An Exploration of the Temporal Dynamics of Circadian Resetting Responses to Short- and Long-Duration Light Exposures: Cross-Species Consistencies and Differences

Abstract

Light is the most effective environmental stimulus for shifting the mammalian circadian pacemaker. Numerous studies have been conducted across multiple species to delineate wavelength, intensity, duration, and timing contributions to the response of the circadian pacemaker to light. Recent studies have revealed a surprising sensitivity of the human circadian pacemaker to short pulses of light. Such responses have challenged photon counting–based theories of the temporal dynamics of the mammalian circadian system to both short- and long-duration light stimuli. Here, we collate published light exposure data from multiple species, including gerbil, hamster, mouse, and human, to investigate these temporal dynamics and explore how the circadian system integrates light information at both short- and long-duration time scales to produce phase shifts. Based on our investigation of these data sets, we propose 3 new interpretations: (1) intensity and duration are independent factors of total phase shift magnitude, (2) the possibility of a linear/log temporal function of light duration that is universal for all intensities for durations less than approximately 12 min, and (3) a potential universal minimum light duration of ~0.7 sec that describes a “dead zone” of light stimulus. We show that these properties appear to be consistent across mammalian species. These interpretations, if confirmed by further experiments, have important practical implications in terms of understanding the underlying physiology and for the design of lighting regimens to reset the mammalian circadian pacemaker.

Inhibitor of DNA binding 2 (Id2) Regulates Photic Entrainment Responses in Mice: Differential Responses of the Id2-/- Mouse Circadian System Are Dependent on Circadian Phase and on Duration and Intensity of Light

“…The relationship between the duration of the light pulse and the magnitude of the resultant phase shift follows a linear/log trajectory during the first hour after light onset. However, after 1 h, it switches to a linear/linear relationship (Kronauer et al, 2019;Nelson and Takahashi, 1991;Comas et al, 2006). In other words, the circadian system is highly responsive early on to exposure to the light and especially during the first 15 min, but after 1 h, it becomes less responsive.…”

“…With this background, it is surprising that the exaggerated phase responses of the Id2-/mice are revealed when challenged by a short (1 min or 4 min [10-100 lux]) or long treatment (10 h [150-300 lux]) but not with a pulse of intermediate duration (30 min [800 lux]). Irradiance may also be an important independent variable in contributing to the phenotype (Nelson and Takahashi, 1991;Kronauer et al, 2019), and separating the duration and intensity factors will be important in future investigations. Thus, the enhanced phase responses are revealed at the extremes of photic stimuli, which in WT animals are known to be in different physiological states of responsiveness.…”

Removing Short Wavelengths From Polychromatic White Light Attenuates Circadian Phase Resetting in Rats

“…Additionally, future studies are needed to assess whether the underlying neural and molecular responses differ between low- and high-intensity spectrally tuned lighting. Recent studies suggest that divergent neural pathways exist for NIF responses (Rupp et al, 2019), and phase resetting response mechanisms may differ based on the duration of the stimulus (Najjar and Zeitzer, 2016; Kaladchibachi et al, 2019; Kronauer et al, 2019), which may also be the case for intensity.…”

Naturalistic Intensities of Light at Night: A Review of the Potent Effects of Very Dim Light on Circadian Responses and Considerations for Translational Research

“…The relationship between timing of the stimulus and the resulting phase shifts is described in a phase-response curve (PRC). While the amplitude of the light PRC can vary depending on the intensity, duration, and spectral properties of light, the shape is very consistent across species ( 76 ). Typically, light induces advances at the end of the (biological) night, delays at the beginning of the biological night, and minimal phase shifts during the middle of the biological day, in both diurnal and nocturnal animals.…”

“…To properly assess how relevant the summarized research on nLAN in model organisms is for human circadian rhythms, in this section we compare the pertinent neurobiology across species. First, the mammalian circadian system is very well-conserved ( 76 , 125 ), including fundamental properties of the primary oscillators. While the main body of mechanistic basic research involved nocturnal rodents (mice, rats, hamsters), circadian rhythms have been well-described in diurnal rodent species, including grass rats, degus and squirrels as well as larger mammals, including sheep and several species of non-human primates [e.g., baboon ( 126 )].…”