Central Mechanisms of Thermoregulation and Fever in Mammals

Thermoregulation is a fundamental homeostatic function in mammals mediated by the central nervous system. The framework of the central circuitry for thermoregulation lies in the hypothalamus and brainstem. The preoptic area (POA) of the hypothalamus integrates cutaneous and central thermosensory information into efferent control signals that regulate excitatory descending pathways through the dorsomedial hypothalamus (DMH) and rostral medullary raphe region (rMR). The cutaneous thermosensory feedforward signals are delivered to the POA by afferent pathways through the lateral parabrachial nucleus, while the central monitoring of body core temperature is primarily mediated by warm-sensitive neurons in the POA for negative feedback regulation. Prostaglandin E₂, a pyrogenic mediator produced in response to infection, acts on the POA to trigger fever. Recent studies have revealed that this circuitry also functions for physiological responses to psychological stress and starvation. Master psychological stress signaling from the medial prefrontal cortex to the DMH has been discovered to drive a variety of physiological responses for stress coping, including hyperthermia. During starvation, hunger signaling from the hypothalamus was found to activate medullary reticular neurons, which then suppress thermogenic sympathetic outflows from the rMR for energy saving. This thermoregulatory circuit represents a fundamental mechanism of the central regulation for homeostasis.