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

July 2025

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.