Cryptochrome, Compound Eyes, Hofbauer-Buchner Eyelets, and Ocelli Play Different Roles in the Entrainment and Masking Pathway of the Locomotor Activity Rhythm in the Fruit Fly Drosophila Melanogaster

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Drosophila melanogaster locomotor activity responds to different seasonal conditions by thermosensitive regulation of splicing of a 3 intron in the period mRNA transcript. Here we demonstrate that the control of locomotor patterns by this mechanism is primarily light-dependent at low temperatures. At warmer temperatures, when it is vitally important for the fly to avoid midday desiccation, more stringent regulation of splicing is observed, requiring the light input received through the visual system during the day and the circadian clock at night. During the course of this study, we observed that a mutation in the no-receptor-potential-A P41 (norpA P41 ) gene, which encodes phospholipase-C, generated an extremely high level of 3 splicing. This cannot be explained simply by the mutation's effect on the visual pathway and suggests that norpA P41 is directly involved in thermosensitivity.period gene ͉ splicing ͉ locomotor ͉ entrainment ͉ norpA T he period (per) gene in Drosophila melanogaster plays a central role in the circadian clock, acting as a negative regulator of its own transcription (reviewed in ref. 1). A number of other positive and negative transcriptional regulators are interwoven with PER to generate the circadian cycles observed in behavior, including TIMELESS (TIM) and the basic helix-loop-helix transcription factors dCLOCK and CYCLE. In addition, kinases such as DOUBLETIME regulate PER at the protein level, thereby contributing to the timing mechanism (1).Under light͞dark cycles (LD) 12:12, D. melanogaster behavior is bimodal, with a small morning locomotor activity peak at ''lights on'' [Zeitgeber time (ZT)0] and a larger evening activity peak around ''lights off'' (ZT12). Two classic per mutations, per s and per L , alter the free-running period, and under a 24-h Zeitgeber either advance (per s ) or delay into the night phase (per L ) the evening peak, while leaving morning locomotor activity largely unaffected (2). Thus per function is particularly relevant for this latter phase of locomotor behavior, and the importance of this response has been underscored by studies in which elevated temperatures delay the evening peak under LD cycles and cooler temperatures advance it (2-4). This is clearly an adaptive response in that under hot desiccating conditions, the locomotor activity of the fly moves toward the cooler later parts of the day, generating an apparent midday ''siesta'' (4).Temperature changes regulate the splicing of an intron within the 3Ј UTR of per, which then determines the position of the evening locomotor activity peak (4). It might be predicted that the regulation of this event would be tightly controlled, particularly at high temperatures when inappropriate locomotor behavior could prove fatal. We therefore examined the levels of per mRNA splicing in a number of different mutant backgrounds that either eliminate clock function (per 01 and tim 01 ) or impair light input [cry b , gl 60j , and no-receptor-potential-A P41 (norpA P41 )], and combinations thereof.The cry b mutation is c...

Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 87%

Seasonal behavior in Drosophila melanogaster requires the photoreceptors, the circadian clock, and phospholipase C

Collins

Rosato

Kyriacou

2004

117

120

“…The latter reaction is known as the ''lights-on effect'' or ''startle response'' and is simply a shock response to light; in contrast, lights-off suppresses the activity of the flies. Both effects (activation by light and suppression by darkness) are independent of the endogenous clock and are called masking effects (11). Under LM conditions, the masking effects disappeared, and the flies became more active during the night (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In Drosophila, these peaks are controlled by distinct groups of circadian pacemaker neurons in the brain, the so-called M and E cells (13)(14)(15). The M activity occurs earlier and the E activity occurs later under long summer days, showing a behavioral adaptation to seasonal changes in day length (9,11). This finding is in accordance with the long-standing two-oscillator model of Pittendrigh and Daan (16) originally developed for rodents that predicts that the M cells should shorten the period of their clock in response to light, whereas the E cells should lengthen their period upon light.…”

