Several transcription factors are expressed at higher levels in the waking than in the sleeping brain. In experiments with rats, the locus coeruleus, a noradrenergic nucleus with diffuse projections, was found to regulate such expression. In brain regions depleted of noradrenergic innervation, amounts of c-Fos and nerve growth factor-induced A after waking were as low as after sleep. Phosphorylation of cyclic adenosine monophosphate response element-binding protein was also reduced. In contrast, electroencephalographic activity was unchanged. The reduced activity of locus coeruleus neurons may explain why the induction of certain transcription factors, with potential effects on plasticity and learning, does not occur during sleep.