Neural correlates and determinants of approach-avoidance conflict in the prelimbic prefrontal cortex
- CIFICEN (UNCPBA-CONICET-CICPBA), Argentina
- The University of Texas Health Science Center at Houston, United States
- 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
Jose A Fernandez-Leon
Guillermo Aquino-Miranda
Fabricio H Do Monte
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.
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.
