Afferent Control of Nucleus Locus Ceruleus: Differential Regulation by “Shell” and “Core” Inputs

Abstract

Publisher Summary The two major afferent inputs to locus ceruleus (LC) arise from nucleus paragigantocellularis (PGi) and nucleus prepositus hypoglossi in the rostral medulla. Light microscopic analysis has revealed that the vast majority of the extranuclear processes of LC neurons extended preferentially into two zones: the region rostral and medial to LC proper, designated as the rostromedial pLC (pLCrm) region and a narrow region adjacent to the fourth ventricle caudomedial to LC proper, designated as the caudal juxtaependymal pLC (pLCcje) region. It is suggested that extranuclear LC dendrites, particularly in the rostromedial and caudal juxtaependymal zones, comprise an extensive postsynaptic receptive surface of LC neurons. Tract-tracing studies have demonstrated that the midbrain periaqueductal gray (PAG), medial preoptic area (MPO), medial prefrontal cortex, central nucleus of the amygdala (CNA), and nucleus tractus solitarius (NTS) send afferents to pLC but provide weak or no innervation of the LC nuclear core. Taken together, these results demonstrate that the dendrites of LC neurons are polarized to extend preferentially into two pericerulear zones located rostromedial and caudomedial to LC proper. This dendritic shell pattern is characteristic of all or most LC neurons. LC extranuclear dendrites receive synaptic contacts and comprise a significant postsynaptic receptive surface of LC neurons. These shell dendrites are selectively targeted by a number of extrinsic afferent inputs that do not project appreciably into the LC core. By contrast, the nuclear core of LC receives two major afferent inputs; these inputs do not appreciably target the dendritic shell. Evidence to date suggests that several inputs to the shell region exert an excitatory influence of LC discharge. Thus, inputs to the core LC nucleus versus extranuclear dendrites may comprise functionally distinct channels for regulating LC neurons.