title: Effects of glycinergic inhibition failure on respiratory rhythm and pattern generation.
abstract: Inhibitory interactions between neurons of the respiratory network are involved in rhythm generation and pattern formation. Using a computational model of brainstem respiratory networks, we investigated the possible effects of suppressing glycinergic inhibition on the activity of different respiratory neuron types. Our study revealed that progressive suppression of glycinergic inhibition affected all neurons of the network and disturbed neural circuits involved in termination of inspiration. Causal was a dysfunction of postinspiratory inhibition targeting inspiratory neurons, which often led to irregular preterm reactivation of these neurons, producing double or multiple short-duration inspiratory bursts. An increasing blockade of glycinergic inhibition led to apneustic inspiratory activity. Similar disturbances of glycinergic inhibition also occur during hypoxia. A clear difference in prolonged hypoxia, however, is that the rhythm terminates in expiratory apnea. The critical function of glycinergic inhibition for normal respiratory rhythm generation and the consequences of its reduction, including in pathological conditions, are discussed.
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA. Electronic address: natalia.shevtsova@drexelmed.edu.
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Shevtsova
authors.affiliation: Weill Cornell Medical College in Qatar, Education City, Doha, Qatar.
authors.forename: Dietrich
authors.initials: D
authors.lastname: Büsselberg
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA; Department of Mathematical Sciences, Indiana University-Purdue University Indianapolis, Indianapolis, IN, USA.
authors.forename: Yaroslav I
authors.initials: YI
authors.lastname: Molkov
authors.affiliation: Department of Neuro- and Sensory Physiology, University of Göttingen, Göttingen, Germany; Excellence Cluster Nanoscale Microscopy and Molecular Physiology of the Brain, Göttingen, Germany.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Bischoff
authors.affiliation: Cellular and Systems Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Smith
authors.affiliation: Department of Neuro- and Sensory Physiology, University of Göttingen, Göttingen, Germany; Excellence Cluster Nanoscale Microscopy and Molecular Physiology of the Brain, Göttingen, Germany.
authors.forename: Diethelm W
authors.initials: DW
authors.lastname: Richter
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Ilya A
authors.initials: IA
authors.lastname: Rybak
mesh_terms: D000818:Animals; D003198:Computer Simulation; D005998:Glycine / Q000378:metabolism*; D006801:Humans; D008959:Models, Neurological; D009474:Neurons / Q000378:metabolism*; D010507:Periodicity; D012125:Respiratory Center / Q000502:physiology*; D012143:Respiratory Physiological Phenomena
chemical_list: D005998:Glycine
keywords: apnea; apneusis; computational modeling; glycinergic inhibition; hypoxia; pre-Bötzinger complex; respiratory rhythm; translational medicine
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