...
首页> 外文期刊>Neuron >The Temporal Dynamics of Arc Expression Regulate Cognitive Flexibility
【24h】

The Temporal Dynamics of Arc Expression Regulate Cognitive Flexibility

机译:弧形表达的时间动态调节认知灵活性

获取原文
获取原文并翻译 | 示例
           

摘要

Neuronal activity regulates the transcription and translation of the immediate-early gene Arc/Arg3.1, a key mediator of synaptic plasticity. Proteasome-dependent degradation of Arc tightly limits its temporal expression, yet the significance of this regulation remains unknown. We disrupted the temporal control of Arc degradation by creating an Arc knockin mouse (ArcKR) where the predominant Arc ubiquitination sites were mutated. ArcKR mice had intact spatial learning but showed specific deficits in selecting an optimal strategy during reversal learning. This cognitive inflexibility was coupled to changes in Arc mRNA and protein expression resulting in a reduced threshold to induce mGluR-LTD and enhanced mGluR-LTD amplitude. These findings show that the abnormal persistence of Arc protein limits the dynamic range of Arc signaling pathways specifically during reversal learning. Our work illuminates how the precise temporal control of activity-dependent molecules, such as Arc, regulates synaptic plasticity and is crucial for cognition.
机译:神经元活性调节立即早期基因ARC / ARG3.1的转录和翻译,是突触塑性的关键介质。弧形弧的弧度劣化紧密限制其时间表达,但该调节的重要性仍然未知。通过在突变主要弧泛素突出位点来突破弧敲盲蛋白(ARCKR),我们扰乱了对电弧劣化的时间控制。 ARCKR小鼠具有完整的空间学习,但在逆转学习期间选择最佳策略时表现出具体的缺陷。这种认知inflexibility偶联与弧mRNA和蛋白质表达的变化导致诱导MgluR-Ltd的降低的阈值和增强的Mglur-Ltd振幅。这些发现表明,弧蛋白的异常持久性在逆转学习期间特别限制了特定于弧信令途径的动态范围。我们的作品阐明了精确的时间控制活动依赖性分子,例如弧,调节突触可塑性,对认知至关重要。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号