Cognitive representations of intracranial self-stimulation of midbrain dopamine neurons depend on stimulation frequency

Nat Neurosci. 2024 Jul;27(7):1253-1259. doi: 10.1038/s41593-024-01643-1. Epub 2024 May 13.


Dopamine neurons in the ventral tegmental area support intracranial self-stimulation (ICSS), yet the cognitive representations underlying this phenomenon remain unclear. Here, 20-Hz stimulation of dopamine neurons, which approximates a physiologically relevant prediction error, was not sufficient to support ICSS beyond a continuously reinforced schedule and did not endow cues with a general or specific value. However, 50-Hz stimulation of dopamine neurons was sufficient to drive robust ICSS and was represented as a specific reward to motivate behavior. The frequency dependence of this effect is due to the rate (not the number) of action potentials produced by dopamine neurons, which differently modulates dopamine release downstream.

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Cognition / physiology
  • Dopamine / metabolism
  • Dopaminergic Neurons* / physiology
  • Electric Stimulation / methods
  • Macaca mulatta
  • Male
  • Mesencephalon / physiology
  • Reward*
  • Self Stimulation* / physiology
  • Ventral Tegmental Area* / physiology


  • Dopamine