Genetic enhancement of memory and long-term potentiation but not CA1 long-term depression in NR2B transgenic rats

Deheng Wang, Zhenzhong Cui, Qingwen Zeng, Hui Kuang, Lei Wang, Joseph Zhuo Tsien, Xiaohua Cao

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

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 sreceptor's optimal coincidence-detection property and for enhancing memory function in adulthood across multiple mammalian species.

Original languageEnglish (US)
Article numbere7486
JournalPloS one
Volume4
Issue number10
DOIs
StatePublished - Oct 19 2009

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Genetic Enhancement
Transgenic Rats
Long-Term Potentiation
Rats
genetically modified organisms
Depression
Data storage equipment
rats
N-Methyl-D-Aspartate Receptors
Long-Term Synaptic Depression
Learning
learning
Genes
Neuronal Plasticity
N-Methylaspartate
receptors
Molecules
Short-Term Memory
Synapses
Object recognition

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Genetic enhancement of memory and long-term potentiation but not CA1 long-term depression in NR2B transgenic rats. / Wang, Deheng; Cui, Zhenzhong; Zeng, Qingwen; Kuang, Hui; Wang, Lei; Tsien, Joseph Zhuo; Cao, Xiaohua.

In: PloS one, Vol. 4, No. 10, e7486, 19.10.2009.

Research output: Contribution to journalArticle

Wang, Deheng ; Cui, Zhenzhong ; Zeng, Qingwen ; Kuang, Hui ; Wang, Lei ; Tsien, Joseph Zhuo ; Cao, Xiaohua. / Genetic enhancement of memory and long-term potentiation but not CA1 long-term depression in NR2B transgenic rats. In: PloS one. 2009 ; Vol. 4, No. 10.
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