Developmental disinhibition: Turning off inhibition turns on breathing in vertebrates

Development requires age-dependent changes in essential behaviors. While th e mechanisms determining the developmental expression of such behavior in v ertebrates remain largely unknown, a few studies have identified permissive mechanisms in which the appearance of promoting signals activates pre-esta blished networks. Here we report a different developmental process. Specifi cally, we show that the neuronal substrate that produces putative lung brea thing in tadpoles is formed early in development, but remains more or less inactive until metamorphosis because of suppression mediated by a GABA(B) r eceptor-dependent mechanism. Blocking this suppression using 2-hydroxy-sacl ofen, a GABA(B) receptor antagonist, results in the precocious production o f 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 disinh ibition) is responsible for the developmental expression of air breathing. (C) 2000 John Wiley & Sons, Inc.