Dopamine neurons projecting to the posterior striatum reinforce avoidance of threatening stimuli

Nat Neurosci. 2018 Oct;21(10):1421-1430. doi: 10.1038/s41593-018-0222-1. Epub 2018 Sep 3.

Abstract

Midbrain dopamine neurons are well known for their role in reward-based reinforcement learning. We found that the activity of dopamine axons in the posterior tail of the striatum (TS) scaled with the novelty and intensity of external stimuli, but did not encode reward value. We demonstrated that the ablation of TS-projecting dopamine neurons specifically inhibited avoidance of novel or high-intensity stimuli without affecting animals' initial avoidance responses, suggesting a role in reinforcement rather than simply in avoidance itself. Furthermore, we found that animals avoided optogenetic activation of dopamine axons in TS during a choice task and that this stimulation could partially reinstate avoidance of a familiar object. These results suggest that TS-projecting dopamine neurons reinforce avoidance of threatening stimuli. More generally, our results indicate that there are at least two axes of reinforcement learning using dopamine in the striatum: one based on value and one based on external threat.

Publication types

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

MeSH terms

  • Animals
  • Avoidance Learning / physiology*
  • Benzazepines / pharmacology
  • Brain / cytology
  • Brain / drug effects
  • Brain / physiology
  • Channelrhodopsins / genetics
  • Channelrhodopsins / metabolism
  • Corpus Striatum / cytology*
  • Cyclic Nucleotide Phosphodiesterases, Type 1 / genetics
  • Cyclic Nucleotide Phosphodiesterases, Type 1 / metabolism
  • Dopamine Agents / pharmacology
  • Dopamine Plasma Membrane Transport Proteins / genetics
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / physiology*
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neural Pathways / physiology*
  • Oxidopamine / pharmacology
  • Protein Binding / drug effects
  • Recognition, Psychology / drug effects
  • Reinforcement, Psychology*
  • Vesicular Glutamate Transport Protein 2 / genetics
  • Vesicular Glutamate Transport Protein 2 / metabolism

Substances

  • Benzazepines
  • Channelrhodopsins
  • Dopamine Agents
  • Dopamine Plasma Membrane Transport Proteins
  • Luminescent Proteins
  • SCH 23390
  • Slc17a6 protein, mouse
  • Slc6a3 protein, mouse
  • Vesicular Glutamate Transport Protein 2
  • Oxidopamine
  • Cyclic Nucleotide Phosphodiesterases, Type 1