Neuroepigenetics of arousal: Gamma oscillations in the pedunculopontine nucleus

Four major discoveries on the function of the pedunculopontine nucleus (PPN) have significantly advanced our understanding of the role of arousal in neurodegenerative disorders. The first was the finding that stimulation of the PPN-induced controlled locomotion on a treadmill in decerebrate animals, the second was the revelation of electrical coupling in the PPN and other arousal and sleep-wake control regions, the third was the determination of intrinsic gamma band oscillations in PPN neurons, and the last was the discovery of gene transcription resulting from the manifestation of gamma activity in the PPN. These discoveries have led to novel therapies such as PPN deep brain stimulation (DBS) for Parkinson's disease (PD), identified the mechanism of action of the stimulant modafinil, determined the presence of separate mechanisms underlying gamma activity during waking versus REM sleep, and revealed the presence of gene transcription during the manifestation of gamma band oscillations. These discoveries set the stage for additional major advances in the treatment of a number of disorders.