Stimulus-dependent dopamine dynamics from locus coeruleus axons

Arousal is essential for survival, and maladaptive arousal processing leads to an inability to focus, anxiety-like behavior, and dysregulated affective states. Norepinephrine (NE) is known to regulate anxiety, arousal, and learning through locus coeruleus (LC) projections throughout the brain. Evidence for co-release of the NE precursor and neurotransmitter dopamine (DA) from LC neurons has been accumulating for years, yet definitive measures of DA release across regions, stimulus paradigms, and behaviors associated with the LC-NE system remain controversial. Here, we identified the physiological and behavioral properties that evoke DA release from LC axon terminals. Using concomitant approaches, we inhibited the LC and ventral tegmental area (VTA) to selectively isolate the contributions of LC-derived DA release. Together these findings establish the constraints by which LC neurons release DA in a modality-dependent manner.