Reciprocal connections between subdivisions of the dorsal raphe and the nuclear core of the locus coeruleus in the rat

The interconnection between two brainstem monoaminergic nuclei, the dorsal raphe (DR) and the locus coeruleus (LC), was analyzed in the rat using retrograde tracing and immunocytochemistry. Gold-conjugated and inactivated wheatgerm agglutinin-horseradish peroxidase (WGA-apo-HRP-gold) was injected into subdivisions of the DR or rostro-caudal levels of the nuclear core of the LC, and labeled LC or DR neurons were identified by dopamine-β-hydroxylase (DBH) or 5-hydroxytryptamine (5-HT) immunostaining, respectively. Within the LC-DR projection, the caudal principal LC projected to the caudal, ventromedial, and interfascicular DR. Mid-LC as well as caudal LC projected with an ipsilateral predominance to the lateral wing subdivision of the DR. A few rostral LC neurons projected to caudal, dorsomedial, and ventromedial DR. Within the DR-LC projection, the rostral LC received inputs mainly from the caudal, dorsomedial, and ventromedial DR. Mid-LC to caudal LC received projections from mid-DR to caudal DR, with the heaviest projection from the ipsilateral lateral wing as well as caudal DR. The DR-LC projection was substantially more robust than LC-DR and included both serotonergic and nonserotonergic components. Thus, the data demonstrate topographically ordered, reciprocal connectivity between DR and LC with particularly strong projections from DR to LC. Communication between these two brainstem monoaminergic nuclei may be critical for a variety of functions including sleep-wake regulation, vigilance, analgesia, cognition, and stress responses.