Figure 19.

Endogenous time structure (chronome) of internally coordinated free-running rhythms (top) through feedsidewards in network of spontaneous (α), reactive (β) and modulatory (γ, δ) rhythms (bottom). Circadian desynchronization after blinding, seen time-macroscopically in IA, is also shown time-microscopically as a chronobiologic serial section in IB, as a summary of individual periodograms in IC, and as time relations among three variables at 24-h synchronized (top) or free-running (bottom) frequencies in mice (left) and a human (right) in ID. Section II shows a spontaneous rhythm in corticosterone (α), in antiphase with a reactive rhythm (β). The components of the chronome are internally coordinated through feedsidewards in a network of spontaneous (α), reactive (β) and modulatory (γ, δ) rhythms. For the case of circadians in experimental animal models (section I), some degree of endogenicity of a desynchronized rhythm was demonstrated, statistically validated and quantified by objective numerical characteristics given with their uncertainty. The role of the eyes as a transducer of the effect of the lighting regimen on the circadian variation emerged from studies in the blinded C mouse and the ZRD mouse born anophthalmic [48]. The slight but statistically significant deviation of the period from precisely 24 hours led to the concept of free-running, as an indirect test of some degree of endogenicity. The work started on eosinophil counts, Figs. 1,2,3,4,5,6,7,8,9,10,11, was complemented by measurements of rectal temperature which was more readily measured longitudinally for the lifespan of several generations of mice. Rhythms being a fundamental feature of life, found at all levels of organization, their coordinating role was also studied. Apart from the spontaneous rhythms characterizing variables such as serum corticosterone or melatonin (IIB), reactive rhythms are found in response to a given stimulus applied under standardized controlled conditions of a laboratory in vivo (α in IIA) or in vitro (β in IIA and IIC-E). A third entity such as melatonin may modulate, in a predictable insofar as rhythmic fashion, the effect of one entity upon the second, such as that of the pituitary upon the adrenal or may act directly upon the adrenal. Reproducible sequences of attenuation, no-effect, and amplification, the time-qualified feedsidewards, replacing time-unqualified feedbacks and feedforwards, can then be found (IIC to E).