Local and global consequences of reward-evoked striatal dopamine release.

Abstract

The neurotransmitter dopamine is required for the reinforcement of actions by rewarding stimuli1. Neuroscientists have tried to define dopamine’s functions in concise conceptual terms2, but the practical significance of dopamine release depends on its diverse brain-wide consequences. Although the molecular and cellular effects of dopaminergic signaling have been extensively studied3, its impact on larger-scale neural activity profiles is less understood. Here we combine dynamic dopamine-sensitive molecular imaging4 and functional magnetic resonance imaging (fMRI) to determine how striatal dopamine release shapes local and global responses to rewarding stimulation in the rodent brain. We find that dopamine consistently alters the duration but not the magnitude of stimulus responses across much of striatum, via quantifiable postsynaptic effects that vary across subregions. Striatal dopamine release also potentiates a network of distal responses we delineate using neurochemically-dependent functional connectivity analyses. Hot spots of dopaminergic drive notably include cortical regions associated with both limbic and motor function. Our results thus reveal distinct neuromodulatory actions of striatal dopamine that extend well beyond its sites of peak release, and that result in enhanced activation of remote neural populations necessary for performance of motivated actions. Our findings also suggest brain-wide biomarkers of dopaminergic function and could provide a basis for improved interpretation of neuroimaging results relevant to learning and addiction.