Identification of a dopamine pathway that regulates sleep and arousal in Drosophila

Abstract

Sleep is required to maintain physiological functions, including memory, and is regulated by monoamines across species. Enhancement of dopamine signals by a mutation in the dopamine transporter (DAT) decreases sleep, but the underlying dopamine circuit responsible for this remains unknown. We found that the D1 dopamine receptor (DA1) in the dorsal fan-shaped body (dFSB) mediates the arousal effect of dopamine in Drosophila. The short sleep phenotype of the DAT mutant was completely rescued by an additional mutation in the DA1 (also known as DopR) gene, but expression of wild-type DA1 in the dFSB restored the short sleep phenotype. We found anatomical and physiological connections between dopamine neurons and the dFSB neuron. Finally, we used mosaic analysis with a repressive marker and found that a single dopamine neuron projecting to the FSB activated arousal. These results suggest that a local dopamine pathway regulates sleep.

Sleep and Development in Genetically Tractable Model Organisms

“…Recently, work in the fly has demonstrated that a small group of dopamine neurons undergo developmentally regulated changes in activity that likely control sleep ontogeny (Kayser et al 2014). These few neurons project to and inhibit a sleep-promoting center in the fly brain, the dorsal fan-shaped body (Liu et al 2012;Ueno et al 2012). In young flies, the dopaminergic neurons are less active, allowing increased activity of the dorsal fan-shaped body (dFSB) and increased sleep; with maturity, dopaminergic activity increases, dFSB activity is reduced, and mature sleep quantity and quality are achieved (Kayser et al 2014).…”

An emerging role for Cullin-3 mediated ubiquitination in sleep and circadian rhythm

“…These studies have highlighted the existence of specific dopaminergic circuitry that control various aspects of sleep and arousal, most likely distinct from other such neurons that regulate a myriad of behaviors such as locomotor drive, learning, reward and aggression. 8,9 As sleep studies improve in power and sophistication (e.g., with the advent of continuous video monitoring of sleep and new methods for statistical analysis of sleep distribution 1,[10][11][12] ) the impact of Drosophila sleep research will continue to contribute in two key areas: the molecular mechanisms that determine the biological requirement of sleep and the molecular pathophysiology of human sleep disorders.…”

Big Lessons from Tiny Flies:<em> Drosophila Melanogaster </em>as a Model to Explore Dysfunction of Dopaminergic and Serotonergic Neurotransmitter Systems

“…(ii) Sleep regulation in flies relies on the fan-shaped body [62,[80][81][82][83]. Dopamine promotes arousal; the neurons involved are somewhat controversial as are the postsynaptic receptors and signaling mechanisms: a single pair of dopaminergic neurons from PPL1 [81] and/or PPM3 [83] suffices to drive the arousal reaction.…”

“…Dopamine promotes arousal; the neurons involved are somewhat controversial as are the postsynaptic receptors and signaling mechanisms: a single pair of dopaminergic neurons from PPL1 [81] and/or PPM3 [83] suffices to drive the arousal reaction. It was originally proposed that the dopamine engaged Dop1R1 and a Gs/cAMP-dependent pathway [81,83].…”

“…Dopamine promotes arousal; the neurons involved are somewhat controversial as are the postsynaptic receptors and signaling mechanisms: a single pair of dopaminergic neurons from PPL1 [81] and/or PPM3 [83] suffices to drive the arousal reaction. It was originally proposed that the dopamine engaged Dop1R1 and a Gs/cAMP-dependent pathway [81,83]. More recently, a (noncanonical, pertussis-toxin-sensitive) Gi/Go-mediated signaling via Dop1R2 was shown to elicit two distinct effects on the postsynaptic neurons of the fan-shaped body, which operate on different time scales: an instant -but transient -hyperpolarization, which was due to stimulation of one or several voltage-activated K+-channels, and an off-state, which relies on the exocytosis of an internal, vesicular store of a two-pore-domain K + -channel; this K2P-channel was termed Sandman [80].…”