Janes TA , Guay LM , Fournier S , Kinkead R .

	Graphical abstract
	Fig. 1. A) Series I protocol: respiratory motor output 18 h post-hypoxia. B-E) Representative traces of raw and integrated respiratory motor output recorded from cranial nerves V and X (trigeminal: CN V; vagus: CN X) of amphibian brainstem preparations. Pre-metamorphic preparations kept under normoxic (oxygenated) conditions exhibit regular, small amplitude gill bursting. High-amplitude lung bursts are sporadic and concurrent with bursting on CN X (B). C) Normoxic brainstem preparations derived from adult frogs exhibit increased lung burst frequency with bursts often grouped into episodes. The amplitude of each burst within an episode may be greater than the previous one, forming a “ramping” episode (i.e. lung inflation cycle). Gill bursting may be present (as illustrated) or absent. D) Example trace of a time control tadpole brainstem preparation following 18 h normoxic incubation showing similar motor output as (B). Gill bursting and sporadic lung bursts are observed. E) Exposing pre-metamorphic brainstems to hypoxia followed by 18 h normoxic incubation augmented lung burst frequency, with bursts often occurring episodically and with amplitude ramping (inset). Gill bursting was observed.
	Fig. 2. Series I: pre-metamorphic brainstems show augmented lung burst frequency 18 h post-hypoxia. Comparison of lung burst frequency (A) and duration (B) at baseline and 18 h following exposure to normoxia (green; time controls) or hypoxia (0% O2, 15 min; orange). The right panel presents data from sexually mature adult frog brainstems (grey) maintained under normoxic conditions for comparison. Main ANOVA results are presented in boxes whereas post-hoc test results are presented as brackets on the graphs. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
	Fig. 3. Series I: prior exposure to hypoxia does not alter gill motor output. Data for gill burst frequency (A) and duration (B) are presented for pre-metamorphic brainstems at baseline and 18 h following exposure to normoxia (green; time controls) or hypoxia (0% O2, 25 min; orange). Data from normoxic adult frog brainstems (grey) is shown in the right panel for comparison. Main ANOVA results are presented in boxes whereas post-hoc test results are presented as brackets on the graphs. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
	Fig. 4. Series I: prior exposure to hypoxia increases expression of lung burst episodes by pre-metamorphic brainstems. A) Comparison of pre-metamorphic lung burst episode frequency at baseline and 18 h following exposure to normoxia (green; time controls) or hypoxia (0% O2, 25 min; orange). Expression of episodes is increased 18 h post-hypoxia compared to time controls. Data from normoxic adult frog brainstems (grey; right panel) illustrates that episode frequency is higher in frogs than time control pre-metamorphic. Results of number of bursts per episode (B) and ratio of preparations exhibiting amplitude ramping (C) are shown as in (A). Following hypoxia, the number of bursts per episode was higher than time controls but less than observed for adults. The ratio of preparations exhibiting amplitude ramping was variable across treatments and development. Main ANOVA results are presented in boxes whereas post-hoc test results are presented as brackets on the graphs. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
	Fig. 5. A) Series II protocol: sensitivity of respiratory motor output to baclofen. B-G) Representative traces of raw and integrated respiratory motor output recorded from pre-metamorphic brainstem preparations in normoxia (B,D,F) and 18 h post-hypoxia (C,E,G). Notation as in Fig. 1. (B) Respiratory motor output from normoxic brainstem preparations showed regular gill bursting with sporadic lung bursts. Baclofen resulted in dose-dependent inhibition of lung and gill motor output that was reversible upon washout (D,F). C) Representative trace of a tadpole brainstem preparation recorded 18 h post-hypoxia. E,F) Despite augmented lung burst frequency in these preparations, baclofen application inhibited lung and gill bursting.
	Fig. 6. Series II: signaling through GABAB receptors inhibits lung and gill motor output in pre-metamorphic tadpoles. Lung burst frequency (A) and gill burst frequency (B) were reversibly inhibited by the selective GABAB agonist, baclofen. Results were similar between baseline (normoxic) preparations and those tested 18 h following hypoxic challenge. Main ANOVA results are presented in boxes; † indicates a value significantly different from corresponding normoxia value at P < 0.05; * indicates a value significantly different from corresponding baseline (0.0 μM) value at P < 0.05.