PV network plasticity mediated by neuregulin1-ErbB4 signalling controls fear extinction

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 concomit...

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Bibliographic Details
Published in:Molecular psychiatry 2022-02, Vol.27 (2), p.896-906
Main Authors: 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
Format: Article
Language:English
Subjects:
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Amygdala
Animals
Behavioral Sciences
Biological Psychology
ErbB-2 protein
Extinction behavior
Extinction, Psychological - physiology
Fear & phobias
Fear - physiology
Fear conditioning
Laboratories
Male
Medicine
Medicine & Public Health
Mice
Neuregulin
Neuregulin 1
Neuronal Plasticity - physiology
Neuroplasticity
Neurosciences
Parvalbumin
Parvalbumins
Pharmacotherapy
Prefrontal cortex
Prefrontal Cortex - physiology
Psychiatry
Receptor, ErbB-4
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Summary: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.
ISSN:1359-4184
1476-5578
DOI:10.1038/s41380-021-01355-z