Body temperature regulation depends on the integrated activities of the autonomic nervous system (ANS), centered predominantly in the hypothalamus. The preoptic and anterior hypothalamus (PO/AH) are assumed to be the brain structures, most responsible for the body temperature regulation. There are two types of thermosensitive neurons in PO/AH: the warm-sensitive and cold-sensitive neurons. These neurons are sensitive to changes in brain temperature. The PO/AH neurons also integrate the thermal signals that arise at these neurons (brain temperature) and the skin (skin temperature). Body (core) temperature is regulated with reference to the set-point temperature, which is determined as a temperature at which the signal rate of the warm-sensitive and the cold-sensitive neurons balance (set-point theory). The set-point temperature is not fixed, but it is altered dynamically by various nonthermal signals that arise at various homeostatic regulatory systems. In the case of fever, which is induced by pyrogen, activities of warm-sensitive neurons decrease, whereas those of cold-sensitive neurons increase, resulting in an upward shift of the set-point. Thus, the body temperature is regulated around an increased set-point.
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