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For more than two millennia, keen observers have noted the circadian rhythms of lowering plants that bloom only in the daytime or of trees with leaves that open during the day and close at night. Such movements are regulated by a clock within each organism ( I ), one that can be reset by light as days get shorter or longer.
Animals show strikingly similar circadian behavioral responses, driven by an internal clock and also reset (or entrained) by light (2). The time-keeping similarities between plants and animals have not been thought to extend to the light receptors (3). Information about chronobiological phototransduction in plants has blossomed, yet the primary visual light-sensitive system in animals-rod or cone photoreceptor molecules-may not be necessary for entrainment at all. But recently animals have started to seem more like plants. The fruit fly Drosophila has autonomous clocks throughout the body, each sensitive to its own intrinsic, as-yet-unidentified photoreceptors (4), and in a report on page 396 of this issue, Campbell and Murphy show that the endogenous clock of humans can be entrained by light application to an unexpected spot, the popliteal region-that is, the back of the knees (5).
The relation of light and other zeitgebers (time setters) to intrinsic biological rhythms is classically defined by phase response curves. These are constructed by exposing the organism to a zeitgeber at all phases of the endogenous rhythm and measuring the resulting effect on the phase of the cycle. With remarkable consistency, zeitgebers shift the rhythms by advancing the phase of the clock at certain parts of the circadian cycle and by delaying the phase when impinging on other parts of the cycle. The magnitude of such phase shifts is dose-dependent, the product of intensity x duration. The new phase response curves for extraretinal popliteal illumination in humans (5) conform to the classic pattern, with phase delays of body temperature and pineal melatonin secretion (outputs of the clock) occurring during the night, followed by phase advances early in the morning.
How is the entrainment signal carried from the knees to the endogenous clock? Presuming the conservation of chronobiological properties of plants and animals, one of us recently made a...