Resetting Central and Peripheral Circadian Oscillators in Transgenic Rats

TLDR

Circadian oscillators form multitissue systems that regulate organismal activity relative to environmental cycles, and a self‑sustained pacemaker in the SCN is hypothesized to entrain peripheral oscillators, a coupling that can be temporarily lost after abrupt light‑cycle shifts. The study aimed to investigate the organization of a mammalian circadian system. To do so, the authors created a transgenic rat line expressing luciferase rhythmically under a mouse Per1 promoter. Light emission from the SCN remained robustly rhythmic for up to 32 days in vitro, while liver, lung, and skeletal muscle rhythms damped after 2–7 cycles, and the SCN rhythm adjusted to light‑cycle advances or delays more rapidly than locomotor behavior or peripheral tissue rhythms.

Abstract

In multicellular organisms, circadian oscillators are organized into multitissue systems which function as biological clocks that regulate the activities of the organism in relation to environmental cycles and provide an internal temporal framework. To investigate the organization of a mammalian circadian system, we constructed a transgenic rat line in which luciferase is rhythmically expressed under the control of the mouse Per1 promoter. Light emission from cultured suprachiasmatic nuclei (SCN) of these rats was invariably and robustly rhythmic and persisted for up to 32 days in vitro. Liver, lung, and skeletal muscle also expressed circadian rhythms, which damped after two to seven cycles in vitro. In response to advances and delays of the environmental light cycle, the circadian rhythm of light emission from the SCN shifted more rapidly than did the rhythm of locomotor behavior or the rhythms in peripheral tissues. We hypothesize that a self-sustained circadian pacemaker in the SCN entrains circadian oscillators in the periphery to maintain adaptive phase control, which is temporarily lost following large, abrupt shifts in the environmental light cycle.