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Hippocampal output suppresses orbitofrontal cortex schema cell formation

Wenhui Zong, Ph.D.

Study author Wenhui Zong, Ph.D.

Hot Off the Press – August 21, 2025

Published in Nature Neuroscience by  Wenhui Zong and Geoffrey Schoenbaum, et al. of the NIDA IRP Behavioral Neurophysiology Neuroscience Section.

Summary

The orbitofrontal cortex (OFC) and hippocampus (HC) are both thought to contribute to the construction of cognitive maps and their generalization into schemas, yet the nature of their interaction remains uncertain. Some accounts propose a serial model, in which the OFC relies on HC-derived task representations to extract key behavioral features. Others argue for a parallel model, where both regions independently generate representations emphasizing different types of information. In this study, we directly tested these competing frameworks by examining how schema-related activity in rat OFC was altered when HC output was disrupted—specifically through inactivation of the ventral subiculum—after learning and during transfer to new problems. We found that post-learning inactivation left the prevalence and content of schema correlates in OFC unchanged, whereas inactivation during transfer accelerated their emergence. These findings support the view that the OFC and HC function in parallel, each contributing distinct features to the construction of cognitive maps and schemas.

Publication Information

Zong, Wenhui; Zhou, Jingfeng; Gardner, Matthew P H; Zhang, Zhewei; Costa, Kauê Machado; Schoenbaum, Geoffrey

Hippocampal output suppresses orbitofrontal cortex schema cell formation Journal Article

In: Nat Neurosci, vol. 28, no. 5, pp. 1048–1060, 2025, ISSN: 1546-1726.

Abstract | Links

@article{pmid40229506,
title = {Hippocampal output suppresses orbitofrontal cortex schema cell formation},
author = {Wenhui Zong and Jingfeng Zhou and Matthew P H Gardner and Zhewei Zhang and Kauê Machado Costa and Geoffrey Schoenbaum},
url = {https://pubmed.ncbi.nlm.nih.gov/40229506/},
doi = {10.1038/s41593-025-01928-z},
issn = {1546-1726},
year = {2025},
date = {2025-05-01},
urldate = {2025-05-01},
journal = {Nat Neurosci},
volume = {28},
number = {5},
pages = {1048--1060},
abstract = {Both the orbitofrontal cortex (OFC) and the hippocampus (HC) are implicated in the formation of cognitive maps and their generalization into schemas. However, how these areas interact in supporting this function remains unclear, with some proposals supporting a serial model in which the OFC draws on task representations created by the HC to extract key behavioral features and others suggesting a parallel model in which both regions construct representations that highlight different types of information. In the present study, we tested between these two models by asking how schema correlates in rat OFC would be affected by inactivating the output of the HC, after learning and during transfer across problems. We found that the prevalence and content of schema correlates were unaffected by inactivating one major HC output area, the ventral subiculum, after learning, whereas inactivation during transfer accelerated their formation. These results favor the proposal that the OFC and HC operate in parallel to extract different features defining cognitive maps and schemas.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

Close

Both the orbitofrontal cortex (OFC) and the hippocampus (HC) are implicated in the formation of cognitive maps and their generalization into schemas. However, how these areas interact in supporting this function remains unclear, with some proposals supporting a serial model in which the OFC draws on task representations created by the HC to extract key behavioral features and others suggesting a parallel model in which both regions construct representations that highlight different types of information. In the present study, we tested between these two models by asking how schema correlates in rat OFC would be affected by inactivating the output of the HC, after learning and during transfer across problems. We found that the prevalence and content of schema correlates were unaffected by inactivating one major HC output area, the ventral subiculum, after learning, whereas inactivation during transfer accelerated their formation. These results favor the proposal that the OFC and HC operate in parallel to extract different features defining cognitive maps and schemas.

Close

  • https://pubmed.ncbi.nlm.nih.gov/40229506/
  • doi:10.1038/s41593-025-01928-z

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