The primary mammalian circadian clock is located within the suprachias
matic nuclei (SCN), but the cellular organization of the clock is not
yet known. We investigated the potential role of glial cells in che cl
ock mechanism by determining whether disrupting glial activity affects
the in vitro circadian rhythm of neuronal activity and the in vivo ci
rcadian activity rhythm in rats. We used two agents (octanol and halot
hane) that block gap junctions, and one (fluorocitrate) that inhibits
glial metabolism. All three agents disrupted the circadian pattern of
neuronal activity. Octanol flattened the rhythm at the highest concent
ration (200 mu M) and induced a small phase delay at a lower concentra
tion (66 mu M). Halothane and fluorocitrate induced ultradian rhythmic
ity. Fluorocitrate injected into the SCN of an intact rat induced arrh
ythmicity for about 1 week, after which the rhythm reappeared with a 1
.6 h delay. These results suggest that glia play an important role in
the SCN circadian clock.