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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月8日

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  • 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

摘要

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.