Prefrontal cortical circuits in anxiety and fear: an overview

Abstract

Pathological anxiety is among the most difficult neuropsychiatric diseases to treat pharmacologically, and it represents a major societal problem. Studies have implicated structural changes within the prefrontal cortex (PFC) and functional changes in the communication of the PFC with distal brain structures in anxiety disorders. Treatments that affect the activity of the PFC, including cognitive therapies and transcranial magnetic stimulation, reverse anxiety- and fear-associated circuit abnormalities through mechanisms that remain largely unclear. While the subjective experience of a rodent cannot be precisely determined, rodent models hold great promise in dissecting well-conserved circuits. Newly developed genetic and viral tools and optogenetic and chemogenetic techniques have revealed the intricacies of neural circuits underlying anxiety and fear by allowing direct examination of hypotheses drawn from existing psychological concepts. This review focuses on studies that have used these circuit-based approaches to gain a more detailed, more comprehensive, and more integrated view on how the PFC governs anxiety and fear and orchestrates adaptive defensive behaviors to hopefully provide a roadmap for the future development of therapies for pathological anxiety.

Keywords

prefrontal cortex / anxiety / fear / neural circuits / optogenetics / DREADD

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Acknowledgements

This work was supported by grants from the National Key R&D Program of China (No. 2021ZD0202704 to Tianming Gao, No. 2022ZD0214300 to Yihua Chen), the National Natural Science Foundation of China (Nos. 82090032 and 31830033 to Tianming Gao); the Key Area Research and Development Program of Guangdong Province (Nos. 2018B030334001 and 2018B030340001 to Tianming Gao); the Guangdong Basic and Applied Basic Research Foundation (No. 2020A1515011310 to Yihua Chen); the Guangdong−Hong Kong−Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence Fund (No. 2019019 to Yihua Chen); and the Science and Technology Program of Guangzhou (No. 202007030013 to Tianming Gao).

Compliance with ethics guidelines

Yihua Chen, Nengyuan Hu, Jianming Yang, and Tianming Gao declare that they have no conflicts of interest. This manuscript is a review article and does not involved a research protocol requiring approval from relevant institutional review board or ethics committee.

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