The Drosophila neuropeptides PDF and sNPF have opposing electrophysiological and molecular effects on central neurons.
The Drosophila neuropeptides PDF and sNPF have opposing electrophysiological and molecular effects on central neurons.
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果蝇神经肽 PDF 和 sNPF 对中枢神经元具有相反的电生理和分子作用。
DOI：
10.1152/jn.00712.2013
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发表时间：
2014
影响因子：
2.5
通讯作者：
Griffith,LeslieC
中科院分区：
文献类型：
--
作者：
Vecsey,ChristopherG;Pírez,Nicolás;Griffith,LeslieC
神经肽对行为有广泛的影响，但这些分子如何改变其目标细胞的活动却知之甚少。我们在果蝇身上使用了一个新的模型系统来评估神经肽的电生理和分子效应，记录了幼虫运动神经元的原位记录，这些神经元表达了一种选择受体。我们重点研究了两种神经肽，色素分散因子(PDF)和小神经肽F(SNPF)，它们在睡眠/节律和摄食/代谢中发挥着重要作用。PDF处理使运动神经元去极化，表达PDF受体(PDFR)，增加兴奋性。SNPF处理有相反的作用，使表达sNPF受体(SNPFR)的神经元超极化。使用基于基因编码的荧光共振能量转移(FRET)的cAMP(CAMP)传感器进行的实时光学成像显示，PDF引起cAMP的大量增加，而sNPF引起cAMP的少量但显著的下降。共表达百日咳毒素或干扰G蛋白Gαo阻断了sNPF的电生理反应，表明sNPFR是通过Gαo信号发挥作用的。使用细胞内钙荧光传感器，我们观察到sNPF诱导的超极化阻断了沿着腹神经索传播的自发活动波，表明sNPF的电效应可以引起脑内自然网络活动的深刻变化。这个新的模型系统为神经肽如何在电子和分子水平上影响目标细胞提供了一个机械分析平台，允许预测它们如何调节控制睡眠和进食等行为的大脑电路。
Neuropeptides have widespread effects on behavior, but how these molecules alter the activity of their target cells is poorly understood. We employed a new model system in Drosophila melanogaster to assess the electrophysiological and molecular effects of neuropeptides, recording in situ from larval motor neurons, which transgenically express a receptor of choice. We focused on two neuropeptides, pigment-dispersing factor (PDF) and small neuropeptide F (sNPF), which play important roles in sleep/rhythms and feeding/metabolism. PDF treatment depolarized motor neurons expressing the PDF receptor (PDFR), increasing excitability. sNPF treatment had the opposite effect, hyperpolarizing neurons expressing the sNPF receptor (sNPFR). Live optical imaging using a genetically encoded fluorescence resonance energy transfer (FRET)-based sensor for cyclic AMP (cAMP) showed that PDF induced a large increase in cAMP, whereas sNPF caused a small but significant decrease in cAMP. Coexpression of pertussis toxin or RNAi interference to disrupt the G-protein Gαo blocked the electrophysiological responses to sNPF, showing that sNPFR acts via Gαo signaling. Using a fluorescent sensor for intracellular calcium, we observed that sNPF-induced hyperpolarization blocked spontaneous waves of activity propagating along the ventral nerve cord, demonstrating that the electrical effects of sNPF can cause profound changes in natural network activity in the brain. This new model system provides a platform for mechanistic analysis of how neuropeptides can affect target cells at the electrical and molecular level, allowing for predictions of how they regulate brain circuits that control behaviors such as sleep and feeding.
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影响因子：
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作者：
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