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Science 333 (6042): 637-642

Copyright © 2011 by the American Association for the Advancement of Science

Impaired Respiratory and Body Temperature Control Upon Acute Serotonergic Neuron Inhibition

Russell S. Ray,1,* Andrea E. Corcoran,2,* Rachael D. Brust,1,* Jun Chul Kim,3 George B. Richerson,4 Eugene Nattie,2 Susan M. Dymecki1,{dagger}

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 (CO2) elevation and acidosis. At the cellular level, CNO suppressed firing rate increases evoked by CO2 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.

1 Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
2 Department of Physiology and Neurobiology, Dartmouth Medical School, Lebanon, NH 03756, USA.
3 Department of Psychology, University of Toronto, Toronto, Ontario M5S 3G3, Canada.
4 Department of Neurology, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, 2007 RCP, Iowa City, IA 52242, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: dymecki{at}genetics.med.harvard.edu


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