Endurance improvements from exercise depend on sustained activation of specific brain neurons after workouts.
Exercise does more than build stronger muscles. It also reshapes activity in the brain. In a study published in the Cell Press journal Neuron, scientists report that the long-term boost in endurance from repeated workouts, such as being able to run farther and faster over time, depends on changes in brain function that support improvements in the heart and muscles.
“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.”
Endurance gains begin in the brain
To investigate, Betley and his team studied mice running on treadmills. After exercise, the animals showed heightened activity in several brain areas, especially in neurons located in the ventromedial hypothalamus (VMH). This region plays a central role in managing how the body uses and stores energy, including control of body weight and blood sugar.
By tracking neural signals in real time, the researchers identified a specific set of VMH neurons known as steroidogenic factor-1 (SF1) neurons that became active during running. Notably, these neurons remained switched on for at least an hour after the mice stopped exercising.
When the mice trained daily for two weeks, their endurance improved. They were able to run longer distances and at higher speeds before tiring. Brain analysis showed that a greater number of SF1 neurons were activated after training, and their overall activity levels were significantly higher than at the start of the program.
The researchers then tested whether these neurons were necessary for building endurance. When they blocked SF1 neurons and prevented them from sending signals to other parts of the brain, the mice fatigued quickly and failed to improve their endurance over the two-week training period.
Post-exercise brain activity drives adaptation
Unexpectedly, shutting down SF1 neurons only after exercise also erased the endurance gains, even though the neurons functioned normally during the workout itself. This finding indicates that what happens in the brain after exercise is critical for long-term physical adaptation.
“When we lift weights, we think we are just building muscle,” says Betley. “It turns out we might be building up our brains when we exercise.”
Although the precise biological steps are still being studied, Betley suggests that active SF1 neurons after exercise may help the body recover more efficiently by improving how stored glucose is used. That improved energy management could allow muscles, lungs, and the heart to adjust more effectively to repeated training.
The team believes these insights could eventually help older adults, stroke survivors, and others with limited mobility remain active, while also supporting athletes and younger individuals 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.”
Reference: “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, 12 February 2026, Neuron.
DOI: 10.1016/j.neuron.2025.12.033
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.
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2 Comments
I’ve never felt sharper or clearer after exercising. Usually I feel exhausted and wish I didn’t have to exercise ever again. Sometimes I actually feel more brain fog and even light headed. Emotionally I feel proud of myself and good about myself because I exercised, but physically I feel crappy, and mentally I feel foggy and drained and off. Quite often I am in more pain, too.
I keep exercising because EVERYTHING that you read/hear/see says it’s a good thing to do for nearly all aspects of health, BUT…is it actually helping me? Sure doesn’t seem like it. With the single exception of my bone density which did improve from osteoporosis to osteopenia in my spine. That has been the ONLY benefit that I have seen from exercising (walking).
It may be that walking does not provide enough stimulation for this effect. My understanding is that these studies were of workouts that involved enough stimulation for an endorphin rush, etc.