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 conti...

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，但目前对于二者相互作用以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神经元及肠内分泌细胞进行特异性热遗传激活，可降低果蝇（Drosophila）的进食量并促进其睡眠。AstA阳性细胞的激活效应由AstA肽类介导，其受体与甘丙肽受体（galanin receptors）同源，而甘丙肽受体在脊椎动物中承担着相似且高度保守的功能。本研究进一步鉴定出PLP神经元作为神经肽色素分散因子（pigment-dispersing factor, PDF）的下游靶标，而PDF是生物钟（circadian clock）的输出因子。表达PDF的节律神经元可与PLP神经元形成突触连接，且通过环腺苷酸成像（cAMP imaging）证实PLP神经元表达功能性PDF受体。对AstA信号通路的沉默及……