The properties of the inner clock—its free-run under constant lighting or darkness, its entrained response to light-dark cycles—were initially understood at the level of oscillating “output” measures, without direct knowledge of the brain mechanisms that produced the oscillation.  For example, behavior showed circadian cycles in running-wheel activity, feeding, and drinking, while similar cycles could be measured in body temperature and  production of the hormone melatonin by the pineal gland.

In 1972, however, the anatomical location of the brain’s clock was finally identified by a set of experiments that homed in on a tiny cluster of neurons at the base of the brain–the suprachiasmatic nuclei (SCN)—just above the well-known pathways that carry light and dark signals from the eye.  The pathway for vision separated from the pathway to the inner clock. Light signals to the SCN are imperceptible!

REFERENCES

Books

Klein DC, Moore RY, Reppert SM. Suprachiasmatic Nucleus: The Mind’s Clock. New York, Oxford University Press, 1991.

Reviews

Weaver DA. The suprachiasmatic nucleus: A 25-year retrospective. Journal of Biological Rhythms, 1998;13:100-112.

Studies

Moore RY, Eichler VB. Loss of a circadian adrenal corticosterone rhythm following suprachiasmatic lesions in the rat. Brain Research 1972;42:201-6.
Stephan FK, Zucker I. Circadian rhythms in drinking behavior and locomotor activity of rats are eliminated by hypothalamic lesions. Proceedings of the National Academy of Sciences U.S.A. 1972;69:1583-1586.
Richter CP. “Dark-active” rat transformed into “light-active” rat by destruction of 24-hr clock: function of 24-hr clock and synchronizers. Proceedings of the National Academy of Sciences, 1978:75;6276-6280.