Data from: Allatostatin A signalling in Drosophila regulates feeding and sleep and is modulated by PDF

Feeding and sleep are fundamental behaviours with significant interconnections and cross-modulations. The circadian system and peptidergic signals are important components of this modulation, but still little is known about the mechanisms and networks by which they interact to regulate feeding and sleep. We show that specific thermogenetic activation of peptidergic Allatostatin A (AstA)-expressing PLP neurons and enteroendocrine cells reduces feeding and promotes sleep in the fruit fly Drosophila. The effects of AstA cell activation are mediated by AstA peptides with receptors homolog to galanin receptors subserving similar and apparently conserved functions in vertebrates. We further identify the PLP neurons as a downstream target of the neuropeptide pigment-dispersing factor (PDF), an output factor of the circadian clock. PLP neurons are contacted by PDF-expressing clock neurons, and express a functional PDF receptor demonstrated by cAMP imaging. Silencing of AstA signalling and continuous input to AstA cells by tethered PDF changes the sleep/activity ratio in opposite directions but does not affect rhythmicity. Taken together, our results suggest that pleiotropic AstA signalling by a distinct neuronal and enteroendocrine AstA cell subset adapts the fly to a digestive energy-saving state which can be modulated by PDF.进食与睡眠是存在显著相互关联与交叉调控的核心行为。昼夜节律系统（circadian system）与肽能信号是这类调控的重要组成部分，但目前对于二者交互调控进食与睡眠的具体机制及神经环路仍知之甚少。本研究证实，对表达咽侧体抑制素A（Allatostatin A, AstA）的PLP神经元以及肠内分泌细胞进行特异性热遗传激活，可减少果蝇（Drosophila）的进食量并促进其睡眠。AstA神经元激活的效应由AstA肽介导，其受体与甘丙肽受体（galanin receptors）同源，在脊椎动物中发挥相似且高度保守的生理功能。本研究进一步确定PLP神经元是神经肽色素分散因子（pigment-dispersing factor, PDF）的下游靶标，而PDF是昼夜节律钟的核心输出因子。表达PDF的节律神经元与PLP神经元形成突触联系，且通过环腺苷酸（cAMP）成像实验验证了其表达功能性PDF受体。抑制AstA信号通路以及通过拴系型PDF（tethered PDF）向AstA细胞持续输入信号，会使睡眠/活动比朝相反方向发生改变，但并不会影响生物节律性。综上，本研究结果显示，由特定神经元与肠内分泌AstA细胞亚群介导的多效性AstA信号通路，可使果蝇进入消化节能状态，而该状态可被PDF调控。