Endogenous clock gene expression in the suprachiasmatic nuclei of previsual newborn rabbits is entrained by nursing

Abstract

ABSTRACT:The rabbit is particularly suitable for investigating the development of mammalian circadian function. Blind at birth, the pups are only visited by the mother to be nursed once every 24 h for about 3 min and so can be studied largely without maternal interference. They anticipate the mother's visit with increased behavioral arousal and with a rise in body temperature, both of which represent endogenous circadian rhythms. We now report that in newborn pups the suprachiasmatic nuclei of the hypothalamus (SCN; the main circadian pacemaker in mammals) show endogenous 24-h rhythmicity in the expression of the clock genes Per1, Per2, and Bmal1. Pups nursed from postnatal days 1 to 7 and fasted to day 9 showed the same rhythms of clock gene expression as normally nursed controls. We also report that these rhythms are entrained by nursing.Pups killed on postnatal days 3-4 showed the same rhythms in gene expression as pups in the previous experiment, whereas littermates subsequently nursed from postnatal days 4 to 7 with nursing delayed 6 h showed a corresponding shift in the diurnal pattern of clock gene expression. Consistent with this, two groups of pups implanted with telemetric thermal sensors and nursed 6 h apart had daily patterns in body temperature synchronized with the two different nursing times. We conclude that the expression of clock genes associated with the newborn rabbit's circadian system is entrained by nonphotic cues accompanying nursing, the exact nature of which now needs to be clarified. '

Maternal Olfactory Cues Synchronize the Circadian System of Artificially Raised Newborn Rabbits

“…For the liver weight and metabolic parameters, the data of the four groups under study were separately analyzed using one-way ANOVA for independent measures to determine the potential differences associated with time followed by a COSINOR analysis to evaluate the 24-h rhythmicity, similar to previous studies [16–18]. In addition, the values of the four groups were compared using two-way ANOVAs for the factors of Group and Time followed by the Scheffe post hoc test (significance level 5%).…”

“…One remarkable example is the European newborn rabbit ( Oryctolagus cuniculus ). This species exhibits 24-h rhythmicity in a range of parameters, at the behavioral [11–13],, physiological [13–16] and molecular levels [16–18]. Maternal care is restricted in rabbits because the mother abandons the nest as soon as she gives birth to the pups and only visits them once every 24 h and nurses for 3 to 5 min [11,19,20].…”

“…This anticipation of nursing persists even if the rabbits are isolated from the mother, indicating that these changes are controlled by the circadian system [13,15]. Interestingly, this anticipatory phenomenon during development has only been reported in rabbits [11–13,15,16,22,23]. It has been widely described in rodents but only during adult life (reviewed in [24,25]).…”

“…The once-daily nursing is an effective non-photic entraining signal for the newborn rabbit circadian system because changes in the nursing schedule produce phase shifts in the expression of core body temperature rhythm and in the SCN clock gene expression [16]. During the brief nursing event, pre-visual rabbits are under the influence of complex sensory cues that include tactile, thermal, vestibular, gustatory, ingestive and olfactory information [16].…”

Circadian Insights into Motivated Behavior

“…In pups fed at the same time each day, clock gene expression (Per1, Per2 and Bmal1) is entrained. When feeding time is shifted, SCN clock gene expression rhythms exhibit a corresponding shift to follow feeding time (Caldelas et al 2009). Entrainment appears to use both food and social cues.…”