title: REM sleep-like episodes of motoneuronal depression and respiratory rate increase are triggered by pontine carbachol microinjections in in situ perfused rat brainstem preparation.
abstract: Hypoglossal nerve activity (HNA) controls the position and movements of the tongue. In persons with compromised upper airway anatomy, sleep-related hypotonia of the tongue and other pharyngeal muscles causes increased upper airway resistance, or total upper airway obstructions, thus disrupting both sleep and breathing. Hypoglossal nerve activity reaches its nadir, and obstructive episodes are longest and most severe, during rapid eye movement stage of sleep (REMS). Microinjections of a cholinergic agonist, carbachol, into the pons have been used in vivo to investigate the mechanisms of respiratory control during REMS. Here, we recorded inspiratory-modulated phrenic nerve activity and HNA and microinjected carbachol (25-50 nl, 10 mm) into the pons in an in situ perfused working heart-brainstem rat preparation (WHBP), an ex vivo model previously validated for studies of the chemical and reflex control of breathing. Carbachol microinjections were made into 40 sites in 33 juvenile rat preparations and, at 24 sites, they triggered depression of HNA with increased respiratory rate and little change of phrenic nerve activity, a pattern akin to that during natural REMS in vivo. The REMS-like episodes started 151 ± 73 s (SD) following microinjections, lasted 20.3 ± 4.5 min, were elicited most effectively from the dorsal part of the rostral nucleus pontis oralis, and were prevented by perfusion of the preparation with atropine. The WHBP offers a novel model with which to investigate cellular and neurochemical mechanisms of REMS-related upper airway hypotonia in situ without anaesthesia and with full control over the cellular environment.
authors.affiliation: Department of Anaesthesiology, Emergency and Intensive Care Medicine, University Medicine Gottingen, Georg August University, Gottingen, Germany.
authors.forename: Ivo F
authors.initials: IF
authors.lastname: Brandes
authors.forename: Georg M
authors.initials: GM
authors.lastname: Stettner
authors.forename: Michael
authors.initials: M
authors.lastname: Mörschel
authors.forename: Leszek
authors.initials: L
authors.lastname: Kubin
authors.forename: Mathias
authors.initials: M
authors.lastname: Dutschmann
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology*; D018679:Cholinergic Agonists / Q000494:pharmacology; D003964:Diaphragm / Q000187:drug effects; D007002:Hypoglossal Nerve / Q000187:drug effects / Q000502:physiology; D008845:Microinjections / Q000379:methods; D009046:Motor Neurons / Q000187:drug effects* / Q000502:physiology; D009123:Muscle Hypotonia / Q000503:physiopathology; D010609:Pharyngeal Muscles / Q000187:drug effects; D010791:Phrenic Nerve / Q000187:drug effects / Q000502:physiology; D011149:Pons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D056152:Respiratory Rate / Q000187:drug effects* / Q000502:physiology; D012895:Sleep, REM / Q000187:drug effects* / Q000502:physiology*
chemical_list: D018679:Cholinergic Agonists; D001285:Atropine; D002217:Carbachol