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Sleep is essential but incompatible with other behaviors, and thus sleep drive competes with other motivations. We previously showed Drosophila males balance sleep and courtship via octopaminergic neurons that act upstream of courtship-regulating P1 neurons (Machado et al., 2017). Here we show nutrition modulates the sleep-courtship balance and identify sleep-regulatory neurons downstream of P1 neurons. Yeast-deprived males exhibited attenuated female-induced nighttime sleep loss yet normal daytime courtship, which suggests male flies consider nutritional status in deciding whether the potential benefit of pursuing female partners outweighs the cost of losing sleep. Trans-synaptic tracing and calcium imaging identified dopaminergic neurons projecting to the protocerebral bridge (DA-PB) as postsynaptic partners of P1 neurons. Activation of DA-PB neurons led to reduced sleep in normally fed but not yeast-deprived males. Additional PB-projecting neurons regulated male sleep, suggesting several groups of PB-projecting neurons act downstream of P1 neurons to mediate nutritional modulation of the sleep-courtship balance.

Molecular and circuit mechanisms for balancing competing drives are not well understood. While circadian and homeostatic mechanisms generally ensure sufficient sleep at night, other pressing needs can overcome sleep drive. Here, we demonstrate that the balance between sleep and sex drives determines whether male flies sleep or court, and identify a subset of octopaminergic neurons (MS1) that regulate sleep specifically in males. When MS1 neurons are activated, isolated males sleep less, and when MS1 neurons are silenced, the normal male sleep suppression in female presence is attenuated and mating behavior is impaired. MS1 neurons do not express the sexually dimorphic FRUITLESS (FRU) transcription factor, but form male-specific contacts with FRU-expressing neurons; calcium imaging experiments reveal bidirectional functional connectivity between MS1 and FRU neurons. We propose octopaminergic MS1 neurons interact with the FRU network to mediate sleep suppression by male sex drive. DOI: http://dx.doi.org/10.7554/eLife.23130.001, eLife digest Most people sleep for around seven or eight hours at night, but if there is something important or interesting to do – for example, taking care of a baby, finishing a task before a deadline, or watching an entertaining movie – we may stay up late. In other words, sleep is regulated by motivational states. The drive to sleep accumulates during wakefulness and decreases during sleep. Thus sleep and other motivational drives compete to decide whether we sleep or engage in other important or interesting activities. The idea that sleep and sex drives might compete with each other is intuitive, but had not been studied experimentally. Machado, Afonso et al. have now studied how this competition determines the behavior of male fruit flies. The presence of a female fly usually keeps a male fly awake at night. However, a male that has recently mated several times (and has low sex drive) or one that was sleep deprived (and has high sleep drive) ignores the female and goes to sleep. Further investigation revealed a small number of previously unknown neurons (termed MS1) are required for sexual arousal to overcome the male’s desire to sleep. These neurons do not belong to a circuit that is known to be important for male sexual behavior, but they do communicate with that circuit using a neurotransmitter called octopamine. This communication suppresses sleep and promotes courtship. The next steps will be to identify the specific neurons that communicate directly with the MS1 neurons and to determine whether MS1 neurons have a direct role in regulating sex drive. Investigating these details will help us to understand more generally how competing drives influence behavioral choices. DOI: http://dx.doi.org/10.7554/eLife.23130.002

Sleep is an essential and conserved behavior whose regulation at the molecular and anatomical level remains to be elucidated. Here, we identify TARANIS (TARA), a Drosophila homolog of the Trip-Br (SERTAD) family of transcriptional coregulators, as a molecule that is required for normal sleep patterns. Through a forward-genetic screen, we isolated tara as a novel sleep gene associated with a marked reduction in sleep amount. Targeted knockdown of tara suggests that it functions in cholinergic neurons to promote sleep. tara encodes a conserved cell-cycle protein that contains a Cyclin A (CycA)-binding homology domain. TARA regulates CycA protein levels and genetically and physically interacts with CycA to promote sleep. Furthermore, decreased levels of Cyclin-dependent kinase 1 (Cdk1), a kinase partner of CycA, rescue the short-sleeping phenotype of tara and CycA mutants, while increased Cdk1 activity mimics the tara and CycA phenotypes, suggesting that Cdk1 mediates the role of TARA and CycA in sleep regulation. Finally, we describe a novel wake-promoting role for a cluster of ∼14 CycA-expressing neurons in the pars lateralis (PL), previously proposed to be analogous to the mammalian hypothalamus. We propose that TARANIS controls sleep amount by regulating CycA protein levels and inhibiting Cdk1 activity in a novel arousal center., National Institutes of Health (R01GM088221 to K.K.) and predoctoral fellowships from the Portuguese Foundation for Science and Technology (SFRH/BD/51726/2011 to D.J.S.A. and SFRH/BD/52321/2013 to D.R.M.). Sequencing was performed at the Kimmel Cancer Center Nucleic Acid Facility, which is supported by a grant from the NIH (P30CA56036)

Sleep is essential for health and cognition, but the molecular and neural mechanisms of sleep regulation are not well understood. We recently reported the identification of TARANIS (TARA) as a sleep-promoting factor that acts in a previously unknown arousal center in Drosophila. tara mutants exhibit a dose-dependent reduction in sleep amount of up to ∼60%. TARA and its mammalian homologs, the Trip-Br (Transcriptional Regulators Interacting with PHD zinc fingers and/or Bromodomains) family of proteins, are primarily known as transcriptional coregulators involved in cell cycle progression, and contain a conserved Cyclin-A (CycA) binding homology domain. We found that tara and CycA synergistically promote sleep, and CycA levels are reduced in tara mutants. Additional data demonstrated that Cyclin-dependent kinase 1 (Cdk1) antagonizes tara and CycA to promote wakefulness. Moreover, we identified a subset of CycA expressing neurons in the pars lateralis, a brain region proposed to be analogous to the mammalian hypothalamus, as an arousal center. In this Extra View article, we report further characterization of tara mutants and provide an extended discussion of our findings and future directions within the framework of a working model, in which a network of cell cycle genes, tara, CycA, and Cdk1, interact in an arousal center to regulate sleep., This work was supported by a grant from the National Institutes of Health (R01NS086887 to K.K.) and predoctoral fellowships from the Portuguese Foundation for Science and Technology (SFRH/BD/51726/2011 to D.J.S.A and SFRH/BD/52321/2013 to D.R.M).