Abstract
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.
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Acknowledgements
We thank Shuji Li, Yingying Fang and Ting Guo (Southern Medical University) for technological support. This work was supported by grants from the National Natural Science Foundation of China (grant numbers 82090032 and 31830033 to T.-M.G. and grant numbers 31801007 and 81881240049 to Y-HC), the Program for Changjiang Scholars and Innovative Research Team in University (grant number IRT_16R37 to T-MG), the Key-Area Research and Development Program of Guangdong Province (grant number 2018B030334001 to T-MG), the Guangdong Basic and Applied Basic Research Foundation (grant number 2020A1515011310 to Y-HC), the Guangdong-Hong Kong-Macao Greater Bay Area Centre for Brain Science and Brain-Inspired Intelligence Fund (grant number 2019019 to Y-HC), the Science and Technology Program of Guangzhou (grant number 202007030013, to T-MG) and the China Postdoctoral Science Foundation Grant (grant number 2020m682786 to N-YH).
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T-MG and Y-HC designed the study. Y-HC and N-YH performed all experiments, except electrophysiological recordings with the help of D-YW, J-LW, L-LB, M-LW, J-TL, S-RZ and Y-LS. Z-YL and LH performed all electrophysiological recordings and analysed the electrophysiological data. Y-HC analysed all other data and generated the figures. X-WL provided technical support. T-MG and Y-HC interpreted the results with critical input from J-MY and S-ZZ. T-MG and Y-HC wrote the manuscript.
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Chen, YH., Hu, NY., Wu, DY. et al. PV network plasticity mediated by neuregulin1-ErbB4 signalling controls fear extinction. Mol Psychiatry 27, 896–906 (2022). https://doi.org/10.1038/s41380-021-01355-z
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DOI: https://doi.org/10.1038/s41380-021-01355-z
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