Chen Yi-Hua, Hu Neng-Yuan, Wu Ding-Yu, Bi Lin-Lin, Luo Zheng-Yi, Huang Lang, Wu Jian-Lin, Wang Meng-Ling, Li Jing-Ting, Song Yun-Long, Zhang Sheng-Rong, Jie Wei, Li Xiao-Wen, Zhang Shi-Zhong, Yang Jian-Ming, Gao Tian-Ming
State Key Laboratory of Organ Failure Research, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Centre for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510515, China.
Mol Psychiatry. 2022 Feb;27(2):896-906. doi: 10.1038/s41380-021-01355-z. Epub 2021 Oct 25.
Neuroplasticity in the medial prefrontal cortex (mPFC) is essential for fear extinction, the process of which forms the basis of the general therapeutic process used to treat human fear disorders. However, the underlying molecules and local circuit elements controlling neuronal activity and concomitant induction of plasticity remain unclear. Here we show that sustained plasticity of the parvalbumin (PV) neuronal network in the infralimbic (IL) mPFC is required for fear extinction in adult male mice and identify the involvement of neuregulin 1-ErbB4 signalling in PV network plasticity-mediated fear extinction. Moreover, regulation of fear extinction by basal medial amygdala (BMA)-projecting IL neurons is dependent on PV network configuration. Together, these results uncover the local molecular circuit mechanisms underlying mPFC-mediated top-down control of fear extinction, suggesting alterative therapeutic approaches to treat fear disorders.
内侧前额叶皮质（mPFC）中的神经可塑性对于恐惧消退至关重要，恐惧消退过程构成了用于治疗人类恐惧障碍的一般治疗过程的基础。然而，控制神经元活动和伴随的可塑性诱导的潜在分子和局部电路元件仍不清楚。在这里，我们表明成年雄性小鼠的恐惧消退需要腹内侧前额叶皮质（IL）mPFC中小清蛋白（PV）神经元网络的持续可塑性，并确定神经调节蛋白1-ErbB4信号传导参与PV网络可塑性介导的恐惧消退。此外，投射到基底内侧杏仁核（BMA）的IL神经元对恐惧消退的调节取决于PV网络配置。总之，这些结果揭示了mPFC介导的自上而下控制恐惧消退的局部分子电路机制，为治疗恐惧障碍提供了替代治疗方法。
