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Paradoxical reversal learning enhancement by stress or prefrontal cortical damage: rescue with BDNF

Nature Neuroscience volume 14, pages 1507–1509 (2011)Cite this article

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Abstract

Stress affects various forms of cognition. We found that moderate stress enhanced late reversal learning in a mouse touchscreen-based choice task. Ventromedial prefrontal cortex (vmPFC) lesions mimicked the effect of stress, whereas orbitofrontal and dorsolateral striatal lesions impaired reversal. Stress facilitation of reversal was prevented by BDNF infusion into the vmPFC. These findings suggest a mechanism by which stress-induced vmPFC dysfunction disinhibits learning by alternate (for example, striatal) systems.

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Figure 1: Stress facilitates late reversal.
Figure 2: vmPFC lesions mimic stress facilitation of reversal.
Figure 3: vmPFC BDNF infusions rescue stress-induced facilitation of reversal.

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Acknowledgements

We thank Y. Shaham, G. Quirk and G. Schoenbaum for valuable discussions. This work was supported by the National Institute on Alcohol Abuse and Alcoholism Intramural Research Program (Z01-AA000411).

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Authors and Affiliations

  1. Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, US National Institutes of Health, Bethesda, Maryland, USA

    Carolyn Graybeal, Michael Feyder, Emily Schulman, Jonathan L Brigman & Andrew Holmes

  2. Department of Experimental Psychology, Medical Research Council and Wellcome Trust Behavioral and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK

    Lisa M Saksida & Timothy J Bussey

Authors
  1. Carolyn Graybeal
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  2. Michael Feyder
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  3. Emily Schulman
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  4. Lisa M Saksida
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  5. Timothy J Bussey
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  6. Jonathan L Brigman
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  7. Andrew Holmes
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Contributions

C.G. and A.H. designed the study. T.J.B. and L.M.S. provided behavioral software. C.G., M.F., E.S. and J.L.B. performed experiments and analyzed data. A.H., T.J.B. and C.G. wrote the manuscript.

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Correspondence to Andrew Holmes.

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The authors declare no competing financial interests.

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Graybeal, C., Feyder, M., Schulman, E. et al. Paradoxical reversal learning enhancement by stress or prefrontal cortical damage: rescue with BDNF. Nat Neurosci 14, 1507–1509 (2011). https://doi.org/10.1038/nn.2954

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