Carbachol microinjections into the dorsal pontine reticular formation repeatedly elicit REM sleep‐like depression of hypoglossal (XII) nerve activity in the rat in situ perfused working heart‐brainstem preparation (WHBP)

Abstract

Obstructive sleep apnea (OSA) is characterized by nocturnal episodes of upper airway collapse and hypoxia, with rapid‐eye‐movement sleep (REMS)‐related apneas being longest and most severe. In OSA patients, upper airway muscle tone is reduced during REMS parallel to the postural atonia characteristic of this state. To assess the central neural mechanisms of REMS, in vivo pharmacological models of REM sleep have been used, including those in which REMS‐like state is elicited by microinjections of a cholinergic agonist, carbachol, into the pontine reticular formation (Kubin, 2001). To test whether upper airway motor tone depression similar to that in in vivo models can be elicited in the rat WHBP, injections of carbachol (25–50 nl, 10mM) were made into the dorsomedial pons in n=33 WHBPs while recording XII and phrenic nerve activities (PNA). In 23 preparations, depression of XII nerve activity lasting 16–24 min occurred within 142 s ± 26(SD). A respiratory rate increase from 8 min−1 ± 4 to 18 ± 9 paralleled the depression, whereas PNA was little affected. The depressant episodes could be elicited repeatedly by injections at the same site at >30 min intervals. Thus, the WHBP offers a novel model with which to pharmacologically manipulate cellular environment and study the mechanisms of REMS‐related respiratory depression. Funded by BCCN Göttingen and HL‐47600.