The locus coeruleus and immediate-early genes in spontaneous and forced wakefulness.

In this study, we mapped the expression of two immediate-early genes to examine the functional activation of the locus coeruleus and other regions of the rat brain after periods of spontaneous wakefulness or sleep and after sleep deprivation. c-fos and NGFI-A are two immediate-early genes that are rapidly induced by physiological stimuli and can be used as molecular markers of neural activation. We used immunocytochemical detection of Fos and NGFI-A proteins associated with double labeling for tyrosine hydroxylase to identify activated noradrenergic cells. We found that the expression of Fos and NGFI-A was markedly increased in the locus coeruleus and other brain areas both after spontaneous wakefulness and after short periods (3-24 h) of sleep deprivation. Several Fos-positive cells and most NGFI-A positive cells found in the locus coeruleus after periods of spontaneous wakefulness were shown to be noradrenergic. This study demonstrates that wakefulness per se, whether spontaneous or induced by total sleep deprivation, results in the functional activation of identified noradrenergic locus coeruleus cells.