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Most mammals maintain their body temperature around 37°C, whereas in hibernators it can approach 0°C without triggering a thermogenic response. The remarkable plasticity of the thermoregulatory system allowed mammals to thrive in variable environmental conditions and occupy a wide range of geographical habitats, but the molecular basis of thermoregulation remains poorly understood. Here we leverage the thermoregulatory differences between mice and hibernating thirteen-lined ground squirrels (Ictidomys tridecemlineatus) to investigate the mechanism of cold sensitivity in the preoptic area (POA) of the hypothalamus, a critical thermoregulatory region. We report that, in comparison to squirrels, mice have a larger proportion of cold-sensitive neurons in the POA. We further show that mouse cold-sensitive neurons express the cyclic nucleotide-gated ion channel CNGA3, and that mouse, but not squirrel, CNGA3 is potentiated by cold. Our data reveal CNGA3 as a hypothalamic cold sensor and a molecular marker to interrogate the neuronal circuitry underlying thermoregulation.
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This content will become publicly available on April 2, 2026
Discovering universal temperature regulation dynamics in animals
Hibernation is an adaptation to extreme environmental seasonality that has been studied for almost 200 years, but our mechanistic understanding of the underlying physiological system remains lacking due to the partially observed nature of the system. During hibernation, small mammals, such as the Arctic ground squirrel, exhibit dramatic oscillations in body temperature, typically one of the only physiological states measured, of up to 40◦C. These spikes are known as interbout arousals and typically occur 10-20 times throughout hibernation. The physiological mechanism that drives interbout arousals is unknown, but two distinct mechanisms have been hypothesized. Using model selection for partially observed systems, we are able to differentiate between these two mechanistic hypotheses using only body temperature data recorded from a free-ranging Arctic ground squirrel. We then modify our discovered physiological model of Arctic ground squirrel to include environmental information and find that we can qualitatively match body temperature data recorded from a wide range of species, including a bird, a shrew, and a bear, which also dynamically modulate body temperature. Our results suggest that a universal, environmentally sensitive mechanism could regulate body temperature across a diverse range of species—a mechanistic restructuring of our current understanding of the physiological organization across species. While the findings presented here are applicable to thermophysiology, the general modeling procedure is applicable to time series data collected from partially observed biological, chemical, physical, mechanical, and cosmic systems for which the goal is to elucidate the underlying mechanism or control structure.
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- Award ID(s):
- 2235451
- PAR ID:
- 10612044
- Publisher / Repository:
- arXiv
- Date Published:
- Journal Name:
- arXivorg
- ISSN:
- 2331-8422
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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