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Ventral striatal astrocytes contribute to reinforcement learning

Pai, J.; Sogukpinar, F.; Ogasawara, K.; Smith, G. J.; Fiocchi, F. R.; Dai, Y.; Wu, Y.; Frank, M. J.; Ching, S.; Lucantonio, F.; Papouin, T.; Pignatelli, M.; Hiratani, N.; Monosov, I. E.

2026-06-29 neuroscience
10.1101/2025.10.20.683205 bioRxiv
Show abstract

Astrocytes influence synaptic plasticity and neuronal function through astrocytic calcium dynamics (ACD). However, astrocyte contribution to cognitive operations like reinforcement learning (RL) remains unclear. To examine this, we trained mice on a RL dependent probabilistic decision-making task. We attenuated ACD across distinct striatal regions, and found ACD attenuation specifically in ventral striatum (VS) increased decision noisiness and impaired reward-guided choice performance. This effect was largely due to a reduction in win-stay behavior. Using in-vivo calcium imaging, we found that VS ACD correlated with reward prediction errors (RPEs). Furthermore, these trial-by-trial ACD fluctuations predicted trial-by-trial choice variability. In-silico lesions of a biologically constrained circuit model suggest that astrocytes could regulate behavioral variability by sharing RPE signals across populations of striatal neurons. Together, these results suggest that VS astrocytes contribute to cortico-striatal functions to mediate decision noisiness.

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