Inhibition of the pontine Kölliker-Fuse nucleus abolishes eupneic inspiratory hypoglossal motor discharge in rat

Neuroscience. 2014 May 16:267:22-9. doi: 10.1016/j.neuroscience.2014.02.027. Epub 2014 Mar 3.

Abstract

The pontine Kölliker-Fuse nucleus (KF) has established functions in the regulation of inspiratory-expiratory phase transition and the regulation of upper airway patency via laryngeal valving mechanisms. Here we studied the role of the KF in the gating and modulation of eupneic hypoglossal motor activity (HNA) using the in situ perfused brainstem preparation, which displays robust inspiratory HNA. Microinjection of glutamate into the KF area triggered complex and often biphasic modulation (excitation/inhibition or inhibition/excitation) of HNA. Subsequent transient pharmacological inhibition of KF by unilateral microinjection of GABA-A receptor agonist isoguvacine reduced HNA and while bilateral microinjections completely abolished HNA. Our results indicate that mixed and overlapping KF pre-motor neurons provide eupneic drive for inspiratory HNA and postinspiratory vagal nerve activity. Both motor activities have important functions in the regulation of upper airway patency during eupnea but also during various oro-pharyngeal behaviors. These results have potential implications in the contribution of state-dependent modulation of KF hypoglossal pre-motor neurons during sleep-wake cycle to obstructive sleep apnea.

Keywords: breathing; parabrachial; pons; respiratory rhythm generation; sleep apnea; upper airway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Electric Stimulation
  • Functional Laterality
  • GABA Agonists / pharmacology
  • Glutamic Acid / pharmacology
  • In Vitro Techniques
  • Isonicotinic Acids / pharmacology
  • Kolliker-Fuse Nucleus / physiology*
  • Microinjections
  • Motor Neurons / physiology*
  • Neural Inhibition / physiology*
  • Phrenic Nerve / physiology*
  • Rats
  • Respiration* / drug effects
  • Respiratory Center / cytology*
  • Vagus Nerve / physiology

Substances

  • GABA Agonists
  • Isonicotinic Acids
  • Glutamic Acid
  • isoguvacine