Prelimbic cortex ensembles promote appetitive learning-associated behavior

Learning & Memory · 3 authors, 3 centres

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TL;DR

Male mice were trained in a 7-day appetitive associative learning task pairing a light cue with sucrose reward, and whole-brain cFos mapping combined with chemogenetic inhibition revealed that the prelimbic cortex is recruited during encoding and drives cue-directed behavior during late stages of learning.

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Male mice underwent a 7-day appetitive associative learning paradigm in which a light cue predicted sucrose water availability, assessed via nose-poke discrimination. Whole-brain cFos mapping at encoding (R1), recent recall (R2), and remote recall (R7) revealed distinct brain-wide activity patterns across learning stages, with the prelimbic (PL) cortex significantly recruited during encoding but decreasing in activity over days. A two-way mixed ANOVA showed a significant main effect of light on poking behavior, F(1,46) = 69.34, P < 0.0001, with a significant light-by-day interaction, F(3,46) = 3.466, P = 0.0236. Chemogenetic inhibition of the PL, both nonspecifically and specifically in memory-bearing tagged cells, indicated that the PL drives behavior during late stages of learning to facilitate appropriate cue-driven behavior. The findings point to the PL as a potential target for modulating disorders involving impaired reward processing.

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other

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preclinical research

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ORIGINAL PAPER

PMC10903945

Prelimbic cortex ensembles promote appetitive learning-associated behavior

Learning & Memory

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ABSTRACT

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.

CITATION EXPORT

Michelle Surets, Albit Caban-Murillo, Steve Ramirez. Prelimbic cortex ensembles promote appetitive learning-associated behavior. Learning & Memory. (2024). https://doi.org/10.1101/lm.053892.123

AUTHORS

3 · 3 CENTRES

Michelle Surets, Albit Caban-Murillo, Steve Ramirez

1Psychological and Brain Sciences, Boston University, Boston, Massachusetts 02215, USA
2Boston University School of Medicine, Boston University, Boston, Massachusetts 02215, USA
3Graduate Program for Neuroscience, Boston University, Boston, Massachusetts 02215, USA