The circadian cycle of mPER clock gene products in the suprachiasmatic nucleus of the Siberian hamster encodes both daily and seasonal time

187

176

Circadian rhythms in neuronal ensemble, subpopulations, and single unit activity were recorded in the suprachiasmatic nuclei (SCN) of rat hypothalamic slices. Decomposition of the ensemble pattern revealed that neuronal subpopulations and single units within the SCN show surprisingly short periods of enhanced electrical activity of Ϸ5 h and show maximal activity at different phases of the circadian cycle. The summed activity accounts for the neuronal ensemble pattern of the SCN, indicating that circadian waveform of electrical activity is a composed tissue property. The recorded single unit activity pattern was used to simulate the responsiveness of SCN neurons to different photoperiods. We inferred predictions on changes in peak width, amplitude, and peak time in the multiunit activity pattern and confirmed these predictions with hypothalamic slices from animals that had been kept in a short or long photoperiod. We propose that the animals' ability to code for day length derives from plasticity in the neuronal network of oscillating SCN neurons.T he suprachiasmatic nuclei (SCN) contain a major pacemaker of circadian rhythms in mammals (1, 2). The SCN control circadian rhythms in the central nervous system and peripheral organs and as such ensures that organisms are able to anticipate and adjust to predictable changes in the environment that occur with the day-night cycle (3-5). The SCN is also involved in adaptation of the organism to the annual cycle by monitoring seasonal changes in day length (6). As an example, animals will accommodate their daily behavioral activity to the photoperiod. A multioscillator structure has been proposed to fulfill this dual task (7).At least nine candidate genes have been identified that play a role in rhythm generation on the basis of a transcriptionaltranslational feedback loop (8, 9). A number of additional genes may be involved to further refine or shape circadian rhythms (10). Although great progress has been made in understanding the molecular basis for circadian rhythm generation, it is unknown how individual neuronal activity rhythms are integrated to render a functioning pacemaker that is able to code for circadian and seasonal rhythms. The SCN each contain Ϸ10,000 neurons, which are small and densely packed (11). After dissociation, isolated SCN neurons express circadian rhythms in their firing patterns (12, 13). The freerunning periods of the individual neurons vary from 20 to 28 h. The average period matches the behavioral activity pattern of Ϸ24 h. In these cultured dispersals, synaptically coupled neurons can sometimes be observed with synchronized firing patterns (14). In SCN tissue explants cultured on multielectrode plates, the variation in free-running period is considerably smaller (15)(16)(17). In these explants, firing patterns can be observed which are in phase, or 6 -12 h out of phase. The range of phase relationships observed within the SCN in vitro suggests a level of temporal complexity that challenges our understanding of how a singular phase and perio...

Section: Discussionsupporting

confidence: 85%

Heterogeneity of rhythmic suprachiasmatic nucleus neurons: Implications for circadian waveform and photoperiodic encoding

Schaap

Albus

vanderLeest

et al. 2003

187

176

“…Jagota et al showed two distinct peaks of electrophysiological activity in the horizontally sectioned SCN culture in hamsters (10) but not in rats and mice (11), which responded differentially to photoperiods. In addition, the circadian rhythms in Per1 and Per2 expression were reported to change in different photoperiods (12)(13)(14)(15)(16)(17)(18)(19)23). The duration of gene expression was extended in long photoperiods, whereas the rhythm amplitudes were increased in short photoperiods, suggesting that the mutual coupling of individual cell oscillations was altered by photoperiods.…”

Section: Discussionmentioning

confidence: 99%

“…More recently, two distinct peaks of electrophysiological activity in the cultured SCN were observed in the Syrian hamster (10,11), and the peaks responded differentially to photoperiods (10). In addition, circadian rhythms in clock gene expression and their protein products were reported to change in different photoperiods (12)(13)(14)(15)(16)(17). Generally, the interval of high Per1 and Per2 expression is extended in long photoperiods, whereas the rhythm amplitudes are increased in short photoperiods.…”

mentioning

confidence: 99%

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

Inagaki

Honma

Ono

et al. 2007

241

248

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...

“…The present study extends this finding to sheep, and of all clock genes studied in this tissue, only the Per genes were photoperiod-responsive. The principal effect of photoperiod on Per gene expression in the SCN of both sheep and rodents appears to be a decompression of the elevated portion of the expression rhythm for both genes under long days, and in Siberian hamsters, this long-day decompression of the PER1 and PER2 protein waveforms persisted, at least in part, when animals were placed in constant darkness (DD) (7). Together, these observations are consistent with a model for SCN function in which photoperiod influences pacemaker activity as a result of coincidence between light and photoinducible phases in the Per expression rhythms (external coincidence model).…”

Section: Scnmentioning

confidence: 99%

“…The expression of the Period genes is robustly rhythmic and shows phase-dependent responses to photic stimuli, suggesting that light entrainment of the SCN pacemaker occurs through effects on Period gene expression (4,5). Moreover, photoperiod-dependent changes in the timing of overt circadian rhythms are associated with effects on the duration of the elevated expression of the Period genes in the SCN (6,7), suggesting that temporal changes in output are caused by corresponding changes in circadian gene expression in this tissue. Per1 also is expressed rhythmically in the PT, with a maximum early in the light phase.…”

mentioning

confidence: 99%

Temporal expression of seven clock genes in the suprachiasmatic nucleus and the pars tuberalis of the sheep: Evidence for an internal coincidence timer

Lincoln

Messager²,

Andersson³

et al. 2002

211

205

The 24-h expression of seven clock genes (Bmal1, Clock, Per1, Per2, Cry1, Cry2, and CK1 ) was assayed by in situ hybridization in the suprachiasmatic nucleus (SCN) and the pars tuberalis (PT) of the pituitary gland, collected every 4 h throughout 24 h, from female Soay sheep kept under long (16-h light͞8-h dark) or short (8-h light͞16-h dark) photoperiods. Locomotor activity was diurnal, inversely related to melatonin secretion, and prolactin levels were increased under long days. All clock genes were expressed in the ovine SCN and PT. In the SCN, there was a 24-h rhythm in Clock expression, in parallel with Bmal1, in antiphase with cycles in Per1 and Per2; there was low-amplitude oscillation of Cry1 and Cry2. The waveform of only Per1 and Per2 expression was affected by photoperiod, with extended elevated expression under long days. In the PT, the high-amplitude 24-h cycles in the expression of Bmal1, Clock, Per1, Per2, Cry1, and Cry2, but not CK1 , were influenced by photoperiod. Per1 and Per2 peaked during the day, whereas Cry1 and Cry2 peaked early in the night. Hence, photoperiod via melatonin had a marked effect on the phase relationship between Per͞Cry genes in the PT. This supports the conclusion that an ''external coincidence model'' best explains the way photoperiod affects the waveform of clock gene expression in the SCN, the central pacemaker, whereas an ''internal coincidence model'' best explains the way melatonin affects the phasing of clock gene expression in the PT to mediate the photoperiodic control of a summer or winter physiology.