Orbitofrontal Circuits Control Multiple Reinforcement-Learning Processes

Neuron. 2019 Aug 21;103(4):734-746.e3. doi: 10.1016/j.neuron.2019.05.042. Epub 2019 Jun 25.


Adaptive decision making in dynamic environments requires multiple reinforcement-learning steps that may be implemented by dissociable neural circuits. Here, we used a novel directionally specific viral ablation approach to investigate the function of several anatomically defined orbitofrontal cortex (OFC) circuits during adaptive, flexible decision making in rats trained on a probabilistic reversal learning task. Ablation of OFC neurons projecting to the nucleus accumbens selectively disrupted performance following a reversal, by disrupting the use of negative outcomes to guide subsequent choices. Ablation of amygdala neurons projecting to the OFC also impaired reversal performance, but due to disruptions in the use of positive outcomes to guide subsequent choices. Ablation of OFC neurons projecting to the amygdala, by contrast, enhanced reversal performance by destabilizing action values. Our data are inconsistent with a unitary function of the OFC in decision making. Rather, distinct OFC-amygdala-striatal circuits mediate distinct components of the action-value updating and maintenance necessary for decision making.

Keywords: amygdala; decision making; nucleus accumbens; orbitofrontal cortex; reinforcement learning.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / physiology
  • Animals
  • Choice Behavior / physiology
  • Diphtheria Toxin / pharmacology
  • Feedback, Physiological
  • Male
  • Models, Neurological
  • Neurons / drug effects
  • Neurons / physiology
  • Nucleus Accumbens / physiology
  • Prefrontal Cortex / physiology*
  • Rats
  • Reinforcement, Psychology*
  • Reversal Learning / physiology*
  • Reward


  • Diphtheria Toxin