When facing freezing temperatures and food deprivation, mice enter a state of low metabolism known as “torpor” from midnight until dawn. Researchers at Nagoya University have now identified the specific brain circuit that controls this timing, running from the brain’s biological clock to its temperature-regulating region.
Image Credit: Daisuke Ono, Nagoya University
Scientific Frontline: Extended "At a Glance" Summary: The Neural Circuit Regulating Torpor
The Core Concept: Researchers have identified the specific neural pathway through which the brain's circadian clock times and controls "torpor," a natural, reversible state of reduced body temperature and metabolism utilized by certain mammals to survive severe environmental stress.
Key Distinction/Mechanism: The circadian clock does not actively initiate torpor. Instead, it continuously sends silencing signals to the preoptic area (POA) during the day to suppress it. During the night, this inhibitory influence decreases, allowing thermoregulatory and energy balance circuits to trigger the low-metabolism state.
Major Frameworks/Components:
- Preoptic Area (POA): The region of the brain primarily responsible for controlling body temperature and initiating torpor.
- Circadian Clock: A cluster of neurons located in the hypothalamus that suppresses the POA via inhibitory signaling during daylight hours.
- Arginine Vasopressin (AVP) Neurons: Specific clock cells responsible for producing a protein that facilitates the inhibitory GABAergic projections from the circadian clock to the POA.
- Optogenetics: The light-based neuromodulation technique utilized by researchers to selectively activate or deactivate these neural pathways in murine models to map the circuit.
Branch of Science: Neuroscience, Chronobiology, Systems Physiology.
Future Application: Elucidating this neural mechanism could advance clinical induced hypothermia techniques to mitigate tissue damage following severe injury or surgery, and may serve as a foundational step toward inducing controlled hypometabolic states (suspended animation) for long-duration human spaceflight.
Why It Matters: Mapping the biological timing of metabolic shutdown provides critical insights into mammalian energy regulation and survival strategies, revealing how complex neurological systems coordinate to protect organisms from acute starvation and hypothermia.
Researchers have identified the neural circuit through which the brain’s circadian clock controls the timing of torpor, a natural state of reduced body temperature and metabolism. The discovery provides new insights into how mammals regulate energy use and may inform future approaches in medicine and long-duration spaceflight.
You have gone without food for days, and the temperature drops to near freezing. What do you do? For some animals, the answer is influenced by the brain’s circadian clock. Hummingbirds, bats, and mice are among the animals that can enter torpor, which reduces body temperature and metabolism. Scientists suspected that the brain’s circadian clock controls the timing of torpor, but until now, the exact mechanism was unknown.
Researchers at Nagoya University in Japan have identified the specific neural circuit responsible for this survival strategy. They have shown that the brain’s circadian clock, a small cluster of neurons located in the hypothalamus at the base of the brain, sends silencing signals through this circuit to a nearby temperature-regulating region, suppressing torpor during the day. The findings were published in Nature Communications.
Torpor from Midnight to Dawn
“The brain’s preoptic area (POA) controls body temperature and has an important role in initiating torpor,” said Daisuke Ono, senior author and lecturer at the Research Institute of Environmental Medicine at Nagoya University. “During the day, the brain’s circadian clock suppresses torpor, which occurs between midnight and dawn in mice.”
Using light-based tools (optogenetics) to switch specific neurons on or off, the researchers showed that activating the circadian clock–POA pathway suppressed torpor. When the circadian clock was disrupted, mice either entered torpor at irregular, unpredictable times or showed a marked reduction in torpor.
Additionally, researchers identified the specific clock cell type responsible for sending these signals. Neurons that produce a protein called arginine vasopressin (AVP neurons) in the circadian clock inhibit neurons in the POA. Mice with impaired inhibitory signaling from AVP neurons to the POA showed abnormal torpor timing, demonstrating that this pathway plays a key role in determining when torpor occurs.
The research team also discovered that the POA becomes more active at night. “The clock does not actively trigger torpor. Instead, it reduces its inhibitory influence at night, allowing neural circuits involved in thermoregulation and energy balance to promote torpor when environmental conditions are favorable. The three systems work in tandem to create the right conditions,” Ono explained.
Implications for Medicine and Space Travel
A clearer understanding of how the brain times metabolic shutdowns may inform techniques that use controlled cooling to limit tissue damage after injury or surgery (induced hypothermia). The findings may also be relevant to extended spaceflight, where the controlled reduction of metabolism could protect the body.
Although humans do not naturally enter torpor, understanding the neural mechanisms that regulate metabolic suppression in mammals could provide clues for developing controlled hypometabolic states in the future.
Rare accounts of people surviving extreme cold exposure with dangerously low body temperatures hint at this possibility. Understanding the brain circuits that control these states in mammals may one day bring researchers closer to inducing suspended animation in humans, a state long imagined for deep space travel.
Funding: This work was supported by the HIROSE Foundation, LOTTE Foundation, Foundation of Kinoshita Memorial Enterprise, Astellas Foundation for Research on Metabolic Disorders, UBE Foundation, JST FOREST Program (JPMJFR211A), and JSPS KAKENHI (25H02445, 24K02060, 24H02006, 23H04939, 21H02526, 25KF0138, 21H00422, 24KJ0102, and 25K18507).
Published in journal: Nature Communications
Authors: Sheikh Mizanur Rahaman, Shota Miyazaki, Chang-Ting Tsai, Akihiro Yamanaka, Chi Jung Hung, Michihiro Mieda, Takahiro J. Nakamura, Hiroshi Yamaguchi, and Daisuke Ono
Source/Credit: Nagoya University
Edited by: Scientific Frontline
Reference Number: ns060426_01
