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

TY - JOUR

T1 - A role for the cerebellum in motor-triggered alleviation of anxiety

AU - Zhang, Xiao-Yang

AU - Wu, Wen-Xia

AU - Shen, Li-Ping

AU - Ji, Miao-Jin

AU - Zhao, Peng-Fei

AU - Yu, Lei

AU - Yin, Jun

AU - Xie, Shu-Tao

AU - Xie, Yun-Yong

AU - Zhang, Yang-Xun

AU - Li, Hong-Zhao

AU - Zhang, Qi-Peng

AU - Yan, Chao

AU - Wang, Fei

AU - De Zeeuw, Chris I

AU - Wang, Jian-Jun

AU - Zhu, Jing-Ning

N1 - Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2024/1/23

Y1 - 2024/1/23

N2 - 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.

AB - 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.

U2 - 10.1016/j.neuron.2024.01.007

DO - 10.1016/j.neuron.2024.01.007

M3 - Article

C2 - 38301648

SN - 0896-6273

VL - 112

SP - 1165-1181.e8

JO - Neuron

JF - Neuron

ER -