Induction of a torpor-like hypothermic and hypometabolic state in rodents by ultrasound
Yaoheng Yang, Jinyun Yuan, Rachael L. Field, Dezhuang Ye, Zhongtao Hu, Kevin Xu, Lu Xu, Yan Gong, Yimei Yue, Alexxai V. Kravitz, Michael R. Bruchas, Jianmin Cui, Jonathan R. Brestoff, Hong Chen
Abstract
Torpor is an energy-conserving state in which animals dramatically decrease their metabolic rate and body temperature to survive harsh environmental conditions. Here, we report the noninvasive, precise and safe induction of a torpor-like hypothermic and hypometabolic state in rodents by remote transcranial ultrasound stimulation at the hypothalamus preoptic area (POA). We achieve a long-lasting (>24 h) torpor-like state in mice via closed-loop feedback control of ultrasound stimulation with automated detection of body temperature. Ultrasound-induced hypothermia and hypometabolism (UIH) is triggered by activation of POA neurons, involves the dorsomedial hypothalamus as a downstream brain region and subsequent inhibition of thermogenic brown adipose tissue. Single-nucleus RNA-sequencing of POA neurons reveals TRPM2 as an ultrasound-sensitive ion channel, the knockdown of which suppresses UIH. We also demonstrate that UIH is feasible in a non-torpid animal, the rat. Our findings establish UIH as a promising technology for the noninvasive and safe induction of a torpor-like state.