Synergy of Distinct Dopamine Projection Populations in Behavioral Reinforcement

Neuron. 2020 Mar 4;105(5):909-920.e5. doi: 10.1016/j.neuron.2019.11.024. Epub 2019 Dec 23.


Dopamine neurons of the ventral tegmental area (VTA) regulate reward association and motivation. It remains unclear whether there are distinct dopamine populations to mediate these functions. Using mouse genetics, we isolated two populations of dopamine-producing VTA neurons with divergent projections to the nucleus accumbens (NAc) core and shell. Inhibition of VTA-core-projecting neurons disrupted Pavlovian reward learning, and activation of these cells promoted the acquisition of an instrumental response. VTA-shell-projecting neurons did not regulate Pavlovian reward learning and could not facilitate acquisition of an instrumental response, but their activation could drive robust responding in a previously learned instrumental task. Both populations are activated simultaneously by cues, actions, and rewards, and this co-activation is required for robust reinforcement of behavior. Thus, there are functionally distinct dopamine populations in the VTA for promoting motivation and reward association, which operate on the same timescale to optimize behavioral reinforcement.

Keywords: dopamine; heterogenity; learning; motivation; nucleus accumbens; ventral tegmental area.

Publication types

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

MeSH terms

  • Animals
  • Association*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Conditioning, Classical / physiology*
  • Dependovirus
  • Dopaminergic Neurons / cytology
  • Dopaminergic Neurons / metabolism
  • Dopaminergic Neurons / physiology*
  • Genetic Vectors
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Mice
  • Motivation*
  • Neural Pathways / physiology
  • Nucleus Accumbens / cytology
  • Nucleus Accumbens / physiology*
  • Receptors, Neuropeptide / genetics
  • Receptors, Neuropeptide / metabolism
  • Reinforcement, Psychology
  • Reward*
  • Ventral Tegmental Area / cytology
  • Ventral Tegmental Area / physiology*


  • Bacterial Proteins
  • Luminescent Proteins
  • Receptors, Neuropeptide
  • yellow fluorescent protein, Bacteria