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bioRxiv · 10.1101/2025.05.26.656228

The influence of nucleus accumbens shell D1 and D2 neurons on outcome-specific Pavlovian instrumental transfer

Soegyono, O.·Pepin, E.·Leung, B. K.·Chieng, B.·Balleine, B. W.·Laurent, V.
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Abstract

The nucleus accumbens shell (NAc-S) and its projections to the ventral pallidum (VP) are thought to be critical for stimulus-based decisions. The NAc-S is predominantly composed of spiny projection neurons (SPNs) that express either the dopamine D1 (D1-SPNs) or the dopamine D2 receptor (D2-SPNs). Yet, the role of these two neuronal subpopulations and their inputs to the VP in stimulus-based decisions remains unknown. Here, we used optogenetics in female and male knock-in rats to selectively silence D1-or D2-SPNs and their projections to the VP at a time when the rats were required to use predictive stimuli to choose between two instrumental actions. Silencing either population of NAc-S SPNs disrupted choice. Silencing NAc-S D1-SPNs terminals in the VP also disrupted choice. However, choice was left intact by silencing NAc-S D2-SPNs terminals in the VP. Together, these findings provide novel insights into the cellular mechanisms and circuitry underlying stimulus-based decisions. We discuss how these insights are consistent with a recent model proposing that these decisions are controlled by an opioid-based memory system residing in the NAc-S.

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Soegyono, O., Pepin, E., Leung, B. K., Chieng, B., Balleine, B. W., Laurent, V.. 2025-05-27. The influence of nucleus accumbens shell D1 and D2 neurons on outcome-specific Pavlovian instrumental transfer. https://doi.org/10.1101/2025.05.26.656228

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