Brain Neurons Control Hibernation-Like State During Fasting in Mice
Scientists identify specific brainstem neurons that orchestrate the body's energy-saving torpor response to food scarcity.
Summary
Researchers discovered that catecholaminergic neurons in the brainstem's ventrolateral medulla control torpor—a hibernation-like state mice enter during fasting. These neurons coordinate dramatic reductions in body temperature, heart rate, and energy expenditure. When scientists blocked these neurons, mice couldn't enter torpor during fasting. When activated, the neurons induced torpor even in well-fed mice. The heart rate drops before body temperature falls, suggesting cardiovascular changes drive the cooling process. These findings reveal how the brain orchestrates energy conservation during food scarcity.
Detailed Summary
This groundbreaking study reveals how the mammalian brain orchestrates torpor, a hibernation-like state that helps animals survive food scarcity. Understanding these mechanisms could inform therapeutic approaches for metabolic disorders and potentially advance human hibernation research for space exploration or medical applications.
Researchers focused on catecholaminergic neurons in the ventrolateral medulla (VLM-CA), a brainstem region known to control autonomic functions. Using mice subjected to 24-hour fasting, they tracked body temperature and activity while monitoring neural activity. During fasting, mice naturally entered torpor after about 7 hours, with body temperatures dropping below 31°C and recovering within 24 hours even without refeeding.
The key discovery was that VLM-CA neurons become highly active just before torpor onset. When researchers chemogenetically inhibited these neurons, 30% of mice failed to enter torpor, and those that did showed significantly impaired responses. Conversely, artificially activating these neurons in well-fed mice induced immediate torpor-like states with dramatic drops in body temperature, heart rate, energy expenditure, and physical activity.
Crucially, the study revealed that heart rate decline precedes body temperature reduction, suggesting cardiovascular changes drive the cooling process rather than vice versa. The researchers traced neural pathways showing VLM-CA neurons likely regulate heart rate through connections to the dorsal motor vagal nucleus and control thermogenesis via the medial preoptic area.
The findings extend beyond laboratory mice—similar neurons exist in Daurian ground squirrels and become active before natural hibernation, suggesting evolutionary conservation of this mechanism. This research provides the first clear demonstration of how specific brainstem circuits coordinate the complex physiological changes underlying energy-saving states, offering new targets for metabolic interventions.
Key Findings
- VLM-CA neurons become active before torpor onset and are required for fasting-induced torpor
- Activating these neurons induces torpor in well-fed mice with 10°C temperature drops
- Heart rate decline precedes body temperature reduction during torpor entry
- These neurons project to brain regions controlling heart rate and thermogenesis
- Similar neurons exist in hibernating ground squirrels, suggesting evolutionary conservation
Methodology
Researchers used chemogenetic manipulation of VLM-CA neurons in mice, combining viral vectors with Cre-recombinase technology for cell-type-specific targeting. Continuous telemetric monitoring tracked body temperature and activity during 24-hour fasting protocols, with electrophysiological validation of neural responses.
Study Limitations
The study was conducted primarily in laboratory mice under controlled conditions. Translation to humans remains uncertain given species differences in torpor capacity. Long-term effects of manipulating these neural circuits and potential off-target effects of the interventions require further investigation.
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