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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.

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NR2B Overexpression Enhanced LTP but not Basal Transmission and LTD in prefrontal cortex.A: No significant difference in input-output curve between Tg and Wt slices. B: No significant difference in pair-pulse responses between Tg and Wt slices. C: LTP induced by tetanic stimulations in Tg slices were significantly larger than that of Wt slices. D: LTD induced by a low frequency stimulation in Tg slices were not significant different from that of Wt slices. All data are presented as mean ± SEM. Statistical differences were evaluated with student's t -test.
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pone-0020312-g003: NR2B Overexpression Enhanced LTP but not Basal Transmission and LTD in prefrontal cortex.A: No significant difference in input-output curve between Tg and Wt slices. B: No significant difference in pair-pulse responses between Tg and Wt slices. C: LTP induced by tetanic stimulations in Tg slices were significantly larger than that of Wt slices. D: LTD induced by a low frequency stimulation in Tg slices were not significant different from that of Wt slices. All data are presented as mean ± SEM. Statistical differences were evaluated with student's t -test.

Mentions: To examine effect of NR2B overexpression on the synaptic transmission of prefrontal cortex in the transgenic NR2B mice, we investigated the synaptic plasticity in prefrontal cortex of NR2B transgenic mice using in vitro field potential recording technique. As shown in Figure 3A and B, there was no significant difference in basal synaptic transmission and pair-pulse depression (PPD) between transgenic and wild-type slice, suggesting that the overexpression of the NR2B subunits does not change basic synaptic transmission and presynaptic function. However, the high frequency stimulation (100 Hz for 1 s, 2 trains, 30 s interval) evoked significantly larger LTP in Tg slices than in Wt slices (Figure 3C; Tg, 174.4±12.6%, n = 9 slices/7mice; Wt, 136.7±3.5%, n = 10 slices/7 mice; p<0.05 compared to Tg mice). In addition, NMDA receptor antagonist, 100 µM AP-5, completely blocked the enhanced LTP (data not shown), suggesting the enhanced LTP was NMDA receptor dependent. The prefrontal cortex LTD was also examined in Tg and Wt mice. No significant difference was measured in prefrontal cortex LTD between Wt (Figure 3D, 74.03±4.39%, n = 9slices/5 mice) and Tg mice (72.26±3.69%, n = 11 slices/4 mice t-test, p>0.05 vs Wt mice), suggesting that overexpression of NR2B subunit does not affect the induction of LTD at the prefrontal cortex.


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)

NR2B Overexpression Enhanced LTP but not Basal Transmission and LTD in prefrontal cortex.A: No significant difference in input-output curve between Tg and Wt slices. B: No significant difference in pair-pulse responses between Tg and Wt slices. C: LTP induced by tetanic stimulations in Tg slices were significantly larger than that of Wt slices. D: LTD induced by a low frequency stimulation in Tg slices were not significant different from that of Wt slices. All data are presented as mean ± SEM. Statistical differences were evaluated with student's t -test.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3105019&req=5

pone-0020312-g003: NR2B Overexpression Enhanced LTP but not Basal Transmission and LTD in prefrontal cortex.A: No significant difference in input-output curve between Tg and Wt slices. B: No significant difference in pair-pulse responses between Tg and Wt slices. C: LTP induced by tetanic stimulations in Tg slices were significantly larger than that of Wt slices. D: LTD induced by a low frequency stimulation in Tg slices were not significant different from that of Wt slices. All data are presented as mean ± SEM. Statistical differences were evaluated with student's t -test.
Mentions: To examine effect of NR2B overexpression on the synaptic transmission of prefrontal cortex in the transgenic NR2B mice, we investigated the synaptic plasticity in prefrontal cortex of NR2B transgenic mice using in vitro field potential recording technique. As shown in Figure 3A and B, there was no significant difference in basal synaptic transmission and pair-pulse depression (PPD) between transgenic and wild-type slice, suggesting that the overexpression of the NR2B subunits does not change basic synaptic transmission and presynaptic function. However, the high frequency stimulation (100 Hz for 1 s, 2 trains, 30 s interval) evoked significantly larger LTP in Tg slices than in Wt slices (Figure 3C; Tg, 174.4±12.6%, n = 9 slices/7mice; Wt, 136.7±3.5%, n = 10 slices/7 mice; p<0.05 compared to Tg mice). In addition, NMDA receptor antagonist, 100 µM AP-5, completely blocked the enhanced LTP (data not shown), suggesting the enhanced LTP was NMDA receptor dependent. The prefrontal cortex LTD was also examined in Tg and Wt mice. No significant difference was measured in prefrontal cortex LTD between Wt (Figure 3D, 74.03±4.39%, n = 9slices/5 mice) and Tg mice (72.26±3.69%, n = 11 slices/4 mice t-test, p>0.05 vs Wt mice), suggesting that overexpression of NR2B subunit does not affect the induction of LTD at the prefrontal cortex.

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