Dorsal tegmental dopamine neurons gate associative learning of fear

Nat Neurosci. 2018 Jul;21(7):952-962. doi: 10.1038/s41593-018-0174-5. Epub 2018 Jun 27.


Functional neuroanatomy of Pavlovian fear has identified neuronal circuits and synapses associating conditioned stimuli with aversive events. Hebbian plasticity within these networks requires additional reinforcement to store particularly salient experiences into long-term memory. Here we have identified a circuit that reciprocally connects the ventral periaqueductal gray and dorsal raphe region with the central amygdala and that gates fear learning. We found that ventral periaqueductal gray and dorsal raphe dopaminergic (vPdRD) neurons encode a positive prediction error in response to unpredicted shocks and may reshape intra-amygdala connectivity via a dopamine-dependent form of long-term potentiation. Negative feedback from the central amygdala to vPdRD neurons might limit reinforcement to events that have not been predicted. These findings add a new module to the midbrain dopaminergic circuit architecture underlying associative reinforcement learning and identify vPdRD neurons as a critical component of Pavlovian fear conditioning. We propose that dysregulation of vPdRD neuronal activity may contribute to fear-related psychiatric disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Association Learning / physiology*
  • Behavior, Animal / physiology
  • Conditioning, Classical / physiology
  • Dopaminergic Neurons / physiology*
  • Fear / physiology*
  • Long-Term Potentiation / physiology
  • Male
  • Mice
  • Neural Pathways / physiology
  • Periaqueductal Gray / cytology
  • Periaqueductal Gray / physiology
  • Tegmentum Mesencephali / cytology
  • Tegmentum Mesencephali / physiology*