We characterized the role of neurons within the midline of the medulla
oblongata on phrenic and hypoglossal nerve responses to hypercapnia d
uring early development. Studies were performed on decorticate or anes
thetized, vagotomized and mechanically ventilated 14-20 day old piglet
s. Reversible withdrawal of midline neuronal activity was induced by m
icroinjections of lidocaine (2%, 300 nl; n = 10) and lesioning was cau
sed by microinjections of the neurotoxic agent, ibotenic acid (n = 12)
, at the same sites. At any given end-tidal CO2, peak phrenic and hypo
glossal activities after lidocaine were significantly lower than in th
e control period (P < 0.01). Similarly, 1-2 h after injections of ibot
enic acid, both phrenic and hypoglossal nerve responses to CO, were si
gnificantly lower than in the control period (P < 0.01). The results i
ndicate for the first time that the medullary midline neurons are requ
ired for full expression of ventilatory responses to hypercapnia and r
aise the possibility that dysfunction of these nuclei may contribute t
o respiratory instability during early postnatal life. (C) 1998 Elsevi
er Science B.V.