Abstract
We developed a method for single-cell resolution longitudinal bioluminescence imaging of PERIOD (PER) protein and TIMELESS (TIM) oscillations in cultured male adult Drosophila brains that captures circadian circuit-wide cycling under simulated day/night cycles. Light input analysis confirms that CRYPTOCHROME (CRY) is the primary circadian photoreceptor and mediates clock disruption by constant light (LL), and that eye light input is redundant to CRY; 3-h light phase delays (Friday) followed by 3-h light phase advances (Monday morning) simulate the common practice of staying up later at night on weekends, sleeping in later on weekend days then returning to standard schedule Monday morning [weekend light shift (WLS)]. PER and TIM oscillations are highly synchronous across all major circadian neuronal subgroups in unshifted light schedules for 11 d. In contrast, WLS significantly dampens PER oscillator synchrony and rhythmicity in most circadian neurons during and after exposure. Lateral ventral neuron (LNv) oscillations are the first to desynchronize in WLS and the last to resynchronize in WLS. Surprisingly, the dorsal neuron group-3 (DN3s) increase their within-group synchrony in response to WLS. In vivo, WLS induces transient defects in sleep stability, learning, and memory that temporally coincide with circuit desynchrony. Our findings suggest that WLS schedules disrupt circuit-wide circadian neuronal oscillator synchrony for much of the week, thus leading to observed behavioral defects in sleep, learning, and memory.
Highlights
The modern workplace results in individuals across the world subjecting themselves to phase-advancing light shifts on Monday morning after staying up later during weekends starting on Friday, with phase-delaying light signals persisting throughout the weekend
Motivated by the many functional similarities between mammalian and fly circadian circuitry, we investigated the effects of light shifts on circadian rhythmicity using Drosophila
LD strobe consists of 15-min periods of light followed by 45 min bouts of darkness each hour during the 12-h “day,” 12 h of darkness during the 12-h “night.” We find that DD behavior following LD strobe is indistinguishable from DD following standard LD (Fig. 1B, left vs right column)
Summary
The modern workplace results in individuals across the world subjecting themselves to phase-advancing light shifts on Monday morning after staying up later during weekends starting on Friday, with phase-delaying light signals persisting throughout the weekend. PERIOD (PER) protein cycling imaging in suprachiasmatic nucleus (SCN) provides detailed functional data on the central neural circuits that govern circadian rhythms and forms the basis for interpreting the linkage between the timing of clock cycling and circadian physiological outputs in mammals (Welsh et al, 1995; Hamada et al, 2001; Yamaguchi et al, 2003; Evans et al, 2013; Azzi et al, 2017). Clock cycling in mammalian SCN slices can be longitudinally imaged, but their ongoing direct responses to environmental light signals cannot be studied this way because of the absence of physiological light input into the SCN in ex vivo preparations (Welsh et al, 1995; Moga and Moore, 1997; Hamada et al, 2001; Evans et al, 2013). Acute physiological responses can be measured in SCN ex vivo slices after stimulating the retinohypothalamic tract with a stimulating electrode (Irwin and Allen, 2007)
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