Neurons that regulate mouse torpor

Sinisa Hrvatin (), Senmiao Sun, Oren F. Wilcox, Hanqi Yao, Aurora J. Lavin-Peter, Marcelo Cicconet, Elena G. Assad, Michaela E. Palmer, Sage Aronson, Alexander S. Banks, Eric C. Griffith and Michael E. Greenberg ()
Additional contact information
Sinisa Hrvatin: Harvard Medical School
Senmiao Sun: Harvard Medical School
Oren F. Wilcox: Harvard Medical School
Hanqi Yao: Harvard Medical School
Aurora J. Lavin-Peter: Harvard Medical School
Marcelo Cicconet: Harvard Medical School
Elena G. Assad: Harvard Medical School
Michaela E. Palmer: Harvard Medical School
Sage Aronson: Neurophotometrics, Ltd.
Alexander S. Banks: Beth Israel Deaconess Medical Center
Eric C. Griffith: Harvard Medical School
Michael E. Greenberg: Harvard Medical School

Nature, 2020, vol. 583, issue 7814, 115-121

Abstract: Abstract The advent of endothermy, which is achieved through the continuous homeostatic regulation of body temperature and metabolism1,2, is a defining feature of mammalian and avian evolution. However, when challenged by food deprivation or harsh environmental conditions, many mammalian species initiate adaptive energy-conserving survival strategies—including torpor and hibernation—during which their body temperature decreases far below its homeostatic set-point3–5. How homeothermic mammals initiate and regulate these hypothermic states remains largely unknown. Here we show that entry into mouse torpor, a fasting-induced state with a greatly decreased metabolic rate and a body temperature as low as 20 °C6, is regulated by neurons in the medial and lateral preoptic area of the hypothalamus. We show that restimulation of neurons that were activated during a previous bout of torpor is sufficient to initiate the key features of torpor, even in mice that are not calorically restricted. Among these neurons we identify a population of glutamatergic Adcyap1-positive cells, the activity of which accurately determines when mice naturally initiate and exit torpor, and the inhibition of which disrupts the natural process of torpor entry, maintenance and arousal. Taken together, our results reveal a specific neuronal population in the mouse hypothalamus that serves as a core regulator of torpor. This work forms a basis for the future exploration of mechanisms and circuitry that regulate extreme hypothermic and hypometabolic states, and enables genetic access to monitor, initiate, manipulate and study these ancient adaptations of homeotherm biology.

Date: 2020
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DOI: 10.1038/s41586-020-2387-5

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