From Cue to Action: The Spatiotemporal Dynamics of Dopamine During Learning

Abstract

Dopamine plays a central role in learning cue-reward associations and motivating behavior, yet how dopaminergic signals are distributed across the cortex during action selection remains unclear. Using widefield GRABDA fluorescence imaging, we measured dopamine dynamics simultaneously across five dorsal cortical regions: primary motor (M1), secondary motor (M2), somatosensory (SS), visual (V1), and retrosplenial (RS) cortex, in mice performing an auditory go/no-go task (56 sessions, 5 animals, approximately 16,600 trials). Cue-evoked dopamine transients were significantly larger on trials in which animals initiated a licking response compared to trials in which they withheld, and this effect was driven by action initiation rather than cue identity. Whole-cortex dopamine robustly predicted licking (B = 2.03, t(55) = 6.60, p < .001, 89% of sessions significant). The effect was spatially graded, with the strongest signals in M2 (F = 24.28) and the weakest in V1 (F = 14.26). Critically, the Cue Type main effect was non-significant in every region even in proficient sessions (d’ > 1.5), confirming that cortical dopamine primarily reflects action initiation rather than cue identity. The dopamine-action coupling was larger in proficient sessions than in pre-discrimination sessions, with the whole-cortex logistic B rising by approximately 71% (Stage 1 vs. Stage 3 contrast p = .14). These findings demonstrate that cortical dopamine carries a spatially organized, learning-modulated signal for action initiation across the dorsal cortex.