Maintenance of superior learning and memory function in NR2B transgenic mice during ageing.
Brain ageing represents a general and evolutionarily conserved phenomenon and is marked by gradual declines in cognitive functions such as learning and memory. As a synaptic coincidence detector, the N-methyl-d-aspartate (NMDA) receptor is known to be essential for the induction of synaptic plasticity and memory formation. Here, we test the hypothesis that up-regulation of NR2B expression is beneficial for learning and memory in the aged animals. Our in vitro recordings show that the aged transgenic mice with the forebrain-specific overexpression of the NR2B subunit indeed exhibit more robust hippocampal long-term potentiation (LTP) induced by either high-frequency stimulation or theta-stimulation protocol. Furthermore, those aged NR2B transgenic mice consistently outperform their wild-type littermates in five different learning and memory tests, namely, novel object recognition, contextual and cued fear conditioning, spatial reference memory, and spatial working memory T-maze task. Thus, we conclude that increased expression of NR2B in the forebrain improves learning and memory function in the aged brain.
Cao
Xiaohua
X
Shanghai Institute of Brain Functional Genomics, The Key laboratories of MOE and SSTC, East China Normal University, Shanghai, China. xhcao@brain.ecnu.edu.cn
Cui
Zhenzhong
Z
Feng
Ruiben
R
Tang
Ya-Ping
YP
Qin
Zhenxia
Z
Mei
Bing
B
Tsien
Joe Z
JZ
D000375:Aging / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal; D003213:Conditioning, Psychological / Q000502:physiology*; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D005106:Exploratory Behavior / Q000502:physiology; D005239:Fear; D006624:Hippocampus / Q000502:physiology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000235:genetics* / Q000528:radiation effects; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D016548:Prosencephalon / Q000502:physiology; D011930:Reaction Time / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D015854:Up-Regulation / Q000502:physiology
C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate