Location and quantification of muscarinic receptor subtypes in rat pons: implications for REM sleep generation

Abstract

Microinjecting cholinomimetics into the pontine reticular formation produces a state that resembles natural rapid eye movement (REM) sleep. Evocation of this REM sleeplike states is anatomically site dependent within the pons and is mediated by muscarinic receptors. The cellular and molecular mechanisms underlying cholinergic REM sleep generation and muscarinic receptor subtype involvement remain to be specified. This study tested the hypothesis that muscarinic receptor subtypes are differentially distributed within the oral and caudal divisions of rat pontine reticular nucleus. In vitro receptor autoradiography was used to localize and quantify M1, M2, and M3 binding sites in the pontine reticular formation and in pontine brain stem regions known to regulate REM sleep. M1-M3 binding sites were present in some REM sleep-related nuclei, such as dorsal raphe and locus ceruleus. The pontine reticular formation was found to have a homogeneous distribution of M2 binding sites across its rostral to caudal extent, indicating that anatomic specificity of cholinergic REM sleep induction cannot be accounted for by a differential density of muscarinic receptors.