Medullary Norepinephrine Projections Release Norepinephrine into the Contralateral Bed Nucleus of the Stria Terminalis

Central norepinephrine signaling influences a wide range of behavioral and physiological processes, and the ventral bed nucleus of the stria terminalis (vBNST) receives some of the densest norepinephrine innervation in the brain. Previous work describes norepinephrine neurons as projecting primarily unilaterally; however, recent evidence for cross-hemispheric catecholamine signaling challenges this idea. Here, we use fast-scan cyclic voltammetry and retrograde tracing to characterize cross-hemispheric norepinephrine signaling in the vBNST. We delivered stimulations to noradrenergic pathways originating in the A1/A2 and locus coeruleus and found hemispherically equivalent norepinephrine release in the vBNST regardless of stimulated hemisphere. Unilateral retrograde tracing revealed that medullary, but not locus coeruleus norepinephrine neurons send cross-hemispheric projections to the vBNST. Further characterization with pharmacological lesions revealed that stimulations of the locus coeruleus and its axon bundles likely elicit vBNST norepinephrine release through indirect activation. These experiments are the first to demonstrate contralateral norepinephrine release and establish that medullary, but not coerulean neurons are responsible for norepinephrine release in the vBNST.