• Xin-Yi Wang, Hong-Quan Zhang, Kun Tong, Jie Han, Xin-Yu Zhao, Yu-Tong Song, Jing-Ru Hao, Nan Sun, and Can Gao.
• NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu 221004, China.
• Neuroscience. 2024 Mar 16; 541: 142214-22.

AbstractInnate defensive behavior is important for animal survival. The Vglut2+ neurons in the ventral tegmental area (VTA) have been demonstrated to play important roles in innate defensive behaviors, but the neural circuit mechanism is still unclear. Here, we find that VTA - zona incerta (ZI) glutamatergic projection is involved in regulating innate fear responses. Combining calcium signal recording and chemogentics, we find that VTA-Vglut2+ neurons respond to foot shock stimulus. Inhibition of VTA-Vglut2+ neurons reduces foot shock-evoked freezing, while chemogentic activation of these neurons results in an enhanced fear response. Using viral tracing and immunofluorescence, we show that VTA - Vglut2+ neurons send direct excitatory outputs to the ZI. Moreover, we find that the activity of VTAVglut2 - ZI projection is pivotal in modulating fear response. Together, our study reveals a new VTA - ZI glutamatergic circuit in mediating innate fear response and provides a potential target for treating post-traumatic stress disorder.Copyright © 2024 IBRO. Published by Elsevier Inc. All rights reserved.

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