title: Surface expression of hippocampal NMDA GluN2B receptors regulated by fear conditioning determines its contribution to memory consolidation in adult rats.
abstract: The number and subtype composition of N-methyl-d-aspartate receptor (NMDAR) at synapses determines their functional properties and role in learning and memory. Genetically increased or decreased amount of GluN2B affects hippocampus-dependent memory in the adult brain. But in some experimental conditions (e.g., memory elicited by a single conditioning trial (1 CS-US)), GluN2B is not a necessary factor, which indicates that the precise role of GluN2B in memory formation requires further exploration. Here, we examined the role of GluN2B in the consolidation of fear memory using two training paradigms. We found that GluN2B was only required for the consolidation of memory elicited by five conditioning trials (5 CS-US), not by 1 CS-US. Strikingly, the expression of membrane GluN2B in CA1was training-strength-dependently increased after conditioning, and that the amount of membrane GluN2B determined its involvement in memory consolidation. Additionally, we demonstrated the increases in the activities of cAMP, ERK, and CREB in the CA1 after conditioning, as well as the enhanced intrinsic excitability and synaptic efficacy in CA1 neurons. Up-regulation of membrane GluN2B contributed to these enhancements. These studies uncover a novel mechanism for the involvement of GluN2B in memory consolidation by its accumulation at the cell surface in response to behavioral training.
authors.affiliation: Institute of Neurobiology and State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Sun
authors.affiliation: Institute of Neurobiology and State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cai
authors.affiliation: Institute of Neurobiology and State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yu
authors.affiliation: Institute of Neurobiology and State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Shu-Su
authors.initials: SS
authors.lastname: Liu
authors.affiliation: Center for Neuron and Disease, Frontier Institutes of Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.|Department of Physiology, Faculty of Medicine, University of Toronto, 1 King's College Circle Toronto, Ontario M5S 1A8, Canada.
authors.forename: Min
authors.initials: M
authors.lastname: Zhuo
authors.affiliation: Institute of Neurobiology and State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Fudan University, Shanghai 200032, China.|Center for Neuropsychiatric Diseases, Institute of Life Science, Nanchang University, Nanchang 330031, China.
authors.forename: Bao-Ming
authors.initials: BM
authors.lastname: Li
authors.affiliation: Institute of Neurobiology and State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Xue-Han
authors.initials: XH
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D003214:Conditioning, Classical; D005239:Fear / Q000523:psychology*; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology; D000069077:Memory Consolidation; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism / Q000502:physiology
chemical_list: C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate