Prenatal activation of 5-HT2A receptor induces expression of 5-HT1B receptor in phrenic motoneurons and alters the organization of their premotor network in newborn mice

Authors

  • Hélène Bras,

    1. Laboratoire Plasticité et Physio-Pathologie de la Motricité, UMR 6196 CNRS, Université de la Méditerranée, 31 Chemin Joseph Aiguier, 13402 Marseille, France
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  • Susana P. Gaytán,

    1. Departamento de Fisiología y Zoología, Facultad de Biología, Universidad de Sevilla, Sevilla, Spain
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  • Paule Portalier,

    1. Laboratoire Plasticité et Physio-Pathologie de la Motricité, UMR 6196 CNRS, Université de la Méditerranée, 31 Chemin Joseph Aiguier, 13402 Marseille, France
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  • Sébastien Zanella,

    1. Equipe MP3-Respiration, Centre de Recherche en Neurobiologie-Neurophysiologie de Marseille, UMR 6231 CNRS, Université Paul Cézanne, Faculté des Sciences et Techniques St. Jérôme, Marseille, France
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    • *

      Present address: Department of Organismal Biology and Anatomy, University of Chicago, 1027 East 57th Street, Chicago, IL 60637, USA.

  • Rosario Pásaro,

    1. Departamento de Fisiología y Zoología, Facultad de Biología, Universidad de Sevilla, Sevilla, Spain
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  • Patrice Coulon,

    1. Laboratoire Plasticité et Physio-Pathologie de la Motricité, UMR 6196 CNRS, Université de la Méditerranée, 31 Chemin Joseph Aiguier, 13402 Marseille, France
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    • P.C. and G.H. contributed equally to this work.

  • Gérard Hilaire

    1. Equipe MP3-Respiration, Centre de Recherche en Neurobiologie-Neurophysiologie de Marseille, UMR 6231 CNRS, Université Paul Cézanne, Faculté des Sciences et Techniques St. Jérôme, Marseille, France
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    • P.C. and G.H. contributed equally to this work.


Dr H. Bras, as above.
E-mail: bras@dpm.cnrs-mrs.fr

Abstract

In newborn mice of the control [C3H/HeJ (C3H)] and monoamine oxidase A-deficient (Tg8) strains, in which levels of endogenous serotonin (5-HT) were drastically increased, we investigated how 5-HT system dysregulation affected the maturation of phrenic motoneurons (PhMns), which innervate the diaphragm. First, using immunocytochemistry and confocal microscopy, we observed a 5-HT2A receptor (5-HT2A-R) expression in PhMns of both C3H and Tg8 neonates at the somatic and dendritic levels, whereas 5-HT1B receptor (5-HT1B-R) expression was observed only in Tg8 PhMns at the somatic level. We investigated the interactions between 5-HT2A-R and 5-HT1B-R during maturation by treating pregnant C3H mice with a 5-HT2A-R agonist (2,5-dimethoxy-4-iodoamphetamine hydrochloride). This pharmacological overactivation of 5-HT2A-R induced a somatic expression of 5-HT1B-R in PhMns of their progeny. Conversely, treatment of pregnant Tg8 mice with a 5-HT2A-R antagonist (ketanserin) decreased the 5-HT1B-R density in PhMns of their progeny. Second, using retrograde transneuronal tracing with rabies virus injected into the diaphragm of Tg8 and C3H neonates, we studied the organization of the premotor network driving PhMns. The interneuronal network monosynaptically connected to PhMns was much more extensive in Tg8 than in C3H neonates. However, treatment of pregnant C3H mice with 2,5-dimethoxy-4-iodoamphetamine hydrochloride switched the premotoneuronal network of their progeny from a C3H- to a Tg8-like pattern. These results show that a prenatal 5-HT excess affects, via the overactivation of 5-HT2A-R, the expression of 5-HT1B-R in PhMns and the organization of their premotor network.

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