Nucleus accumbens acetylcholine dips track reward value and temporal costs to shape delay discounting

As an organism chooses between competing rewards, it must often integrate learned reward value with the changing costs associated with obtaining them. Yet, the brain mechanisms through which these factors jointly guide choice are not well understood. Previous studies have shown that dopamine signals in the nucleus accumbens (NAc) track reward value and are modulated by their associated delay costs. Our prior work further implicated NAc cholinergic interneurons by demonstrating that dopamine D2 receptors in these neurons influence choice under temporal, but not probabilistic, costs. However, whether NAc acetylcholine (ACh) dynamics track reward value and/or delay, and whether they contribute to adaptive choice, remains unknown. Using in vivo fiber photometry during a delay discounting task in which mice choose between a small, immediate reward and a larger, delayed reward, we reveal that cue-evoked ACh dips dynamically track relative reward magnitude and are diminished by increasing delays. Our data further show that optogenetically enhancing these dips attenuates the delay-dependent decline in choice of the larger, delayed reward. These findings identify a previously unrecognized role for NAc cue-evoked ACh dips in shaping adaptive choice as temporal costs increase.

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Publication Details

Journal
bioRxiv (Cold Spring Harbor Laboratory)
Published
2026-11-02
DOI
https://doi.org/10.64898/2026.10.30.760841
Primary Topic
Neurotransmitter Receptor Influence on Behavior
Type
preprint
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preprint

Nucleus accumbens acetylcholine dips track reward value and temporal costs to shape delay discounting

Eduardo F. Gallo, Julianna Cavallaro, Dustin R. Zuelke, Ruby Setara et al.
bioRxiv (Cold Spring Harbor Laboratory)
Neurotransmitter Receptor Influence on Behavior
preprint

Nucleus accumbens acetylcholine dips track reward value and temporal costs to shape delay discounting

Eduardo F. Gallo, Julianna Cavallaro, Dustin R. Zuelke, Ruby Setara, Czarina Maysonet, Ronald E. Salazar
preprint en

Abstract

As an organism chooses between competing rewards, it must often integrate learned reward value with the changing costs associated with obtaining them. Yet, the brain mechanisms through which these factors jointly guide choice are not well understood. Previous studies have shown that dopamine signals in the nucleus accumbens (NAc) track reward value and are modulated by their associated delay costs. Our prior work further implicated NAc cholinergic interneurons by demonstrating that dopamine D2 receptors in these neurons influence choice under temporal, but not probabilistic, costs. However, whether NAc acetylcholine (ACh) dynamics track reward value and/or delay, and whether they contribute to adaptive choice, remains unknown. Using in vivo fiber photometry during a delay discounting task in which mice choose between a small, immediate reward and a larger, delayed reward, we reveal that cue-evoked ACh dips dynamically track relative reward magnitude and are diminished by increasing delays. Our data further show that optogenetically enhancing these dips attenuates the delay-dependent decline in choice of the larger, delayed reward. These findings identify a previously unrecognized role for NAc cue-evoked ACh dips in shaping adaptive choice as temporal costs increase.

bioRxiv (Cold Spring Harbor Laboratory)
Fordham University (US)
Neurotransmitter Receptor Influence on Behavior
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