Demonstration of two separate descending noradrenergic pathways to the rat spinal cord: evidence for an intragriseal trajectory of locus coeruleus axons in the superficial layers of the dorsal horn.

The rat spinal cord receives noradrenergic (NA) projections from the locus coeruleus (LC) and the A5 and A7 groups. In contradiction to previous statements about the distribution of descending NA axons, we have recently proposed that in the rat LC neurons project primarily to the dorsal horn and intermediate zone, whereas A5 and A7 neurons project to somatic motoneurons and the intermediolateral cell column. The aim of the present study was to determine the funicular course and terminal distribution of descending NA axons from the LC and from the A5 and A7 groups. The organization of the coeruleospinal projection was analyzed by using the anterograde tracer Phaseolus vulgaris leucoagglutinin in combination with dopamine-beta-hydroxylase immunohistochemistry. The trajectory of A5 and A7 axons was studied in spinal cord sections of rats following ablation of the coeruleospinal projection with the neurotoxin DSP-4. To assess the relative contribution of the LC and the A5 and A7 groups to the NA innervation of the spinal cord, unilateral injections of the retrograde tracer True Blue were made at cervical, thoracic, and lumbar levels, and retrogradely labeled NA neurons were identified by dopamine-beta-hydroxylase immunofluorescence. The results of the anterograde tracing experiments confirm our previous findings that LC neurons project most heavily to the dorsal horn and intermediate zone. Analysis of horizontal sections revealed that LC axons descend the length of the spinal cord within layers I and II. In contrast to the intragriseal course of LC fibers, A5 and A7 axons travel in the ventral and dorsolateral funiculi and terminate in the ventral horn and the intermediolateral cell column. Retrograde transport studies indicate that the contribution of the A5 and A7 groups to the NA projection to the spinal cord is greater than that of the LC. We conclude that descending axons of the LC and A5 and A7 groups differ in their course and distribution within the spinal cord. The documentation of a definite topographic order in the bulbospinal NA projections suggests that the LC and the A5 and A7 groups have different functional capacities. The LC is in a position to influence the processing of sensory inputs, in particular nociceptive inputs, whereas A5 and A7 neurons are likely to influence motoneurons.