Specialized coding patterns among dorsomedial prefrontal neuronal ensembles predict conditioned reward seeking

Abstract

Non-overlapping cell populations within dorsomedial prefrontal cortex (dmPFC), defined by gene expression or projection target, control dissociable aspects of reward seeking through unique activity patterns. However, even within these defined cell populations considerable cell-to-cell variability is found, suggesting that greater resolution is needed to understand information processing in dmPFC. Here we use two-photon calcium imaging in awake, behaving mice to monitor the activity of dmPFC excitatory neurons throughout Pavlovian reward conditioning. We characterize five unique neuronal ensembles that each encode specialized information related to a sucrose reward, reward-predictive cues, and behavioral responses to those cues. The ensembles differentially emerge across daily training sessions - and stabilize after learning - in a manner that improves the predictive validity of dmPFC activity dynamics for deciphering variables related to behavioral conditioning. Our results characterize the complex dmPFC neuronal ensemble dynamics that stably predict reward availability and initiation of conditioned reward seeking following cue-reward learning.

Data availability

All data generated for this study are available on Dryad Digital Repository, accessible here: https://doi.org/10.5061/dryad.xksn02vg8. We are in the process of uploading raw videos for these data to the Image Data Resource (https://idr.openmicroscopy.org/), as there is a 3 week lead time to get the data uploaded and special considerations are required for datasets of >1TB. Code will be uploaded to GitHub upon publication. All data, code, and raw imaging files will be uploaded to these open-source repositories prior to publication.

The following data sets were generated

Article and author information

Author details

  1. Roger I Grant

    Neuroscience, Medical University of South Carolina, Charleston, SC, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Elizabeth M Doncheck

    Neuroscience, Medical University of South Carolina, Charleston, SC, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Kelsey M Vollmer

    Neuroscience, Medical University of South Carolina, Charleston, SC, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Kion T Winston

    Neuroscience, Medical University of South Carolina, Charleston, SC, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Elizaveta V Romanova

    Neuroscience, Medical University of South Carolina, Charleston, SC, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Preston N Siegler

    Neuroscience, Medical University of South Carolina, Charleston, SC, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Heather Holman

    Neuroscience, Medical University of South Carolina, Charleston, SC, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Christopher W Bowen

    Neuroscience, Medical University of South Carolina, Charleston, SC, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. James M Otis

    Neuroscience, Medical University of South Carolina, Charleston, SC, United States
    For correspondence
    otis@musc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0953-9283

Funding

National Institute of Drug Abuse (R01-DA051650)

  • James M Otis

MUSC Cocaine and Opioid Center on Addiction Pilot Award (P50-DA046374)

  • Roger I Grant

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

Ethics

Animal experimentation: Experiments were performed in the dark phase and in accordance with the NIH Guide for the Care and Use of Laboratory Animals with approval from the Institutional Animal Care and Use Committee at the Medical University of South Carolina (Approval ID: IACUC-2018-00363; Renewed November 30, 2020).

Reviewing Editor

  1. Mario Penzo, National Institute of Mental Health, United States

Publication history

  1. Received: December 15, 2020
  2. Accepted: June 22, 2021
  3. Accepted Manuscript published: June 29, 2021 (version 1)
  4. Version of Record published: July 13, 2021 (version 2)

Copyright

© 2021, Grant 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.

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  1. Roger I Grant
  2. Elizabeth M Doncheck
  3. Kelsey M Vollmer
  4. Kion T Winston
  5. Elizaveta V Romanova
  6. Preston N Siegler
  7. Heather Holman
  8. Christopher W Bowen
  9. James M Otis
(2021)
Specialized coding patterns among dorsomedial prefrontal neuronal ensembles predict conditioned reward seeking
eLife 10:e65764.
https://doi.org/10.7554/eLife.65764

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