C-fos mRNA in the Suprachiasmatic Nuclei In Vitro Shows a Circadian Rhythm and Responds to a Serotonergic Agonist

The mammalian suprachiasmatic nuclei (SCN) contain a circadian clock that produces approximately 24 h rhythms of physiology and behavior even during constant dark. Under such conditions, light stimuli applied during the subjective night induce phase shifts of circadian rhythms and increase immediate early gene expression (c-fos) in the SCN. In vitro preparations of the SCN continue to show circadian rhythms of metabolic rate and neuronal firing rates, which can be phase shifted by non-photic stimuli. This study was designed to investigate whether the SCN display a rhythm of c-fos mRNA levels in vitro and whether quipazine, which phase-shifts the SCN circadian clock, induces c-fos expression in vitro. Levels of c-fos mRNA were found to be significantly higher in the subjective day than subjective night in the SCN in vitro. This rhythm parallels other in vivo and in vitro rhythms in SCN metabolic and neuronal activity and is consistent with previous in vivo work showing higher daytime levels of Fos-like immunoreactivity in animals maintained under constant dark conditions. Quipazine treatment during the subjective day (which phase-advances the circadian rhythm of neuronal firing in the SCN) decreased c-fos mRNA levels in the dorsomedial but not ventrolateral SCN, but quipazine did not affect c-fos levels when administered at night. This effect is consistent with serotonergic agonists inhibiting SCN neuronal activity and is the first evidence that a non-photic phase-shifting stimulus alters c-fos in the SCN at a phase-appropriate time.