Projections from the ventral tegmental area to zona incerta regulate fear generalization in a mouse model of PTSD

IF 3.5 3区医学 Q2 NEUROSCIENCES Brain Research Bulletin Pub Date : 2024-09-11 DOI:10.1016/j.brainresbull.2024.111079

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Abstract

Generalized fear is a maladaptive behavior in which non-threatening stimuli elicit a fearful response. The ventral tegmental area (VTA) has been demonstrated to play important roles in fear response and fear memory generalization, but the precious neural circuit mechanism is still unclear. Here, we demonstrated that VTA-zona incerta (ZI) glutamatergic projection is involved in regulating high-intensity threatening training induced generalization and anxiety. Combining calcium signal recording and chemogentics, our work reveals that VTA glutamatergic neurons respond to closed arm entering in the model of PTSD. Inhibition of VTA glutamatergic neurons or the glutamatergic projection to ZI could both relieve fear generalization and anxiety. Together, our study proves the VTA - ZI glutamatergic circuit is involved in mediating fear generalization and anxiety, and provides a potential target for treating post-traumatic stress disorder.

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在创伤后应激障碍小鼠模型中，从腹侧被盖区向内侧区的投射调节恐惧泛化

泛化恐惧是一种适应不良行为，即非威胁性刺激引起恐惧反应。腹侧被盖区（VTA）已被证实在恐惧反应和恐惧记忆泛化中发挥重要作用，但其重要的神经回路机制仍不清楚。在这里，我们证明了VTA-zona incerta（ZI）谷氨酸能投射参与调节高强度威胁训练诱导的泛化和焦虑。结合钙信号记录和化学效应，我们的研究揭示了在创伤后应激障碍模型中，VTA 谷氨酸能神经元对手臂闭合进入有反应。抑制VTA谷氨酸能神经元或谷氨酸能投射到ZI都能缓解恐惧泛化和焦虑。总之，我们的研究证明了VTA-ZI谷氨酸能回路参与介导恐惧泛化和焦虑，并为治疗创伤后应激障碍提供了一个潜在的靶点。

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来源期刊

Brain Research Bulletin 医学-神经科学

CiteScore

6.90

自引率

2.60%

发文量

253

审稿时长

67 days

期刊介绍： The Brain Research Bulletin (BRB) aims to publish novel work that advances our knowledge of molecular and cellular mechanisms that underlie neural network properties associated with behavior, cognition and other brain functions during neurodevelopment and in the adult. Although clinical research is out of the Journal''s scope, the BRB also aims to publish translation research that provides insight into biological mechanisms and processes associated with neurodegeneration mechanisms, neurological diseases and neuropsychiatric disorders. The Journal is especially interested in research using novel methodologies, such as optogenetics, multielectrode array recordings and life imaging in wild-type and genetically-modified animal models, with the goal to advance our understanding of how neurons, glia and networks function in vivo.