Fig. 1.

The retinorecipient ventrolateral core of the suprachiasmatic nucleus (SCN) contains a high concentration of neurons that express vasoactive intestinal polypeptide (VIP). These neurons have a critical role in coordinating rhythms of clock gene expression in the dorsomedial, vasopressin-rich shell of the SCN (dmSCN). About half of the VIP neurons and half of the arginine vasopressin (AVP) neurons also express prokineticin 2 (PK2), and all 3 of these peptides comprise SCN outputs that govern circadian rhythmicity in other brain regions through axonal projections, humoral release, or some combination of both of these routes. Extra-SCN structures may project back to the pacemaker to regulate its function. The gradual loss of circadian rhythms of locomotor behavior in V1a^−/− mice reported by Li et al. (9) may reflect V1a-mediated action of AVP upon VIP neurons within the SCN (indicated by the ?), vasopressinergic regulation of PK2 production and release, and/or a role of V1a in receipt of vasopressinergic signals by extra-SCN targets. V1a, vasopressin receptor; Vl SCN, ventrolateral SCN.