A causal link between prediction errors, dopamine neurons and learning

Nat Neurosci. 2013 Jul;16(7):966-73. doi: 10.1038/nn.3413. Epub 2013 May 26.


Situations in which rewards are unexpectedly obtained or withheld represent opportunities for new learning. Often, this learning includes identifying cues that predict reward availability. Unexpected rewards strongly activate midbrain dopamine neurons. This phasic signal is proposed to support learning about antecedent cues by signaling discrepancies between actual and expected outcomes, termed a reward prediction error. However, it is unknown whether dopamine neuron prediction error signaling and cue-reward learning are causally linked. To test this hypothesis, we manipulated dopamine neuron activity in rats in two behavioral procedures, associative blocking and extinction, that illustrate the essential function of prediction errors in learning. We observed that optogenetic activation of dopamine neurons concurrent with reward delivery, mimicking a prediction error, was sufficient to cause long-lasting increases in cue-elicited reward-seeking behavior. Our findings establish a causal role for temporally precise dopamine neuron signaling in cue-reward learning, bridging a critical gap between experimental evidence and influential theoretical frameworks.

Publication types

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

MeSH terms

  • Acoustic Stimulation
  • Animals
  • Association Learning / physiology*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Channelrhodopsins
  • Conditioning, Operant / physiology*
  • Cues
  • Dopaminergic Neurons / physiology*
  • Electric Stimulation
  • Estrous Cycle / genetics
  • Extinction, Psychological / physiology
  • Female
  • Food Preferences / physiology
  • Functional Laterality / genetics
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Optogenetics
  • Predictive Value of Tests
  • Rats
  • Rats, Long-Evans
  • Rats, Transgenic
  • Reward
  • Tyrosine 3-Monooxygenase / genetics
  • Tyrosine 3-Monooxygenase / metabolism
  • Ventral Tegmental Area / cytology*


  • Bacterial Proteins
  • Channelrhodopsins
  • Luminescent Proteins
  • yellow fluorescent protein, Bacteria
  • Tyrosine 3-Monooxygenase