C-FOS MESSENGER-RNA IS SPONTANEOUSLY INDUCED IN THE RAT-BRAIN DURING THE ACTIVITY PERIOD OF THE CIRCADIAN CYCLE

The basal expression of the proto-oncogene c-fos was studied by Northe rn blot analysis in different regions of the rat brain during 24 h. A striking spontaneous oscillation of c-fos mRNA expression was detected in animals kept in basal conditions with a 12 h light/12 h dark cycle . In these animals c-fos mRNA was just detectable during the rest hour s (morning through afternoon), and was high during the activity hours (night). The periodicity of this oscillation persisted and became free -running when the animals were exposed for 6 consecutive days to const ant light or darkness. It was thus demonstrated that the fluctuation o f c-fos expression is circadian and is not created by the light-dark c ycle, but the latter exerts a synchronizing effect. The oscillation of c-fos mRNA was modified by manipulations of the rest-activity cycle. In particular, the fluctuation observed in basal conditions was invert ed, keeping the animals awake during the rest hours (diurnal) and allo wing them to sleep in the activity period (nocturnal). These data indi cated a close relationship between the oscillation of c-fos expression and the rest-activity cycle. Finally, electroencephalographic (EEG) m onitoring was performed under behavioural control for 3 h before the a nimals were killed. These experiments confirmed that, irrespective of the time of day, the EEG pattern typical of a state of sleep (includin g both slow waves and paradoxical sleep) was associated with low or un detectable c-fos levels, whereas the protracted EEG desynchronization corresponding to wakefulness was associated with high c-fos expression . Altogether these results indicate that c-fos mRNA undergoes during t he circadian cycle spontaneous oscillations related to the activation of genomic expression subserving the behavioural and electrical correl ates of wakefulness. On the other hand, the behavioural and electrical correlates of sleep are associated with low c-fos expression