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

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.

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Acknowledgements

This research was supported by a grant from the Scientific and Technological Research Council of Turkey (TÜBİTAK; research grant 114K991) to FB and AK, and partially by a grant from the Turkish Academy of Sciences (GEBİP-2015 award) to FB. TÜBİTAK supported EG through the National Scholarship Program for Ph.D. students (BİDEB 2211E). We thank Dr. Murat Kasap and Dr. Gürler Akpınar for their support throughout this study. The authors gratefully acknowledge the use of the services and facilities of the Koç University Research Center for Translational Medicine (KUTTAM), funded by the Presidency of Turkey, Presidency of Strategy and Budget. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Presidency of Strategy and Budget.

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EG: conceptualization, methodology, software, investigation, formal analysis, writing—original draft, writing—review and editing, visualization. YAD: software, investigation. ET: software, formal analysis, writing—original draft, visualization. SA: investigation, formal analysis, visualization. AK: conceptualization, methodology, formal analysis, writing—review and editing, visualization, funding acquisition. FB: conceptualization, methodology, software, investigation, formal analysis, writing—original draft, writing—review and editing, visualization, supervision, project administration, funding acquisition.

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Correspondence to Fuat Balcı.

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All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted (Koç University Animal Research Local Ethics Committee. Protocol number: 2014-13).

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This study is a part of Ezgi Gür’s Ph.D. thesis.

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Gür, E., Duyan, Y.A., Türkakın, E. et al. Aging impairs perceptual decision-making in mice: integrating computational and neurobiological approaches. Brain Struct Funct 225, 1889–1902 (2020). https://doi.org/10.1007/s00429-020-02101-x

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Keywords

  • Decision-making
  • Cognitive aging
  • Two-alternative forced-choice task
  • Hierarchical drift–diffusion model
  • Dopamine
  • Mice