Evidence That REM Sleep Is Controlled by the Activation of Brain Stem Pedunculopontine Tegmental Kainate Receptor

Abstract

Glutamate, the neurotransmitter, enhances rapid-eye-movement (REM) sleep when microinjected into the brain stem pedunculopontine tegmentum (PPT) of the cat and rat. Glutamate and its various receptors are normally present in the PPT cholinergic cell compartment. The aim of this study was to identify which specific receptor(s) in the cholinergic cell compartment of the PPT are involved in glutamate-induced-REM sleep. To identify these glutamate-induced REM-sleep-generating receptor(s) in the PPT cholinergic cell compartment, specific receptors were pharmacologically blocked differentially by localized pretreatment of specific glutamate receptor antagonists; glutamate was then microinjected into the PPT cholinergic cell compartment while quantifying the effects on REM sleep in freely moving chronically instrumented rats. The results demonstrate that when kainate receptors were blocked by pretreatment with a kainate-specific receptor antagonist, microinjection of glutamate was unable to induce REM sleep. Pharmacological blockade of specific N-methyl-d-aspartate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors was unable to block glutamate-microinjection-induced-REM sleep. These findings suggest, for the first time, that the activation of kainate receptors within the cholinergic cell compartment of the PPT is an essential portion of the mechanism for the generation of glutamate-induced REM sleep in the rat.