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Behavioral deficits and subregion-specific suppression of LTP in mice expressing a population of mutant NMDA receptors throughout the hippocampus

Chen, P. E., Errington, M. L., Kneussel, M., Chen, G., Annala, A. J., Rudhard, Y. H., Rast, G. F., Specht, C. G., Tigaret, C. M., Nassar, M. A., Morris, R. G. M., Bliss, T. V. P. and Schoepfer, R. 2009. Behavioral deficits and subregion-specific suppression of LTP in mice expressing a population of mutant NMDA receptors throughout the hippocampus. Learning and Memory 16 (10) , pp. 635-644. 10.1101/lm.1316909

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Abstract

The NMDA receptor (NMDAR) subunit GluN1 is an obligatory component of NMDARs without a known functional homolog and is expressed in almost every neuronal cell type. The NMDAR system is a coincidence detector with critical roles in spatial learning and synaptic plasticity. Its coincidence detection property is crucial for the induction of hippocampal long-term potentiation (LTP). We have generated a mutant mouse model expressing a hypomorph of the Grin1N598R allele, which leads to a minority (about 10%) of coincidence detection-impaired NMDARs. Surprisingly, these animals revealed specific functional changes in the dentate gyrus (DG) of the hippocampal formation. Early LTP was expressed normally in area CA1 in vivo, but was completely suppressed at perforant path-granule cell synapses in the DG. In addition, there was a pronounced reduction in the amplitude of the evoked population spike in the DG. These specific changes were accompanied by behavioral impairments in spatial recognition, spatial learning, reversal learning, and retention. Our data show that minor changes in GluN1-dependent NMDAR physiology can cause dramatic consequences in synaptic signaling in a subregion-specific fashion despite the nonredundant nature of the GluN1 gene and its global expression.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Neuroscience and Mental Health Research Institute (NMHRI)
Publisher: Cold Spring Harbor Laboratory Press: 12 month Embargo
ISSN: 1072-0502
Date of First Compliant Deposit: 14 January 2020
Date of Acceptance: 21 July 2009
Last Modified: 16 Jan 2020 12:45
URI: http://orca.cf.ac.uk/id/eprint/128526

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