Postnatal changes in ventilation during normoxia and acute hypoxia in the rat: implication for a sensitive period

Previously, we found heightened expression of inhibitory neurochemicals and depressed expression of excitatory neurochemicals with a sudden drop in metabolic activity around postnatal day (P) 12 in rat brainstem respiratory nuclei, suggesting that this period is a critical window during which respiratory control or regulation may be distinctly different. To test this hypothesis, the hypoxic ventilatory responses (HVR) to 10% oxygen were tested in rats every day from P0 to P21. Our data indicate that (1) during normoxia (N), breathing frequency (f) increased with age, peaking at P13, followed by a gradual decline, whereas both tidal volume (V-T) and minute ventilation (V-E) significantly increased in the second postnatal week, followed by a progressive increase in V-T and a relative plateau in V-E; (2) during 5 min of hypoxia (H), V-E exhibited a biphasic response from P3 onward. Significantly, the ratio of V-E(H) to V-E(N) was generally > 1 during development, except for P13-16, when it was < 1 after the first 1-2 min, with the lowest value at P13; (3) the H : N ratio for f, V-T and V-E during the first 30 s and the last minute of hypoxia all showed a distinct dip at P13, after which the V-T and V-E values rose again, while the f values declined through P21; and (4) the H : N ratios for f, V-T and V-E averaged over 5 min of hypoxia all exhibited a sudden fall at P13. The f ratio remained low thereafter, while those for V-T and V-E increased again with age until P21. Thus, hypoxic ventilatory response is influenced by both f and V-T before P13, but predominantly by V-T after P13. The striking changes in normoxic ventilation as well as HVR at or around P13, together with our previous neurochemical and metabolic data, strongly suggests that the end of the second postnatal week is a critical period of development for brainstem respiratory nuclei in the rat.