Figure 1.

Mice lacking 5-HT neurons have severe and frequent apnea during early development, which resolves with maturation. A, Plethysmography recording from a P4 Lmx1b^f/f/p mouse with a prolonged (35 s) apnea and erratic low-amplitude breaths (raw trace; inspiration is an upward deflection, and expiration is downward). B, Recordings from two P4 mice (upper traces). The WT mouse (black trace) had continuous, rhythmic breathing, whereas the Lmx1b^f/f/p mouse (blue trace) had short periods of low-amplitude and low-frequency rhythmic breathing separated by prolonged apnea. The WT and Lmx1b^f/f/p mice both had episodes of vocalization (arrows) that were equivalent in amplitude (after normalization to weight; see Results), demonstrating that Lmx1b^f/f/p mice were capable of large-amplitude inspiratory efforts and that these could be accurately measured. Recordings from the same two mice at P12 (lower traces) show marked improvement of the Lmx1b^f/f/p mouse, with regular breathing and no apnea. C, Changes in apnea with age in WT (black; n = 13) and Lmx1b^f/f/p (blue; n = 14) mice. Lmx1b^f/f/p mice spent more time apneic (total apnea duration as a percentage of total study time, measured at ambient temperatures of 24 and 30°C; **p ≤ 0.013), and had a greater apnea frequency [inset (24°C)], up to the age of P9 (*p ≤ 0.001). D, The percentage of Lmx1b^f/f/p (blue) mice with prolonged (>5 s) apnea was greater (*p < 0.006; χ² with Yates correction) relative to WT mice (black) at the ages of P2 and P4, and this declined with postnatal development. E, The frequency of prolonged apneas was also greater (*p < 0.001) in Lmx1b^f/f/p mice at these same ages.