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

Authors:
Vitaliy Marchenko
Vitaliy Marchenko
Univ. of Delaware
United States
Hidehiko Koizumi
Hidehiko Koizumi
Osaka University
Japan
Bryan Mosher
Bryan Mosher
National Institute of Neurological Disorders and Stroke
Naohiro Koshiya
Naohiro Koshiya
National Institute of Neurological Disorders and Stroke
United States
Mohammad F Tariq
Mohammad F Tariq
National Institute of Neurological Disorders and Stroke
Yaroslav I Molkov
Yaroslav I Molkov
Drexel University College of Medicine

eNeuro 2016 Mar-Apr;3(2). Epub 2016 May 13.

Cellular and Systems Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, Maryland 20892.

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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http://dx.doi.org/10.1523/ENEURO.0011-16.2016DOI ListingPossible
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4867025PMCFound
December 2016
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6 PubMed Central Citations(source)

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