Temporal Precision in the Mammalian Circadian System: A Reliable Clock from Less Reliable Neurons

Abstract

The mammalian SCN contains a biological clock that drives remarkably precise circadian rhythms in vivo and in vitro. This study asks whether the cycle-to-cycle variability of behavioral rhythms in mice can be attributed to precision of individual circadian pacemakers within the SCN or their interactions. The authors measured the standard deviation of the cycle-to-cycle period from 7-day recordings of running wheel activity, Period1 gene expression in cultured SCN explants, and firing rate patterns of dispersed SCN neurons. Period variability of the intact tissue and animal was lower than single neurons. The median variability of running wheel and Period1 rhythms was less than 40 min per cycle compared to 2.1 h in firing rate rhythms of dispersed SCN neurons. The most precise SCN neuron, with a period deviation of 1.1 h, was 10 times noisier than the most accurate SCN explant (0.1 h) or mouse (0.1 h) but comparable to the least stable explant (2.1 h) and mouse (1.1 h). This variability correlated with intrinsic period in mice and SCN explants but not with single cells. Precision was unrelated to the amplitude of rhythms and did not change significantly with age up to 1 year after birth. Analysis of the serial correlation of cycle-to-cycle period revealed that approximately half of this variability is attributable to noise outside the pacemaker. These results indicate that cell-cell interactions within the SCN reduce pacemaker noise to determine the precision of circadian rhythms in the tissue and in behavior.

Development of the mouse suprachiasmatic nucleus: Determination of time of cell origin and spatial arrangements within the nucleus

“…In particular, the number of cells and the proportions of different cell types affect period and the stability of rhythms [8,19,12,18]. If functionally different cells are produced at different times, as the present results indicate [4], then small changes in the duration or intensity of proliferation of SCN progenitors at different times in development could be one source of variation (both within and between species) in the overall function of the nucleus.…”

Synchrony and entrainment properties of robust circadian oscillators

“…It is a network of multiple autonomous noisy oscillators, which communicate via neuropeptides to synchronize and form a coherent oscillator (Herzog et al 2004;Liu et al 2007). This coherent oscillator then coordinates the timing of daily behaviours, such as the sleep/wake cycle.…”

Mechanists Must be Holists Too! Perspectives from Circadian Biology

“…Although in Welsh et al's preparation a substantial number of neural connections remained, in a tissue explant from the SCN even more are retained. Herzog, Aton, Numano, Sakaki, and Tei (2004) showed that over a seven--day interval the SD of Per1 expression in explants was much less than the SD for the firing rate of dispersed neurons and closely approximated that of the running wheel behavior in the intact mouse. As shown in panels A and B of Figure 6, using a luciferase knock--in under the Per2 gene in SCN slices dispersed SCN neurons, Liu, Welsh, Ko, Tran, Zhang, Priest, Buhr, Singer, Meeker, Verma, Doyle, Takahashi, and Kay (2007) provided a compelling demonstration of the contrast in synchronization obtained between a SCN slice and dispersed neurons.…”