Mediodorsal thalamus is required for discrete phases of goal-directed behavior in macaques

Abstract
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Abstract

Reward contingencies are dynamic: outcomes that were valued at one point may subsequently lose value. Action selection in the face of dynamic reward associations requires several cognitive processes: registering a change in value of the primary reinforcer, adjusting the value of secondary reinforcers to reflect the new value of the primary reinforcer, and guiding action selection to optimal choices. Flexible responding has been evaluated extensively using reinforcer devaluation tasks. Performance on this task relies upon amygdala, Areas 11 and 13 of orbitofrontal cortex (OFC), and mediodorsal thalamus (MD). Differential contributions of amygdala and Areas 11 and 13 of OFC to specific sub-processes have been established, but the role of MD in these sub-processes is unknown. Pharmacological inactivation of the macaque MD during specific phases of this task revealed that MD is required for reward valuation and action selection. This profile is unique, differing from both amygdala and subregions of the OFC.

Data availability

The data generated and analyzed during this study are all presented in the manuscript. Raw data for object selection during the testing sessions are shown in Supplemental File 1a and d

Article and author information

Author details

Evan Wicker

Department of Pharmacology and Physiology, Georgetown University, Washington, United States

Competing interests
The authors declare that no competing interests exist.
Janita Turchi

Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health, Bethesda, United States

Competing interests
The authors declare that no competing interests exist.
Ludise Malkova

Department of Pharmacology and Physiology, Georgetown University, Washington, United States

Competing interests
The authors declare that no competing interests exist.
Patrick Alexander Forcelli

Department of Pharmacology and Physiology, Georgetown University, Washington, United States

For correspondence
paf22@georgetown.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-1763-060X

Funding

National Center for Advancing Translational Sciences (KL2TR001432)

Patrick Alexander Forcelli

National Institute of Mental Health (R01MH099505)

Ludise Malkova

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: The study was conducted under a protocol approved by the Georgetown University Animal Care and Use Committee (#2016-1115) and in accordance with the Guide for Care and Use of Laboratory Animals (26).

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.