AKH-FOXO pathway regulates starvation-induced sleep loss through remodeling of the small ventral lateral neuron dorsal projections

Starvation caused by adverse feeding stresses or food shortages has been reported to result in sleep loss in animals. However, how the starvation signal interacts with the central nervous system is still unknown. Here, the adipokinetic hormone (AKH)—Fork head Box-O (FOXO) pathway is shown to respond to energy change and adjust the sleep of Drosophila through remodeling of the s-LNv (small ventral lateral neurons) dorsal projections. Our results show that starvation prevents flies from going to sleep after the first light-dark transition. The LNvs are required for starvation-induced sleep loss through extension of the pigment dispersing factor (PDF)-containing s-LNv dorsal projections. Further studies reveal that loss of AKH or AKHR (akh receptor) function blocks starvation-induced extension of s-LNv dorsal projections and rescues sleep suppression during food deprivation. FOXO, which has been reported to regulate synapse plasticity of neurons, acts as starvation response factor downstream of AKH, and down regulation of FOXO level considerably alleviates the influence of starvation on s-LNv dorsal projections and sleep. Taking together, our results outline the transduction pathways between starvation signal and sleep, and reveal a novel functional site for sleep regulation.Author summary: Sleep of Drosophila is regulated by circadian rhythm and homeostasis on the normal condition, in the presence of cellular stress or injury, the central nervous system neurons adjust sleep on the basis of impulse, which is transmitted by neuropeptides generated by cytokines from either peripheral tissues or nervous system cells. Metabolism and sleep are inextricably linked, energy deficiency has an enormous impact on the sleep, starvation induced sleep loss in the Drosophila has been reported and many genes play roles in this process. However, how the starvation signals transmit to nervous system and then make the sleep loss are still no clear. In this study we find the starvation prevent flies going to sleep, PDF/PDFR and LNvs are required for starvation induced sleep loss, during starvation flies show more expanded s-LNvs dorsal projection compared to flies on the normal condition. LNvs are vital awakening neurons, they transmit arousal signal to downstream neurons through its dorsal projections, more patulous s-LNvs dorsal projections accelerate the transmission of awakening signals, can prevent flies from going to sleep. Flies losing AKH/AKHR/FOXO function limit starvation induced sleep loss. Flies with blocked AKH-FOXO pathway also limit starvation induced s-LNvs dorsal projections opening, indicating that the s-LNvs dorsal projections are function sites of starvation signal on sleep regulation.