A Neural Circuit Underlying the Generation of Hot Flushes

Hot flushes are a sudden feeling of warmth commonly associated with the decline of gonadal hormones at menopause. Neurons in the arcuate nucleus of the hypothalamus that express kisspeptin and neurokinin B (Kiss1^ARH neurons) are candidates for mediating hot flushes because they are negatively regulated by sex hormones. We used a combination of genetic and viral technologies in mice to demonstrate that artificial activation of Kiss1^ARH neurons evokes a heat-dissipation response resulting in vasodilation (flushing) and a corresponding reduction of core-body temperature in both females and males. This response is sensitized by ovariectomy. Brief activation of Kiss1^ARH axon terminals in the preoptic area of the hypothalamus recapitulates this response, while pharmacological blockade of neurokinin B (NkB) receptors in the same brain region abolishes it. We conclude that transient activation of Kiss1^ARH neurons following sex-hormone withdrawal contributes to the occurrence of hot flushes via NkB release in the rostral preoptic area.