Roles of Dopamine in Circadian Rhythmicity and Extreme Light Sensitivity of Circadian Entrainment

Abstract

Summary Light has profound behavioral effects on almost all animals, and nocturnal animals show sensitivity to extremely low light levels [1–4]. Crepuscular, i.e., dawn/dusk-active animals such as Drosophila melanogaster are thought to show far less sensitivity to light [5–8]. Here we report that Drosophila respond to extremely low levels of monochromatic blue light. Light levels 3–4 orders of magnitude lower than previously believed impact circadian entrainment and the light-induced stimulation of locomotion known as positive behavioral masking. We use GAL4; UAS- mediated rescue of tyrosine hydroxylase (DTH) mutant (ple) flies to study the roles of dopamine in these processes. We present evidence for two roles of dopamine in circadian behaviors. First, rescue with either a wild type DTH or a DTH mutant lacking neural expression leads to weak circadian rhythmicity, indicating a role for strictly regulated DTH and dopamine in robust circadian rhythmicity. Second, the DTH rescue strain deficient in neural dopamine selectively shows a defect in circadian entrainment to low light, whereas another response to light, positive masking, has normal light sensitivity. These findings imply separable pathways from light input to the behavioral outputs of masking versus circadian entrainment, with only the latter dependent on dopamine.

Dispensable, Redundant, Complementary, and Cooperative Roles of Dopamine, Octopamine, and Serotonin inDrosophila melanogaster

“…The failure of a transgene expressing TH to rescue circadian rhythmicity in the TH-deficient pale mutant has been attributed to a hypothesized lack in the temporal cycling of the TH transcript (Hirsh et al 2010). Similarly, we cannot rule out the possibility that some of the circadian deficits we observed were caused by incomplete temporal regulation of DVMAT expression.…”

“…An earlier study indicated that 5-HT is required for light input to the clock circuitry via the 5-HT1B receptor and glycogen synthase kinase 3b signaling (Yuan et al 2005). More recently, it has been shown that flies with reduced neural DA exhibit defects in circadian light sensitivity, circadian entrainment, and free-running rhythmicity [i.e., in DD after entrainment (Hirsh et al 2010)]. We find that dVMAT mutants lacking vesicular release of 5-HT, DA, and OA show decreased activity in the DAMS monitor (Figure S7A) and exhibit an altered profile of daily activity in LD.…”

“…Of note, increased activity is observed in mutant individuals in response to the lights-off signal, so the effect on masking may be selective for the lights-on signal. To our knowledge, it is not known whether distinct circuits control responses to lights on vs. lights off in Drosophila, although DA has been shown to be required for the circadian entrainment in low light (Hirsh et al 2010).…”

“…In Drosophila, molecular-genetic and pharmacologic analyses have demonstrated the importance of DA in sleep, arousal, light perception, circadian entrainment, feeding, and aversive conditioning (Schwaerzel et al 2003;Andretic et al 2005;Kume et al 2005;Neckameyer and Weinstein 2005;Chang et al 2006;Draper et al 2007;Bayersdorfer et al 2010;Hirsh et al 2010;Riemensperger et al 2011); of 5-HT in aggression, place memory, circadian rhythms, and sleep (Yuan et al 2005(Yuan et al , 2006Sitaraman et al 2008;Alekseyenko et al 2010); and of OA in sleep, locomotion, female fertility, aggression, place memory, and the fly's response to environmental stressors (Hirashima et al 2000;Lee et al 2003;Fox et al 2006;Hardie et al 2007;Crocker and Sehgal 2008;Zhou et al 2008;Crocker et al 2010;Sitaraman et al 2010). However, as in mammals, the relative importance of each aminergic system for particular behaviors and their potential interplay remain unclear.…”

Genomic Patterns of Geographic Differentiation in Drosophila simulans

“…While many of these genes have only one or two shared same-direction outliers, two genes, Dopamine transporter (DAT) and RpS14b, stand out for containing four or more differentiated SNPs within relatively short genomic regions in the UTR and upstream regions (and therefore may be associated with regulation of expression). Dopamine is a neurotransmitter that has many biological roles, one of which is the circadian rhythm (Hirsh et al 2010), a clinally varying trait in D. melanogaster . A mutation in D. melanogaster DAT is associated with decreased sleep duration and arousal threshold (Kume et al 2005;Kume 2006), as well as metabolic rate and thermal preference and tolerance (Ueno et al 2012).…”