Neurons that regulate mouse torpor

ABSTRACT: The advent of endothermy more than a hundred million years ago is thought to have been a defining feature of mammalian and avian evolution, achieved through continuous fine-tuned homeostatic regulation of core body temperature and metabolism. 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 core body temperature decreases far below its homeostatic setpoint. How homeothermic mammals initiate and regulate these extraordinary hypothermic states remains largely unknown. Here, we discover that entry into mouse torpor, a fasting-induced state with greatly decreased metabolic rate and body temperature as low as 20°C, is regulated by a population of neurons in the preoptic area of the hypothalamus. We show that re-stimulation of neurons activated during a previous bout of torpor is sufficient to initiate torpor, even in animals that are not calorically restricted. We localize these torpor-regulating neurons to the anteroventral medial and lateral preoptic area and molecularly identify a population of glutamatergic Adcyap1+ neurons whose activity accurately determines when calorically-restricted animals naturally initiate and exit torpor, and whose inhibition disrupts the natural process of torpor entry, maintenance and arousal. Taken together, we discover a specific hypothalamic neuronal subpopulation in the mouse brain that serves as a core regulator of torpor. This work forms the basis for future explorations of mechanisms and circuitry regulating extreme hypothermic and hypometabolic states, enabling genetic access to monitor, initiate, manipulate and study these ancient adaptations of homeotherm biology.

ORGANISM(S): Mus musculus

PROVIDER: GSE149344 | GEO | 2020/04/30

REPOSITORIES: GEO