title: Perturbations of Respiratory Rhythm and Pattern by Disrupting Synaptic Inhibition within Pre-Bötzinger and Bötzinger Complexes.
abstract: The pre-Bötzinger (pre-BötC) and Bötzinger (BötC) complexes are the brainstem compartments containing interneurons considered to be critically involved in generating respiratory rhythm and motor pattern in mammals. Current models postulate that both generation of the rhythm and coordination of the inspiratory-expiratory pattern involve inhibitory synaptic interactions within and between these regions. Both regions contain glycinergic and GABAergic neurons, and rhythmically active neurons in these regions receive appropriately coordinated phasic inhibition necessary for generation of the normal three-phase respiratory pattern. However, recent experiments attempting to disrupt glycinergic and GABAergic postsynaptic inhibition in the pre-BötC and BötC in adult rats in vivo have questioned the critical role of synaptic inhibition in these regions, as well as the importance of the BötC, which contradicts previous physiological and pharmacological studies. To further evaluate the roles of synaptic inhibition and the BötC, we bilaterally microinjected the GABAA receptor antagonist gabazine and glycinergic receptor antagonist strychnine into the pre-BötC or BötC in anesthetized adult rats in vivo and in perfused in situ brainstem-spinal cord preparations from juvenile rats. Muscimol was microinjected to suppress neuronal activity in the pre-BötC or BötC. In both preparations, disrupting inhibition within pre-BötC or BötC caused major site-specific perturbations of the rhythm and disrupted the three-phase motor pattern, in some experiments terminating rhythmic motor output. Suppressing BötC activity also potently disturbed the rhythm and motor pattern. We conclude that inhibitory circuit interactions within and between the pre-BötC and BötC critically regulate rhythmogenesis and are required for normal respiratory motor pattern generation.
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine , Philadelphia, Pennsylvania 19129.
authors.forename: Vitaliy
authors.identifier: 0000-0001-8737-2541
authors.initials: V
authors.lastname: Marchenko
authors.affiliation: Cellular and Systems Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, Maryland 20892.
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Koizumi
authors.affiliation: Cellular and Systems Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, Maryland 20892.
authors.forename: Bryan
authors.initials: B
authors.lastname: Mosher
authors.affiliation: Cellular and Systems Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, Maryland 20892.
authors.forename: Naohiro
authors.identifier: 0000-0002-2952-8779
authors.initials: N
authors.lastname: Koshiya
authors.affiliation: Cellular and Systems Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, Maryland 20892.
authors.forename: Mohammad F
authors.initials: MF
authors.lastname: Tariq
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine , Philadelphia, Pennsylvania 19129.
authors.forename: Tatiana G
authors.identifier: 0000-0001-6086-3332
authors.initials: TG
authors.lastname: Bezdudnaya
authors.affiliation: Cellular and Systems Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, Maryland 20892.
authors.forename: Ruli
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Mathematics and Statistics, Georgia State University , Atlanta, Georgia 30302.
authors.forename: Yaroslav I
authors.initials: YI
authors.lastname: Molkov
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine , Philadelphia, Pennsylvania 19129.
authors.forename: Ilya A
authors.identifier: 0000-0003-3461-349X
authors.initials: IA
authors.lastname: Rybak
authors.affiliation: Cellular and Systems Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, Maryland 20892.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Smith
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D003391:Cranial Nerves / Q000502:physiology; D004195:Disease Models, Animal; D018756:GABA Antagonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000633:toxicity; D018684:Glycine Agents / Q000494:pharmacology; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012120:Respiration Disorders / Q000209:etiology / Q000503:physiopathology*; D012125:Respiratory Center / Q000187:drug effects / Q000502:physiology*; D056152:Respiratory Rate / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology; D013331:Strychnine / Q000494:pharmacology; D014628:Vagotomy / Q000009:adverse effects
chemical_list: D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D018684:Glycine Agents; D011724:Pyridazines; D009118:Muscimol; D018698:Glutamic Acid; C049853:gabazine; D013331:Strychnine
keywords: Bötzinger complex; brainstem; central pattern generation; pre-Bötzinger complex; respiration; synaptic inhibition