Abstract: Life on Earth has adapted to a consistent 24-h solar cycle. Circadian rhythms in physiology and behavior remain synchronized to the environment using light as the most potent entraining cue. During the past century, however, the widespread adoption of electric light has led to `round-the-clock’ societies. Instead of aligning with the environment, individuals follow artificial and often erratic light cycles created by social and work schedules. In particular, exposure to artificial light at night (LAN), termed “light pollution”, has become pervasive over the past 100 years. Virtually every individual living in the U.S. and Europe experiences this aberrant light exposure, and moreover about 20% of the population performs shift work. LAN may disrupt physiological timekeeping, leading to dysregulation of internal processes and misalignment between behavior and the environment. Recent evidence suggests that individuals exposed to excessive LAN, such as night shift workers, have increased risk for depressive disorders, but the biological mechanism remains unspecified. In mammals, intrinsically photosensitive retinal ganglion cells (ipRGCs) project light information to (1) the suprachiasmatic nucleus (SCN) in the hypothalamus, regulating circadian rhythms, and (2) to limbic regions, putatively regulating mood. Thus, LAN has the potential to affect both circadian timekeeping and mood. In this dissertation, I present evidence from rodent studies supporting the novel hypothesis that night-time exposure to light disrupts circadian organization and contributes to depressed mood. First, I consider the physiological and behavioral consequences associated with unnatural exposure to LAN. The effects of LAN on circadian output are considered in terms of locomotor activity, the diurnal cortisol rhythm, and diurnal clock protein expression in the brain in Chapter 2. The influence of LAN on behavior and brain plasticity is discussed, with particular focus on depressive-like behavior (Chapter 3) and effects of SSRI treatment (Chapter 4). Effects of LAN on structural plasticity and gene expression in the brain are described, with emphasis on potential correlates of the depressive-like behavior observed under LAN in Chapter 5. Given the prevalence of LAN exposure and its importance, strategies for reversing the effects are offered. Specifically, eliminating LAN quickly reverses behavioral and physiological effects of exposure as described in Chapter 5. In Chapter 6 I report that administration of a pharmacological cytokine inhibitor prevents depressive-like behaviors in LAN, implicating brain inflammation in the behavioral effect. Finally, I demonstrate in Chapter 7 that exposure to red wavelength LAN reduces the effects on brain and behavior, suggesting that LAN acts through specific retinal pathways involving melanopsin. Taken together, these studies demonstrate the consequences of LAN, but also outline potential avenues for prevention or intervention.

Abstract: Light synchronizes mammalian circadian rhythms with environmental time by modulating retinal input to the circadian pacemaker-the suprachiasmatic nucleus (SCN) of the hypothalamus. Such photic entrainment requires neither rods nor cones, the only known retinal photoreceptors. Here, we show that retinal ganglion cells innervating the SCN are intrinsically photosensitive. Unlike other ganglion cells, they depolarized in response to light even when all synaptic input from rods and cones was blocked. The sensitivity, spectral tuning, and slow kinetics of this light response matched those of the photic entrainment mechanism, suggesting that these ganglion cells may be the primary photoreceptors for this system.

Abstract: Brightness perception under different light sources is an important visual response, because it is related to perceptions of safety. A growing number of studies have been conducted to assess perceptions of scene brightness under light sources differing in spectral content, including results consistent with a role of melanopsin-containing, intrinsically photosensitive retinal ganglion cells in scene brightness. Data from recent studies of scene brightness perception at light levels experienced under nighttime driving conditions are used to compare different models of brightness perception. The data support a role of increased short-wavelength sensitivity for scene brightness perception and a provisional spectral sensitivity model that takes into account the possible influence of melanopsin-containing, intrinsically photoreceptive retinal ganglion cells is suggested as a basis for further investigation. The implications of such a model on brightness perception under several light sources used in transportation lighting are described.