The search for circadian rhythm pacemakers in the light of lesion experiments.

Considering the huge phylogenetic tree of evolution of the animal kingdom, only very limited observations have been made on the pacemaker mechanism of the circadian rhythms of various biological phenomena. If there is a master clock controlling the circadian rhythmicity in the animal body, lesions in it should certainly produce arrhythmic activity. On the basis of very scattered data available at present, it can be presumed that in the central nervous system there is a group of cells which functions as a master clock. Its location is close enough to the primary photoreceptors to be entrained by the environmental light-dark cycle. The clock unidirectionally controls all body activities and also other secondary pacemakers, if they exist. The influence of a secondary pacemaker is seen in pathological conditions or after destruction of the master clock. Lesions in the coupling site between the clock and overt activity may result in arrhythmia without damaging clock activity. Hence, care must be taken in assessing the data recorded. Up to now, the optic lobes in several insect species and the suprachiasmatic nucleus in several rodent species are the most likely sites of a master clock, and lesions in these instantaneously induce arrhythmia. Increasing study of the retinohypothalamic projection in other mammals and birds will throw more and more light on this nucleus. A search for the circadian master clock in the body should, therefore, be extended to all species of animals and this will clarify the circadian clock mechanism, no matter whether it functions as a result of membrane activity, genetic influence or a very specific biochemical mechanism resistant to environmental changes.