Inhibitory and excitatory networks balance cell coupling in the suprachiasmatic nucleus: A modeling approach.

Neuronal coupling contributes to circadian rhythms formation in the suprachiasmatic nucleus (SCN). While the neurotransmitter vasoactive intestinal polypeptide (VIP) is considered essential for synchronizing the oscillations of individual neurons, γ-aminobutyric acid (GABA) does not have a clear functional role despite being highly concentrated in the SCN. While most studies have examined the role of either GABA or VIP, our mathematical modeling approach explored their interplay on networks of SCN neurons. Tuning the parameters that control the release of GABA and VIP enabled us to optimize network synchrony, which was achieved at a peak firing rate during the subjective day of about 7Hz. Furthermore, VIP and GABA modulation could adjust network rhythm amplitude and period without sacrificing synchrony. We also performed simulations of SCN networks to phase shifts during 12h:12h light-dark cycles and showed that GABA networks reduced the average time for the SCN model to re-synchronize. We hypothesized that VIP and GABA balance cell coupling in the SCN to promote synchronization of heterogeneous oscillators while allowing flexibility for adjustment to environmental changes.