficits in social interaction and sensorimotor gating. Our results suggest that an impairment in NR1 phosphorylation leads to glutamatergic hypofunction that can contribute to behavioral deficits associated with psychiatric disorders.

Author information

Author/s: Li, Bo (B); Devidze, Nino (N); Barengolts, Denis (D); Prostak, Naseem (N); Sphicas, Eleana (E); Apicella, Alfonso J (AJ); Malinow, Roberto (R); Emamian, Effat S (ES);

Affiliation: The Rockefeller University, New York, New York 10021, USA.

Grants: R01137MH04159 (Agency:NIMH NIH HHS)

Journal and publication information

Publication Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci), published in United States. (Language: eng)

Reference: 2009-Sep; vol 29 (issue 38) : pp 11965-72

Dates: Created 2009/09/24; Completed 2009/10/09;

PMID: 19776282, status: MEDLINE (last retrieval date: 10/9/2009, 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
Behavior, Animal - physiology
Brain - physiology; ultrastructure
Gene Knock-In Techniques
Long-Term Potentiation - genetics; physiology
Male
Mice
Mice, Inbred C57BL
Mutation, Missense

Neuronal Plasticity - genetics
Neurons - physiology; ultrastructure
Phosphorylation
Receptors, AMPA - metabolism
Receptors, N-Methyl-D-Aspartate - genetics; metabolism
Schizophrenia - genetics
Social Behavior
Synapses - genetics; physiology; ultrastructure
Synaptic Transmission - genetics; physiology

Associated Chemicals: NR1 NMDA receptor (0) ; Receptors, AMPA (0) ; Receptors, N-Methyl-D-Aspartate (0) ; glutamate receptor ionotropic, AMPA 1 (0)

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