Constant Light Desynchronizes Olfactory versus Object and Visuospatial Recognition Memory Performance

Abstract

Circadian rhythms optimize physiology and behavior to the varying demands of the 24 h day. The master circadian clock is located in the suprachiasmatic nuclei (SCN) of the hypothalamus and it regulates circadian oscillators in tissues throughout the body to prevent internal desynchrony. Here, we demonstrate for the first time that, under standard 12 h:12 h light/dark (LD) cycles, object, visuospatial, and olfactory recognition performance in C57BL/6J mice is consistently better at midday relative to midnight. However, under repeated exposure to constant light (rLL), recognition performance becomes desynchronized, with object and visuospatial performance better at subjective midday and olfactory performance better at subjective midnight. This desynchrony in behavioral performance is mirrored by changes in expression of the canonical clock genes Period1 and Period2 (Per1 and Per2), as well as the immediate-early gene Fos in the SCN, dorsal hippocampus, and olfactory bulb. Under rLL, rhythmic Per1 and Fos expression is attenuated in the SCN. In contrast, hippocampal gene expression remains rhythmic, mirroring object and visuospatial performance. Strikingly, Per1 and Fos expression in the olfactory bulb is reversed, mirroring the inverted olfactory performance. Temporal desynchrony among these regions does not result in arrhythmicity because core body temperature and exploratory activity rhythms persist under rLL. Our data provide the first demonstration that abnormal lighting conditions can give rise to temporal desynchrony between autonomous circadian oscillators in different regions, with different consequences for performance across different sensory domains. Such a dispersed network of dissociable circadian oscillators may provide greater flexibility when faced with conflicting environmental signals.SIGNIFICANCE STATEMENT A master circadian clock in the suprachiasmatic nuclei (SCN) of the hypothalamus regulates physiology and behavior across the 24 h day by synchronizing peripheral clocks throughout the brain and body. Without the SCN, these peripheral clocks rapidly become desynchronized. Here, we provide a unique demonstration that, under lighting conditions in which the central clock in the SCN is dampened, peripheral oscillators in the hippocampus and olfactory bulb become desynchronized, along with the behavioral processes mediated by these clocks. Multiple clocks that adopt different phase relationships may enable processes occurring in different brain regions to be optimized to specific phases of the 24 h day. Moreover, such a dispersed network of dissociable circadian clocks may provide greater flexibility when faced with conflicting environmental signals (e.g., seasonal changes in photoperiod).

Light and the laboratory mouse

“…Finally, all three rhythms persisted in constant conditions, demonstrating that these were circadian rhythms and not just driven by the light/dark cycle ( Chaudhury and Colwell, 2002 ). Moreover, data from a within-subjects study in our own laboratory have shown that object recognition performance in mice is similarly better during the light phase than the dark phase, and this pattern persists under constant conditions ( Tam et al, 2017 ). Why learning and memory should be better during a nocturnal animal’s normally inactive phase is unclear, but may relate to the effects of preceding sleep and arousal or differences in response to handling.…”

Light and Cognition: Roles for Circadian Rhythms, Sleep, and Arousal

“…The environmental context is almost certain to influence acute sleep induction, as light exposure in the home cage may produce quite different effects on sleep in comparison to a novel environment. For example, in novel environments, such as an open field or novel object testing arena, sleep induction is not observed in response to light ( 89 , 90 ). In addition, it should also be considered that while c-Fos has been used as a marker of VLPO activation during sleep ( 91 ), induction of Fos in response to light may simply reflect the subsequent sleep/wake status of the animal rather than providing a marker of light input as has been widely used in the SCN ( 92 ).…”

“…Again, data from animal studies are less conclusive. Some studies report increased performance during the subjective night in aversive ( 98 ) and appetitive tasks ( 99 , 100 ), whereas others found better performance during the subjective day ( 89 , 101 , 102 ). These contradictory findings may reflect the nature of the behavioral tasks employed.…”

“…Interval timing has also been reported to be disrupted by constant light ( 199 ). Recent studies using repeated constant light on different aspects of recognition memory have shown a dampening of SCN clock gene rhythms, resulting in desynchrony between clocks in the SCN, hippocampus, and olfactory bulb ( 89 ). As described above, constant light may cause period lengthening and in some cases arrhythmia.…”

Dim light in the evening causes coordinated realignment of circadian rhythms, sleep, and short-term memory

“…We used the spontaneous recognition memory task ( Fig. 4 A ) ( 58 ), which is sensitive to effects of aberrant lighting ( 23 , 59 – 61 ). Initial analyses confirmed that under LD, there was a day/night difference in short-term object and odor recognition memory performance, with better performance at ZT2 than at ZT14 [main effect of Time of Day F (1, 15) = 6.59, P = 0.021; SI Appendix , Fig.…”