Circadian Rhythm Generation and Entrainment in Astrocytes

Open Access
Publisher Website
Google Scholar
Abstract
In mammals, the master circadian pacemaker is considered the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN consists of a heterogeneous population of neurons and relatively understudied glia. We investigated whether glia, like neurons, rhythmically express circadian genes. We generated pure cultures of cortical astrocytes fromPeriod2::luciferase(Per2::luc) knock-in mice andPeriod1::luciferase(Per1::luc) transgenic rats and recorded bioluminescence as a real-time reporter of gene activity. We found that ratPer1::lucand mousePer2::lucastroglia express circadian rhythms with a genetically determined period. These rhythms damped out after several days but were reinitiated by a variety of treatments, including a full volume exchange of the medium. If cultures were treated before damping out, the phase ofPer1::lucrhythmicity was shifted, depending on the time of the pulse relative to the peak ofPer1expression. Glial rhythms entrained to daily 1.5°C temperature cycles and were significantly sustained when cocultured with explants of the adult SCN but not with cortical explants. Thus, multiple signals, including a diffusible factor(s) from the SCN, are sufficient to either entrain or restart circadian oscillations in cortical glia.