NMDA receptors subserve persistent neuronal firing during working memory in dorsolateral prefrontal cortex.
NMDA receptors subserve persistent neuronal firing during working memory in dorsolateral prefrontal cortex.
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DOI：
10.1016/j.neuron.2012.12.032
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发表时间：
2013-02-20
期刊：
影响因子：
16.2
通讯作者：
Arnsten AF
中科院分区：
文献类型：
--
作者：
Wang M;Yang Y;Wang CJ;Gamo NJ;Jin LE;Mazer JA;Morrison JH;Wang XJ;Arnsten AF
灵长类动物背外侧前额叶皮层（dlPFC）的神经元在没有感觉刺激的情况下产生持续放电，这是心理表征的基础。持续放电是由锥体延迟细胞网络中的反复兴奋引起的。在这里，我们研究了谷氨酸受体的影响下持续放电在灵长类动物dlPFC在空间工作记忆任务。计算模型预测了对NMDA受体（NMDAR）NR 2B刺激的依赖性，并且通过局部NR 2B NMDAR阻断或全身氯胺酮给药消除了延迟细胞持续放电。AMPA受体（AMPAR）有助于背景去极化维持网络放电。相比之下，许多反应细胞-可能在啮齿动物PFC中占主导地位-对AMPAR阻断敏感，并且在全身性氯胺酮后放电增加，这表明氯胺酮作用的模型应进行改进以反映神经元异质性。延迟细胞对NMDAR的依赖可以解释为什么精神分裂症或阿尔茨海默病中对NMDAR的损伤会严重损害认知。
Neurons in the primate dorsolateral prefrontal cortex (dlPFC) generate persistent firing in the absence of sensory stimulation, the foundation of mental representation. Persistent firing arises from recurrent excitation within a network of pyramidal Delay cells. Here, we examined glutamate receptor influences underlying persistent firing in primate dlPFC during a spatial working memory task. Computational models predicted dependence on NMDA receptor (NMDAR) NR2B stimulation, and Delay cell persistent firing was abolished by local NR2B NMDAR blockade or by systemic ketamine administration. AMPA receptors (AMPAR) contributed background depolarization to sustain network firing. In contrast, many Response cells -which likely predominate in rodent PFC- were sensitive to AMPAR blockade and increased firing following systemic ketamine, indicating that models of ketamine actions should be refined to reflect neuronal heterogeneity. The reliance of Delay cells on NMDAR may explain why insults to NMDARs in schizophrenia or Alzheimer’s Disease profoundly impair cognition.
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