Role of vasoactive intestinal peptide in seasonal encoding by the suprachiasmatic nucleus clock

Abstract

The neuropeptide vasoactive intestinal peptide (VIP) is critical for the proper functioning of the neural circuit that generates circadian rhythms. Mice lacking VIP show profound deficits in the ability to generate many behavioral and physiological rhythms. To explore how the loss of VIP impacts on the intact circadian system, we carried out in vivo multiunit neural activity (MUA) recordings from the suprachiasmatic nucleus of freely moving VIP knockout (KO) mice. The MUA rhythms were largely unaltered in the VIP KO mice, with no significant differences being seen in the amplitude or phase of the rhythms in light-dark conditions. Robust differences between the genotypes were revealed when the mice were transferred from light-dark to constant darkness conditions. In addition, the ability of the VIP KO mice to encode changes in photoperiod was examined. Strikingly, the behavioral and physiological rhythms of VIP KO mice showed no adaptation to short or long photoperiods. The data indicate that the intact circadian system can compensate for some of the consequences of the loss of VIP, whereas this peptide is indispensable for endogenous encoding of seasonal information.

A neuropeptide speeds circadian entrainment by reducing intercellular synchrony

“…Following a perturbation, the model cells from short days all shift similarly, producing a larger net shift than the perturbation delivered to the less synchronized summertime SCN (54,55). Although VIP has been implicated in the slow adaptation to changing day length (56), the desynchronizing effects of VIP pretreatment described here function at any time of day, do not require many days to affect the phase-shifting properties of the circadian system, and appear to result from the intrinsically variable responses of different SCN cells. We found that VIP reduces the amplitude of SCN rhythms more at CT22 than at other times and, when applied daily, entrains the SCN so that the time of VIP application falls at CT4, a time of relative phase stability.…”

Collective timekeeping among cells of the master circadian clock

“…In particular, VIP is involved in photic signaling (An, et al 2013; Colwell et al 2003; Dragich, et al 2010; Hughes, et al 2004; Kuhlman et al 2003; Lucassen, et al 2012; Shen, et al 2000), and light influences VIP expression in the SCN (Duncan et al 1995; Francl, et al 2010; Isobe and Nishino 1998; Shinohara and Inouye 1995; Smith and Canal 2009). Deficits in VIP signaling cause abnormal responses to light, with one result being an unusual responsiveness to light during the day.…”

In synch but not in step: Circadian clock circuits regulating plasticity in daily rhythms

“…It is clear that VIP signaling plays an important role in stabilizing circadian waveform in the absence of environmental time cues (Harmar et al, 2002, Colwell et al, 2003), but additional work should test whether the DD phenotype of VIP-deficient mice is caused directly by loss of the VIP-related synchronizing cue or indirectly by a GABA-related desynchronizing signal (Freeman et al, 2013). Moreover, VIP knockout mice fail to maintain photoperiodic changes in α and SCN electrical activity upon release into DD (Lucassen et al, 2012), but the strength of rhythms displayed by VIP mice is enhanced by short day entrainment. In addition to short day lengths, rhythms of VIP-deficient mice are improved by constant light and use of a running-wheel (Power et al, 2010, Hughes et al, 2015).…”