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Published May 1, 2023 | public
Journal Article

Orchestration of innate and conditioned defensive actions by the periaqueductal gray

Abstract

The midbrain periaqueductal gray (PAG) has been recognized for decades as having a central role in the control of a wide variety of defensive responses. Initial discoveries relied primarily on lesions, electrical stimulation and pharmacology. Recent developments in neural activity imaging and in methods to control activity with anatomical and genetic specificity have revealed additional streams of data informing our understanding of PAG function. Here, we discuss both classic and modern studies reporting on how PAG-centered circuits influence innate as well as learned defensive actions in rodents and humans. Though early discoveries emphasized the PAG's role in rapid induction of innate defensive actions, emerging new data indicate a prominent role for the PAG in more complex processes, including representing behavioral states and influencing fear learning and memory.

Additional Information

© 2023 Elsevier. This work was supported by the National Institute for Mental Health (R00 MH106649 and R01 MH119089) (AA), the Brain and Behavior Research Foundation (Grant # 22663 to AA, and Grants # 27654 and # 31093 to FMCVR), the São Paulo Research Foundation (FAPESP), Research Grant #2014/05432-9 (N.S.C.), and the Hellman Foundation (AA). We thank Judy Genshaft and Steven Greenbaum, and the Brain & Behavior Research Foundation for funding Young Investigator Awards (FMCVR), and Nancy and Jon Glaser Family and the Friends of Semel Scholar Program (FMCVR). Author contributions: FMCVR and AA conceptualized the review. AA and FMCVR wrote the abstract and introduction. FMCVR wrote the innate fear section and conclusion, NSC wrote the learned fear section, and DM wrote the human fear section. None of the authors has relevant financial interests to disclose or a conflict of interest. Data availability: No data was used for the research described in the article.

Additional details

Created:
August 22, 2023
Modified:
October 20, 2023