The secretion of hormones is temporally precise and periodic, oscillating over hours, days and months. The circadian time-keeper within the suprachiasmatic nuclei (SCN) is central to this co-ordination, modulating the frequency of pulsatile release, maintaining daily cycles of secretion and defining the time-base for longer term rhythms. This central clock is driven by cell-autonomous, transcriptional/post-translational feedback loops incorporating Period (Per) and other "clock" genes. SCN neurons exist, however, within neural circuits and an unresolved question is how do SCN clock cells interact. By monitoring the SCN molecular clockwork using fluorescence and bioluminescence video-microscopy of organotypic slices from mPer1::GFP and mPer1::luciferase transgenic mice, we show that inter-neuronal neuropeptidergic signalling via the VPAC2 receptor for vasoactive intestinal peptide (VIP) (an abundant SCN neuropeptide) is necessary to maintain both the amplitude and the synchrony of clock cells in the SCN. Acute induction of mPer1 by light is, however, independent of VIP/VPAC2 signalling, demonstrating dissociation between cellular mechanisms mediating circadian control of the clockwork and those mediating its retinally dependent entrainment to the light/dark cycle. The latter likely involves the Ca⁺⁺/cAMP response elements (CREs) of mPer genes, triggered by a MAP-kinase cascade activated by retinal afferents to the SCN. In the absence of VPAC2 signalling, however, this cascade is inappropriately responsive to light during circadian daytime. Hence VPAC2-mediated signalling sustains the SCN cellular clockwork, and is necessary both for inter-neuronal synchronisation and appropriate entrainment to the light/dark cycle. In its absence behavioural and endocrine rhythms are severely compromised.