1. Neuroscience

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

  1. Evan Wicker
  2. Janita Turchi
  3. Ludise Malkova
  4. Patrick Alexander Forcelli  Is a corresponding author
  1. Georgetown University, United States
  2. National Institutes of Health, United States
https://doi.org/10.7554/eLife.37325
Share this article
Cite this article
  1. Evan Wicker
  2. Janita Turchi
  3. Ludise Malkova
  4. Patrick Alexander Forcelli
(2018)
Mediodorsal thalamus is required for discrete phases of goal-directed behavior in macaques
eLife 7:e37325.
https://doi.org/10.7554/eLife.37325
  2. Download BibTeX
  3. Download .RIS

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

  1. Evan Wicker

    Department of Pharmacology and Physiology, Georgetown University, Washington, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. 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.

  3. Ludise Malkova

    Department of Pharmacology and Physiology, Georgetown University, Washington, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. 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.
    ORCID icon "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.

Reviewing Editor

  1. Geoffrey Schoenbaum, National Institute on Drug Abuse, National Institutes of Health, United States

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).

Version history

  1. Received: April 6, 2018
  2. Accepted: May 31, 2018
  3. Accepted Manuscript published: May 31, 2018 (version 1)
  4. Version of Record published: June 20, 2018 (version 2)

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.

Metrics

  • 1,564
    Page views
  • 241
    Downloads
  • 13
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Evan Wicker
  2. Janita Turchi
  3. Ludise Malkova
  4. Patrick Alexander Forcelli
(2018)
Mediodorsal thalamus is required for discrete phases of goal-directed behavior in macaques
eLife 7:e37325.
https://doi.org/10.7554/eLife.37325

Share this article

https://doi.org/10.7554/eLife.37325

Categories and tags

Research organism

Further reading

    1. Neuroscience

    Disruption of awake sharp-wave ripples does not affect memorization of locations in repeated-acquisition spatial memory tasks

    Lies Deceuninck, Fabian Kloosterman
    Research Article Updated

    Storing and accessing memories is required to successfully perform day-to-day tasks, for example for engaging in a meaningful conversation. Previous studies in both rodents and primates have correlated hippocampal cellular activity with behavioral expression of memory. A key role has been attributed to awake hippocampal replay – a sequential reactivation of neurons representing a trajectory through space. However, it is unclear if awake replay impacts immediate future behavior, gradually creates and stabilizes long-term memories over a long period of time (hours and longer), or enables the temporary memorization of relevant events at an intermediate time scale (seconds to minutes). In this study, we aimed to address the uncertainty around the timeframe of impact of awake replay by collecting causal evidence from behaving rats. We detected and disrupted sharp wave ripples (SWRs) - signatures of putative replay events - using electrical stimulation of the ventral hippocampal commissure in rats that were trained on three different spatial memory tasks. In each task, rats were required to memorize a new set of locations in each trial or each daily session. Interestingly, the rats performed equally well with or without SWR disruptions. These data suggest that awake SWRs - and potentially replay - does not affect the immediate behavior nor the temporary memorization of relevant events at a short timescale that are required to successfully perform the spatial tasks. Based on these results, we hypothesize that the impact of awake replay on memory and behavior is long-term and cumulative over time.

    1. Neuroscience

    Exposure Therapy: Enhancing fear extinction

    Sydney Trask, Nicole C Ferrara
    Insight

    Gradually reducing a source of fear during extinction treatments may weaken negative memories in the long term.

    1. Cell Biology
    2. Neuroscience

    Tissue-specific O-GlcNAcylation profiling identifies substrates in translational machinery in Drosophila mushroom body contributing to olfactory learning

    Haibin Yu, Dandan Liu ... Kai Yuan
    Research Article

    O-GlcNAcylation is a dynamic post-translational modification that diversifies the proteome. Its dysregulation is associated with neurological disorders that impair cognitive function, and yet identification of phenotype-relevant candidate substrates in a brain-region specific manner remains unfeasible. By combining an O-GlcNAc binding activity derived from Clostridium perfringens OGA (CpOGA) with TurboID proximity labeling in Drosophila, we developed an O-GlcNAcylation profiling tool that translates O-GlcNAc modification into biotin conjugation for tissue-specific candidate substrates enrichment. We mapped the O-GlcNAc interactome in major brain regions of Drosophila and found that components of the translational machinery, particularly ribosomal subunits, were abundantly O-GlcNAcylated in the mushroom body of Drosophila brain. Hypo-O-GlcNAcylation induced by ectopic expression of active CpOGA in the mushroom body decreased local translational activity, leading to olfactory learning deficits that could be rescued by dMyc overexpression-induced increase of protein synthesis. Our study provides a useful tool for future dissection of tissue-specific functions of O-GlcNAcylation in Drosophila, and suggests a possibility that O-GlcNAcylation impacts cognitive function via regulating regional translational activity in the brain.