title: GluN2A-/- Mice Lack Bidirectional Synaptic Plasticity in the Dentate Gyrus and Perform Poorly on Spatial Pattern Separation Tasks.
abstract: The different secondary subunits of the N-methyl-d-aspartate (NMDA) receptor each convey unique biophysical properties to the receptor complex, and may be key in determining the functional role played by NMDA receptors. In the hippocampus, the GluN2A and GluN2B subunits are particularly abundant; however, their exact roles in synaptic plasticity and behavior remain controversial. Here, we show that mice carrying a deletion for the GluN2A subunit (GluN2A(-/-)) demonstrate a severely compromised NMDA to AMPA receptor current ratio in granule cells from the dentate gyrus (DG), while granule cell morphology is unaltered. This deficit is accompanied by significant impairments in both LTP and LTD in the DG, whereas only minor impairments are observed in the CA1. In accordance with these hippocampal region-specific deficits, GluN2A(-/-) mice show impaired performance on the DG-associated task of spatial pattern separation. In contrast, GluN2A(-/-) mice show no deficit in temporal pattern separation, a process associated with CA1 functioning. Thus, our results establish the GluN2A subunit as a significant contributor to both bidirectional synaptic plasticity and spatial pattern separation in the DG.
authors.affiliation: Division of Medical Sciences Department of Cellular and Physiological Sciences Graduate Programs of Neuroscience and the Brain Research Centre, University of British Columbia, Vancouver, BC, Canada, V6T 1Z3.
authors.forename: Timal S
authors.initials: TS
authors.lastname: Kannangara
authors.affiliation: Division of Medical Sciences Department of Cellular and Physiological Sciences Graduate Programs of Neuroscience and the Brain Research Centre, University of British Columbia, Vancouver, BC, Canada, V6T 1Z3.
authors.forename: Brennan D
authors.initials: BD
authors.lastname: Eadie
authors.affiliation: Division of Medical Sciences Department of Biology, University of Victoria, BC, Canada, V8P 5C2 and.
authors.forename: Crystal A
authors.initials: CA
authors.lastname: Bostrom
authors.affiliation: Division of Medical Sciences.
authors.forename: Kristin
authors.initials: K
authors.lastname: Morch
authors.affiliation: Division of Medical Sciences.
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Brocardo
authors.affiliation: Division of Medical Sciences Department of Biology, University of Victoria, BC, Canada, V8P 5C2 and Department of Cellular and Physiological Sciences Graduate Programs of Neuroscience and the Brain Research Centre, University of British Columbia, Vancouver, BC, Canada, V6T 1Z3.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Christie
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000473:pathology / Q000503:physiopathology; D003712:Dendrites / Q000473:pathology / Q000502:physiology; D018891:Dentate Gyrus / Q000473:pathology / Q000503:physiopathology*; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009483:Neuropsychological Tests; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000473:pathology / Q000502:physiology; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000172:deficiency* / Q000235:genetics; D013028:Space Perception / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D013998:Time Perception / Q000502:physiology; D046509:Tissue Culture Techniques
chemical_list: D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate
keywords: N-methyl-d-aspartate; NR2A; dentate gyrus; long-term depression; long-term potentiation