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Impaired respiratory and body temperature control upon acute serotonergic neuron inhibition.


ABSTRACT: Physiological homeostasis is essential for organism survival. Highly responsive neuronal networks are involved, but their constituent neurons are just beginning to be resolved. To query brain serotonergic neurons in homeostasis, we used a neuronal silencing tool, mouse RC::FPDi (based on the synthetic G protein-coupled receptor Di), designed for cell type-specific, ligand-inducible, and reversible suppression of action potential firing. In mice harboring Di-expressing serotonergic neurons, administration of the ligand clozapine-N-oxide (CNO) by systemic injection attenuated the chemoreflex that normally increases respiration in response to tissue carbon dioxide (CO(2)) elevation and acidosis. At the cellular level, CNO suppressed firing rate increases evoked by CO(2) acidosis. Body thermoregulation at room temperature was also disrupted after CNO triggering of Di; core temperatures plummeted, then recovered. This work establishes that serotonergic neurons regulate life-sustaining respiratory and thermoregulatory networks, and demonstrates a noninvasive tool for mapping neuron function.

SUBMITTER: Ray RS 

PROVIDER: S-EPMC3729433 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Impaired respiratory and body temperature control upon acute serotonergic neuron inhibition.

Ray Russell S RS   Corcoran Andrea E AE   Brust Rachael D RD   Kim Jun Chul JC   Richerson George B GB   Nattie Eugene E   Dymecki Susan M SM  

Science (New York, N.Y.) 20110701 6042


Physiological homeostasis is essential for organism survival. Highly responsive neuronal networks are involved, but their constituent neurons are just beginning to be resolved. To query brain serotonergic neurons in homeostasis, we used a neuronal silencing tool, mouse RC::FPDi (based on the synthetic G protein-coupled receptor Di), designed for cell type-specific, ligand-inducible, and reversible suppression of action potential firing. In mice harboring Di-expressing serotonergic neurons, admin  ...[more]

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