Multi-Oscillator Interactions of Hamster Circadian Rhythms

University Of California-San Diego, La Jolla CA

Investigators

Abstract

Lay Abstract Gorman: IBN 9985676 In all mammalian species, marked daily variations in behavioral and physiological function are generated by an endogenous clock-like mechanism located in the suprachiasmatic nuclei (SCN) of the hypothalamus. Although this generator of circadian rhythms has been profitably conceptualized and studied as a single, integrated clock mechanism, considerable research suggests that it is, in fact, comprised of multiple oscillators which interact, or couple, to generate coherent daily rhythms. To date, the multi-oscillatory basis of the clock has proven difficult to study because separate oscillatory units cannot be temporally resolved in the normal, tightly coupled state. Conditions which facilitate temporal reorganization of oscillators into an alternative coupled state in which they can be temporally resolved, moreover, are incompatible with the most important circadian techniques. Specifically, previous studies have been unable to a) manipulate the timing of oscillators relative to one another to assess their interactions or b) probe their responses to light pulses which normally synchronize the clock mechanism with environmental day. The present proposal utilizes a novel preparation in which circadian rhythms of hamsters are split into two distinct components which may be separately controlled with manipulations of the light/dark environment. The proposed experiments will allow for the first time a description of the most informative outputs of component oscillators within the SCN. Additionally, the nature of interactions between oscillators, postulated on mathematical grounds, can be tested empirically by manipulations of the relative phase relationships between component oscillators. These studies will be juxtaposed with manipulations of oscillator relations in the normal, unsplit state. These studies may suggest new avenues for rapid manipulation of human circadian rhythms.