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.
- Viktor V Feketa
- Elena O Gracheva
- Elena O Gracheva
- Sviatoslav N Bagriantsev
- Sviatoslav N Bagriantsev
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All animal procedures were performed in compliance with the Office of Animal Research Support of Yale University (protocols 2018-11497 and 2018-11526). Thirteen-lined ground squirrels (Ictidomys tridecemlineatus), wild-type mice (Mus musculus), and frogs (Xenopus laevis) were used for this study. Wild-type C57Bl/6J mice were purchased from Jackson Laboratory (Bar Harbor, ME). All animals were housed on a 12-h light/dark cycle (lights on at 0700) under standard laboratory conditions with ad libitum access to food and water. Both male and female mice 6-16 weeks of age weighing 17-34 g and male thirteen-lined ground squirrels 6 months-3 years of age weighing approximately 150-300 g were used for experiments. All ground squirrels were in their active (non-hibernating) state verified by daily body temperature measurements and maintained on a diet of dog food (Iams) supplemented with sunflower seeds, superworms, and fresh vegetables. Frogs were housed using standard conditions.
- Polina V Lishko, University of California, Berkeley, United States
© 2020, Feketa et al.
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