Light and electron microscopic evidence for topographic and monosynaptic projections from neurons in the ventral medulla to noradrenergic dendrites in the rat locus coeruleus

Physiological studies have shown that afferents from the nucleus paragigantocellularis (PGi) in the rostral ventral medulla underlie the modulation of locus coeruleus (LC) activity by a variety of stimuli. However, there have been no anatomical demonstrations of a monosynaptic projection from neurons in the PGi to the LC. Thus, biotinylated dextran amine (BDA) was iontophoretically injected into the ventral medulla and single-tissue sections were processed for peroxidase localization of BDA and gold-silver labeling of tyrosine hydroxylase (TH). Discrete microinjections of BDA were placed into either the medial or lateral aspects of the ventral medulla. For medially placed injections, a medio-dorsal pathway to the LC was observed. This trajectory resulted in a predominant innervation of the ventral LC. Lateral injection placements yielded a fiber pathway that coursed more laterally within the medullo-pontine reticular formation and primarily innervated the dorsolateral LC. These light microscopic data suggested that neurons in the PGi use distinct pathways to innervate the LC and are topographically organized within this structure. Electron microscopic analyses of the LC region indicated that axon terminals originating from either subregion were equally likely to contact noradrenergic neurons in the LC. Approximately 57% and 62% of BDA-labeled terminals originating from the medial (n = 150) or lateral (n = 150) aspects of the ventral medulla, respectively, formed heterogeneous synaptic contacts (i.e., inhibitory- and excitatory-type) with dendrites containing TH. It is well known that the PGi is a functionally diverse region that is involved in sensory integration, autonomic regulation and pain modulation. It is also known that LC efferents are spatially organized with respect to their postsynaptic targets. Taken together, our findings that subdivisions of the ventral medulla topographically and monosynaptically innervate the LC suggest that regionally specific PGi neurons target subsets of LC neurons with efferent targets that may possess analogous functional correlates.