Abstract
One output arm of the sleep homeostat in Drosophila appears to be a group of neurons with projections to the dorsal fan-shaped body (dFB neurons) of the central complex in the brain. However, neurons that regulate the sleep homeostat remain poorly understood. Using neurogenetic approaches combined with Ca2+ imaging, we characterized synaptic connections between dFB neurons and distinct sets of upstream sleep-regulatory neurons. One group of the sleep-promoting upstream neurons is a set of circadian pacemaker neurons that activates dFB neurons via direct glutaminergic excitatory synaptic connections. Opposing this population, a group of arousal-promoting neurons downregulates dFB axonal output with dopamine. Co-activating these two inputs leads to frequent shifts between sleep and wake states. We also show that dFB neurons release the neurotransmitter GABA and inhibit octopaminergic arousal neurons. We propose that dFB neurons integrate synaptic inputs from distinct sets of upstream sleep-promoting circadian clock neurons, and arousal neurons.
Highlights
Many of the regulatory mechanisms controlling sleep have been deciphered in model organisms such as flies and mice, and appear to be conserved in humans (Borbely, 1982; Griffith, 2013; Harbison et al, 2009; Sehgal and Mignot, 2011; Shaw et al, 2000; Tomita et al, 2017; Weber and Dan, 2016)
Hyperactivation of dorsal FB layer (dFB) neurons using UAS-NaChBac and the 23E10-Gal4 (Donlea et al, 2018; Pimentel et al, 2016), which includes an enhancer from the Allatostatin-A receptor 1 (AstA-R1) gene, greatly increases daytime sleep to levels that normally occur at night (Figure 1B,D,E and F)
Consistent with a previous report (Chen et al, 2016), we found that hyperactivation of neurons with UAS-NaChBac and 65D05-Gal4 phenocopied the sleep-promoting effects caused by hyperactivating dFB neurons with NaChBac (Figure 1C,D and E)
Summary
Many of the regulatory mechanisms controlling sleep have been deciphered in model organisms such as flies and mice, and appear to be conserved in humans (Borbely, 1982; Griffith, 2013; Harbison et al, 2009; Sehgal and Mignot, 2011; Shaw et al, 2000; Tomita et al, 2017; Weber and Dan, 2016) These include dual regulation of sleep by the circadian clock and by homeostatic-drive, both of which are essential for maintaining regular sleep patterns (Allada et al, 2017; Borbely, 1982). Our results indicate that dFB neurons integrate different signals reflecting the circadian clock, arousal, as well as sleep drive These signals originate from distinct populations of upstream neurons and converge on and influence the activity of common dFB neurons
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