Partially dissociable roles of the orbitofrontal cortex and dorsal hippocampus in context-dependent hierarchical associations
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Abstract
Reward cues are often ambiguous; what is good in one context is not necessarily good in another. To solve this ambiguity, animals form hierarchical associations in which the context gates the retrieval of appropriate cue-evoked memories. These hierarchical associations regulate cue-elicited behavior and influence subsequent learning, promoting the inference of context-dependency. The orbitofrontal cortex (OFC) and dorsal hippocampus (DH) are both proposed to encode a "cognitive map" encompassing hierarchical, context-dependent associations. However, OFC- and DH-specific contributions to the different functional properties of hierarchical associations remain controversial. Using chemogenetic inactivation in rats, we show that the OFC is essential to both properties of hierarchical associations (performance regulation and learning bias). In contrast, DH's role appears limited to the contextual learning bias conferred by hierarchical associations. This work establishes the OFC as a critical orchestrator of hierarchical associations and provides insights into the extended circuits mediating the functional properties of these associations.
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OFC is critical for contextual knowledge of outcome expectation, which hierarchically regulates performance of already acquired behaviors.
“In addition, it has been reported that the OFC is critical for contextual knowledge of outcome expectation, which hierarchically regulates performance of already acquired behaviors51,52.”
From Dissociable roles of prefrontal plasticity in decision-making strategy and execution of habitual behavior (2026) · cites this paper as [52]
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Asaoka, N., Pagano, D., & Hayashi, Y. (2026) · Nature Communications · doi:10.1038/s41467-026-75706-1
“In addition, it has been reported that the OFC is critical for contextual knowledge of outcome expectation, which hierarchically regulates performanceof already acquired behaviors 51,52 .”
- Authors
- Peterson, S., Chavira, J., Garcia Arango, J. A., Seamans, D., Cimino, E. D., & Keiflin, R.
- Affiliations
- University of California, Santa Barbara (US)
- Corresponding author
- Keiflin, Ronald
- ORCID
- Keiflin, Ronald
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2024-12
- Volume
- 34
- Issue
- 23
- Pages
- 5532-5545.e3
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W4404533963
- Cited by
- 7
- References
- 70
- Citations by year
- 2026: 5 · 2025: 1 · 2024: 1
- FWCI
- 1.70
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Current Biology (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- University of California Santa Barbara
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- orbitofrontal cortex, dorsal hippocampus, contextual memory, chemogenetic inactivation, performance regulation, cognitive maps, memory retrieval
- MeSH terms
- Animals, Cues, Hippocampus, Learning, Male, Reward, Prefrontal Cortex, Rats, Long-Evans, Rats
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