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The Journal of Neuroscience, July 15, 2001, 21(14):5212-5221

Altered Respiratory Activity and Respiratory Regulations in Adult Monoamine Oxidase A-Deficient Mice

Henri Burnet¹, Michelle Bévengut¹, Fouad Chakri¹, Céline Bou-Flores¹, Patrice Coulon², Susana Gaytán³, Rosario Pásaro³, and Gérard Hilaire¹

¹ Centre National de la Recherche Scientifique-Développement et Pathologie du Mouvement, Biologie des Rythmes et du Développement, 13402 Marseille Cedex 20, France, ² Centre National de la Recherche Scientifique, Neurocybernetique Cellulaire, 13009 Marseille, France, and ³ Departamento Fisiología y Biología Animal, Facultad de Biología, Universitad de Sevilla 41012-Sevilla, Spain

The abnormal metabolism of serotonin during the perinatal period alters respiratory network maturation at birth as revealed by comparing the monoamine oxidase A-deficient transgenic (Tg8) with the control (C3H) mice (Bou-Flores et al., 2000). To know whether these alterations occur only transiently or induce persistent respiratory dysfunction during adulthood, we studied the respiratory activity and regulations in adult C3H and Tg8 mice. First, plethysmographic and pneumotachographic analyses of breathing patterns revealed weaker tidal volumes and shorter inspiratory durations in Tg8 than in C3H mice. Second, electrophysiological studies showed that the firing activity of inspiratory medullary neurons and phrenic motoneurons is higher in Tg8 mice and that of the intercostal motoneurons in C3H mice. Third, histological studies indicated abnormally large cell bodies of Tg8 intercostal but not phrenic motoneurons. Finally, respiratory responses to hypoxia and lung inflation are weaker in Tg8 than in C3H mice. DL-p-chlorophenyl-alanine treatments applied to Tg8 mice depress the high serotonin level present during adulthood; the treated mice recover normal respiratory responses to both hypoxia and lung inflation, but their breathing parameters are not significantly affected. Therefore in Tg8 mice the high serotonin level occurring during the perinatal period alters respiratory network maturation and produces a permanent respiratory dysfunction, whereas the high serotonin level present in adults alters the respiratory regulatory processes. In conclusion, the metabolism of serotonin plays a crucial role in the maturation of the respiratory network and in both the respiratory activity and the respiratory regulations.

Key words: breathing patterns; inspiratory neuron and motoneuron firing activity; respiratory regulations; morphology of motoneurons; serotonin; maturation; transgenic mice

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Copyright © 2001 Society for Neuroscience  0270-6474/01/21145212-10$05.00/0

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