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Role and origin of the GABAergic innervation of dorsal raphe serotonergic neurons

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Serotonin and Sleep: Molecular, Functional and Clinical Aspects

Abstract

Extracellular electrophysiological recordings in freely moving cats have shown that serotonergic neurons from the dorsal raphe nucleus are tonically active during waking, decrease their activity during slow-wave sleep, and are nearly quiescent during paradoxical sleep. However, the mechanisms at the origin of the modulation of activity of these neurons were not identified. To fill this gap, we developed a method allowing extracellular single-unit recordings of neurons, combined with iontophoresis of agonists and antagonists in the head-restrained rat. Using this method, we were able to show that GABA is responsible for the decrease of activity of the dorsal raphe serotonergic cells both during slow-wave sleep and paradoxical sleep. In addition, combining retrograde tracing with cholera toxin B subunit and GAD immunohistochemistry, we showed that the GABAergic innervation of the dorsal raphe nucleus arises from multiple distant sources and not only from local interneurons as classically accepted. Among these afferents, we propose that GABAergic neurons located in the lateral and ventrolateral preoptic area and the pontine ventral periaqueductal gray are responsible for the reduction of activity of the serotonergic neurons of the dorsal raphe nucleus during slow-wave sleep and paradoxical sleep, respectively.

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Author information

Authors and Affiliations

  1. Physiopathologie des réseaux neuronaux du cycle veille-sommeil, Faculté de Médecine Laënnec, CNRS UMR 5167, 7, Rue Guillaume Paradin, 69372, Lyon cedex 08, France

    Pierre-Hervé Luppi, Damien Gervasoni, Christelle Peyron, Lucienne Leger, Denise Salvert & Patrice Fort

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  1. Pierre-Hervé Luppi
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  2. Damien Gervasoni
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  3. Christelle Peyron
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  4. Lucienne Leger
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  5. Denise Salvert
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  6. Patrice Fort
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Editor information

Editors and Affiliations

  1. Pharmacology and Therapeutics, School of Medicine, Clinics Hospital, Montevideo, 11300, Uruguay

    Jaime M. Monti

  2. Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, College of Physicians and Surgeons of Columbia University, 630 West 168th Street - Rm # BB813, New York, NY, 10032, USA

    S. R. Pandi-Perumal

  3. Green Hall, Program in Neuroscience, Princeton University, Princeton, NJ, 08540, USA

    Barry L. Jacobs

  4. Psychopharmacology Unit, Dorothy Hodgkin Building Whitson Street, Bristol, BS1 3NY, UK

    David J. Nutt

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Luppi, PH., Gervasoni, D., Peyron, C., Leger, L., Salvert, D., Fort, P. (2008). Role and origin of the GABAergic innervation of dorsal raphe serotonergic neurons. In: Monti, J.M., Pandi-Perumal, S.R., Jacobs, B.L., Nutt, D.J. (eds) Serotonin and Sleep: Molecular, Functional and Clinical Aspects. Birkhäuser Basel. https://doi.org/10.1007/978-3-7643-8561-3_9

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