Separate oscillating cell groups in mouse suprachiasmatic nucleus couple photoperiodically to the onset and end of daily activity

Abstract

The pattern of circadian behavioral rhythms is photoperioddependent, highlighted by the conservation of a phase relation between the behavioral rhythm and photoperiod. A model of two separate, but mutually coupled, circadian oscillators has been proposed to explain photoperiodic responses of behavioral rhythm in nocturnal rodents: an evening oscillator, which drives the activity onset and entrains to dusk, and a morning oscillator, which drives the end of activity and entrains to dawn. Continuous measurement of circadian rhythms in clock gene Per1 expression by a bioluminescence reporter enabled us to identify the separate oscillating cell groups in the mouse suprachiasmatic nucleus (SCN), which composed circadian oscillations of different phases and responded to photoperiods differentially. The circadian oscillation in the posterior SCN was phase-locked to the end of activity under three photoperiods examined. On the other hand, the oscillation in the anterior SCN was phase-locked to the onset of activity but showed a bimodal pattern under a long photoperiod [light-dark cycle (LD)18:6]. The bimodality in the anterior SCN reflected two circadian oscillatory cell groups of early and late phases. The anterior oscillation was unimodal under intermediate (LD12:12) and short (LD6:18) photoperiods, which was always phase-lagged behind the posterior oscillation when the late phase in LD18:6 was taken. The phase difference was largest in LD18:6 and smallest in LD6:18. These findings indicate that three oscillating cell groups in the SCN constitute regionally specific circadian oscillations, and at least two of them are involved in photoperiodic response of behavioral rhythm.bioluminescence reporter ͉ circadian rhythm ͉ clock gene ͉ photoperiod ͉ behavioral rhythm A daptation to seasonal changes in environment is critical to the survival of many organisms. Photoperiodic time measurement by the circadian clock is one of the strategies by which they conserve the phase relation between behavioral events such as the activity onset and dawn or dusk (1). A dramatic change induced by photoperiod is in the length of an activity band, the duration of activity in behavioral rhythms. Nocturnal rodents such as rats and mice exhibit compressed activity bands in long photoperiods and decompressed bands in short photoperiods. A long-standing hypothesis for the photoperiodic time measurement assumes two separate, but mutually coupled, circadian oscillators that drive the activity onset and end of activity, respectively, and respond to dawn and dusk differentially. Therefore, their phase-relationship encodes day lengths and changes the length of an activity band (1).The circadian clock in mammals is located in the suprachiasmatic nucleus (SCN) of the hypothalamus; it entrains to a light-dark cycle (LD) and determines the phases of overt circadian rhythms in behavior and physiology (2). Over the last decade, our understanding of the circadian clock in the SCN has advanced tremendously (3-5). The SCN consists of a number of oscillating cel...

Intrinsic, nondeterministic circadian rhythm generation in identified mammalian neurons

“…This changeable rhythmicity is reminiscent of the circadian properties of Drosophila neurons, which vary according to experience (31), and of Per1-, Per2-, or Cry1-mutant SCN neurons, which show ''stuttering'' circadian rhythms (7). The present results indicate that intercellular interactions acting on noisy gene expression within SCN neurons stabilize cycling, which may contribute to both the improved precision (32) and adaptable coding of, for example, day length by a population of heterogeneous oscillators (33,34). With each neuron having the ability to generate 24-h oscillations or to be driven, the SCN is a multipotential system.…”

“…Future studies will likely pursue how intercellular signals impact timekeeping processes, including rates of translation and degradation of clock proteins. It remains to be seen how changes in intracellular state, changes in connectivity within the SCN, or their combined effects mediate some of the developmental or seasonal adaptations in mammalian circadian rhythms (33,(40)(41)(42)(43).…”

Exploring Spatiotemporal Organization of SCN Circuits

“…Electrophysiological data show that in freely moving mice, rhythms in SCN multiunit activity (MUA) (high during subjective day) become compressed in short days and more distributed in long days, and these changes persist even after animals have been transferred into constant darkness (VanderLeest et al 2007). Corresponding changes are observed in vitro in SCN slices taken from animals under these conditions (Mrugala et al 2000;Inagaki et al 2007;VanderLeest et al 2007). …”

“…Measurements of clock gene expression indicate that circadian oscillation in the posterior SCN is phase-locked to the end of activity, whereas oscillations of some cells in the anterior SCN are phase-locked to the onset of activity (Hazlerigg et al 2005;Johnston 2005;Inagaki et al 2007).…”

“…(E) Photoperiod induces both temporal and spatial changes in the circadian phase of oscillators within the SCN. In short photoperiods, the oscillators are mostly inphase; in long photoperiods, the phases of the oscillators change along the rostrocaudal axis (Johnson 2005;Inagaki 2007). (F) New networks of SCN oscillators are seen under unusual environmental conditions.…”