1. Neuroscience
Download icon

Persistent coding of outcome-predictive cue features in the rat nucleus accumbens

  1. Jimmie M Gmaz
  2. James E Carmichael
  3. Matthijs AA van der Meer  Is a corresponding author
  1. Dartmouth College, United States
Research Article
  • Cited 4
  • Views 1,395
  • Annotations
Cite this article as: eLife 2018;7:e37275 doi: 10.7554/eLife.37275

Abstract

The nucleus accumbens (NAc) is important for learning from feedback, and for biasing and invigorating behavior in response to cues that predict motivationally relevant outcomes. NAc encodes outcome-related cue features such as the magnitude and identity of reward. However, little is known about how features of cues themselves are encoded. We designed a decision making task where rats learned multiple sets of outcome-predictive cues, and recorded single-unit activity in the NAc during performance. We found that coding of cue identity and location occurred alongside coding of expected outcome. Furthermore, this coding persisted both during a delay period, after the rat made a decision and was waiting for an outcome, and after the outcome was revealed. Encoding of cue features in the NAc may enable contextual modulation of ongoing behavior, and provide an eligibility trace of outcome-predictive stimuli for updating stimulus-outcome associations to inform future behavior.

Article and author information

Author details

  1. Jimmie M Gmaz

    Department of Psychological and Brain Sciences, Dartmouth College, Hanover, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. James E Carmichael

    Department of Psychological and Brain Sciences, Dartmouth College, Hanover, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Matthijs AA van der Meer

    Department of Psychological and Brain Sciences, Dartmouth College, Hanover, United States
    For correspondence
    mvdm@dartmouth.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2206-4473

Funding

Natural Sciences and Engineering Research Council of Canada

  • James E Carmichael

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

Ethics

Animal experimentation: All experimental procedures were approved by the the University of Waterloo Animal Care Committee (protocol# 11-06) and carried out in accordance with Canadian Council for Animal Care (CCAC) guidelines.

Reviewing Editor

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

Publication history

  1. Received: April 5, 2018
  2. Accepted: September 15, 2018
  3. Accepted Manuscript published: September 20, 2018 (version 1)
  4. Version of Record published: October 16, 2018 (version 2)

Copyright

© 2018, Gmaz et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,395
    Page views
  • 235
    Downloads
  • 4
    Citations

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

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)

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

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

Further reading

    1. Neuroscience
    Amy A Worth et al.
    Research Article Updated

    The cytokine, GDF15, is produced in pathological states which cause cellular stress, including cancer. When over expressed, it causes dramatic weight reduction, suggesting a role in disease-related anorexia. Here, we demonstrate that the GDF15 receptor, GFRAL, is located in a subset of cholecystokinin neurons which span the area postrema and the nucleus of the tractus solitarius of the mouse. GDF15 activates GFRALAP/NTS neurons and supports conditioned taste and place aversions, while the anorexia it causes can be blocked by a monoclonal antibody directed at GFRAL or by disrupting CCK neuronal signalling. The cancer-therapeutic drug, cisplatin, induces the release of GDF15 and activates GFRALAP/NTS neurons, as well as causing significant reductions in food intake and body weight in mice. These metabolic effects of cisplatin are abolished by pre-treatment with the GFRAL monoclonal antibody. Our results suggest that GFRAL neutralising antibodies or antagonists may provide a co-treatment opportunity for patients undergoing chemotherapy.

    1. Neuroscience
    Jessica M Jones et al.
    Tools and Resources

    Objective and automatic measurement of pain in mice remains a barrier for discovery in neuroscience. Here we capture paw kinematics during pain behavior in mice with high-speed videography and automated paw tracking with machine and deep learning approaches. Our statistical software platform, PAWS (Pain Assessment at Withdrawal Speeds), uses a univariate projection of paw position over time to automatically quantify seven behavioral features that are combined into a single, univariate pain score. Automated paw tracking combined with PAWS reveals a behaviorally-divergent mouse strain that displays hyper-sensitivity to mechanical stimuli. To demonstrate the efficacy of PAWS for detecting spinally- versus centrally-mediated behavioral responses, we chemogenetically activated nociceptive neurons in the amygdala, which further separated the pain-related behavioral features and the resulting pain score. Taken together, this automated pain quantification approach will increase objectivity in collecting rigorous behavioral data, and it is compatible with other neural circuit dissection tools for determining the mouse pain state.