Retino-hypothalamic regulation of light-induced murine sleep

Abstract

The temporal organization of sleep is regulated by an interaction between the circadian clock and homeostatic processes. Light indirectly modulates sleep through its ability to phase shift and entrain the circadian clock. Light can also exert a direct, circadian-independent effect on sleep. For example, acute exposure to light promotes sleep in nocturnal animals and wake in diurnal animals. The mechanisms whereby light directly influences sleep and arousal are not well understood. In this review, we discuss the direct effect of light on sleep at the level of the retina and hypothalamus in rodents. We review murine data from recent publications showing the roles of rod-, cone- and melanopsin-based photoreception on the initiation and maintenance of light-induced sleep. We also present hypotheses about hypothalamic mechanisms that have been advanced to explain the acute control of sleep by light. Specifically, we review recent studies assessing the roles of the ventrolateral preoptic area (VLPO) and the suprachiasmatic nucleus (SCN). We also discuss how light might differentially promote sleep and arousal in nocturnal and diurnal animals respectively. Lastly, we suggest new avenues for research on this topic which is still in its early stages.

Keywords: diurnal; melanopsin; nocturnal; photoreception; suprachiasmatic nucleus.

Figure 1

Initiation and maintenance of sleep across different genotypes early in the dark period to a bright saturating light pulse. The induction of sleep can be maintained for at least 3-h early in the dark period in WT mice (black line). In the absence of melanopsin (MKO) or rod-cone photoreception (rd/rd cl), there is an initial increase in sleep but lack of maintenance for the remainder of the light pulse in both genotypes (Altimus et al., ; Muindi et al., ; red and blue lines). When the melanopsin expressing RGCs are selectively ablated by the expression via the expression diphtheria toxin-A (aDTA) in the melanopsin locus (Altimus et al., 2008) the light-induced sleep response is completely abolished (black dotted line). This suggests that these cells serve as an exclusive pathway for mediating the acute effects of light. The sleep response in the triple knockout (rd/rd cl/MKO) is currently not known, but is likely to mimic the results from the melanopsin aDTA mice (green dotted line).

Figure 2

A summary diagram showing the pathways and areas that may be involved in the direct modulation of sleep by light in nocturnal animals. At low light intensities, rod photoreception relays light information to RGCs expressing melanopsin and RGCs not expressing melanopsin. Light activates both the SCN and the VLPO via the RHT and most likely causes the inhibition of the downstream wake promoting areas. At higher intensities, the rod-, cone-, and melanopsin photoreception work together to initiate and maintain the activation of the VLPO and SCN resulting in the maintenance of sleep during a light pulse early in the dark period. Similarly, the inhibition of the wake promoting areas by the VLPO and presumably the SCN via the SPZ and DMH would facilitate the promotion of sleep by light at high intensities. However, it is not known whether the inhibition is across some or all of the wake promoting areas. Abbreviations: Retinal Ganglion Cells, RGCs; Retino-hypothalamic tract, RHT; Suprachiasmatic Nucleus, SCN; Ventrolateral Preoptic Area, VLPO; Lateral Geniculate Complex, LGC; Olivary Pretectal Nucleus, OPN; Superior Colliculus, SC; Dorsomedial hypothalamus, DMH; Dorsal Raphe, DR; Locus coeruleus, LC; Tubero-mammillary nucleus, TMN; Hypocretin, HCRT.