Effects of Anesthetics on Hypoglossal Nerve Discharge and c-Fos Expression in Brainstem Hypoglossal Premotor Neurons

Abstract

This study examined the effects of anesthesia on the hypoglossal nerve and diaphragm activities and on c-Fos expression in brainstem hypoglossal premotor neurons (pmXII). Experiments were performed in 71 rats by using halothane inhalation, pentobarbital sodium, or mixtures of α-chloralose and urethane or ketamine and xylazine. First, various cardiorespiratory parameters were measured in the rats (n = 31) during both awake and anesthetized conditions. The volatile anesthetic halothane, but not the other anesthetics, was always associated with a strong phasic inspiratory activity in the hypoglossal nerve. Second, a double-immunohistochemical study was performed in awake and anesthetized rats (n = 40) to gauge the level of activity of pmXII neurons. Brainstem pmXII neurons were identified after microiontophoresis of the retrograde tracer Fluoro-Gold in the right hypoglossal motor nucleus. Patterns of c-Fos expression at different brainstem levels were compared in five groups of rats (i.e., awake or anesthetized with halothane, pentobarbital, chloralose-urethane, and ketamine-xylazine). Sections were processed for double detection of c-Fos protein and Fluoro-Gold by using the standard ABC method and a two-color peroxidase technique. Anesthesia with halothane induced the strongest c-Fos expression in a restricted pool of pmXII located in the pons at the level of the Kölliker-Fuse nucleus and the intertrigeminal region. The results demonstrated a major effect of halothane in inducing changes in hypoglossal activity and revealed a differential expression of c-Fos protein in pmXII neurons among groups of anesthetized rats. We suggest that halothane mediates changes in respiratory hypoglossal nerve discharge by altering activity of premotor neurons in the Kölliker-Fuse and intertrigeminal region. © 2003 Wiley-Liss, Inc.