Cholinergic modulation enables scalable action selection learning in a computational model of the striatum

The striatum plays a central role in action selection and reinforcement learning, integrating cortical inputs with dopaminergic signals encoding reward prediction errors. While dopamine modulates synaptic plasticity underlying value learning, the mechanisms that enable selective reinforcement of behaviorally relevant stimulus-action associations-the structural credit assignment problem-remain poorly understood, especially in environments with multiple competing stimuli and actions. Here, we present a computational model in which acetylcholine (ACh), released by striatal cholinergic interneurons, acts as a channel-specific gating signal that restricts plasticity to brief temporal windows following action execution. The model implements a biologically plausible three-factor learning rule requiring presynaptic activity, postsynaptic depolarization, and phasic dopamine, with plasticity gated by cholinergic pauses that temporally align with behaviorally relevant events. This mechanism ensures that only synapses involved in the selected behavior are eligible for modification. Through systematic evaluation across tasks with distractors and contingency reversals, we show that ACh-gated learning promotes synaptic specificity, suppresses cross-channel interference, and yields increasingly competitive performance relative to Q-learning in complex tasks, reflecting the scalability of the proposed learning mechanism. Moreover, the model reveals distinct roles for striatal pathways: direct pathway (D1) neurons maintain stimulus-specific responses, while indirect pathway (D2) neurons are progressively recruited to suppress outdated associations during policy adaptation. These findings provide a mechanistic account of how coordinated cholinergic and dopaminergic signaling can support scalable and efficient reinforcement learning in the striatum, consistent with experimental observations of pathway-specific plasticity.

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Publication Details

Journal
Scientific Reports
Published
2025-10-07
DOI
https://doi.org/10.1038/s41598-025-18776-3
Primary Topic
Neural dynamics and brain function
Type
article
Field-Weighted Citation Impact
0.00

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article

Cholinergic modulation enables scalable action selection learning in a computational model of the striatum

Jesús A. Garrido, Sten Grillner, Álvaro González-Redondo, Jeanette Hellgren Kotaleski et al.
Scientific Reports
Neural dynamics and brain function
article

Cholinergic modulation enables scalable action selection learning in a computational model of the striatum

Jesús A. Garrido, Sten Grillner, Álvaro González-Redondo, Jeanette Hellgren Kotaleski, Eduardo Ros
article en

Abstract

The striatum plays a central role in action selection and reinforcement learning, integrating cortical inputs with dopaminergic signals encoding reward prediction errors. While dopamine modulates synaptic plasticity underlying value learning, the mechanisms that enable selective reinforcement of behaviorally relevant stimulus-action associations-the structural credit assignment problem-remain poorly understood, especially in environments with multiple competing stimuli and actions. Here, we present a computational model in which acetylcholine (ACh), released by striatal cholinergic interneurons, acts as a channel-specific gating signal that restricts plasticity to brief temporal windows following action execution. The model implements a biologically plausible three-factor learning rule requiring presynaptic activity, postsynaptic depolarization, and phasic dopamine, with plasticity gated by cholinergic pauses that temporally align with behaviorally relevant events. This mechanism ensures that only synapses involved in the selected behavior are eligible for modification. Through systematic evaluation across tasks with distractors and contingency reversals, we show that ACh-gated learning promotes synaptic specificity, suppresses cross-channel interference, and yields increasingly competitive performance relative to Q-learning in complex tasks, reflecting the scalability of the proposed learning mechanism. Moreover, the model reveals distinct roles for striatal pathways: direct pathway (D1) neurons maintain stimulus-specific responses, while indirect pathway (D2) neurons are progressively recruited to suppress outdated associations during policy adaptation. These findings provide a mechanistic account of how coordinated cholinergic and dopaminergic signaling can support scalable and efficient reinforcement learning in the striatum, consistent with experimental observations of pathway-specific plasticity.

Scientific ReportsVol. 15(1)
Universidad de Granada (ES), Science for Life Laboratory (SE), Karolinska Institutet (SE), KTH Royal Institute of Technology (SE)
Swedish e-Science Research Centre, European Commission, Vetenskapsrådet, Universidad de Granada, Horizon 2020 Framework Programme, HORIZON EUROPE Framework Programme, Agencia Estatal de Investigación
Openalex Percentile: Top 72%
Neural dynamics and brain function
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