J Neurosci. 2021 Apr 30:JN-RM-3074-19. doi: 10.1523/JNEUROSCI.3074-19.2021. Online ahead of print.
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, and that eye light input is redundant to CRY. 3hr light phase delays (Friday) followed by 3hr 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 days. 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.SIGNIFICANCE STATEMENTThe circadian clock controls numerous aspects of daily animal physiology, metabolism and behavior. Much of our understanding of circadian circuit-level oscillations stem from ex vivo imaging of mammalian suprachiasmatic nucleus (SCN) brain slices. Humans regularly subject themselves to weekday/weekend light shifts but the effects of phase-shifting light signals cannot be measured in SCN. We measured circuit-level circadian responses to a weekday/weekend light shift (WLS) protocol in light-sensitive ex vivo Drosophila whole-brain preparation that shows temporal coincidence to circadian behavioral events. Robust sub-circuit-specific oscillator desynchrony/resynchrony responses to light coincide with functional defects in learning and memory, and sleep pattern disruption in vivo Our results reflect that WLS causes circadian-circuit desynchronization and correlates with disrupted cognitive and sleep performance.
PMID:33931552 | DOI:10.1523/JNEUROSCI.3074-19.2021
