Reward Memories Bias Instrumental Rule Selection via the Orbitofrontal-to-Secondary Motor cortex Pathway
- 1University of California, Santa Barbara
Abstract
Reward-predictive cues can influence decision-making and promote the pursuit of specific outcomes. This influence is classically studied using specific Pavlovian-to-instrumental transfer (sPIT), in which Pavlovian cues bias action selection and promote the instrumental action (often a left or right lever press) directed toward the cued outcome. However, naturalistic reward pursuit often extends beyond selecting discrete actions and requires selecting abstract rules that organize multiple actions into goal-directed sequences. The influence of cued reward memories on such rule selection has received less attention, and the neural circuits mediating this effect remains largely unknown. Here, we developed the specific Pavlovian-to-Rules-to-Instrumental Transfer (sPRInT) task, an adaptation of sPIT designed to examine how Pavlovian reward cues bias instrumental rule selection. We then used pathway-specific chemogenetic silencing to test the contribution of orbitofrontal cortex projections to secondary motor cortex (OFC[->]M2) to this effect. Rats expressing hM4Di or mCherry in OFC[->]M2 neurons learned a three-step instrumental sequence (sample lever [->] nosepoke [->] choice lever). In alternating blocks, rats used either a delayed non-match-to-sample rule or a visually guided rule to select the final action in the sequence and earn distinct outcomes (dNMTS-O1; VIS-O2). In a second phase, two distinct auditory cues were established as Pavlovian predictors of the two outcomes (S1-O1; S2-O2). Finally, in nonrewarded probe tests preceded by DCZ injections, we examined how presentation of these Pavlovian cues biased instrumental choices by promoting the use of an abstract rule. In control (mCherry) rats, Pavlovian cues promoted the adoption of the rule corresponding to the cued outcome (S1 promoted dNMTS; S2 promoted the VIS rule). In hM4Di rats, DCZ-mediated inactivation of OFC[->]M2 projection neurons diminished this effect. In contrast, OFC[->]M2 inhibition spared conventional sPIT, in which reward-predictive cues directly biased action selection without requiring abstract rules or extended action sequences. These findings demonstrate that cued reward memories can govern abstract rule selection and identify OFC[->]M2 as a critical circuit for translating those memories into goal-appropriate behavioral strategies.
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BibTeX
@misc{le2026reward,
title = {{Reward Memories Bias Instrumental Rule Selection via the Orbitofrontal-to-Secondary Motor cortex Pathway}},
author = {M. Le and J. Milmoe and L. Nungesser and A. Maheras and R. Keiflin},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.29.748039},
url = {https://www.biorxiv.org/content/10.64898/2026.08.29.748039v1},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - Reward Memories Bias Instrumental Rule Selection via the Orbitofrontal-to-Secondary Motor cortex Pathway
AU - M. Le
AU - J. Milmoe
AU - L. Nungesser
AU - A. Maheras
AU - R. Keiflin
PY - 2026
DA - 2026/08/29
PB - bioRxiv
DO - 10.64898/2026.08.29.748039
UR - https://www.biorxiv.org/content/10.64898/2026.08.29.748039v1
AB - Reward-predictive cues can influence decision-making and promote the pursuit of specific outcomes. This influence is classically studied using specific Pavlovian-to-instrumental transfer (sPIT), in which Pavlovian cues bias action selection and promote the instrumental action (often a left or right lever press) directed toward the cued outcome. However, naturalistic reward pursuit often extends beyond selecting discrete actions and requires selecting abstract rules that organize multiple actions into goal-directed sequences. The influence of cued reward memories on such rule selection has received less attention, and the neural circuits mediating this effect remains largely unknown. Here, we developed the specific Pavlovian-to-Rules-to-Instrumental Transfer (sPRInT) task, an adaptation of sPIT designed to examine how Pavlovian reward cues bias instrumental rule selection. We then used pathway-specific chemogenetic silencing to test the contribution of orbitofrontal cortex projections to secondary motor cortex (OFC[->]M2) to this effect. Rats expressing hM4Di or mCherry in OFC[->]M2 neurons learned a three-step instrumental sequence (sample lever [->] nosepoke [->] choice lever). In alternating blocks, rats used either a delayed non-match-to-sample rule or a visually guided rule to select the final action in the sequence and earn distinct outcomes (dNMTS-O1; VIS-O2). In a second phase, two distinct auditory cues were established as Pavlovian predictors of the two outcomes (S1-O1; S2-O2). Finally, in nonrewarded probe tests preceded by DCZ injections, we examined how presentation of these Pavlovian cues biased instrumental choices by promoting the use of an abstract rule. In control (mCherry) rats, Pavlovian cues promoted the adoption of the rule corresponding to the cued outcome (S1 promoted dNMTS; S2 promoted the VIS rule). In hM4Di rats, DCZ-mediated inactivation of OFC[->]M2 projection neurons diminished this effect. In contrast, OFC[->]M2 inhibition spared conventional sPIT, in which reward-predictive cues directly biased action selection without requiring abstract rules or extended action sequences. These findings demonstrate that cued reward memories can govern abstract rule selection and identify OFC[->]M2 as a critical circuit for translating those memories into goal-appropriate behavioral strategies.
ER -