Limits...
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

Diagram of the Odor Span Task.At span 0, mice are first presented with a random scented cup buried 2 pellets (e.g., A+). After consumption of the reward, the mouse and the cup were removed. At span 1, a second new scented cup with 2 pellets (e.g., B+) and another cup refilled with A odor woodchip without reward (e.g., A-) was pseudo-randomly relocated in the box. Mice were return to the box and were required to remember odor A and to dig at the cup with the new B odor. Then, additional cups of woodchip scented with different odors were placed in the same manner until 12 cups (span 11) were presented.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3105019&req=5

pone-0020312-g001: Diagram of the Odor Span Task.At span 0, mice are first presented with a random scented cup buried 2 pellets (e.g., A+). After consumption of the reward, the mouse and the cup were removed. At span 1, a second new scented cup with 2 pellets (e.g., B+) and another cup refilled with A odor woodchip without reward (e.g., A-) was pseudo-randomly relocated in the box. Mice were return to the box and were required to remember odor A and to dig at the cup with the new B odor. Then, additional cups of woodchip scented with different odors were placed in the same manner until 12 cups (span 11) were presented.

Mentions: After learning ‘non-matching to sample’ rule, the mouse was subject to the odor span task (Figure 1). The correct response of mouse is to dig the novel scented cup, which is not presented to the mouse at previous spans of a session. The procedure is similar to that of NMS task. Briefly, at span 0, a random scented cup with 2 pellets (e.g., cup A+) was pseudo-randomly placed in the box. After consumption of the reward, the mouse and the cup was removed. At span 1, a second new scented cup with 2 pellets (e.g., cup B+) was randomly selected and the location was randomly generated, and another cup refilled with A odor woodchip without reward (cup A-) was pseudo-randomly relocated in the box. If the mouse dug in the novel scented cup (cup B+) and it was allowed to consume the reward, and span 2 started with a third novel scented cup (e.g., cup C+), the refilled cup A- and B- were placed at the randomly selected locations. If incorrect, the mouse was removed and the refilled cup B+ and cup A- were randomly relocated, span 1 was repeated until a correct choice was made. The accuracy of this span (2-odor discrimination) was recorded and was considered as a measure of the olfactory discriminatory ability. The span numbers increased with every correct response until span 11 was reached. As soon as mouse making incorrect response, mouse and all cups removed from the box, cups were refilled with same odor but previously non sampled scented mixture and relocated randomly to repeat the same span. If a mouse made 10 consecutive incorrect responses, the task would be ended. Between mice, the box was wiped down with ethanol (75%).


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)

Diagram of the Odor Span Task.At span 0, mice are first presented with a random scented cup buried 2 pellets (e.g., A+). After consumption of the reward, the mouse and the cup were removed. At span 1, a second new scented cup with 2 pellets (e.g., B+) and another cup refilled with A odor woodchip without reward (e.g., A-) was pseudo-randomly relocated in the box. Mice were return to the box and were required to remember odor A and to dig at the cup with the new B odor. Then, additional cups of woodchip scented with different odors were placed in the same manner until 12 cups (span 11) were presented.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3105019&req=5

pone-0020312-g001: Diagram of the Odor Span Task.At span 0, mice are first presented with a random scented cup buried 2 pellets (e.g., A+). After consumption of the reward, the mouse and the cup were removed. At span 1, a second new scented cup with 2 pellets (e.g., B+) and another cup refilled with A odor woodchip without reward (e.g., A-) was pseudo-randomly relocated in the box. Mice were return to the box and were required to remember odor A and to dig at the cup with the new B odor. Then, additional cups of woodchip scented with different odors were placed in the same manner until 12 cups (span 11) were presented.
Mentions: After learning ‘non-matching to sample’ rule, the mouse was subject to the odor span task (Figure 1). The correct response of mouse is to dig the novel scented cup, which is not presented to the mouse at previous spans of a session. The procedure is similar to that of NMS task. Briefly, at span 0, a random scented cup with 2 pellets (e.g., cup A+) was pseudo-randomly placed in the box. After consumption of the reward, the mouse and the cup was removed. At span 1, a second new scented cup with 2 pellets (e.g., cup B+) was randomly selected and the location was randomly generated, and another cup refilled with A odor woodchip without reward (cup A-) was pseudo-randomly relocated in the box. If the mouse dug in the novel scented cup (cup B+) and it was allowed to consume the reward, and span 2 started with a third novel scented cup (e.g., cup C+), the refilled cup A- and B- were placed at the randomly selected locations. If incorrect, the mouse was removed and the refilled cup B+ and cup A- were randomly relocated, span 1 was repeated until a correct choice was made. The accuracy of this span (2-odor discrimination) was recorded and was considered as a measure of the olfactory discriminatory ability. The span numbers increased with every correct response until span 11 was reached. As soon as mouse making incorrect response, mouse and all cups removed from the box, cups were refilled with same odor but previously non sampled scented mixture and relocated randomly to repeat the same span. If a mouse made 10 consecutive incorrect responses, the task would be ended. Between mice, the box was wiped down with ethanol (75%).

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