Keep Your Mask On: The Benefits of Masking for Behavior and the Contributions of Aging and Disease on Dysfunctional Masking Pathways

Abstract

Environmental cues (e.g., light-dark cycle) have an immediate and direct effect on behavior, but these cues are also capable of “masking” the expression of the circadian pacemaker, depending on the type of cue presented, the time-of-day when they are presented, and the temporal niche of the organism. Masking is capable of complementing entrainment, the process by which an organism is synchronized to environmental cues, if the cues are presented at an expected or predictable time-of-day, but masking can also disrupt entrainment if the cues are presented at an inappropriate time-of-day. Therefore, masking is independent of but complementary to the biological circadian pacemaker that resides within the brain (i.e., suprachiasmatic nucleus) when exogenous stimuli are presented at predictable times of day. Importantly, environmental cues are capable of either inducing sleep or wakefulness depending on the organism’s temporal niche; therefore, the same presentation of a stimulus can affect behavior quite differently in diurnal vs. nocturnal organisms. There is a growing literature examining the neural mechanisms underlying masking behavior based on the temporal niche of the organism. However, the importance of these mechanisms in governing the daily behaviors of mammals and the possible implications on human health have been gravely overlooked even as modern society enables the manipulation of these environmental cues. Recent publications have demonstrated that the effects of masking weakens significantly with old age resulting in deleterious effects on many behaviors, including sleep and wakefulness. This review will clearly outline the history, definition, and importance of masking, the environmental cues that induce the behavior, the neural mechanisms that drive them, and the possible implications for human health and medicine. New insights about how masking is affected by intrinsically photosensitive retinal ganglion cells, temporal niche, and age will be discussed as each relates to human health. The overarching goals of this review include highlighting the importance of masking in the expression of daily rhythms, elucidating the impact of aging, discussing the relationship between dysfunctional masking behavior and the development of sleep-related disorders, and considering the use of masking as a non-invasive treatment to help treat humans suffering from sleep-related disorders.

Regulation of mouse exploratory behaviour by irradiance and cone-opponent signals

“…The present data also align with established views positing the SPZ as a key site for acute-light-dependent control of mouse behaviour [ 4 , 5 , 50 , 51 ], confirming the presence of robust cone-opponent modulation of SPZ neuronal activity that matches the observed chromatic modulation of mouse exploratory activity. We should note, however, that there is still some uncertainty as to the primary retinorecipient site that actually forms the origin of light-induced suppression of activity in nocturnal rodents.…”

“…It is certainly possible, however, that cone-opponent IGL or SCN cells contribute to the behavioural effects of spectral content observed in the present study. In either case, while we cannot definitively distinguish the relative roles of direct vs. indirect retinal inputs to the SPZ, the presence of an overall decreased neuronal activation of the SPZ for ‘bluer’ stimuli is fully consistent with the prevailing view [ 4 , 5 ] that the SPZ is a key node within the brain networks underlying acute effects of light on mouse behaviour (including the chromatic effects observed here).…”

“…4 G). In summary, then, our data highlight the ventral SPZ (a brain region previously strongly implicated in masking responses [ 4 , 5 , 50 , 51 ]) as a potential locus for cone-opponent modulation of mouse activity.…”

“…Since the retinohypothalamic tract (RHT) is known to be the primary driver of negative masking responses [ 4 , 50 , 51 ], we first counted c-Fos expressing neurons across portions of the anterior hypothalamus that encompassed RHT target regions [ 52 ] (Fig. 4 A), to construct average maps of the density of activated neurons for ‘Yellow’ and ‘Blue’ light steps (Fig.…”

“…Alongside this, however, light can rapidly and acutely influence behaviour. For example, nocturnal mammals will actively avoid brightly illuminated areas if possible or will dramatically reduce their behavioural activity and rest when bright light cannot be avoided [2][3][4]. Alongside circadian control mechanisms, such acute effects of light on behaviour therefore constitute a major determinant of the daily patterns of mammalian rest and activity [4,5].…”