Entrainment to Feeding but Not to Light: Circadian Phenotype of VPAC₂Receptor-Null Mice

Abstract

The master clock driving mammalian circadian rhythms is located in the suprachiasmatic nuclei (SCN) of the hypothalamus and entrained by daily light/dark cycles. SCN lesions abolish circadian rhythms of behavior and result in a loss of synchronized circadian rhythms of clock gene expression in peripheral organs (e.g., the liver) and of hormone secretion (e.g., corticosterone). We examined rhythms of behavior, hepatic clock gene expression, and corticosterone secretion in VPAC 2 receptor-null (Vipr2 Ϫ/Ϫ ) mice, which lack a functional SCN clock. Unexpectedly, although Vipr2 Ϫ/Ϫ mice lacked robust circadian rhythms of wheel-running activity and corticosterone secretion, hepatic clock gene expression was strongly rhythmic, but advanced in phase compared with that in wild-type mice. The timing of food availability is thought to be an important entrainment signal for circadian clocks outside the SCN. Vipr2 Ϫ/Ϫ mice consumed food significantly earlier in the 24 h cycle than wild-type mice, consistent with the observed timing of peripheral rhythms of circadian gene expression. When restricted to feeding only during the daytime (RF), mice develop rhythms of activity and of corticosterone secretion in anticipation of feeding time, thought to be driven by a food-entrainable circadian oscillator, located outside the SCN. Under RF, mice of both genotypes developed food-anticipatory rhythms of activity and corticosterone secretion, and hepatic gene expression rhythms also became synchronized to the RF stimulus. Thus, food intake is an effective zeitgeber capable of coordinating circadian rhythms of behavior, peripheral clock gene expression, and hormone secretion, even in the absence of a functional SCN clock.

Phase-dependent resetting of the adrenal clock by ACTH in vitro

“…Adrenocortical innervation includes VIPergic fibers (23). Because corticosterone rhythms are suppressed in constitutive VIP knockout (26,27) and VIP receptor knockout mice (13,45), ACTH could complement VIPergic innervation to mediate photic entrainment of the adrenal clock.…”

Maternity-related plasticity in circadian rhythms of bumble-bee queens

“…Similar dim red light illumination is commonly used for monitoring locomotor activity in circadian studies (e.g. [4,5,7,[24][25][26]). We monitored locomotor activity and analysed circadian rhythms with the CLOCKLAB data acquisition and analysis system (Actimetrics Co., Wilmette, IL, USA).…”

Circadian clocks: regulators of endocrine and metabolic rhythms

“…As a consequence of this molecular disorganisation, the rhythms of electrical firing in the SCN and the circadian behaviour of the mice are compromised (Harmar et al 2002, Aton et al 2005. The loss of SCN competence in Vpac2 null mice leads to disrupted corticosteroid and oestrous rhythms, which in turn are accompanied by changes in circadian gene expression in peripheral tissues (Dolatshad et al 2006, Sheward et al 2007). The interdependence of the core molecular loop and SCN neural circuit activity is illustrated further in mice lacking either Cry1 or Per1.…”