Aging impairs perceptual decision-making in mice: integrating computational and neurobiological approaches

Brain Struct Funct. 2020 Jul;225(6):1889-1902. doi: 10.1007/s00429-020-02101-x. Epub 2020 Jun 22.

Abstract

Decision-making is one of the cognitive domains which has been under-investigated in animal models of cognitive aging along with its neurobiological correlates. This study investigated the latent variables of the decision process using the hierarchical drift-diffusion model (HDDM). Neurobiological correlates of these processes were examined via immunohistochemistry. Young (n = 11, 4 months old), adult (n = 10, 10 months old), and old (n = 10, 18 months old) mice were tested in a perceptual decision-making task (i.e. two-alternative forced-choice; 2AFC). Observed data showed that there was an age-dependent decrease in the accuracy rate of old mice while response times were comparable between age groups. HDDM results revealed that age-dependent accuracy difference was a result of a decrease in the quality of evidence integration during decision-making. Significant positive correlations observed between evidence integration rate and the number of tyrosine hydroxylase positive (TH+) neurons in the ventral tegmental area (VTA) and axon terminals in dorsomedial striatum (DMS) suggest that decrease in the quality of evidence integration in aging is related to decreased function of mesocortical and nigrostriatal dopamine.

Keywords: Cognitive aging; Decision-making; Dopamine; Hierarchical drift–diffusion model; Mice; Two-alternative forced-choice task.

MeSH terms

  • Animals
  • Brain / physiology*
  • Cholinergic Neurons / physiology
  • Cognitive Aging / physiology*
  • Cognitive Aging / psychology*
  • Corpus Striatum / physiology
  • Decision Making / physiology*
  • Dopaminergic Neurons / physiology*
  • Male
  • Mice, Inbred C57BL
  • Models, Neurological
  • Pars Compacta / physiology
  • Septal Nuclei / physiology
  • Tyrosine 3-Monooxygenase / metabolism
  • Ventral Tegmental Area / physiology
  • Visual Perception / physiology*

Substances

  • Tyrosine 3-Monooxygenase