Phase preference for the display of activity is associated with the phase of extra-suprachiasmatic nucleus oscillators within and between species

Abstract

Many features of the suprachiasmatic nucleus (SCN) are the same in diurnal and nocturnal animals, suggesting that differences in phase preference are determined by mechanisms downstream from the SCN. Here, we examined this hypothesis by characterizing rhythmic expression of PER1 and PER2 in several extra-SCN areas in the brains of a diurnal murid rodent, Arvicanthis niloticus (grass rats). In the shell of the nucleus accumbens, dorsal striatum, piriform cortex, and CA1 of the hippocampus, both PER1 and PER2 were rhythmic, with peak expression occurring at ZT10. PER1 in the dentate gyrus also peaked at ZT10, but PER2 was arrhythmic in this region. In general, these patterns are 180° out of phase with those reported for nocturnal species. In a second study, we examined inter-individual differences in the multioscillator system of grass rats. Here, we housed grass rats in cages with running wheels, under which conditions some individuals spontaneously adopt a day active (DA) and others a night active (NA) phase preference. In the majority of the extra-SCN regions sampled, the patterns of PER1 and PER2 expression of NA grass rats resembled those of nocturnal species, while those of DA grass rats were similar to the ones seen in grass without access to running wheels. In contrast, the rhythmic expression of both PER proteins was identical in the SCN and ventral subparaventricular zone (vSPZ) of DA and NA animals. Differences in the phase of oscillators downstream from the SCN, and perhaps the vSPZ, appear to determine the phase preference of particular species, as well as that of members of a diurnal species that show voluntary phase reversals. The latter observation has important implications for the understanding of health problems associated with human shift work.

Circadian Clock Gene Expression in Brain Regions of Alzheimer ’s Disease Patients and Control Subjects

“…Interestingly, following manipulations that uncouple the phase of locomotor activity from the light-dark cycle, Per1 and Per2 RNA rhythms in the cortex of nocturnal rodents, which normally peak in the dark (active) phase, remain phaselocked to the rhythm of locomotor activity, even showing multiple daily peaks in animals with a split locomotor activity rhythm (Abe et al, 2001;Masubuchi et al, 2000). Furthermore, in the grass rat Arvicanthis niloticus, a diurnal rodent that presents a nighttime activity pattern under some experimental conditions, the PeR1 and PeR2 protein rhythms presented similar phases in the piriform cortex and BNST, and the peak protein levels of both proteins in the 2 brain regions occurred during the active phase, no matter whether the animals were presenting a day-active or a nightactive pattern (Ramanathan et al, 2010). In our data, PER2 RNA also peaked in the active phase in the cortex, thus out of phase with usual nocturnal rodent data, but with a similar phase relationship to the rest/activity cycle and in a similar way to diurnal rodents.…”

The flexible clock: predictive and reactive homeostasis, energy balance and the circadian regulation of sleep–wake timing

“…Furthermore, the phase of cellular clocks has been linked to tissue-specific rhythms in gene expression (Storch et al, 2002), giving rise to circadian rhythms in cell function and sensitivity, and leading to rhythmic activation of tissue-specific pathways (Oster et al, 2006;Zhang et al, 2014). The importance of maintaining an appropriate phase of peripheral oscillators is illustrated by the observation that the phase of several local tissue clocks in nightactive (nocturnal) species is shifted ∼12 h compared with that of day-active (diurnal) species (Challet, 2007;Hut et al, 2012;Lambert and Weaver, 2006;Ramanathan et al, 2010).…”

Plastic oscillators and fixed rhythms: Changes in the phase of clock-gene rhythms in the PVN are not reflected in the phase of the melatonin rhythm of grass rats

“…Particularly, when given access to running wheels a proportion of diurnal grass rats become predominantly night-active (NA), whereas other individuals retain their day-active (DA) profile, even when wheels are available (Blanchong et al, 1999). The phase of brain extra-hypothalamic oscillators of NA grass rats appears to be 180° out of phase with respect to that of DA animals, thus resembling the phase typical of nocturnal species (Ramanathan et al, 2010b). However, at least in the ventral subparaventricular zone [vSPZ;(Ramanathan et al, 2006)], the hypothalamic dorsal tuberommamillary nuclei (dTMN) and the dorsomedial hypothalamus (DMN;Nunez et al 2012), that reversal of phase is not complete, and thus the circadian profile of the hypothalamus of NA grass rats retains features typical of diurnal animals.…”

“…Irrespective of phase preference for the display of activity, the phase of the melatonin rhythm is more or less the same across mammalian species (Reiter, 1991b), yet recent observations about the phases of extra-SCN, non-hypothalamic oscillators demonstrate that those of diurnal grass rats (Ramanathan et al 2010b), Octodon degus (Otalora et al, 2013) and humans (Li et al, 2013) are 180° out of phase compared to those of nocturnal rodents (Amir et al, 2004, Amir and Robinson, 2006). Thus, given the common phase of the melatonin rhythm across diurnal and nocturnal mammalian species and the involvement of the PVN in the mediation of that rhythm, one question addressed here relates to potential differences as well as similarities between the phase of the PVN oscillator in diurnal and nocturnal mammalian species.…”

“…Our aim was to determine if the phase profile of PER1 and 2 rhythms described for other brain regions of the grass rats (Ramanathan et al, 2010a, Ramanathan et al, 2010b) generalize to a nucleus that regulates autonomic functions, including the rhythm of melatonin production by the pineal gland. With respect to control of the pineal gland, the two levels of the PVN used for this analysis contain a significant proportion of the PVN neurons that communicate with the pineal via the sympathetic outflow to the gland (Teclemariam-Mesbah et al, 1999).…”