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Parallel neuronal structural plasticity with memory trace formation in the orbitofrontal cortex.

Abstract

Flexible decision making is fundamental to day-to-day life. It often requires us to form expectations regarding the consequences of potential actions and to later retrieve those memories to guide choices. We used a task in which mice must develop, remember, and recall novel strategies to obtain rewards. Chemogenetically inactivating neurons within the orbitofrontal cortex (OFC) that are active during memory encoding obstructed later memory retrieval, impeding action flexibility. Meanwhile, stimulating these same neurons induced action flexibility. Thus, OFC neurons form stable memory traces (MTs) that are necessary and sufficient for action flexibility. Long-term storage of action variables may require new experiences to trigger durable cellular changes. Accordingly, MT neurons had higher proportions of mature dendritic spine types than neighboring non-MT neurons, this profile closely associated with successful learning. Further, activity of excitatory neurons and neurotrophin signaling within the basolateral amygdala were necessary for new memory formation and concurrent dendritic spine plasticity on MT neurons in the OFC. Thus, amygdalo-OFC interactions encode new reward information, which is retained by specific structurally-plastic neurons within the OFC and utilized during choice behavior.
© 2025. The Author(s).

Authors

Sophie T Yount, Dan C Li, Kathryn M Stachowicz, Esther H Seo, Kristopher A Knight, Aryanna Wiggins-Gamble, Aylet T Allen, Shannon L Gourley

Graduate Program in Molecular and Systems Pharmacology, Emory University, Atlanta, GA, USA. shannon.l.gourley@emory.edu, Emory National Primate Research Center, Emory University, Atlanta, GA, USA. shannon.l.gourley@emory.edu, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA. shannon.l.gourley@emory.edu, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA. shannon.l.gourley@emory.edu, Graduate Program in Neuroscience, Emory University, Atlanta, GA, USA. shannon.l.gourley@emory.edu, Children's Healthcare of Atlanta, Atlanta, GA, USA. shannon.l.gourley@emory.edu.

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8 products referenced in this paper

(4369542) TaqMan™ Gene Expression Master Mix

a Kit by Thermo Scientific

(003782) B6.Cg-Tg(Thy1-YFP)HJrs/J

an Experimental Model by The Jackson Laboratory

(007914) B6.Cg-Gt(ROSA)26Sor/J

an Experimental Model by The Jackson Laboratory

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Journal Nature Communications

Volume 16

Issue 1

Pages 8521

Publication Date 26 September 2025

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Publication metadata is provided by PubMed®, courtesy of the U.S. National Library of Medicine. Information for this publication was last updated on 2026-05-05 07:35:58 UTC.

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