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<p>NR2A and NR2B are the major GluR2 subunits of N-methyl-D-aspartate (NMDA) receptor. NR2B-containing NMDA receptor was found to be exclusively expressed in post-synapses in layer III pyramidal cells of the prefrontal cortex (PFC). Many studies have suggested the importance of PFC NR2B-containing NMDA receptor for working memory, especially for the persistent delay cell firing. However, direct evidence for the necessity of PFC NR2B-containing NMDA receptor on working memory is still absent, especially in non-human primates. Here, we directly evaluated the necessity of PFC synaptic NR2B for working memory in both rats and monkeys. We first examined the synaptosome expression ratio of NR2B/2A in the PFC, hippocampus and visual cortex, and confirmed a relatively higher expression ratio of NR2B/2A in the PFC than in the hippocampus and visual cortex in both species. We then investigated the effects of intra-PFC blockade of NR2B on the performance of spatial working memory and pattern discrimination, and found that the spatial working memory, but not pattern discrimination, was robustly impaired in a delay length-dependent way in both species. The present study provided behavioral and neuropharmacological evidence for the critical role of PFC NR2B-containing receptors in working memory performance in non-human primates.</p>

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Prefrontal cortical NR2B-containing NMDA receptors are essential for spatial working memory performance

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月6日

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  • Jiyun Peng,
  • Gongwu Wang,
  • Yingying Han,
  • Lili Qu,
  • Min Wang,
  • Amy F. T. Arnsten,
  • Jingxia Cai,
  • Baoming Li

摘要

NR2A and NR2B are the major GluR2 subunits of N-methyl-D-aspartate (NMDA) receptor. NR2B-containing NMDA receptor was found to be exclusively expressed in post-synapses in layer III pyramidal cells of the prefrontal cortex (PFC). Many studies have suggested the importance of PFC NR2B-containing NMDA receptor for working memory, especially for the persistent delay cell firing. However, direct evidence for the necessity of PFC NR2B-containing NMDA receptor on working memory is still absent, especially in non-human primates. Here, we directly evaluated the necessity of PFC synaptic NR2B for working memory in both rats and monkeys. We first examined the synaptosome expression ratio of NR2B/2A in the PFC, hippocampus and visual cortex, and confirmed a relatively higher expression ratio of NR2B/2A in the PFC than in the hippocampus and visual cortex in both species. We then investigated the effects of intra-PFC blockade of NR2B on the performance of spatial working memory and pattern discrimination, and found that the spatial working memory, but not pattern discrimination, was robustly impaired in a delay length-dependent way in both species. The present study provided behavioral and neuropharmacological evidence for the critical role of PFC NR2B-containing receptors in working memory performance in non-human primates.