Endogenous Timekeeping Mechanisms Research Articles

Biological time-keeping mechanisms: A need for broader perspectives?

Biological time-keeping mechanisms play fundamental roles in the regulation of behavior and physiology, disruption of which can lead to increased incidence of many disorders. Consequently, these mechanisms continue to be investigated intensively. For almost four decades they have been known to be able to store and program complex behaviors, and to be susceptible to the influences of light and day length. Yet present-day research concerns almost exclusively the means by which circadian and lesser time intervals are measured. Even within this narrow focus disagreements exist. Some early studies of small nocturnal rodents and primates running in exercise wheels illustrate the program-clock-like capabilities of endogenous time-keeping mechanisms and their degrees of susceptibility to external influences, such as artificial twilights and shortened light cycles. Broadening perspectives for research on biological clocks to take into account these often overlooked capabilities and susceptibilities could lead to a deeper understanding of them.

Endogenous 24-hour cycle of core temperature and oxygen consumption in week-old Zucker rat pups.

Experiments were designed to test whether or not the 24-h core temperature fluctuations in week-old rat pups are of endogenous origin. Lean (Fa/-) Zucker rat pups born on the same day to mothers maintained in two different colonies with light/dark cycles 12 h out of phase with each other were mother-reared through the first 3-4 days of life and then artificially reared simultaneously in constant dim light. Continuous, automatic measurement of core temperature and oxygen consumption during artificial rearing showed clear 24-h rhythms in 5- to 8-day-old pups. Each rhythm reached a daily minimum at a time corresponding to the beginning of the light period in the colony of origin. The amplitude of these rhythms did not diminish during artificial rearing, nor did the phase difference between the rhythms of pups originating in the two colonies systematically change. The persistent 12-h phase differences between these two groups of pups prove that the observed rhythms are not caused by exogenous stimuli. We conclude that the rat pup possesses an endogenous time-keeping mechanism that permits the expression of overt rhythmicity at the age of 1 week.

Melatonin and thyroxine: Influence on compass orientation in salamanders

Tiger salamanders (Ambystoma tigrinum) trained as larvae to orient in a particular compass direction reverse their direction of movement approximately at metamorphosis, but the timing of reversal is not closely related to developmental stage. Although exogenous thyroxine facilitates metamorphosis, it does not simultaneously trigger reversal of movement (Fig. 1). The reversal occurs even if the animals are deprived of a continuous view of the sky. Administration of pulses of exogenous melatonin at noon, but not serotonin or thyroxine, caused the larvae to shift their directional response about 90° clockwise (Figs. 2, 3). This result is consistent with the view that melatonin pulses mimic “lights-on” and act to phase-delay the animal's endogenous timekeeping mechanism.