Spatially confined dopamine from locus coeruleus axons selectively shapes hippocampal dynamics and action timing

Neuromodulatory systems project broadly, yet computations engage specific neuronal populations. Whether neuromodulation can selectively influence task-engaged neurons remains unclear. During goal-directed navigation, neurons in the locus coeruleus (LC), the brain's principal norepinephrine source, responded at navigation onset. Concurrently, dopamine transients arose in micrometer-scale domains around LC axons in CA1. These transients preferentially enhanced nearby CA1 neurons with ramping dynamics, whose higher activity predicted later reward-anticipatory action. Brief LC activation evoked local dopamine, enhanced ramping dynamics, and delayed action initiation seconds later. Blocking D1-like, but not adrenergic, receptors weakened ramping dynamics and impaired reward anticipation. Modeling showed that selectivity can emerge when localized dopamine coincides with strong ongoing neuronal activity, without dedicated wiring. Thus, a widely projecting system can selectively modulate task-engaged neurons and shape behavior.