title: Forebrain NR2B overexpression facilitating the prefrontal cortex long-term potentiation and enhancing working memory function in mice.
abstract: Prefrontal cortex plays an important role in working memory, attention regulation and behavioral inhibition. Its functions are associated with NMDA receptors. However, there is little information regarding the roles of NMDA receptor NR2B subunit in prefrontal cortical synaptic plasticity and prefrontal cortex-related working memory. Whether the up-regulation of NR2B subunit influences prefrontal cortical synaptic plasticity and working memory is not yet clear. In the present study, we measured prefrontal cortical synaptic plasticity and working memory function in NR2B overexpressing transgenic mice. In vitro electrophysiological data showed that overexpression of NR2B specifically in the forebrain region resulted in enhancement of prefrontal cortical long-term potentiation (LTP) but did not alter long-term depression (LTD). The enhanced LTP was completely abolished by a NR2B subunit selective antagonist, Ro25-6981, indicating that overexpression of NR2B subunit is responsible for enhanced LTP. In addition, NR2B transgenic mice exhibited better performance in a set of working memory paradigms including delay no-match-to-place T-maze, working memory version of water maze and odor span task. Our study provides evidence that NR2B subunit of NMDA receptor in prefrontal cortex is critical for prefrontal cortex LTP and prefrontal cortex-related working memory.
authors.affiliation: Shanghai Institute of Brain Functional Genomics, The Key Laboratory of MOE, East China Normal University, Shanghai, China.
authors.forename: Yihui
authors.initials: Y
authors.lastname: Cui
authors.forename: Jing
authors.initials: J
authors.lastname: Jin
authors.forename: Xuliang
authors.initials: X
authors.lastname: Zhang
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
authors.forename: Liguo
authors.initials: L
authors.lastname: Yang
authors.forename: Dan
authors.initials: D
authors.lastname: Du
authors.forename: Qingwen
authors.initials: Q
authors.lastname: Zeng
authors.forename: Joe Z
authors.initials: JZ
authors.lastname: Tsien
authors.forename: Huiting
authors.initials: H
authors.lastname: Yu
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Cao
mesh_terms: D000818:Animals; D004594:Electrophysiology; D017774:Long-Term Potentiation / Q000235:genetics / Q000502:physiology*; D008570:Memory, Short-Term / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D017397:Prefrontal Cortex / Q000378:metabolism*; D016548:Prosencephalon / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*
chemical_list: C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate