Dopamine Is a Regulator of Arousal in the Fruit Fly

By K. Kume, S. Kume, Sang Ki Park, J. Hirsh, F. Jackson. 2005

536 citations recorded by the source corpus.

Sleep and arousal are known to be regulated by both homeostatic and circadian processes, but the underlying molecular mechanisms are not well understood. It has been reported that the Drosophila rest/activity cycle has features in common with the mammalian sleep/wake cycle, and it is expected that use of the fly genetic model will facilitate a molecular understanding of sleep and arousal. Here, we report the phenotypic characterization of a Drosophila rest/activity mutant known as fumin (fmn). We show that fmn mutants have abnormally high levels of activity and reduced rest (sleep); genetic mapping, molecular analyses, and phenotypic rescue experiments demonstrate that these phenotypes result from mutation of the Drosophila dopamine transporter gene. Consistent with the rest phenotype, fmn mutants show enhanced sensitivity to mechanical stimuli and a prolonged arousal once active, indicating a decreased arousal threshold. Strikingly,fmn mutants do not show significant rebound in response to rest deprivation as is typical for wild-type flies, nor do they show decreased life span. These results provide direct evidence that dopaminergic signaling has a critical function in the regulation of insect arousal.

Subfields: Cellular and Molecular Neuroscience, Endocrine and Autonomic Systems, Genetics

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Citations in the corpus

Coordinated and Compartmentalized Neuromodulation Shapes Sensory Processing in Drosophila (2015, positive): “We therefore examined synaptic responses in mutants for the dopamine reuptake transporter ( DAT ), which mediates clearance of dopamine from the synaptic cleft (Kume et al., 2005) and regulates dopamine signaling independent of any specific receptor.”
A genetically-encoded fluorescent sensor enables rapid and specific detection of dopamine in flies, fish, and mice (2018, background): “…a wide range of complex processes, including reward signaling (Schultz, 2016; Wise, 2004), reinforcement learning (Holroyd and Coles, 2002), attention (Nieoullon, 2002), motor control (Graybiel et al., 1994), arousal (Kume et al., 2005; Wisor et al., 2001), and stress (Abercrombie et al., 1989).”
High-Resolution Positional Tracking for Long-Term Analysis of Drosophila Sleep and Locomotion Using the “Tracker” Program (2012, background): “Sleepless [24] and Hyperkinetic [23], dopaminergic signaling genes such as DopR1 [15] and fumin [25], and stress and immunity response genes like relish [26], BiP [27], and Hsp83 [28] all lead to complex behavioral phenotypes.”
A neural circuit mechanism integrating motivational state with memory expression in Drosophila (2009, background): “Drosophila can be efficiently trained to associate odorants with sucrose reward (Tempel et al., 1983; Krashes and Waddell, 2008).”
Eight Different Types of Dopaminergic Neurons Innervate the Drosophila Mushroom Body Neuropil: Anatomical and Physiological Heterogeneity (2009, unknown): “In insects like Drosophila, DA is involved in locomotion (Pendleton et al., 2002), sleep and arousal (Andretic et al., 2005; Foltenyi et al., 2007; Kume et al., 2005), courtship behavior (Liu et al., 2008; Neckameyer, 1998), inhibition of startle-induced hyperexcitability (Friggi-Grelin et al.,…”