Primate Nigrostriatal Dopamine System Regulates Saccadic Response Inhibition

Neuron. 2018 Dec 19;100(6):1513-1526.e4. doi: 10.1016/j.neuron.2018.10.025. Epub 2018 Nov 8.

Abstract

Animals need to inhibit inappropriate actions that would lead to unwanted outcomes. Although this ability, called response inhibition, is impaired in neurological/psychiatric disorders with dopaminergic dysfunctions, how dopamine regulates response inhibition remains unclear. Here we investigated neuronal signals of the nigrostriatal dopamine system in monkeys performing a saccadic countermanding task. Subsets of dopamine neurons in the substantia nigra and striatal neurons receiving the dopaminergic input were activated when the monkey was required to cancel a planned saccadic eye movement. These activations were stronger when canceling the eye movements was successful compared with failed and were enhanced in demanding trials. The activated dopamine neurons were distributed mainly in the dorsolateral, but not in the ventromedial, part of the nigra. Furthermore, pharmacological blockade of dopaminergic neurotransmission in the striatum dampened the performance of canceling saccadic eye movements. The present findings indicate that disruption of nigrostriatal dopamine signaling causes impairments in response inhibition.

Keywords: basal ganglia; caudate nucleus; dopamine neurons; inhibitory control; primates; response inhibition; substantia nigra pars compacta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Benzazepines / pharmacology
  • Corpus Striatum / physiology*
  • Dopamine Antagonists / pharmacology
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / physiology*
  • Functional Laterality
  • Haloperidol / pharmacology
  • Macaca mulatta
  • Male
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology*
  • ROC Curve
  • Reaction Time / drug effects
  • Saccades / drug effects
  • Saccades / physiology*
  • Signal Detection, Psychological / drug effects
  • Signal Detection, Psychological / physiology*
  • Substantia Nigra / physiology*

Substances

  • Benzazepines
  • Dopamine Antagonists
  • SCH 23390
  • Haloperidol