The role of neuronal excitation and inhibition in the pre-Bötzinger complex on the cough reflex in the cat

J Neurophysiol. 2022 Jan 1;127(1):267-278. doi: 10.1152/jn.00108.2021. Epub 2021 Dec 8.

Abstract

Brainstem respiratory neuronal network significantly contributes to cough motor pattern generation. Neuronal populations in the pre-Bötzinger complex (PreBötC) represent a substantial component for respiratory rhythmogenesis. We studied the role of PreBötC neuronal excitation and inhibition on mechanically induced tracheobronchial cough in 15 spontaneously breathing, pentobarbital anesthetized adult cats (35 mg/kg, iv initially). Neuronal excitation by unilateral microinjection of glutamate analog d,l-homocysteic acid resulted in mild reduction of cough abdominal electromyogram (EMG) amplitudes and very limited temporal changes of cough compared with effects on breathing (very high respiratory rate, high amplitude inspiratory bursts with a short inspiratory phase, and tonic inspiratory motor component). Mean arterial blood pressure temporarily decreased. Blocking glutamate-related neuronal excitation by bilateral microinjections of nonspecific glutamate receptor antagonist kynurenic acid reduced cough inspiratory and expiratory EMG amplitude and shortened most cough temporal characteristics similarly to breathing temporal characteristics. Respiratory rate decreased and blood pressure temporarily increased. Limiting active neuronal inhibition by unilateral and bilateral microinjections of GABAA receptor antagonist gabazine resulted in lower cough number, reduced expiratory cough efforts, and prolongation of cough temporal features and breathing phases (with lower respiratory rate). The PreBötC is important for cough motor pattern generation. Excitatory glutamatergic neurotransmission in the PreBötC is involved in control of cough intensity and patterning. GABAA receptor-related inhibition in the PreBötC strongly affects breathing and coughing phase durations in the same manner, as well as cough expiratory efforts. In conclusion, differences in effects on cough and breathing are consistent with separate control of these behaviors.NEW & NOTEWORTHY This study is the first to explore the role of the inspiratory rhythm and pattern generator, the pre-Bötzinger complex (PreBötC), in cough motor pattern formation. In the PreBötC, excitatory glutamatergic neurotransmission affects cough intensity and patterning but not rhythm, and GABAA receptor-related inhibition affects coughing and breathing phase durations similarly to each other. Our data show that the PreBötC is important for cough motor pattern generation, but cough rhythmogenesis appears to be controlled elsewhere.

Keywords: DLH; cough; gabazine; kynurenic acid; pre-Bötzinger complex.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdominal Muscles / drug effects
  • Abdominal Muscles / physiopathology
  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Cats
  • Central Pattern Generators* / drug effects
  • Central Pattern Generators* / metabolism
  • Central Pattern Generators* / physiopathology
  • Cough* / drug therapy
  • Cough* / metabolism
  • Cough* / physiopathology
  • Electromyography
  • Excitatory Amino Acid Antagonists / administration & dosage
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Female
  • GABA-A Receptor Antagonists / administration & dosage
  • GABA-A Receptor Antagonists / pharmacology*
  • Glutamic Acid / administration & dosage
  • Glutamic Acid / analysis
  • Glutamic Acid / pharmacology*
  • Homocysteine / analogs & derivatives
  • Homocysteine / pharmacology
  • Inhalation* / drug effects
  • Inhalation* / physiology
  • Kynurenic Acid / pharmacology
  • Male
  • Medulla Oblongata* / drug effects
  • Medulla Oblongata* / metabolism
  • Medulla Oblongata* / physiopathology
  • Pyridazines / pharmacology
  • Reflex* / drug effects
  • Reflex* / physiology
  • Respiratory Rate* / drug effects
  • Respiratory Rate* / physiology

Substances

  • Excitatory Amino Acid Antagonists
  • GABA-A Receptor Antagonists
  • Pyridazines
  • Homocysteine
  • homocysteic acid
  • Glutamic Acid
  • gabazine
  • Kynurenic Acid