title: Role of inhibition in respiratory pattern generation.
abstract: Postsynaptic inhibition is a key element of neural circuits underlying behavior, with 20-50% of all mammalian (nongranule) neurons considered inhibitory. For rhythmic movements in mammals, e.g., walking, swimming, suckling, chewing, and breathing, inhibition is often hypothesized to play an essential rhythmogenic role. Here we study the role of fast synaptic inhibitory neurotransmission in the generation of breathing pattern by blocking GABA(A) and glycine receptors in the preBötzinger complex (preBötC), a site essential for generation of normal breathing pattern, and in the neighboring Bötzinger complex (BötC). The breathing rhythm continued following this blockade, but the lung inflation-induced Breuer-Hering inspiratory inhibitory reflex was suppressed. The antagonists were efficacious, as this blockade abolished the profound effects of the exogenously applied GABA(A) receptor agonist muscimol or glycine, either of which under control conditions stopped breathing in vagus-intact or vagotomized, anesthetized, spontaneously breathing adult rats. In vagotomized rats, GABA(A)ergic and glycinergic antagonists had little, if any, effect on rhythm. The effect in vagus-intact rats was to slow the rhythm to a pace equivalent to that seen after suppression of the aforementioned Breuer-Hering inflation reflex. We conclude that postsynaptic inhibition within the preBötC and BötC is not essential for generation of normal respiratory rhythm in intact mammals. We suggest the primary role of inhibition is in shaping the pattern of respiratory motor output, assuring its stability, and in mediating reflex or volitional apnea, but not in the generation of rhythm per se.
authors.affiliation: Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095-1763, USA. victoraj@mednet.ucla.edu
authors.forename: Wiktor A
authors.initials: WA
authors.lastname: Janczewski
authors.forename: Alexis
authors.initials: A
authors.lastname: Tashima
authors.forename: Paul
authors.initials: P
authors.lastname: Hsu
authors.forename: Yan
authors.initials: Y
authors.lastname: Cui
authors.forename: Jack L
authors.initials: JL
authors.lastname: Feldman
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003964:Diaphragm / Q000187:drug effects / Q000503:physiopathology; D004576:Electromyography; D007839:Functional Laterality; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology; D018684:Glycine Agents / Q000494:pharmacology; D007211:Indoles; D007823:Laryngeal Nerves / Q000502:physiology; D008297:Male; D008845:Microinjections; D009118:Muscimol / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects; D012119:Respiration / Q000187:drug effects; D012125:Respiratory Center / Q000166:cytology* / Q000187:drug effects / Q000293:injuries / Q000502:physiology*; D013331:Strychnine / Q000494:pharmacology; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology
chemical_list: D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D018684:Glycine Agents; D007211:Indoles; D009118:Muscimol; C007293:DAPI; D002795:Choline O-Acetyltransferase; D013331:Strychnine; D005998:Glycine; D001640:Bicuculline
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