Genetic enhancement of memory and long-term potentiation but not CA1 long-term depression in NR2B transgenic rats.
One major theory in learning and memory posits that the NR2B gene is a universal genetic factor that acts as rate-limiting molecule in controlling the optimal NMDA receptor's coincidence-detection property and subsequent learning and memory function across multiple animal species. If so, can memory function be enhanced via transgenic overexpression of NR2B in another species other than the previously reported mouse species? To examine these crucial issues, we generated transgenic rats in which NR2B is overexpressed in the cortex and hippocampus and investigated the role of NR2B gene in NMDA receptor-mediated synaptic plasticity and memory functions by combining electrophysiological technique with behavioral measurements. We found that overexpression of the NR2B subunit had no effect on CA1-LTD, but rather resulted in enhanced CA1-LTP and improved memory performances in novel object recognition test, spatial water maze, and delayed-to-nonmatch working memory test. Our slices recordings using NR2A- and NR2B-selective antagonists further demonstrate that the larger LTP in transgenic hippocampal slices was due to contribution from the increased NR2B-containing NMDARs. Therefore, our genetic experiments suggest that NR2B at CA1 synapses is not designated as a rate-limiting factor for the induction of long-term synaptic depression, but rather plays a crucial role in initiating the synaptic potentiation. Moreover, our studies provide strong evidence that the NR2B subunit represents a universal rate-limiting molecule for gating NMDA receptor's optimal coincidence-detection property and for enhancing memory function in adulthood across multiple mammalian species.
Shanghai Institute of Brain Functional Genomics, Key Laboratories of MOE and STCSM and College of Life Sciences, East China Normal University, Shanghai, China.
Deheng
D
Wang
Zhenzhong
Z
Cui
Qingwen
Q
Zeng
Hui
H
Kuang
L Phillip
LP
Wang
Joe Z
JZ
Tsien
Xiaohua
X
Cao
D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D017774:Long-Term Potentiation / Q000235:genetics*; D018782:Maze Learning; D008568:Memory; D009473:Neuronal Plasticity; D051381:Rats; D020318:Rats, Long-Evans; D055647:Rats, Transgenic; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000473:pathology*; D009435:Synaptic Transmission / Q000235:genetics
C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate