The nursing rhythms of 14 rabbit does and the activity of 18 litters from birth to days 14-16 were monitored continuously, as were the circadian rhythms of different behavioral functions of 10 young rabbits from weaning until day 380 of life. The does gave birth 2 hr, 26 min +/- 2 hr, 8 min after lights-on in a light-dark cycle (LD 12:12). The first nursing occurred 20 hr, 30 min +/- 2 hr, 21 min after parturition. Does that had continuous access to the next boxes exhibited a regular once-a-day nursing rhythm; the nursing visits to the litters occurred during the dark phase (D). The nursing visits lasted 3 min, 42 sec +/- 25 sec. Nursing advanced during the first 10 days of lactation by an average of 42 +/- 16 min/day, and thus shifted to the first half of D. The pups anticipated nursing by a significant increase of activity, which was established between days 1 and 5 of life. In two does, the nursing rhythm split into two nursing visits per day, one during D and one during the light phase (L). When scheduled to nurse at an "artificial" phase in L with T = 24 hr, the pups' anticipatory activity was entrained by the 24-hr nursing rhythm. During a 48-hr fast, the elevated activity persisted around the phase of prior nursing time, demonstrating that it was controlled by an endogenous oscillator entrained by the zeitgeber of maternal nursing. Of 10 weanlings, 6 first exhibited a trimodal rhythm, which turned bimodal within 3-6 days. Stable entrainment by the external LD zeitgeber was attained by about days 45-80, and full nocturnality was attained by about days 200-250 after weaning. Having attained steady-state conditions, 7 of 10 rabbits exhibited a stable unimodal, nocturnal rhythm in each of the five functions, while the other 3 retained a bimodal rhythm.

No abstract

Three main concerns underlie this review: 1) The need to draw together the widely dispersed information available on the circadian biology of the rabbit. Although the rabbit is a classic laboratory mammal, this extensive body of information is often overlooked by chronobiologists, and despite several advantages of this species. In terms of its general biology the rabbit is the best studied laboratory mammal in the wild, it demonstrates a wide variety of robust circadian functions, and being a lagomorph, it provides a useful comparison with more commonly studied rodent species. 2) The need to more fully exploit a developmental approach to understanding circadian function, and the particular suitability of the rabbit for this. Female rabbits only visit their altricial young for a few minutes once every 24 h to nurse, and survival of the young depends on the tight circadian-controlled synchronization in behavior and physiology of the two parties. Patterns of circadian rhythmicity in neonatal pups associated with nursing do not form a smooth continuum into weaning and adult life, and may reflect the action of separate mechanisms operating in their own right. 3) Using information from the first two points, to emphasize the diversity and complexity of circadian rhythms underlying behavioral and physiological functions in adult and developing mammals. Information accruing on circadian functions in the rabbit makes it increasingly difficult to account for these in terms of one or two regulatory mechanisms or "oscillators." Thus, it is argued that in addition to the reductionist, molecular approaches currently dominating much of chronobiology, the study of circadian systems as emergent characteristics of whole organisms operating in complex environments merits special attention.

The rabbit pup is well suited to track the age-dependent development of periodic thermoregulation during the suckling period. Since the litters are regularly nursed once per day for a total of 3 to 4 min, an exogenous, metabolic, nonphotic periodic variable is supposed to have an impact on the 24-h rhythm of body temperature. The authors monitored the course of core body temperature during the suckling period of 20 pups by means of a transmitter implanted intraperitoneally on day 3 postpartum. The 24-h mean rose from an average of 37.8+/-0.3 degrees C on day 4 of life to 39.5+/-0.2 degrees C at weaning on day 27, for 2 out of 20 pups, and day 28, for 18 out of 20 pups. In constant dim illumination, the pups exhibited a 24-h rhythm even on postnatal day 4, which consolidated around days 5 to 7. The rhythm consisted of a significant anticipatory rise of 0.4 to 0.6 degrees C above the respective 24-h mean commencing 2.5 to 3.5 h prior to nursing. Milk intake was followed by a further increase of temperature for an additional 0.3 to 0.6 degrees C. Then the temperature dropped for 1.2 to 1.5 degrees C within 1 to 3 h and returned to average 3 to 5 h later. During a 48-h fast, the rhythm continued to exist, though in a modified shape: the anticipatory component persisted almost unchanged; a further elevation of temperature, however, did not occur. Thus, the anticipatory component apparently is generated endogenously and the second surge represents an exogenous suckling-induced, thermogenic peak. When maternal nursing was advanced for 15 min/day for a total of 5 h, the temperature rhythm of the pups followed the shift of the zeitgeber in parallel. These data confirm the assumption that a circadian rhythm exists during the first postnatal days of the rabbit and that this rhythm is entrained by the 24-h nursing rhythm. The authors suggest that the biological significance of a feeding entrainable oscillator (FEO) in the rabbit might be to activate the pups prior to the periodic nursing visit of the rabbit doe. Thus, the pups are prepared to quantitatively use the one and only short nursing episode per day for maximal milk ingestion.

Background IL-2 deficient (IL-2−/−) mice mono-colonized with E. coli mpk develop colitis whereas IL-2−/−-mice mono-colonized with B. vulgatus mpk do not and are even protected from E. coli mpk induced colitis.Methodology/Principal FindingsWe investigated if mono-colonization with E. coli mpk or B. vulgatus mpk differentially modulates distribution, activation and maturation of intestinal lamina propria (LP) dendritic cells (DC). LP DC in mice mono-colonized with protective B. vulgatus mpk or co-colonized with E. coli mpk/B. vulgatus mpk featured a semi-mature LP DC phenotype (CD40loCD80loMHC-IIhi) whereas mono-colonization with colitogenic E. coli mpk induced LP DC activation and maturation prior to onset of colitis. Accordingly, chemokine receptor (CCR) 7 surface expression was more strikingly enhanced in mesenteric lymph node DC from E. coli mpk than B. vulgatus mpk mono- or co-colonized mice. Mature but not semi-mature LP DC promoted Th1 polarization. As B. vulgatus mpk promotes differentiation of semi-mature DC presumably by IL-6, mRNA and protein expression of IL-6 was investigated in LP DC. The data demonstrated that IL-6 mRNA and protein was increased in LP DC of B. vulgatus mpk as compared to E. coli mpk mono-colonized IL-2−/−-mice. The B. vulgatus mpk mediated suppression of CCR7 expression and DC migration was abolished in IL-6−/−-DC in vitro.Conclusions/SignificanceFrom this data we conclude that the B. vulgatus triggered IL-6 secretion by LP DC in absence of proinflammatory cytokines such as IL-12 or TNF-α induces a semi-mature LP DC phenotype, which might prevent T-cell activation and thereby the induction of colitis in IL-2−/−-mice. The data provide new evidence that IL-6 might act as an immune regulatory cytokine in the mucosa by targeting intestinal DC.