Divergent projections from Locus Coeruleus to the cortico-basal ganglia system and ventral tegmental area of the zebra finch

The locus coeruleus (LC) is a small brainstem nucleus that is the primary source of noradrenaline (NA) throughout the vertebrate brain. Understanding the anatomical organization of the LC is important because NA plays a central role in regulating arousal, attention, and performance. In the mammalian brain, individual LC neurons make highly divergent axonal projections to different brain regions, which are distinguished in part by which NA receptor subtypes they express. Here we sought to determine whether similar organizational features - divergent LC projections acting regionally through different receptor subtypes - characterize cortico-basal ganglia (CBG) circuitry important to birdsong learning and performance. Single and dual retrograde tracer injections reveal that single LC-NA neurons make divergent projections to both cortical and basal ganglia components of this circuit, as well as to dopaminergic nuclei that innervate this circuit. Moreover, in situ hybridization revealed that differential expression of the α2A and α2C adrenoreceptor distinguish LC-recipient song nuclei. Therefore, LC - NA signaling in the songbird CBG circuit could employ a similar strategy as in mammals, which allows a relatively small number of LC neurons to exert widespread yet distinct effects across multiple brain regions. Key Points The locus coeruleus projects to most of the song system (HVC, RA, LMAN, Area X, DLM). Noradrenergic receptors are regionally specialized in BG despite divergent connectivity of LC neurons. Noradrenergic projections to dopaminergic nuclei could influence vocal variability and learning.