Dual and plasticity-dependent regulation of cerebello-zona incerta circuits on anxiety-like behaviors

Abstract Clinical observation has identified cerebellar cognitive affective syndrome, which is characterized by various non-motor dysfunctions such as social disorders and anxiety. Increasing evidence has revealed reciprocal mono-/poly-synaptic connections of cerebello-cerebral circuits, forming the...

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Main Authors: Yue Zhao, Jin-Tao Wu, Jia-Bin Feng, Xin-Yu Cai, Xin-Tai Wang, Luxi Wang, Wei Xie, Yan Gu, Jun Liu, Wei Chen, Lin Zhou, Ying Shen
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-58727-0
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Summary:Abstract Clinical observation has identified cerebellar cognitive affective syndrome, which is characterized by various non-motor dysfunctions such as social disorders and anxiety. Increasing evidence has revealed reciprocal mono-/poly-synaptic connections of cerebello-cerebral circuits, forming the concept of the cerebellar connectome. In this study, we demonstrate that neurons in the cerebellar nuclei (CN) of male mice project to a subset of zona incerta (ZI) neurons through long-range glutamatergic and GABAergic transmissions, both capable of encoding acute stress. Furthermore, activating or inhibiting glutamatergic and GABAergic transmissions in the CN → ZI pathway can positively or negatively regulate anxiety and place preference through presynaptic plasticity-dependent mechanisms, as well as mediate motor-induced alleviation of anxiety. Our data support the close relationship between the cerebellum and emotional processes and suggest that targeting cerebellar outputs may be an effective approach for treating anxiety.
ISSN:2041-1723