Serotonin-producing neurons are implicated in regulating crucial physiological processes such as breathing and body temperature. Defective serotonin networks are associated with disorders such as sudden infant death syndrome (SIDS) and depression. To assess the involvement of serotonergic neurons in respiration and thermoregulation, Ray et al. developed a system to acutely and specifically inhibit these neurons. The authors engineered mice that express a synthetic G-protein coupled receptor (Di) almost exclusively in serotogenic neurons; Di is activated only by a synthetic, biologically inert and reversible ligand called clozapine-N-oxide (CNO). Following administration of CNO, serotonergic neuronal activity was rapidly inhibited by Di. In mice, CNO triggering of Di resulted in an impaired respiratory response to tissue acidosis and an acute decrease in core body temperature to near that of the surrounding air. The data directly demonstrate the requirement of an intact serotonin network for respiratory and temperature homeostasis, and introduce a powerful model to examine underlying mechanisms of SIDS and other disorders associated with serotonin abnormalities.

Ray R. S., Corcoran A. E., Brust R. D., Kim J. C., Richerson G. B., Nattie E., Dymecki S. M. (2011). Impaired respiratory and body temperature control upon acute serotonergic neuron inhibition. Science 333, 637642.

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