NMDA Receptor-mediated Ca2+ Influx in the Absence of Mg2+ Block Disrupts Rest: Activity Rhythms in Drosophila
NMDA Receptor-mediated Ca2+ Influx in the Absence of Mg2+ Block Disrupts Rest: Activity Rhythms in Drosophila
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DOI：
10.1093/sleep/zsx166
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发表时间：
2017-12-01
期刊：
影响因子：
5.6
通讯作者：
Ping, Yong
中科院分区：
文献类型：
--
作者：
Song, Qian;Feng, Ge;Ping, Yong
研究目标：突触前和突触后神经元的相关激活是NMDA受体介导的Ca ~（2+）内流通过从阻滞部位去除Mg ~（2+）而必需的，并且NMDA受体已被牵连到生物钟的相位重置中。我曾评价过，方法：利用果蝇运动监测系统，在恒定黑暗（DD）和光暗（LD）条件下，检测不同突变体的昼夜静息：活动节律。结果：Mg ~（2+）阻断缺陷突变果蝇在DD条件下表现为完全性痴呆。为了进一步理解Mg 2+阻断在每日昼夜节律休息活动中的作用，我们观察了LD周期下的突变体文件，并且我们发现与对照果蝇相比，早晨预期严重减少，晚上高峰提前。我们还使用了组织特异性表达的Mg 2+块缺陷的NMDA受体，并证明色素分散因子受体（PDFR）表达昼夜神经元参与介导昼夜休息：活动缺陷。内源性功能性NMDA受体在大多数果蝇神经元中表达，包括在背神经元（DN 1 s）的亚组中。随后，我们确定，不相关的额外的Ca 2+内流可能部分通过Ca 2 +/钙调素（CaM）刺激的PDE 1c途径导致早晨行为phenotypes.Conclusions：这些结果表明，在静息电位下，Mg 2+阻断NMDA受体对每日昼夜节律休息是必不可少的：活动节律，我们提出Mg 2+阻滞功能抑制静息电位下CaM刺激的PDE 1c激活，从而调节昼夜节律和睡眠回路中的Ca 2+和环AMP振荡。
Study Objectives: The correlated activation of pre- and postsynaptic neurons is essential for the NMDA receptor-mediated Ca2+ influx by removing Mg2+ from block site and NMDA receptors have been implicated in phase resetting of circadian clocks. So we assessed rest: activity rhythms in Mg2+ block defective animals.Methods: Using Drosophila locomotor monitoring system, we checked circadian rest: activity rhythms of different mutants under constant darkness (DD) and light: dark (LD) conditions. We recorded NMDA receptor-mediated currents or Ca2+ increase in neurons using patch-clamp and Ca2+ imaging techniques.Results: We found that Mg2+ block defective mutant flies were completely arrhythmic under DD. To further understand the role of Mg2+ block in daily circadian rest: activity, we observed the mutant files under LD cycles, and we found severely reduced morning anticipation and advanced evening peak compared to control flies. We also used tissue-specific expression of Mg2+ block defective NMDA receptors and demonstrated pigment-dispersing factor receptor (PDFR)-expressing circadian neurons were implicated in mediating the circadian rest: activity deficits. Endogenous functional NMDA receptors are expressed in most Drosophila neurons, including in a subgroup of dorsal neurons (DN1s). Subsequently, we determined that the uncorrelated extra Ca2+ influx may act in part through Ca2+/Calmodulin (CaM)-stimulated PDE1c pathway leading to morning behavior phenotypes.Conclusions: These results demonstrate that Mg2+ block of NMDA receptors at resting potential is essential for the daily circadian rest: activity rhythms and we propose that Mg2+ block functions to suppress CaM-stimulated PDE1c activation at resting potential, thus regulating Ca2+ and cyclic AMP oscillations in circadian and sleep circuits.