Interactions between GABAergic and Cholinergic Processes in the Nucleus Pontis Oralis: Neuronal Mechanisms Controlling Active (Rapid Eye Movement) Sleep and Wakefulness

Abstract

The cholinergic system within the nucleus pontis oralis (NPO) of the pontine tegmentum is critically involved in the generation of active (rapid eye movement) sleep. Previously, we demonstrated that a GABAergic system in the NPO also plays an important role in the control of the behavioral states of wakefulness as well as active sleep. The present study examined interactions between these two neuronal systems vis-a-vis the occurrence of these behavioral states. Accordingly, cholinergic and GABAergic agonists and antagonists were injected into the NPO, and their combined effects on sleep and waking states of chronic, unanesthetized cats were examined. Microinjections of carbachol into the NPO elicited active sleep with a short latency. However, a preinjection of muscimol (a GABA(A) agonist) completely blocked the active sleep-inducing effects of carbachol. The induction of active sleep by carbachol was also suppressed by a subsequent injection of muscimol. On the other hand, the microinjection of scopolamine (a muscarinic receptor antagonist) did not block the induction of active sleep by bicuculline (a GABA(A) antagonist). We conclude that the excitatory cholinergic control of NPO neurons that are involved in the generation of active sleep is gated by a pontine GABAergic system that exerts its effects postsynaptically by inhibiting NPO neurons, resulting in the suppression of active sleep and the generation of wakefulness. In the absence of the activation of this GABAergic gating mechanism, active sleep occurs. These results reveal that specific interactions between cholinergic and GABAergic processes in the NPO play a critical role in the generation of active sleep and wakefulness.