The role of brain stem muscarinic receptors in the regulation of breathing

holinergic mechanisms play key role in regulating breathing, but the distribution of muscarinic cholinergic receptor (mAChR) subtypes has not been localized within brain stem respiratory nuclei. The first part of this thesis examined the hypothesis that mAChR subtypes are heterogeneously distributed across brain stem nuclei that control breathing. Using in vitro receptor autoradiography, this study provided the first simultaneous labeling and quantitative mapping of M1, M2, and M3 mAChR subtypes in cat brain stem regions known to regulate breathing. Among brain stem nuclei known to contain respiratory-related neurons, the greatest amount of mAChR binding was measured in the lateral and medial parabrachial nuclei and the lateral nucleus of the solitary tract. Fewer mAChRs were localized in nucleus ambiguus, retrofacial nucleus, retrotrapezoid nucleus and ventrolateral medulla. These data are an essential first step for future studies aiming to specify the functional roles of mAChR subtypes within brain stem respiratory nuclei.;Having localized the distribution of mAChR subtypes in respiratory-related brain stem nuclei, the second part of this thesis examined the respiratory effects of administering the muscarinic cholinergic agonist bethanechol and the muscarinic antagonists methoctramine and 4-DAMP. Microinjecting bethanechol (BETH) into the medial pontine reticular formation (mPRF) of intact, conscious cat produced a rapid eye movement (REM) sleep-like state and sleep-dependent respiratory depression. Administering 4-DAMP or methoctramine into the mPRF tested the hypothesis that the bethanechol-induced decrease in respiratory rate could not be dissociated from the bethanechol-induced increase in the REM sleep. Control measures of respiratory rate (breaths/min) were obtained during wakefulness, non-REM (NREM) sleep, and REM sleep. Bethanechol significantly (p...