Acute inhibition of serotonergic neurons using clozapine-N-oxide attenuated the chemoreflex response to CO2 and disrupted body thermoregulation in mice.
Does silencing serotonergic neurons with CNO impair respiratory and thermoregulatory responses in mice?
Serotonergic neurons play a critical role in regulating life-sustaining respiratory and thermoregulatory networks in mice.
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.
Ray et al. (Thu,) conducted a other in Physiological homeostasis (respiratory and body temperature control). Clozapine-N-oxide (CNO) was evaluated on Chemoreflex response to CO2 elevation/acidosis and body thermoregulation. Acute inhibition of serotonergic neurons using clozapine-N-oxide attenuated the chemoreflex response to CO2 and disrupted body thermoregulation in mice.
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