Functional network inference of the suprachiasmatic nucleus.

In the mammalian suprachiasmatic nucleus (SCN), noisy cellular oscillators communicate within a neuronal network to generate precise system-wide circadian rhythms. Although the intracellular genetic oscillator and intercellular biochemical coupling mechanisms have been examined previously, the network topology driving synchronization of the SCN has not been elucidated. This network has been particularly challenging to probe, due to its oscillatory components and slow coupling timescale.

A neuropeptide speeds circadian entrainment by reducing intercellular synchrony.

Shift work or transmeridian travel can desynchronize the body's circadian rhythms from local light-dark cycles. The mammalian suprachiasmatic nucleus (SCN) generates and entrains daily rhythms in physiology and behavior. Paradoxically, we found that vasoactive intestinal polypeptide (VIP), a neuropeptide implicated in synchrony among SCN cells, can also desynchronize them.

Wavelet measurement suggests cause of period instability in mammalian circadian neurons.

Cells in the suprachiasmatic nucleus (SCN) display remarkable precision, while either physically or chemically decoupling these cells from each other leads to a dramatic increase in period-to-period variability. Where previous studies have classified cells as either arrhythmic or circadian, our wavelet analysis reveals that individual cells, when removed from network interactions, intermittently express circadian and/or longer infradian periods. We reproduce the characteristic period distribution of uncoupled SCN cells with a stochastic model of the uncoupled SCN cell near a bifurcation in Bmal1 transcription repression.

Synchrony and entrainment properties of robust circadian oscillators.

Systems theoretic tools (i.e. mathematical modelling, control, and feedback design) advance the understanding of robust performance in complex biological networks.

Intercellular coupling confers robustness against mutations in the SCN circadian clock network.

Molecular mechanisms of the mammalian circadian clock have been studied primarily by genetic perturbation and behavioral analysis. Here, we used bioluminescence imaging to monitor Per2 gene expression in tissues and cells from clock mutant mice. We discovered that Per1 and Cry1 are required for sustained rhythms in peripheral tissues and cells, and in neurons dissociated from the suprachiasmatic nuclei (SCN).