It was once thought possible that the brain clock, located in the suprachiasmatic nucleus (SCN) of the hypothalamus, could be understood as a homogeneous population of cells that produced a synchronous daily oscillatory signal. Instead, it is now clear that SCN subregions exhibit orderly phase dispersal. The mechanisms enforcing regional phase differences, however, are not well understood. Hong et al. (in press) propose that calcium contributes to synchronization through two mechanisms acting over different time scales and distances. Using all possible oscillating cell pairs as data points, the plot of temporal phase difference against pair separation distance suggests the coexistence of two modes of signaling: progressively propagating waves of a diffusing signal in adjacent cells, and phase-synchronizing neural networks acting at long range. In the first, a sharp wedge-shaped boundary in the region of small pair separation distances was inferred to represent a calcium wave sweeping through the SCN. The slope of this boundary represents the travel velocity of the wave, which, by itself, was calculated to be too slow to pass through the SCN in 24 h. A second mode of signaling was indicated by the finding that some cell pairs showed large spatial separations but nevertheless had small phase differences. For these cell pairs, the Fluorescence Resonance Energy Transfer signal was sufficiently bright to illuminate cell processes, revealing that anatomically joined cells oscillated in phase.
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