Prelimbic cortex ensembles promote appetitive learning-associated behavior

Author:

Surets Michelle,Caban-Murillo Albit,Ramirez Steve

Abstract

Memories of prior rewards bias our actions and future decisions. To determine the neural correlates of an appetitive associative learning task, we trained male mice to discriminate a reward-predicting cue over the course of 7 d. Encoding, recent recall, and remote recall were investigated to determine the areas of the brain recruited at each stage of learning. Using cFos as a proxy for neuronal activity, we found unique brain-wide patterns of activity across days that seem to correlate with distinct stages of learning. In particular, the prelimbic (PL) cortex was significantly recruited during the encoding of a novel association presentation, but its activity decreases as learning continues. To causally dissect the role of the PL in a reward memory across days, we chemogenetically inhibited first the PL entirely and then only tagged memory-bearing cells that were active during encoding in two stages of learning: early and late. Both nonspecific and specific PL inhibition experiments indicate that the PL drives behavior during late stages of learning to facilitate appropriate cue-driven behavior. Overall, our work underscores memory's role in discriminative reward seeking, and points to the PL as a target for modulating disorders in which impaired reward processing is a core component.

Funder

NIH

Air Force Office of Scientific Research

Publisher

Cold Spring Harbor Laboratory

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