Physical training improves endurance through adaptations in the muscles and the cardiovascular and immune systems, but a new study indicates that the brain controls these changes. Scientists found that activation of a particular group of neurons in the ventromedial hypothalamus immediately after exercise is essential for increasing physical endurance in mice. Published in the journal Neuron, the study changes traditional views of exercise physiology: structural changes in the brain do more than reflect peripheral adaptations; they initiate them.
SF1 neurons in the ventromedial hypothalamus
The ventromedial hypothalamus is a region deep within the brain that controls energy expenditure, feeding behaviour and blood sugar levels. It contains a population of neurons that express the protein steroidogenic factor-1 (SF1). Because these cells regulate metabolism, the researchers hypothesised that they might play an active role in the body’s response to the physical stress associated with intense exercise.
Researcher Morgan Kindel of the University of Pennsylvania, Ryan J. Post of Providence College and their colleagues tested whether SF1 neurons respond to exercise. They hypothesised that the brain actively coordinates the metabolic changes that lead to improved endurance. To test this, they conducted a series of experiments in mice, manipulating this small group of cells and assessing the effects on overall physical endurance.
Experiments blocking and stimulating neurons
First, a small group of mice underwent a single bout of treadmill running, after which their brain tissue was analysed. Staining revealed an increase in the number of SF1 neurons expressing the Bdnf gene (which is activated when neurons are excited) and in the total number of transcripts of this gene per cell. This indicated that exercise had stimulated this population of neurons.
To test the effect of blocking these neurons, the researchers introduced a genetic tool into the mice’s brains that produces tetanus toxin, which prevents SF1 neurons from releasing chemical signals. When running on a treadmill at gradually increasing speeds, mice with their SF1 neurons ‘switched off’ reached exhaustion sooner than control mice. Indirect calorimetry (measuring oxygen consumption and carbon dioxide production) revealed that the modified mice burned through their carbohydrate reserves prematurely instead of using fat.
The mice then underwent a three-week treadmill training programme. Control mice gradually increased their running time and maximum distance. Mice with blocked SF1 neurons failed to develop endurance. Analysis of their leg muscles revealed an absence of the genetic changes that usually optimise energy use after regular training—in other words, blocking the brain cells stopped muscle adaptation.
To track neuronal activity in real time, the researchers used miniature head-mounted microscopes that recorded calcium levels (calcium enters neurons when they are excited). Over a week of daily training, they observed a specific subgroup of SF1 neurons that consistently became active immediately after exercise ended. Over time, both the number of these post-exercise neurons and the intensity of their firing increased.
Brain tissue was then collected from mice that had trained for three weeks, and the electrical properties of individual SF1 neurons were measured. Compared with cells from sedentary animals, those from trained mice were more electrically excitable and generated spontaneous action potentials more frequently. High-resolution imaging of dendrites showed that trained mice had twice as many tiny protrusions, known as dendritic spines, indicating a structural adaptation to accommodate more synaptic connections.
Because activity peaked immediately after running, the researchers tested whether post-exercise excitation was the main driver of endurance. Using optogenetics (controlling neurons with light), they suppressed SF1 neurons through fibre-optic implants for exactly 15 minutes immediately after each daily run. This brief suppression reduced the endurance gains that would normally have been achieved. In the final test, they used a different optogenetic approach to stimulate SF1 neurons artificially for an hour immediately after daily exercise. Activation during this recovery period increased endurance gains beyond the usual physiological plateau. Artificial stimulation raised blood sugar levels and overall energy expenditure, which the researchers believe may trigger metabolic recovery signals that prepare the muscles for future exertion.
Limitations and future directions
The experiments were conducted in mice running on treadmills, and rodent metabolism does not fully correspond to human physiology. Endurance adaptation in humans takes longer and involves a wider variety of training types. The findings show that activation of these brain cells is essential for developing endurance in mice, but do not establish exactly how the brain receives the signal that exercise has ended. Identifying the physical pathways that carry signals from fatigued muscles back to the ventromedial hypothalamus remains a goal for future research.
It also remains to be determined whether different types of exercise, such as weightlifting or high-intensity interval training, engage the same neural pathways. Mapping this ‘brain–body’ loop could eventually help in developing therapeutic approaches for people who cannot safely undertake intense physical exercise.
The study ‘Exercise-induced activation of ventromedial hypothalamic steroidogenic factor-1 neurons mediates improvements in endurance’ was published in May 2026. Authors: Morgan Kindel, Ryan J. Post, Kyle Grose, Louise Lantier, Eunsang Hwang, Jamie R. E. Carty, Lenka Dohnalova, Lauren Lipic, Hallie K. Kern, Rachel Villari, Nitzan Goldstein, Emily Lo, Albert Yeung, Lucas Ritchie, Bridget Skelly, Jenna Golub, Manmeet Rai, Teppei Fujikawa, Julio E. Ayala, Joel K. Elmquist, Christoph A. Thaiss, David H. Wasserman, Kevin W. Williams, Eric B. Bloss and J. Nicholas Betley.
Source: PsyPost – Psychology News
