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

The recollection of environmental cues associated with threat or reward allows animals to select the most appropriate behavioral responses. Neurons in the prelimbic (PL) cortex 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: (1) rats that continued to press a lever for food (Pressers) and (2) 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.


Sample-size estimation
• You should state whether an appropriate sample size was computed when the study was being designed • You should state the statistical method of sample size computation and any required assumptions • If no explicit power analysis was used, you should describe how you decided what sample (replicate) size (number) to use Please outline where this information can be found within the submission (e.g., sections or figure legends), or explain why this information doesn't apply to your submission:

Replicates
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All data were obtained from at least three cohorts tested at different occasions in the presence of control animals. The results from each cohort were successfully replicated. A small percentage of rats (3 %) were excluded from analysis because they did not pass the bar press criteria conditioning (10 presses/min during the variable interval training).
No further exclusions were made. All the information described above is presented in the Methods section.

Statistical reporting
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Group allocation
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All animals were randomly assigned to experimental or control groups and were tested in a counterbalanced order. Behavioral data was extracted using Anymaze and DeepLabCut software. For data that needed manual counting, all experiments were blinded in which the experimenter did not know the groups during quantification. All the information provided above is described in the methods section.