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

Nat Neurosci. 2011 Nov 6;14(12):1507-9. doi: 10.1038/nn.2954.


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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / pharmacology
  • Brain-Derived Neurotrophic Factor / therapeutic use
  • Chi-Square Distribution
  • Discrimination Learning / physiology
  • Disease Models, Animal
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Photic Stimulation / methods
  • Prefrontal Cortex* / drug effects
  • Prefrontal Cortex* / injuries
  • Prefrontal Cortex* / physiology
  • Reaction Time / drug effects
  • Reversal Learning / physiology*
  • Stress, Psychological / drug therapy*
  • Stress, Psychological / physiopathology*
  • Swimming / psychology
  • Time Factors


  • Brain-Derived Neurotrophic Factor