Sleep deprivation-induced c-fos and junB expression in the rat brain: effects of duration and timing

Expression of the immediate-early genes (IEGs) c-fos and junB in the rat br ain was studied in response to sleep deprivation (SD) starting at four time points during the light phase of a 12:12 light:dark cycle. Animals were co nfined to slowly rotating wheels for 3 or 6 h in order to prevent sleep. Th e numbers of c-Fos- and JunB-immunoreactive cells were assessed in seven br ain regions previously reported to respond to SD with increased c-fos expre ssion (medial preoptic area (MPA), cortex, anterior and posterior paraventr icular thalamic nuclei, amygdala, caudate-putamen, and laterodorsal tegment al nucleus). While c-Fos was induced by SD in all regions studied, there we re differences in levels of induction depending on the duration of deprivat ion and on the timing of the deprivation period during the light phase. The most robust induction occurred in most regions in response to 3-h deprivat ion periods beginning 3 h into the light phase. A similarly timed peak of i nduction was observed in the MPA and cortex after 6 h of SD. In two regions , the posterior paraventricular thalamic nucleus and amygdala, 6 h of depri vation induced greater c-Fos immunoreactivity than did 3 h of deprivation, collapsed across all phases tested. Increased JunB immunoreactivity in resp onse to either duration of deprivation was more limited and was significant only in the MPA, cortex, caudate-putamen and amygdala. c-Fos and JunB immu noreactivity in the paraventricular hypothalamic nucleus was low and simila r in control and deprived animals. These results indicate that both duratio n of prior wakefulness and time of day influence the extent of IEG expressi on differentially in brain regions responsive to SD. The results also sugge st that the posterior paraventricular thalamic nucleus and amygdala might b e primarily responsive to length of wakefulness (sleep drive), while the MP A and anterior paraventricular thalamic nucleus might integrate input relat ed to both homeostatic sleep drive and circadian clock influences on sleep regulation. (C) 2001 Elsevier Science B.V. All rights reserved.