mentioning

confidence: 99%

Moonlight shifts the endogenous clock of Drosophila melanogaster

Bachleitner

Kempinger

Wülbeck

et al. 2007

Self Cite

118

133

The ability to be synchronized by light-dark cycles is a fundamental property of circadian clocks. Although there are indications that circadian clocks are extremely light-sensitive and that they can be set by the low irradiances that occur at dawn and dusk, this has not been shown on the cellular level. Here, we demonstrate that a subset of Drosophila's pacemaker neurons responds to nocturnal dim light. At a nighttime illumination comparable to quartermoonlight intensity, the flies increase activity levels and shift their typical morning and evening activity peaks into the night. In parallel, clock protein levels are reduced, and clock protein rhythms shift in opposed direction in subsets of the previously identified morning and evening pacemaker cells. No effect was observed on the peripheral clock in the eye. Our results demonstrate that the neurons driving rhythmic behavior are extremely light-sensitive and capable of shifting activity in response to the very low light intensities that regularly occur in nature. This sensitivity may be instrumental in adaptation to different photoperiods, as was proposed by the morning and evening oscillator model of Pittendrigh and Daan. We also show that this adaptation depends on retinal input but is independent of cryptochrome.circadian rhythm ͉ dual-oscillator model ͉ PERIOD ͉ synchronization ͉ TIMELESS E ndogenous circadian clocks prepare organisms according to the most reliable and predictable of environmental changes, the cycle of day and night. To function as reliable timers, circadian clocks themselves are synchronized to the 24-h cycle. This synchronization is accomplished mainly by light. Whereas light during the day has little effect on circadian clocks, they are most susceptible to light in the early and late night. Bright light pulses applied during the early night delay the phase of the clock; light pulses during the late night advance it (1). Stable synchronization occurs when the delaying and advancing effects of light on the clock in the early (at dusk) and late night (at dawn) are of equal strength. In nature, stable synchronization is a challenging task, because irradiances during dawn and dusk can vary largely from day to day because of the weather. Bünning (2) measured irradiances systematically throughout day and night and found that day-to-day fluctuations are smallest during early dawn and late dusk, when the irradiances are still Ͻ10 lux. Therefore, he proposed that organisms time their clocks to the very low irradiances occurring during early dawn and late dusk and thus must be very light-sensitive. Indeed, he found that bean plants synchronize to light of moonlight intensity (0.6-0.8 lux) and that artificial moonlight applied during the night phase shifted the rhythm of leaf movement (2). Bean plants lower their leaves during the night, and Bünning suggested that they need to do so to decrease the moonlight reaching the leaf surface to avoid their light-sensitive clocks interpreting the moonlight as the coming dawn (2).In animals, it is under deb...

“…We then tested slo 1 , another arrhythmic mutant (13), which has a relatively normal lights on response but lacks the ability to anticipate the night-day transition. Because the circadian anticipation to dawn and dusk largely overlaps with the startle effect under a 12:12-h LD regime, we chose to test a 16:8-h LD cycle following a 12:12-h entrainment (36) to better resolve these responses. Inspection of the average activity plots indicate that both wild type and slo 4 displayed the lights on/off response as well as the evening peak; the latter became even more evident when evaluating slo 1 (13) clearly indicating that this circadian-controlled behavior was unaffected in the mutant (SI Fig.…”

Section: Lack Of Rhythmicity In Slo Mutants Is Consistent With a Disrmentioning

confidence: 99%

Impaired clock output by altered connectivity in the circadian network

Fernández

Chu

Villella

et al. 2007

Substantial progress has been made in elucidating the molecular processes that impart a temporal control to physiology and behavior in most eukaryotes. In Drosophila, dorsal and ventral neuronal networks act in concert to convey rhythmicity. Recently, the hierarchical organization among the different circadian clusters has been addressed, but how molecular oscillations translate into rhythmic behavior remains unclear. The small ventral lateral neurons can synchronize certain dorsal oscillators likely through the release of pigment dispersing factor (PDF), a neuropeptide central to the control of rhythmic rest-activity cycles. In the present study, we have taken advantage of flies exhibiting a distinctive arrhythmic phenotype due to mutation of the potassium channel slowpoke (slo) to examine the relevance of specific neuronal populations involved in the circadian control of behavior. We show that altered neuronal function associated with the null mutation specifically impaired PDF accumulation in the dorsal protocerebrum and, in turn, desynchronized molecular oscillations in the dorsal clusters. However, molecular oscillations in the small ventral lateral neurons are properly running in the null mutant, indicating that slo is acting downstream of these core pacemaker cells, most likely in the output pathway. Surprisingly, disrupted PDF signaling by slo dysfunction directly affects the structure of the underlying circuit. Our observations demonstrate that subtle structural changes within the circadian network are responsible for behavioral arrhythmicity.circadian circuitry ͉ Drosophila ͉ pigment dispersing factor ͉ potassium channels ͉ slowpoke R hythmicity in rest-activity cycles in Drosophila is under control of the circadian clock, which is based on selfsustaining, cell-autonomous transcriptional negative feedback loops. These feedback loops ultimately give rise to rhythms in the abundance, phosphorylation state, and nuclear localization of key intracellular proteins, such as period (PER) and timeless (TIM) (1). To date, several neuronal clusters have been shown to include a molecular oscillator. The one best understood encompasses the small ventral lateral neurons (LNvs), comprised of five cells, of which four rhythmically release the neuropeptide pigment dispersing factor (PDF) at their dorsal terminals. Other oscillators within the fly brain include the dorsal lateral neurons (LNds) together with the dorsal neurons (DN1-3) (2). Ablation of all LNvs by overexpression of proapoptotic genes, as well as null mutations on the pdf gene or its receptor, cause behavioral arrhythmicity a few days upon transfer to constant conditions (3-6) likely through the gradual loss of synchronization among the components of the small LNv cluster (7).The question of how the intracellular molecular oscillations taking place within specific neuronal clusters ultimately drive rhythmic locomotor activity has only recently been approached in Drosophila (7-11). Molecular oscillations must be somehow transduced into neuronal function to...