Mapping sleep-wake control with the transcription factor c-Fos

States of wakefulness and sleep are remarkably different not only in behavior, polygraphic signs, and neuronal firing patterns, but also in the expression of genes, such as immediate-early genes (IEGs; reviewed in Bentivoglio and Grassi-Zucconi, 1999; Cirelli and Tononi, 2000b). IEGs are a class of genes that are rapidly and transiently expressed in neurons (and other cells) in response to various stimuli, such as sensory stimuli, trophic factors, neurotransmitters, and drugs (reviewed in Morgan and Curran, 1991; Hughes and Dragunow, 1995; Herdegen and Leah, 1998). This responsiveness to stimuli forms the basis for using IEGs as markers of neuronal activation. Of the commonly studied IEGs in contemporary neuroscience, c-fos has been the most extensively studied and its protein product, c-Fos, is the focus of this review. We will first discuss the advantages and limitations of using c-Fos as an anatomical marker of neuronal activity for studying sleep-wake control, and how it has been used successfully to identify the location, neurochemical phenotype, and connectivity of sleep- and wake-active neurons. We will then discuss recent advances in understanding the role of c-Fos in the transcriptional regulation of sleep and wake states.