Fine Topography of Brain Areas Activated by Cold Stress

Neuronal activity in response to acute cold exposure was mapped in the central nervous system of adult rats using Fos immunostaining. A single, 3-hour exposure to cold elicited strong Fos-like immunoreactivity in the medial preoptic nucleus that is known as the thermoregulatory center of the brain. By this technique, pontine and medullary thermosensitive areas have been first localized and outlined anatomically. The medullary thermosensitive neurons occupy well-demarcated areas immediately ventral and dorsal to the spinal trigeminal nucleus, termed peritrigeminal and paratrigeminal nuclei, respectively. Cold-sensitive neurons were present in the dorsal part of the pontine reticular formation. Topographically, this area corresponds to the 'pontine thermoregulatory area', named on the basis of neurophysiological observations. In addition, thermosensitive neurons were found in the rostral thalamus and zona incerta. Several cell groups that showed strong Fos-like immunoreactivity in our previous pain-related stress experiments were also activated by cold exposure. The midline thalamic, hypothalamic dorsomedial, supramamillary and lateral parabrachial nuclei were targets of cold stress-induced noxious stimuli. Fos-positive neurons established specific topographical patterns in the paraventricular, arcuate, central amygdaloid nuclei, and the nucleus of the solitary tract. The possible involvement of central noradrenergic neurons in stress response to acute cold exposure was investigated by double immunostaining for tyrosine hydroxylase (TH) and Fos. None of the tyrosine hydroxylase positive neurons in the brain stem established Fos-like immunoreactivity, suggesting that the central noradrenergic system may have a minor, if any, role in cold-induced stress responses. Based on the topographical distribution of Fos-activated neurons, this study suggests that in addition to the hypothalamo-pituitary-adrenal axis, some other stress effector systems may play an important role in the maintenance of homeostasis during cold stress.