Summary: Exercise does more than just build muscle; it fundamentally rewires the brain to boost physical stamina. Researchers have discovered that the lasting gains in endurance from repeated physical activity are driven by a specific group of nerve cells in the ventromedial hypothalamus (VMH).
These neurons, known as SF1 neurons, become hyperactive during workouts and remain active for hours afterward to coordinate how the body uses energy and glucose. This neural “afterburn” is essential for physical adaptation; without this sustained brain activity, the heart and muscles fail to become stronger, regardless of how much physical effort is exerted.
Key Facts
- The Endurance Switch: A specific group of nerve cells (SF1 neurons) must remain active for at least an hour after exercise for the body to realize any long-term endurance benefits.
- Brain-Driven Recovery: If these neurons are silenced specifically during the post-exercise recovery window, the body shows zero improvement in stamina, even if the workout itself was performed perfectly.
- Efficiency Gains: Repeated training increases the number of active SF1 neurons, which helps the heart, lungs, and muscles adapt more quickly by optimizing glucose metabolism.
Source: Cell Press
Exercise does more than strengthen muscles; it also rewires the brain.
In a study publishing February 12 in the Cell Press journal Neuron, researchers reveal that the lasting gain in endurance from repeated exercise—such as the ability to run farther and faster over time—involves changes in brain activity that help muscles and hearts to become stronger.
“A lot of people say they feel sharper and their minds are clearer after exercise,” says corresponding author J. Nicholas Betley of the University of Pennsylvania. “So we wanted to understand what happens in the brain after exercise and how those changes influence the effects of exercise.”
In their experiments, Betley and his colleagues noticed that mice had increased brain activity after running on the treadmill, especially in the nerve cells located in their ventromedial hypothalamus (VMH). This brain region plays an important role in how the body uses energy, including regulating body weight and blood sugar.
By monitoring neural activity in mice, the team found that a specific group of nerve cells in the VMH, called steroidogenic factor-1 (SF1) neurons, became active when the animals ran on a treadmill. These neurons also stayed active for at least an hour after the mice finished running.
After daily exercise for two weeks, these mice showed improvement in endurance. They were able to run faster and longer before becoming exhausted. When researchers looked at the mice’s brains, they saw that more SF1 neurons in mice became active, and the activity levels were significantly higher than at the beginning of training.
When the team blocked SF1 neuron activity and prevented them from sending signals to the rest of the brain, these animals got tired quickly and showed no improvements in endurance over the two-week training period.
To the researchers’ surprise, blocking SF1 neurons only after exercise also prevented endurance gains even though the neurons functioned normally during exercise itself. This result suggests the important role for SF1 activity after exercise.
“When we lift weights, we think we are just building muscle,” says Betley. “It turns out we might be building up our brain when we exercise.”
While the underlying mechanism remains unclear, Betley says that active SF1 neurons post-exercise may help the body recover faster by using glucose stored in the body more efficiently. This may allow other parts of the body—like the muscle, lungs, and heart—to adapt more quickly to harder workouts.
Betley hopes that this research could one day help older people or people recovering from stroke stay active while also benefiting athletes and younger people recovering from injury.
“This study opens the door for understanding how we can get more out of exercise,” he says. “If we can shorten the timeline and help people see benefits sooner, it may encourage them to keep exercising.”
Funding: This work was supported by the University of Pennsylvania, the National Institutes of Health, the National Science Foundation, the National Research Foundation of Korea, the Rhode Island Institutional Development Award, the Rhode Island Foundation, and Providence College.
Key Questions Answered:
A: Yes. That “sharp” feeling many experience after exercise corresponds with a surge of activity in the ventromedial hypothalamus. This research suggests that while you are training your body, you are simultaneously training your brain to manage energy more efficiently.
A: It may come down to how the brain responds after the workout is over. Because the SF1 neurons must stay active post-exercise to trigger muscle and heart adaptations, individuals with more responsive neural circuits may “lock in” their fitness gains more effectively than others.
A: That is the ultimate goal. By understanding how these neurons shorten the timeline for physical adaptation, scientists hope to develop ways to help stroke victims, the elderly, or injured athletes see the benefits of movement much sooner.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this exercise and neuroplasticity research news
Author: Julia Grimmett
Source: Cell Press
Contact: Julia Grimmett – Cell Press
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Exercise induced activation of VMH SF1 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, J. Nicholas Betley. Neuron
DOI:10.1016/j.neuron.2025.12.033
Abstract
Exercise induced activation of VMH SF1 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.
