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

Abstract

The same clock-genes, including Period (PER) 1 and 2, that show rhythmic expression in the suprachiasmatic nucleus (SCN) are also rhythmically expressed in other brain regions that serve as extra-SCN oscillators. Outside the hypothalamus, the phase of these extra-SCN oscillators appears to be reversed when diurnal and nocturnal mammals are compared. Based on mRNA data, PER1 protein is expected to peak in the late night in the paraventricular nucleus of the hypothalamus (PVN) of nocturnal laboratory rats, but comparable data are not available for a diurnal species. Here we use the diurnal grass rat (Arvicanthis niloticus) to describe rhythms of PER1 and 2 protein in the PVN of animals that either show the species-typical day-active profile, or that adopt a night-active profile when given access to running wheels. For day-active animals housed with or without wheels, significant rhythms of PER1 or PER2 protein expression featured peaks in the late morning; night-active animals showed patterns similar to those expected from nocturnal laboratory rats. Since the PVN is part of the circuit that controls pineal rhythms, we also measured circulating levels of melatonin during the day and night in day-active animals with and without wheels and in night-active wheel runners. All three groups showed elevated levels of melatonin at night, with higher levels during both the day and night being associated with the levels of activity displayed by each group. The differential phase of rhythms in clock-gene protein in the PVN of diurnal and nocturnal animals presents a possible mechanism for explaining species differences in the phase of autonomic rhythms controlled, in part, by the PVN. The present study suggests that the phase of the oscillator of the PVN does not determine that of the melatonin rhythm in diurnal and nocturnal species or in diurnal and nocturnal chronotypes within a species.

Circadian regulation of membrane physiology in neural oscillators throughout the brain

“…When grass rats are given access to running wheels at night, they become nocturnally active, and the PVN expression of Per1 and Per2 rhythms resembles that of other nocturnal rodents, namely peaking during the dark phase. Neither diurnal nor nocturnal temporal niche changes nocturnal increases in melatonin (Martin‐Fairey et al., ). This result suggests that PVN oscillations of clock genes may be more closely related to the activity preference of the animals, highlighting potential roles for the purported role of the SPZ as a switch as discussed elsewhere in this review, and indicates that the nocturnal rise in melatonin may not depend on the phase of the local PVN oscillator.…”

Melatonin and the pathologies of weakened or dysregulated circadian oscillators

“…The role of the SCN is now seen as that of a pacemaker and master clock, on which peripheral oscillators depend to a variable degree, from strongly dependent slave oscillators to others that are partially or almost fully autonomous . Besides the SCN, additional oscillators exist in the mammalian central nervous system, including pituitary, retina, paraventricular nucleus, and pineal gland . In the case of the pineal gland, its intrinsic oscillator seems to be more of the type of a slave that is largely controlled by the SCN.…”

The Cost of Activity during the Rest Phase: Animal Models and Theoretical Perspectives

“…While this hypothesis promotes the adaptive value ( 32 ) of the temporal niche switch ( 31 ), there may also be costs, as activity during the natural rest phase of the mice was accompanied by changes in synchrony of internal rhythms. Specifically, peripheral oscillators shifted their phase angles with respect to the SCN and likely with respect to the melatonin rhythm, which remains nocturnal in other models of temporal niche switching ( 29 , 36 ).…”

“…The retention of some diurnal tendencies in NA grass rats may be due to the diverse responses of extra-SCN brain oscillators to the switch to nocturnal activity. Perhaps not surprisingly, the adoption of a NA profile does not affect the phase of clock gene [PERIOD 1 and 2 (PER1/2)] rhythms in the SCN ( 41 ) or the nocturnal production of melatonin ( 36 ). However, most extra-SCN brain regions that express rhythms in PER 1/2 display a complete reversal of the time of peak expression when grass rats become NA, thus making the circadian profile of NA grass rats similar to that of nocturnal rodents ( 41 ).…”

“…Outside the hypothalamus, the central amygdala shows a very similar pattern in NA and DA grass rats that contrasts with what is seen in the rest of the extrahypothalamic brain ( 41 ). In the extra-SCN hypothalamus (Figure 1 ), the paraventricular nucleus (PVN) shows a phase reversal in NA grass rats ( 36 ), but the ventral subparaventricular zone remains fixed and similar in phase to that of DA animals ( 41 ). Most relevant for understanding the sleep fragmentation of NA grass rats during the day is the response of the hypothalamic histaminergic nuclei [i.e., the dorsal and ventral tuberomammillary nuclei (dTMN and vTMN), respectively] to the switch to nocturnality in these animals.…”