Neural correlates and determinants of approach-avoidance conflict in the prelimbic prefrontal cortex

  1. Jose A Fernandez-Leon
  2. Douglas S Engelke
  3. Guillermo Aquino-Miranda
  4. Alexandria Goodson
  5. Maria N Rasheed
  6. Fabricio H Do Monte  Is a corresponding author
  1. CIFICEN (UNCPBA-CONICET-CICPBA), Argentina
  2. The University of Texas Health Science Center at Houston, United States
  3. Rice University, United States

Abstract

The recollection of environmental cues associated with threat or reward allows animals to select the most appropriate behavioral responses. Neurons in the prelimbic cortex (PL) respond to both threat- and reward-associated cues. However, it remains unknown whether PL regulates threat-avoidance vs. reward-approaching responses when an animals' decision depends on previously associated memories. Using a conflict model in which male Long-Evans rats retrieve memories of shock- and food-paired cues, we observed two distinct phenotypes during conflict: i) rats that continued to press a lever for food (Pressers); and ii) rats that exhibited a complete suppression in food seeking (Non-pressers). Single-unit recordings revealed that increased risk-taking behavior in Pressers is associated with persistent food-cue responses in PL, and reduced spontaneous activity in PL glutamatergic (PLGLUT) neurons during conflict. Activating PLGLUT neurons in Pressers attenuated food-seeking responses in a neutral context, whereas inhibiting PLGLUT neurons in Non-pressers reduced defensive responses and increased food approaching during conflict. Our results establish a causal role for PLGLUT neurons in mediating individual variability in memory-based risky decision making by regulating threat-avoidance vs. reward-approach behaviors.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting file; Source Data files have been provided for all main figures and and supplementary data. We also have included detailed statistical analises supplementary table availale.

Article and author information

Author details

  1. Jose A Fernandez-Leon

    CIFICEN (UNCPBA-CONICET-CICPBA), Buenos Aires, Argentina
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7166-9738
  2. Douglas S Engelke

    Department of Neurobiology and Anatomy, The University of Texas Health Science Center at Houston, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Guillermo Aquino-Miranda

    Department of Neurobiology and Anatomy, The University of Texas Health Science Center at Houston, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6185-4112
  4. Alexandria Goodson

    Rice University, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Maria N Rasheed

    Department of Neurobiology and Anatomy, The University of Texas Health Science Center at Houston, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Fabricio H Do Monte

    Department of Neurobiology and Anatomy, The University of Texas Health Science Center at Houston, Houston, United States
    For correspondence
    fabricio.h.domonte@uth.tmc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1079-0064

Funding

NIH Blueprint for Neuroscience Research (MH120136-01A1)

  • Douglas S Engelke
  • Guillermo Aquino-Miranda
  • Fabricio H Do Monte

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 Center for Laboratory Animal Medicine and Care of The University of Texas Health Science Center at Houston. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (AWC-19-0103). The National Institutes of Health guidelines for the care and use of laboratory animals were strictly followed to minimize any potential discomfort and suffering of the animals.

Reviewing Editor

  1. Mihaela D Iordanova, Concordia University, Canada

Version history

  1. Preprint posted: May 27, 2021 (view preprint)
  2. Received: October 24, 2021
  3. Accepted: December 13, 2021
  4. Accepted Manuscript published: December 16, 2021 (version 1)
  5. Version of Record published: February 17, 2022 (version 2)

Copyright

© 2021, Fernandez-Leon 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. Jose A Fernandez-Leon
  2. Douglas S Engelke
  3. Guillermo Aquino-Miranda
  4. Alexandria Goodson
  5. Maria N Rasheed
  6. Fabricio H Do Monte
(2021)
Neural correlates and determinants of approach-avoidance conflict in the prelimbic prefrontal cortex
eLife 10:e74950.
https://doi.org/10.7554/eLife.74950

Share this article

https://doi.org/10.7554/eLife.74950

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