Blockade of IP3-mediated SK channel signaling in the rat medial prefrontal cortex improves spatial working memory
Blockade of IP3-mediated SK channel signaling in the rat medial prefrontal cortex improves spatial working memory
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DOI：
10.1101/lm.767408
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发表时间：
2008-03-01
影响因子：
2
通讯作者：
Arnsten, Amy F. T.
中科院分区：
文献类型：
--
作者：
Brennan, Avis R.;Dolinsky, Beth;Arnsten, Amy F. T.
计划和指导思想和行为需要前额叶皮层的工作记忆（WM）功能。WM受到应激的损害，其激活磷脂酰肌醇（PI）介导的IP 3-PKC胞内信号传导。PKC过度激活损害WM操作，体外研究表明，IP 3受体（IP 3R）诱发的钙释放导致前额叶神经元SK通道依赖性超极化。然而，IP 3R信号传导对前额叶功能的影响尚未得到研究。目前的研究结果表明，IP 3R或SK通道在前额叶皮层的阻断增强WM性能的大鼠，这表明，两个手臂的PI级联影响前额叶认知功能。
Planning and directing thought and behavior require the working memory (WM) functions of prefrontal cortex. WM is compromised by stress, which activates phosphatidylinositol (PI)-mediated IP3-PKC intracellular signaling. PKC overactivation impairs WM operations and in vitro studies indicate that IP3 receptor (IP3R)-evoked calcium release results in SK channel-dependent hyperpolarization of prefrontal neurons. However, the effects of IP3R signaling on prefrontal function have not been investigated. The present findings demonstrate that blockade of IP3R or SK channels in the prefrontal cortex enhances WM performance in rats, suggesting that both arms of the PI cascade influence prefrontal cognitive function.