April 3, 2024 | Xiao-Yang Zhang, Wen-Xia Wu, Li-Ping Shen, Miao-Jin Ji, Peng-Fei Zhao, Lei Yu, Jun Yin, Shu-Tao Xie, Yun-Yong Xie, Yang-Xun Zhang, Hong-Zhao Li, Qi-Peng Zhang, Chao Yan, Fei Wang, Chris I. De Zeeuw, Jian-Jun Wang, Jing-Ning Zhu
Physical exercise is known to reduce anxiety, but the underlying brain mechanisms remain unclear. This study identifies a hypothalamocerebello-amygdalar circuit that mediates motor-dependent alleviation of anxiety. The circuit involves the cerebellar dentate nucleus (DN), which connects the motor system with the emotional system. Motor activity activates this circuit, leading to an anxiolytic effect. Challenging movement recruits orexinergic projections from the hypothalamus to the DN, further enhancing the anxiolytic effect. The study reveals that the cerebello-limbic pathway may contribute to motor-triggered alleviation of anxiety, particularly during challenging physical exercise. The findings suggest that cerebellar DN glutamatergic neurons directly innervate and excite CeL PKCδ⁺ neurons in the amygdala. The study also shows that challenging exercise increases orexin levels in the DN, which may contribute to the anxiolytic effects. The results highlight the role of the cerebellum in motor-triggered anxiety relief and suggest that cerebellar-targeted interventions could be beneficial for anxiety disorders. The study also demonstrates that the cerebello-amygdalar circuit is involved in anxiety alleviation and that the level of motor challenge can be optimized to maximize the anxiolytic effect. The findings provide insights into the neural mechanisms underlying the effects of exercise on anxiety and suggest potential therapeutic strategies for anxiety disorders.Physical exercise is known to reduce anxiety, but the underlying brain mechanisms remain unclear. This study identifies a hypothalamocerebello-amygdalar circuit that mediates motor-dependent alleviation of anxiety. The circuit involves the cerebellar dentate nucleus (DN), which connects the motor system with the emotional system. Motor activity activates this circuit, leading to an anxiolytic effect. Challenging movement recruits orexinergic projections from the hypothalamus to the DN, further enhancing the anxiolytic effect. The study reveals that the cerebello-limbic pathway may contribute to motor-triggered alleviation of anxiety, particularly during challenging physical exercise. The findings suggest that cerebellar DN glutamatergic neurons directly innervate and excite CeL PKCδ⁺ neurons in the amygdala. The study also shows that challenging exercise increases orexin levels in the DN, which may contribute to the anxiolytic effects. The results highlight the role of the cerebellum in motor-triggered anxiety relief and suggest that cerebellar-targeted interventions could be beneficial for anxiety disorders. The study also demonstrates that the cerebello-amygdalar circuit is involved in anxiety alleviation and that the level of motor challenge can be optimized to maximize the anxiolytic effect. The findings provide insights into the neural mechanisms underlying the effects of exercise on anxiety and suggest potential therapeutic strategies for anxiety disorders.