Suprachiasmatic nucleus: cellular clocks and networks.

The suprachiasmatic nucleus (SCN), the master circadian clock of mammals, is composed of multiple circadian oscillator neurons. Most of them exhibit significant circadian rhythms in their clock gene expression and spontaneous firing when cultured in dispersed cells, as well as in an organotypic slice. The distribution of periods depends on the SCN tissue organization, suggesting that cell-to-cell interaction is important for synchronization of the constituent oscillator cells. This cell-to-cell interaction involves both synaptic interactions and humoral mediators. Cellular oscillators form at least three separate but mutually coupled regional pacemakers, and two of them are involved in the photoperiodic regulation of behavioral rhythms in mice. Coupling of cellular oscillators in the SCN tissue compensates for the dysfunction due to clock gene mutations, on the one hand, and desynchronization within and between the regional pacemakers that suppresses the coherent rhythm expression from the SCN, on the other hand. The multioscillator pacemaker structure of the SCN is advantageous for responding to a wide range of environmental challenges without losing coherent rhythm outputs.