Ventral striatal astrocytes contribute to reinforcement learning

Astrocytes influence synaptic plasticity and neuronal function through astrocytic calcium dynamics (ACD). However, astrocytes 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, finding that ACD attenuation specifically in ventral striatum (VS) increased decision noisiness and impaired reward-guided choice. 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. Finally, ex-vivo slice electrophysiology and computational modeling revealed two mechanisms through which astrocytes could regulate behavioral variability: by regulating presynaptic excitatory-inhibitory balance, and 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.