On the functional significance of c-fos induction during the sleep-waking cycle

A striking finding in recent years has been that the transition from sleep to waking is accompanied in many brain regions by a widespread activation o f c-fos and other immediate-early genes (IEGs). IEGs are induced by various electrical or chemical signals to which neural cells are exposed and their protein products act as transcription factors to regulate the expression o f other genes. After a few hours of sleep, the expression of these transcri ption factors in the brain is absent or restricted to very few cells. Howev er, after a few hours of spontaneous waking or sleep deprivation, the expre ssion of c-fos and other IEGs is high in cerebral cortex, hypothalamus, sep tum, and several thalamic and brainstem nuclei. While cells expressing c-fo s during waking are widely distributed, they represent only a subset of all neurons in any given area. These observations raise several questions: Why is c-fos expressed during waking and not during sleep? Is waking always ac companied by c-fos induction? Which subset of cells express c-fos during wa king and why only a subset? Once c-fos has been induced, what are the funct ional consequences of its activation? In this review, we summarize our curr ent understanding of the meaning of c-fos activation in the brain in relati on to the sleep-waking cycle and suggest that c-fos induction in the cerebr al cortex during waking might be related to the occurrence of plastic pheno mena.