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A role for the cerebellum in motor-triggered alleviation of anxiety

Research group De Zeeuw
Publication year 2024
Published in Neuron
Authors 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. Here, we explore a hypothalamo-cerebello-amygdalar circuit that may mediate motor-dependent alleviation of anxiety. This three-neuron loop, in which the cerebellar dentate nucleus takes center stage, bridges the motor system with the emotional system. Subjecting animals to a constant rotarod engages glutamatergic cerebellar dentate neurons that drive PKCδ+ amygdalar neurons to elicit an anxiolytic effect. Moreover, challenging animals on an accelerated rather than a constant rotarod engages hypothalamic neurons that provide a superimposed anxiolytic effect via an orexinergic projection to the dentate neurons that activate the amygdala. Our findings reveal a cerebello-limbic pathway that may contribute to motor-triggered alleviation of anxiety and that may be optimally exploited during challenging physical exercise.

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