Activation of extracellular signal-regulated kinase signaling in the pedunculopontine tegmental cells is involved in the maintenance of sleep in rats

Abstract

Considerable evidence suggests that receptor-mediated excitation and inhibition of brainstem pedunculopontine tegmental (PPT) neurons are critically involved in the regulation of sleep-wake states. However, the molecular mechanisms operating within the PPT-controlling sleep-wake states remain relatively unknown. This study was designed to examine sleep-wake state-associated extracellular-signal-regulated kinase 1 and 2 (ERK1/2) transduction changes in the PPT of freely moving rats. The results of this study demonstrate that the levels of ERK1/2 expression, phosphorylation, and activity in the PPT increased with increased amount of time spent in sleep. The sleep-associated increases in ERK1/2 expression, phosphorylation, and activity were not observed in the cortex, or in the immediately adjacent medial pontine reticular formation. The results of regression analyses revealed significant positive relationships between the levels of ERK1/2 expression, phosphorylation, and activity in the PPT and amounts of time spent in slow-wave sleep, rapid eye movement sleep, and total sleep. Additionally, these regression analyses revealed significant negative relationships between the levels of ERK1/2 expression, phosphorylation, and activity in the PPT and amounts of time spent in wakefulness. Collectively, these results, for the first time, suggest that the increased ERK1/2 signaling in the PPT is associated with maintenance of sleep via suppression of wakefulness.