Evidence for in vivo thermosensitivity of serotonergic neurons in the rat dorsal raphe nucleus and raphe pallidus nucleus implicated in thermoregulatory cooling

The ability to sense and respond appropriately to increases in ambient and body temperatures is critical for the survival of all animals. Although evidence suggests that brain serotonergic systems play a role in thermoregulation, including thermoregulatory cooling, evidence for activation of brainstem serotonergic neurons in vivo, in unanesthetized animals, during heat exposure is lacking. In this experiment we tested the hypothesis that populations of serotonergic neurons in the midbrain and medullary raphe complex are activated following exposure to warm ambient temperature. Rats were exposed to an incubation chamber at either warm ambient temperature (37 °C) or room temperature (RT; 23 °C) for 105 min. Brains then were removed and processed for immunohistochemical detection of the protein product of the immediate-early gene c-fos (as a marker of neuronal activation) and tryptophan hydroxylase (as a marker of serotonergic neurons). Exposure to warm ambient temperature increased body temperature and c-Fos expression in topographically organized populations of serotonergic neurons in the dorsal raphe nucleus. Activation of the dorsal raphe nucleus serotonergic system was positively correlated with body temperature following exposure to the incubation chamber. In the medulla, exposure to warm ambient temperature, compared with exposure to RT, decreased c-Fos expression in serotonergic neurons in the raphe pallidus nucleus and in non-serotonergic cells in the rostral ventrolateral medulla. Together, these results provide evidence for multiple but anatomically discrete thermosensitive serotonergic systems that may have implications for the regulation of body temperature, as well as, via projections to forebrain targets, cognitive and affective functions.

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► Exposure to warm ambient temperature increases c-Fos expression in a subset of midbrain serotonergic neurons.
► Increases in c-Fos expression were observed in serotonergic neurons in the dorsal raphe nucleus, interfascicular part (DRI), which is known to project to forebrain structures involved in thermoregulation.
► Increases in c-Fos expression were observed in serotonergic neurons in the dorsal raphe nucleus, ventrolateral part/ventrolateral periaqueductal gray region (DRVL/VLPAG), which is known to project, via multisynaptic pathways, to presympathomotor regions regulating sympathetic outflow.
► Increases in c-Fos expression in serotonergic neurons were correlated with the rectal temperature.
► These data support previous pharmacological studies suggesting that serotonergic systems play an important neuromodulatory role in thermoregulatory cooling responses.