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Maintained gamma band activity is a key element of higher brain function, participating in perception, executive function, and memory. The pedunculopontine nucleus (PPN), as part of the reticular activating system (RAS), is a major source of the "bottom-up" flow of gamma activity to higher regions. However, interruption of gamma band activity is associated with a number of neurological and psychiatric disorders. This review will focus on the role of the PPN in activating higher regions to induce arousal and descending pathways to modulate posture and locomotion. As such, PPN deep brain stimulation (DBS) can not only help regulate arousal and stepping, but continuous application may help maintain necessary levels of gamma band activity for a host of other brain processes. We will explore the potential future applications of PPN DBS for a number of disorders that are characterized by disturbances in gamma band maintenance. • The salutary use of PPN DBS in Parkinson's disease suggests improvement in a number of symptoms other than motor. • The PPN, as a major source of gamma band activity, can be considered a target for regulating the maintenance of gamma band activity using DBS. • Disturbances in gamma band activity are present in a number of disorders that may be amenable to such therapy in intractable cases. [ABSTRACT FROM AUTHOR]

The fact that the pedunculopontine nucleus (PPN) is part of the reticular activating system places it in a unique position to modulate sensory input and fight-or-flight responses. Arousing stimuli simultaneously activate ascending projections of the PPN to the intralaminar thalamus to trigger cortical high-frequency activity and arousal, as well as descending projections to reticulospinal systems to alter posture and locomotion. As such, the PPN has become a target for deep brain stimulation for the treatment of Parkinson's disease, modulating gait, posture, and higher functions. This article describes the latest discoveries on PPN physiology and the role of the PPN in a number of disorders. It has now been determined that high-frequency activity during waking and REM sleep is controlled by two different intracellular pathways and two calcium channels in PPN cells. Moreover, there are three different PPN cell types that have one or both calcium channels and may be active during waking only, REM sleep only, or both. Based on the new discoveries, novel mechanisms are proposed for insomnia as a waking disorder. In addition, neuronal calcium sensor protein-1 (NCS-1), which is over expressed in schizophrenia and bipolar disorder, may be responsible for the dysregulation in gamma band activity in at least some patients with these diseases. Recent results suggest that NCS-1 modulates PPN gamma band activity and that lithium acts to reduce the effects of over expressed NCS-1, accounting for its effectiveness in bipolar disorder. [ABSTRACT FROM AUTHOR]