Enhancement of Spatial Working Memory in NR2B Transgeni

Forebrain NR2B overexpression facilitating the prefrontal cortex long-term potentiation and enhancing working memory function in mice. Cui Y, Jin J, Zhang X, Xu H, Yang L, Du D, Zeng Q, Tsien JZ, Yu H, Cao X - PLoS ONE (2011) Bottom Line: Its functions are associated with NMDA receptors.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.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. View Article: PubMed Central - PubMed Affiliation: Shanghai Institute of Brain Functional Genomics, The Key Laboratory of MOE, East China Normal University, Shanghai, China. 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. Show MeSH Major Long-Term Potentiation/genetics/physiology* Memory, Short-Term/physiology* Prefrontal Cortex/metabolism* Prosencephalon/metabolism* Receptors, N-Methyl-D-Aspartate/genetics/metabolism* Minor Animals Electrophysiology Mice Mice, Transgenic Related in: MedlinePlus	© Copyright Policy Related In: Results - Collection Show All Figures getmorefigures.php?uid=PMC3105019&req=5 pone-0020312-g005: Enhancement of Spatial Working Memory in NR2B Transgenic Mice.A–B: Performance of mice in T-maze task. A: There was no difference in accuracy between Wt and Tg mice in training session. B: Tg mice exhibited superior performance both in 1- and 3 min-delay retention test. C–D: Performance of mice in the working memory version of water maze task. C: There was no difference in swim speed between Wt and Tg mice in pre-training. D: In the 2nd trial of training, the latency of transgenic mice was significantly shorter than that of wild type. All values are mean ± SEM (denotes p<0.01 when compared to Wt controls). Mentions:** In the training session of T-maze task, the accuracy of NR2B transgenic mice and Wt mice was comparable (F(1,22) = 1.75, p>0.05, two-way repeated measures ANOVA, Figure 5A). However, the accuracy of Wt mice was significantly reduced compared to that of Tg mice during 1 min (Wt: 55.2%; Tg: 75.1%, p<0.01 compared to Wt) and 3 min retention test (Wt: 50%, Tg: 63.5%; p<0.01 compared to Wt, Figure 5B). This result indicates that the transgenic mice have better spatial working memory.

Forebrain NR2B overexpression facilitating the prefrontal cortex long-term potentiation and enhancing working memory function in mice.

Cui Y, Jin J, Zhang X, Xu H, Yang L, Du D, Zeng Q, Tsien JZ, Yu H, Cao X - PLoS ONE (2011)

Bottom Line: Its functions are associated with NMDA receptors.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.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.

View Article: PubMed Central - PubMed

Affiliation: Shanghai Institute of Brain Functional Genomics, The Key Laboratory of MOE, East China Normal University, Shanghai, China.

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.

Show MeSH

Related in: MedlinePlus

Enhancement of Spatial Working Memory in NR2B Transgenic Mice.A–B: Performance of mice in T-maze task. A: There was no difference in accuracy between Wt and Tg mice in training session. B: Tg mice exhibited superior performance both in 1- and 3 min-delay retention test. C–D: Performance of mice in the working memory version of water maze task. C: There was no difference in swim speed between Wt and Tg mice in pre-training. D: In the 2nd trial of training, the latency of transgenic mice was significantly shorter than that of wild type. All values are mean ± SEM (**denotes p<0.01 when compared to Wt controls).

Related In: Results - Collection

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pone-0020312-g005: Enhancement of Spatial Working Memory in NR2B Transgenic Mice.A–B: Performance of mice in T-maze task. A: There was no difference in accuracy between Wt and Tg mice in training session. B: Tg mice exhibited superior performance both in 1- and 3 min-delay retention test. C–D: Performance of mice in the working memory version of water maze task. C: There was no difference in swim speed between Wt and Tg mice in pre-training. D: In the 2nd trial of training, the latency of transgenic mice was significantly shorter than that of wild type. All values are mean ± SEM (**denotes p<0.01 when compared to Wt controls).

Mentions: In the training session of T-maze task, the accuracy of NR2B transgenic mice and Wt mice was comparable (F(1,22) = 1.75, p>0.05, two-way repeated measures ANOVA, Figure 5A). However, the accuracy of Wt mice was significantly reduced compared to that of Tg mice during 1 min (Wt: 55.2%; Tg: 75.1%, p<0.01 compared to Wt) and 3 min retention test (Wt: 50%, Tg: 63.5%; p<0.01 compared to Wt, Figure 5B). This result indicates that the transgenic mice have better spatial working memory.