Summary: When you finish a grueling run, you might think your muscles are doing all the hard work of adapting. However, a new study suggests that your brain is the true master of your fitness gains.
Researchers discovered a specific cluster of neurons in the hypothalamus, known as SF1 neurons, that activate for about an hour after exercise. Without the activity of these “post-run” neurons, mice failed to improve their endurance, no matter how much they trained. This discovery upends the traditional view of exercise, proving that the brain must send a signal to the body to initiate muscle remodeling and metabolic recovery.
Key Facts
- The “Golden Hour”: SF1 neurons in the hypothalamus spring into action for approximately one hour after exercise ends, signaling the body to start the recovery and adaptation process.
- Brain-Muscle Connection: When researchers silenced these neurons, mice showed zero endurance gains and their muscles failed to undergo the gene expression changes required for remodeling.
- The Endurance Boost: Artificially stimulating these neurons after moderate exercise allowed mice to gain more endurance than usual, reaching higher speeds and longer distances.
- Neuroplasticity through Sweat: Each exercise session strengthens the connections between these SF1 neurons; mice that exercised regularly had twice as many neural connections in this circuit as sedentary mice.
- Future Therapeutics: This circuit could eventually be targeted to mimic or enhance the benefits of exercise for older adults or those with mobility issues who cannot perform intense physical activity.
Source: Jackson Laboratory
When you finish a run, your muscles may feel like they did all the work. But researchers at The Jackson Laboratory (JAX) and the University of Pennsylvania (UPenn) have discovered that what happens in your brain after a run may determine whether you gain endurance over time.
Specialized neurons in the brain’s hypothalamus spring into action after a bout of exercise, the team reported in Neuron.
Without the activity of these neurons, mice fail to show endurance gains, no matter how hard they sprint on a treadmill. And when the researchers artificially activated the neurons after exercise, the animals gained even more endurance than usual.
“The idea that muscle remodeling requires the output of these brain neurons is a pretty big surprise,” said Erik Bloss, associate professor at JAX and a co-senior author of the new work. “It really challenges conventional thinking about how exercise works.”
Scientists have long known that exercise has long-term effects on the brain, boosting cognition and strengthening connections between neurons. Bloss, in collaboration with J. Nicholas Betley of UPenn, wanted to know the more immediate effects of exercise in the brain.
The researchers tracked the activity of hypothalamus cells in the brains of mice during and after running. That let them home in on a particular cluster of neurons that express a protein called steroidogenic factor-1 (SF1) and become active for about an hour after mice finish running.
“The fact that these neurons are most active post-run was quite intriguing,” said Bloss. “It suggested that they play a role in signaling the body to start the recovery process.”
As mice trained over weeks, more and more SF1 neurons became activated after each exercise session. Experiments conducted at JAX showed that the connections between the SF1 neurons also became stronger and more numerous with each run. Animals that exercised had about twice as many connections between these neurons as animals that did not.
To test whether these neurons impacted the animals’ ability to gain endurance, Bloss and Betley’s groups used optogenetics—a technique that allows precise control of specific neurons using light. When they turned off the SF1 neurons for 15 minutes after each training session, mice stopped improving their endurance, despite following the same rigorous daily running regimen for three weeks.
Using other modes of silencing, the muscles of exercising mice failed to show the changes in gene expression that usually follow exercise and are required to remodel muscle tissue with endurance gains.
At the same time, the animals began to fare worse on voluntary run tests.
“If you give a normal mouse access to a running wheel, they will run kilometers at a time,” said Bloss. “When we silence these neurons, they effectively don’t run at all. They hop on briefly but can’t sustain it.”
In a complementary experiment, the team stimulated SF1 neurons for an hour after treadmill sessions. Mice receiving this post-exercise boost showed enhanced endurance gains compared to control animals, running longer distances and reaching higher maximum speeds by the end of the training period.
The findings challenge the traditional view that exercise benefits come solely from muscles adapting over time. Instead, they suggest the brain acts as a master coordinator, orchestrating metabolic changes and muscle remodeling throughout the body. This discovery could eventually lead to strategies to enhance or mimic the effects of physical activity or help people build endurance.
“There’s the very real possibility that we can eventually take advantage of this circuit to boost the effects of moderate exercise,” said Bloss.
“If we can mimic or enhance exercise-like patterns in the brain, that could be particularly valuable for older adults or people with mobility limitations who can’t engage in intensive physical activity but could still benefit from exercise’s protective effects on the brain and body.”
Other authors include Lauren Lepeak of JAX.
Key Questions Answered:
A: Not quite, but your brain determines if your physical effort pays off. If these SF1 neurons don’t fire after your workout, your muscles won’t receive the “instruction manual” they need to grow stronger and more efficient.
A: The hypothalamus is the body’s control center for survival. It needs to know that you just expended significant energy so it can coordinate metabolic changes across your entire body, ensuring you’re better prepared (i.e., more “fit”) for the next challenge.
A: Researchers are hopeful. By understanding how the brain “signals” fitness gains, scientists might be able to develop treatments that trigger these same neural pathways, helping people with physical disabilities reap the cardiovascular and metabolic rewards of exercise.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this neuroscience and exercise research news
Author: Roberto Molar
Source: Jackson Laboratory
Contact: Roberto Molar – Jackson Laboratory
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Exercise-induced activation of ventromedial hypothalamic steroidogenic factor-1 neurons mediates improvements in endurance” by Morgan Kindel, Ryan J. Post, Kyle Grose, Louise Lantier, Eunsang Hwang, Jamie R.E. Carty, Lenka Dohnalová, Lauren Lepeak, Hallie C. Kern, Rachael Villari, Nitsan Goldstein, Emily Lo, Albert Yeung, Lukas Richie, Bridget Skelly, Jenna Golub, Manmeet Rai, Teppei Fujikawa, Julio E. Ayala, Joel K. Elmquist, Christoph A. Thaiss, David H. Wasserman, Kevin W. Williams, Erik B. Bloss, and J. Nicholas Betley. Neuron
DOI:10.1016/j.neuron.2025.12.033
Abstract
Exercise-induced activation of ventromedial hypothalamic steroidogenic factor-1 neurons mediates improvements in endurance
Repeated exercise produces robust physiological benefits and is the leading lifestyle intervention for human health. The benefits from exercise training result from the remodeling of skeletomuscular, cardiovascular, metabolic, and endocrine systems.
In mice, we find that activation of the central nervous system following exercise is essential for subsequent endurance performance and metabolism benefits. Ventromedial hypothalamic steroidogenic factor-1 (SF1) neurons are activated following exercise, and repeated training results in increased post-exercise SF1 neuron activation.
Exercise training increases the intrinsic excitability and density of excitatory synapses on SF1 neurons, suggesting that exercise history is encoded through hypothalamic plasticity.
Inhibition of SF1 neuron output blocks endurance gains and metabolic improvements that result from exercise training. Conversely, stimulation of SF1 neurons following exercise enhances gains in endurance.
These results demonstrate that exercise-induced hypothalamic SF1 neuron activity is essential for the coordination of physiological improvements following exercise training.
