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Whole-body plethysmography showed irregular respiration and lower ventilatory response to hypercapnia in the null mutants. Furthermore, a medulla\u2013spinal cord preparation of<jats:italic>Dscam<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice showed that the C4 ventral root activity, which drives diaphragm contraction for inspiration, had an irregular rhythm with frequent apneas. Optical imaging of the preparation using voltage-sensitive dye revealed that the pre-inspiratory neurons located in the rostral ventrolateral medulla and belonging to the rhythm generator for respiration, lost their synchroneity in<jats:italic>Dscam<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice.<jats:italic>Dscam<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup>mice, which survived to adulthood without any overt abnormalities, also showed irregular respiration but milder than<jats:italic>Dscam<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice. 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