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Prefrontal cortical circuits in anxiety and fear: an overview

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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.

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  1. State Key Laboratory of Organ Failure Research, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center 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

    Yihua Chen, Nengyuan Hu, Jianming Yang & Tianming Gao

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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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Chen, Y., Hu, N., Yang, J. et al. Prefrontal cortical circuits in anxiety and fear: an overview. Front. Med. 16, 518–539 (2022). https://doi.org/10.1007/s11684-022-0941-2

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