Retinal pathways influence temporal niche

Abstract

In mammals, light input from the retina entrains central circadian oscillators located in the suprachiasmatic nuclei (SCN). The phase of circadian activity rhythms with respect to the external light:dark cycle is reversed in diurnal and nocturnal species, although the phase of SCN rhythms relative to the light cycle remains unchanged. Neural mechanisms downstream from the SCN are therefore believed to determine diurnality or nocturnality. Here, we report a switch from nocturnal to diurnal entrainment of circadian activity rhythms in double-knockout mice lacking the inner-retinal photopigment melanopsin (OPN4) and RPE65, a key protein used in retinal chromophore recycling. These mice retained only a small amount of rod function. The change in entrainment phase of Rpe65 ؊/؊ ;Opn4 ؊/؊ mice was accompanied by a reversal of the rhythm of clock gene expression in the SCN and a reversal in acute masking effects of both light and darkness on activity, suggesting that the nocturnal to diurnal switch is due to a change in the neural response to light upstream from the SCN. A switch from nocturnal to diurnal activity rhythms was also found in wild-type mice transferred from standard intensity light:dark cycles to light:dark cycles in which the intensity of the light phase was reduced to scotopic levels. These results reveal a novel mechanism by which changes in retinal input can mediate acute temporalniche switching.I n mammals, the external light:dark cycle is the predominant environmental cue that synchronizes the central circadian clock in the suprachiasmatic nuclei (SCN) of the hypothalamus to the 24-h solar day. The temporal niche (nocturnal, diurnal, crepuscular, etc.) occupied by an animal reflects the phase relationship between activity and the synchronized clock. Several fundamental features of the relationship of the SCN to light, such as the association between the timing of resetting light pulses and phase changes in the clock (i.e., phase-response curves), are very similar among mammalian species regardless of their temporal niche (1, 2). Daily rhythms of SCN electrical activity, metabolism, and expression of genes that comprise the core molecular clock mechanism are also similarly timed with respect to the external light:dark cycle in both nocturnal and diurnal mammals [for review, see Smale et al. (3)]. These similarities have led to the widely accepted idea that temporal niche is not controlled through pathways that communicate light information to the clock or by the response of the clock to light, but rather by neural mechanisms downstream from the SCN.However, temporal-niche switching has recently been reported in mouse models of photoreceptor dysfunction, suggesting that input pathways may play a more important role in determining temporal niche than was previously believed (4-7). Retinal rods, cones, and intrinsically photosensitive retinal ganglion cells containing the photopigment melanopsin (OPN4) all provide light information for mammalian photo-entrainment (8, 9). We have previously reported a rob...

Rods-cones and melanopsin detect light and dark to modulate sleep independent of image formation

“…This response is surprising because dark pulses do not induce wheel running activity (24). We further show that there was no overall effect in animals lacking ipRGCs (i.e., aDTA).…”

“…Using wheel-running activity, it has been shown that WT mice do not significantly increase activity during a dark pulse presented during the daytime (24). However, EEG/EMG recording is a direct measure of sleep state and therefore a more accurate representation of behavioral changes.…”

Control of Sleep-Wake Cycles in Drosophila

“…In mammals, a given animal can stably and predictably switch back and forth between different patterns in context-dependent ways (Kas and Edgar 1999;Mrosovsky 2003). The choice of a temporal niche takes place downstream of the suprachiasmatic nucleus (SCN) clock and is strongly influenced by light inputs (Mrosovsky and Hattar 2005;Doyle et al 2008). A comparable plasticity is observed in flies.…”

Retina-clock relations dictate nocturnal to diurnal behaviors

“…This suggests that the phase difference in the activity of nocturnal and diurnal animals is not caused by differences in the circadian clock but rather by how the clock couples to output mechanisms (3). In this issue of PNAS, Doyle et al (4) present a possible mechanism for how retinal mutations could also lead to a switch between nocturnal and diurnal behavior.…”

“…In this issue of PNAS, Doyle et al (4) used the Per2 luciferase reporter line to show that the molecular clock is phased oppositely in doubleknockout and wild-type animals. In addition, the rhythms in peripheral tissues are also reversed.…”