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

Sophie T. Yount, Dan C. Li, Kathryn M. Stachowicz, Esther H. Seo, Kristopher A. Knight, Aryanna Wiggins-Gamble, Aylet T. Allen and Shannon L. Gourley ()
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Sophie T. Yount: Emory University
Dan C. Li: Emory University
Kathryn M. Stachowicz: Emory University
Esther H. Seo: Emory University
Kristopher A. Knight: Emory University
Aryanna Wiggins-Gamble: Emory University
Aylet T. Allen: Emory University
Shannon L. Gourley: Emory University

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-63542-8

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