Developmental disinhibition: turning off inhibition turns on breathing in vertebrates.
Development requires age-dependent changes in essential behaviors. While the mechanisms determining the developmental expression of such behavior in vertebrates remain largely unknown, a few studies have identified permissive mechanisms in which the appearance of promoting signals activates pre-established networks. Here we report a different developmental process. Specifically, we show that the neuronal substrate that produces putative lung breathing in tadpoles is formed early in development, but remains more or less inactive until metamorphosis because of suppression mediated by a GABA(B) receptor-dependent mechanism. Blocking this suppression using 2-hydroxy-saclofen, a GABA(B) receptor antagonist, results in the precocious production of the putative lung breathing motor pattern. This blocker failed to augment putative lung breaths after metamorphosis. Thus, our results suggest that loss of an inhibitory signal during development (i.e., developmental disinhibition) is responsible for the developmental expression of air breathing.
Straus
C
C
Respiratory Research Group, Department of Medical Physiology, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1, Canada. christian.strauss@psl.ap-hop-paris.fr
Wilson
R J
RJ
Remmers
J E
JE
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000375:Aging / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives* / Q000494:pharmacology; D001933:Brain Stem / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D004525:Efferent Pathways / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D018756:GABA Antagonists / Q000494:pharmacology; D008675:Metamorphosis, Biological / Q000187:drug effects* / Q000502:physiology; D009415:Nerve Net / Q000254:growth & development* / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011892:Rana catesbeiana / Q000033:anatomy & histology / Q000254:growth & development / Q000378:metabolism; D018080:Receptors, GABA-B / Q000187:drug effects* / Q000378:metabolism; D012119:Respiration / Q000187:drug effects*; D012143:Respiratory Physiological Phenomena / Q000187:drug effects; D012137:Respiratory System / Q000294:innervation*
D018756:GABA Antagonists; D018080:Receptors, GABA-B; D001418:Baclofen; C057491:2-hydroxysaclofen