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

Abstract

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.