1. Neuroscience
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Responding to preconditioned cues is devaluation sensitive and requires orbitofrontal cortex during cue-cue learning

  1. Evan E Hart  Is a corresponding author
  2. Melissa J Sharpe
  3. Matthew PH Gardner
  4. Geoffrey Schoenbaum  Is a corresponding author
  1. National Institute on Drug Abuse, National Institutes of Health, United States
  2. University of California, Los Angeles, United States
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Cite this article as: eLife 2020;9:e59998 doi: 10.7554/eLife.59998

Abstract

The orbitofrontal cortex (OFC) is necessary for inferring value in tests of model-based reasoning, including in sensory preconditioning. This involvement could be accounted for by representation of value or by representation of broader associative structure. We recently reported neural correlates of such broader associative structure in OFC during the initial phase of sensory preconditioning (Sadacca et al., 2018). Here, we used optogenetic inhibition of OFC to test whether these correlates might be necessary for value inference during later probe testing. We found that inhibition of OFC during cue-cue learning abolished value inference during the probe test, inference subsequently shown in control rats to be sensitive to devaluation of the expected reward. These results demonstrate that OFC must be online during cue-cue learning, consistent with the argument that the correlates previously observed are not simply downstream readouts of sensory processing and instead contribute to building the associative model supporting later behavior.

Data availability

All data generated are contained within the source data files for Figure 2 and 3

Article and author information

Author details

  1. Evan E Hart

    Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, United States
    For correspondence
    evan.hart@nih.gov
    Competing interests
    No competing interests declared.
  2. Melissa J Sharpe

    University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5375-2076
  3. Matthew PH Gardner

    Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9146-5043
  4. Geoffrey Schoenbaum

    Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, United States
    For correspondence
    geoffrey.schoenbaum@nih.gov
    Competing interests
    Geoffrey Schoenbaum, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8180-0701

Funding

National Institute on Drug Abuse (zia-da000587)

  • Geoffrey Schoenbaum

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Experiments were performed at the National Institute on Drug Abuse Intramural Research Program, in accordance with NIH guidelines, and approved by the IRP animal care and use committee (#18-CNRB-108, A4149-01).

Reviewing Editor

  1. Michael J Frank, Brown University, United States

Publication history

  1. Received: June 15, 2020
  2. Accepted: August 24, 2020
  3. Accepted Manuscript published: August 24, 2020 (version 1)
  4. Version of Record published: September 9, 2020 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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