Chronic Light Exposure in the Middle of the Night Disturbs the Circadian System and Emotional Regulation

Abstract

In mammals, the circadian system is composed of a principal circadian oscillator located in the suprachiasmatic nucleus (SCN) and a number of subordinate oscillators in extra-SCN brain regions and peripheral tissues/organs. However, how the time-keeping functions of this multiple oscillator circuit are affected by aberrant lighting environments remains largely unknown. In the present study, we investigated the effects of chronic light exposure in the middle of the night on the circadian system by comparing the mice housed in a 12:4:4:4-h L:DLD condition with the controls in 12:12-h L:D condition. Daily rhythms in locomotor activity were analyzed and the expression patterns of protein products of clock genes Period1 and Period2 (PER1 and PER2) were examined in the SCN and extra-SCN brain regions, including the dorsal striatum, hippocampus, paraventricular nucleus (PVN), and basolateral amygdala (BLA). Following 2 weeks of housing in the L:DLD condition, animals showed disturbed daily rhythms in locomotor activity and lacked daily rhythms of PER1 and PER2 in the SCN. In the extra-SCN brain regions, the PER1 and PER2 rhythms were affected in a region-specific pattern, such that they were relatively undisturbed in the striatum and hippocampus, phase-shifted in the BLA, and abolished in the PVN. In addition, mice in the L:DLD condition showed increased anxiety-like behaviors and reduced brain-derived neurotropic factor messenger RNA expression in the hippocampus, amygdala, and medial prefrontal cortex, which are brain regions that are involved in emotional regulation. These results indicate that nighttime light exposure leads to circadian disturbances not only by abolishing the circadian rhythms in the SCN but also by inducing misalignment among brain oscillators and negatively affects emotional processing. These observations serve to identify risks associated with decisions regarding lifestyle in our modern society.

Long days enhance recognition memory and increase insulin-like growth factor 2 in the hippocampus

“…In contrast, mice exposed to long days consistently displayed 60–70% discrimination even though their behavior during training did not differ from control mice. This result is distinct from other models where cognitive deficits arise after exposure to non-naturalistic light manipulations (e.g., simulated jetlag, exposure to intermittent light pulses or above-threshold illumination throughout the night) 25, 41 . But our findings are consistent with previous work indicating that decreased intensity or length of daytime illumination produce affective and/or cognitive deficits in nocturnal and diurnal rodents 42, 43 .…”

Output from VIP cells of the mammalian central clock regulates daily physiological rhythms

“…Of note, we also find that the timing of peak firing among VIP in cells is substantially more variable than that of VIP cells themselves, implying that these daily variations in firing do not entirely reflect a passive response to circadian rhythms in inhibitory GABAergic input from SCN VIP cells. Rhythmic expression of core clock genes has been observed in those locations where we find VIP in cells [53][54][55] , thus local clocks might also (directly or indirectly) contribute to the circadian variation observed in their activity. Similarly, SCN cells other than those that express VIP also send projections to SPZ, PVN and ventral thalamus [8][9][10] and could, in principle, also influence the firing of VIP in cells in some way.…”

“…Since chemogenetic inhibition of SCN VIP cells during their mid-day peak does not produce correspondingly large increases in heart rate, we infer that the ability of endogenous VIP cell firing to influence heart rate is restricted under our experimental conditions. This presumably reflects other ongoing rhythmic process that impact heart rate throughout the diurnal cycle, including gross changes in activity, arousal state and autonomic tone as well as potentially circadian clock mechanisms located in the heart and/or circuity downstream of the SCN [53][54][55]64 .…”

Circadian regulation of membrane physiology in neural oscillators throughout the brain

“…While both brain regions express the core clock components, there is some inconsistency regarding the timing of rhythmic clock gene expression in these areas. Many studies have found that in the BLA and sometimes in the CeA, Period ( Per1 , Per2 , and Per3 ) mRNA expression peaks in the night with PER2 protein expression lagging behind with a peak at the night–day transition (Chun et al., ; Harbour, Weigl, Robinson, & Amir, ; Ikeno & Yan, ; Lamont, Robinson, Stewart, & Amir, ; Moriya, Tahara, Sasaki, Ishigooka, & Shibata, ; Pantazopoulos, Dolatshad, & Davis, ). Rhythmic Bmal1 mRNA expression in the BLA or whole amygdala has been demonstrated in several studies but with variability in circadian phase (Chun et al., ; Moriya et al., ; Savalli, Diao, Schulz, Todtova, & Pollak, ).…”