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Perturbations of Respiratory Rhythm and Pattern by Disrupting Synaptic Inhibition within Pre-Bötzinger and Bötzinger Complexes
Journal article   Open access   Peer reviewed

Perturbations of Respiratory Rhythm and Pattern by Disrupting Synaptic Inhibition within Pre-Bötzinger and Bötzinger Complexes

Vitaliy Marchenko, Hidehiko Koizumi, Bryan Mosher, Naohiro Koshiya, Mohammad F Tariq, Tatiana G Bezdudnaya, Ruli Zhang, Yaroslav I Molkov, Ilya A Rybak and Jeffrey C Smith
eNeuro, v 3(2), pp 3033-3046
Mar 2016
DOI: https://doi.org/10.1523/ENEURO.0011-16.2016
PMID: 27200412
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1523/eneuro.0011-16.2016View
Published, Version of Record (VoR)CC BY V4.0,  Open
url
https://doi.org/10.1523/ENEURO.0011-16.2016View
Published, Version of Record (VoR) Open

Abstract

Action Potentials - drug effects Action Potentials - physiology Animals Cranial Nerves - physiology Disease Models, Animal GABA Antagonists - pharmacology GABA-A Receptor Agonists - pharmacology Glutamic Acid - toxicity Glycine Agents - pharmacology Male Muscimol - pharmacology Nerve Net - drug effects Nerve Net - physiology Neural Inhibition - drug effects Neural Inhibition - physiology Pyridazines - pharmacology Rats Rats, Sprague-Dawley Respiration Disorders - etiology Respiration Disorders - physiopathology Respiratory Center - drug effects Respiratory Center - physiology Respiratory Rate - drug effects Respiratory Rate - physiology Spinal Cord - physiology Strychnine - pharmacology Vagotomy - adverse effects
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.

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Collaboration types
Domestic collaboration
Web of Science research areas
Neurosciences
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