Impaired Respiratory and Body Temperature Control Upon Acute Serotonergic Neuron Inhibition

• Published in: Science (American Association for the Advancement of Science) Vol. 333; no. 6042; pp. 637 - 642
• Main Authors: Ray, Russell S., Corcoran, Andrea E., Brust, Rachael D., Kim, Jun Chul, Richerson, George B., Nattie, Eugene, Dymecki, Susan M.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 29.07.2011; The American Association for the Advancement of Science
• Subjects: Acidosis - physiopathology; Action potentials; Action Potentials - drug effects; Animals; Behavioral neuroscience; Biological and medical sciences; Body temperature; Body Temperature Regulation; Brain stem; Brain Stem - cytology; Carbon Dioxide - blood; Chemoreceptor Cells - physiology; Climate; Clozapine - analogs & derivatives; Clozapine - metabolism; Clozapine - pharmacology; G Protein-Coupled Inwardly-Rectifying Potassium Channels - metabolism; Homeostasis; Hydrogen-Ion Concentration; Ligands; Medical sciences; Mice; Mice, Transgenic; Models, Neurological; Neural Inhibition; Neurons; Neurons - physiology; Neuropharmacology; Pharmacology. Drug treatments; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Respiration; Respiratory system; Room temperature; Serotonin - physiology; Serotonin syndrome; Temperature effects; Ventilation systems; Psychotropic; Acute; Body temperature; Rodentia; Central nervous system; Electrophysiology; Homeostasis; Acid base balance disorder; Neural network; Survival; Encephalon; Serotoninergic neuron; Metabolic disorder; Vertebrata; Mammalia; Treatment; Mouse; Animal; Inhibition; Respiration; Tool; G protein; Biological receptor
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1205295

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.