A Circadian Output Center Controlling Feeding:Fasting Rhythms In Drosophila

PLOS GENETICS(2019)

引用 31|浏览4
暂无评分
摘要
Circadian rhythms allow animals to coordinate behavioral and physiological processes with respect to one another and to synchronize these processes to external environmental cycles. In most animals, circadian rhythms are produced by core clock neurons in the brain that generate and transmit time-of-day signals to downstream tissues, driving overt rhythms. The neuronal pathways controlling clock outputs, however, are not well understood. Furthermore, it is unclear how the central clock modulates multiple distinct circadian outputs. Identifying the cellular components and neuronal circuitry underlying circadian regulation is increasingly recognized as a critical step in the effort to address health pathologies linked to circadian disruption, including heart disease and metabolic disorders. Here, building on the conserved components of circadian and metabolic systems in mammals and Drosophila melanogaster, we used a recently developed feeding monitor to characterize the contribution to circadian feeding rhythms of two key neuronal populations in the Drosophila pars intercerebralis (PI), which is functionally homologous to the mammalian hypothalamus. We demonstrate that thermogenetic manipulations of PI neurons expressing the neuropeptide SIFamide (SIFa) as well as mutations of the SIFa gene degrade feeding:fasting rhythms. In contrast, manipulations of a nearby population of PI neurons that express the Drosophila insulin-like peptides (DILPs) affect total food consumption but leave feeding rhythms intact. The distinct contribution of these two PI cell populations to feeding is accompanied by vastly different neuronal connectivity as determined by trans-Tango synaptic mapping. These results for the first time identify a non-clock cell neuronal population in Drosophila that regulates feeding rhythms and furthermore demonstrate dissociable control of circadian and homeostatic aspects of feeding regulation by molecularly-defined neurons in a putative circadian output hub.Author summary Circadian (similar to 24-hr) rhythms allow organisms to organize behavioral and physiological processes with respect to one another and the external environment. Circadian information is generated by central clock neurons in the brain that keep time through the presence of molecular clocks. To modulate behavioral processes, circadian signals must be transmitted through output pathways to control relevant downstream neuronal populations. We have investigated control of feeding behavior by two molecularly-distinct populations of neurons in a putative circadian output center in the fruit fly, Drosophila melanogaster. We identify for the first time a population of neurons, marked by expression of the SIFa peptide, that act as part of the circadian output circuit controlling feeding:fasting rhythms, and furthermore show that SIFa expression within these cells is necessary for normal feeding rhythms. Interestingly, manipulation of a nearby population of neurons that express the Drosophila insulin-like peptides alters the amount of feeding independent of effects on feeding rhythms, indicating that circadian and homeostatic aspects of feeding behavior are regulated by independent neuronal subsets. These findings have important implications for our understanding of how the central clock coordinately modulates distinct behavioral outputs.
更多
查看译文
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要