Dopamine release effects on striatal blood oxygenation and whole brain plasticity underlying associative learning

Dopaminergic signaling in the nucleus accumbens (NAc) is central to reward-based learning, but its relationship to brain-wide hemodynamics remains unclear. Using concurrent fMRI and dopamine photometry in awake, behaving mice, we reveal that associative learning induces a gradual temporal shift in NAc blood oxygenation responses that mirrors dopamine release dynamics. This shift emerges with cue-reward learning and extends across a distributed network including prefrontal, insular, and hypothalamic regions. Further, dopamine transients tightly correspond with local BOLD signals, and variations in reward value modulate delayed BOLD responses in both the NAc and additional subcortical structures. Removing dopaminergic contributions abolishes this reward-related modulation, demonstrating that BOLD signals encode dopaminergic value prediction. These findings establish a mechanistic link between dopamine signaling and widespread neural plasticity during learning.