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Image showing the legs of multiple people running in the street. 
Accelerating motor activity reduced anxiety by activating a hypothalamo-cerebello-amygdalar circuit in a chronic stress model. 
©ISTOCK.COM, tibor5

According to a recent survey conducted by the Anxiety and Depression Association of America, 14% of Americans intentionally incorporate exercise into their routines as a proactive strategy to cope with stress.1 Whether it is a leisurely stroll in the park, a brisk run around the block, or lifting weights at the gym, there are many ways to exercise. However, not all exercises affect mood equally. “We find that more challenging exercises will have a better effect on anxiety reduction,” said Jing Ning Zhu, a neuroscientist at Nanjing University.

Numerous studies affirm the protective role of physical exercise against anxiety and depression.2 With this in mind, in a study recently published in Neuron, Zhu’s team studied the neural circuits activated in rats running on a wheel.3 “We wanted to find the brain mechanism responsible for the motor effect on emotions,” Zhu said. Typically in the brain, motor functions follow emotional processing. The amygdala, responsible for assessing experiences through an emotional lens, communicates via neuronal projections with the cerebellum, the center for motor function, to evoke expressions such as tears or a smile.4 However, Zhu’s team found that exercising resulted in movement-derived activation of the amygdala. In normal rats running at a constant speed, neurons projecting from the cerebellum to the amygdala were activated. 

Next, the researchers placed the rats within a maze designed to test anxiety-related behaviors. The maze was elevated off of the ground and shaped like a plus sign, with two arms open on the sides and two enclosed. When positioned in the center of the maze, rats engaged in constant-speed running entered the open arms more frequently than control rats that did not run beforehand, indicating a greater willingness to explore and lower anxiety levels.  

To determine if this exercise effect could be used therapeutically, the researchers studied neuronal activation in a chronic stress model, in which rats display depressive and anxiety-related behaviors such as an inability to feel pleasure, social withdrawal, and reduced exploratory behavior. The researchers discovered that more strenuous exercise—running at an acceleration of 0.2rpm/s on the wheel—enabled the activation of neurons projecting from the cerebellum to the hypothalamus in addition to the neurons projecting to the amygdala. The hypothalamus regulates hormone release, including orexin, a neurohormone known to facilitate stress resilience. 5 In fact, accelerated running increased orexin levels and reduced anxiety-related behaviors more than running at a constant speed. Because the cerebellum links the hypothalamus and the amygdala, the researchers stimulated the cerebellum directly using electrodes and found that higher frequencies of cerebellar stimulation increased neuronal firing and reduced anxiety-related behaviors in these rats. 

We wanted to find the brain mechanism responsible for the motor effect on emotions.  -Jing Ning Zhu, Nanjing University

Because researchers had previously shown the relationship between the cerebellum and amygdala in patients with mood disorders,Zhu’s team also used functional magnetic resonance imaging (fMRI) to study this connection in patients with bipolar disorder, where anxiety is the major comorbidity. fMRI can detect changes in blood flow and oxygenation that occur due to increased oxygen and glucose demand when neurons are active, providing insights into connectivity between brain regions. Using this method, the researchers observed a significant reduction in connectivity between the cerebellum and amygdala for patients with bipolar disorder when compared to healthy controls. 

     Histology cross section of cerebellum tissue stained in pink and viewed under a light microscope.
The cerebellum’s intricate folds are linked to other brain regions, like the amygdala, through neuronal projections.
©ISTOCK.COM, tonaquatic

“This research could lead to better ways of managing anxiety,” said Ben Singh, a sports science researcher at the University of South Australia, who was not involved in this study. To further investigate the anti-anxiety effect of exercising, Zhu’s team is preparing to test exercise therapies on patients and university students who report stress and anxiety. This study suggests that exercise and stimulating the cerebellum could emerge as a novel approach to treating anxiety and mood disorders. 

References

  1. Anxiety and Depression Association of America. Physical Activity Reduces Stress. ADAA. Adaa.org. 2021.
  2. Noakes T, et al. Run for your life. Nature. 2012;487(7407):295-96.
  3. Zhang XY, et al. A role for the cerebellum in motor-triggered alleviation of anxiety. Neuron. 2024;112(7):1165-81.e8.
  4. Taub AH, Mintz M. Amygdala conditioning modulates sensory input to the cerebellum. Neurobiol Learn Mem. 2010;94(4):521-29.
  5. Ji MJ, et al. Orexin prevents depressive-like behavior by promoting stress resilience. Mol Psychiatry. 2018;24(2):282-93.
  6. Phillips JR, et al. The cerebellum and psychiatric disorders. Front Public Health. 2015;3:132123.

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