April 3, 2024 | Xiao-Yang Zhang, Wen-Xia Wu, Li-Ping Shen, ..., Chris I. De Zeeuw, Jian-Jun Wang, Jing-Ning Zhu
The study explores the brain mechanisms by which exercise improves mood, focusing on a hypothalamo-cerebello-amygdalar circuit that bridges the subcortical motor and limbic systems. The cerebellar dentate nucleus (DN) is central to this three-neuron loop, which connects the motor system with the emotional system. The DN projects directly to the centrolateral amygdala (CeL), where it excites PKCδ+ neurons, which are involved in anxiolytic processes. Motor activity, particularly challenging movements like accelerating rotarod running, activates this circuit, leading to reduced anxiety. Additionally, challenging movements recruit orexinergic projections from the perifornical area (PFA) of the hypothalamus to the DN, further enhancing the anxiolytic effects. The study reveals that this hypothalamo-cerebello-amygdalar circuit operates at two levels of intensity, providing a potential mechanism for motor-triggered anxiety alleviation. The findings suggest that optimizing the level of motor challenge can maximize the anxiolytic effects of exercise, and that targeting this circuit may offer new strategies for treating anxiety disorders.The study explores the brain mechanisms by which exercise improves mood, focusing on a hypothalamo-cerebello-amygdalar circuit that bridges the subcortical motor and limbic systems. The cerebellar dentate nucleus (DN) is central to this three-neuron loop, which connects the motor system with the emotional system. The DN projects directly to the centrolateral amygdala (CeL), where it excites PKCδ+ neurons, which are involved in anxiolytic processes. Motor activity, particularly challenging movements like accelerating rotarod running, activates this circuit, leading to reduced anxiety. Additionally, challenging movements recruit orexinergic projections from the perifornical area (PFA) of the hypothalamus to the DN, further enhancing the anxiolytic effects. The study reveals that this hypothalamo-cerebello-amygdalar circuit operates at two levels of intensity, providing a potential mechanism for motor-triggered anxiety alleviation. The findings suggest that optimizing the level of motor challenge can maximize the anxiolytic effects of exercise, and that targeting this circuit may offer new strategies for treating anxiety disorders.