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

Abstract

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...

The suprachiasmatic nucleus functions beyond circadian rhythm generation

“…This strongly suggests that the apparent ultradian rhythms observed in activity are the result of SCN signaling with a 24-h waveform that is not purely sinusoidal. Indeed, an endogenous circadian waveform of locomotor activity with multiple peaks over 24 hour is consistent with the recent observations in rat of distinct neuronal populations in the circadian pacemaker all with ~24 h periodicities but with 4 to 5-h peaks in electrophysiological discharge rate occurring at different relative phases (Schaap et al, 2003). An alternative hypothesis is that ultradian rhythms in activity are generated from locations outside the SCN, but the fact that they occur at precise harmonics of the fundamental circadian oscillation and are abolished with lesioning of the SCN suggests that such ultradian rhythms must interact with and be coupled to the SCN pacemaker.…”

“…If each individual oscillation within the SCN has a similar sinusoidal waveform, generation of scale-invariant correlations and nonlinearities from 24 hour down to 4 hour would be mathematically unlikely within the SCN itself. However, it has been shown in rat that neuronal populations in the SCN display non-sinusoidal waveform with 4 to 5-hour peaks in electrophysiological discharge rate, and the positions of peaks are different for distinct neurons (Schaap et al, 2003). With nonlinear coupling between individual clock cells in the SCN network consisting of 20,000 coupled neurons (Yamaguchi et al, 2003), raises the possibility that the SCN could be a self-contained multioscillator system.…”

Pigment Dispersing Factor-Dependent and -Independent Circadian Locomotor Behavioral Rhythms

“…Thus, NaChBac expression, although altering intrinsic membrane electrical properties, does not obliterate its rhythmic feature. Our results suggests that although different components of the circadian pacemaker circuit may regulate different aspects of activity behavior, they are coupled by strong interactions and that distribution of oscillators in the network is subject to plasticity evoked by changes in electrical activity or environmental conditions (Quintero et al, 2003;Schaap et al, 2003;Yamaguchi et al, 2003).…”

Tracking the seasons: the internal calendars of vertebrates

“…The SCN exhibits endogenous circadian rhythms that are photoperiod dependent in pinealectomized animals (Sumová & Illnerová 1996;Jacob et al 1997). In the Syrian hamster and rat SCN, rhythms of photosensitivity (Sumová et al 1995;Vuillez et al 1996), electrical activity (Mrugala et al 2000;Schaap et al 2003) and gene expression (see Schwartz et al 2001 andde la Iglesia et al 2004 for references) display intervals of high activity that expand and contract in concert with changes in the ambient photophase and scotophase. Light, by both entraining the circadian pacemaker in the SCN and suppressing NAT activity in the pineal, restricts melatonin secretion to the scotophase.…”