Induction of a torpor-like hypothermic and hypometabolic state in rodents by ultrasound

Using ultrasound to activate noninvasively specific neurons in the hypothalamus, a temporary hypothermic and hypometabolic state is induced in rodents. 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.

Automated summary

By using ultrasound to activate specific neurons in the hypothalamus, researchers have successfully induced a torpor-like state in rodents, characterized by hypothermia and reduced metabolic rate. This noninvasive technique involves closed-loop feedback control of ultrasound stimulation and automated detection of body temperature. The study identifies TRPM2 as an ultrasound-sensitive ion channel in the hypothalamus preoptic area, and demonstrates the feasibility of ultrasound-induced hypothermia and hypometabolism in non-torpid animals.