Spinal projections of the A5, A6 (locus coeruleus), and A7 noradrenergic cell groups in rats

Abstract

The pontine noradrenergic cell groups, A5, A6 (locus coeruleus), and A7, provide the only noradrenergic innervation of the spinal cord, but the individual contribution of each of these populations to the regional innervation of the spinal cord remains controversial. We have used an adeno-associated viral (AAV) vector encoding green fluorescent protein under an artificial dopamine beta-hydroxylase (PRSx8) promoter, to trace the spinal projections from the A5, A6, and A7 groups. Projections from all three groups travel through the spinal cord in both the lateral and ventral funiculi and in the dorsal surface of the dorsal horn, but A6 axons take predominantly the dorsal and ventral routes whereas A5 and A7 axons take a predominantly lateral route. The A6 group provides the densest innervation at all levels, and includes all parts of the spinal gray matter, but it is particularly dense in the dorsal horn. The A7 group provides the next most dense innervation, again including all parts of the spinal cord, but is it denser in the ventral horn. The A5 group supplies only sparse innervation to the dorsal and ventral horns and to the cervical and lumbosacral levels, but provides the densest innervation to the thoracic intermediolateral cell column, and in particular to the sympathetic preganglionic neurons. Thus, the pontine noradrenergic cell groups project in a roughly topographic and complementary fashion onto the spinal cord. The pattern of spinal projections observed suggests that the locus coeruleus might have the greatest effect on somatosensory transmission, the A7 group on motor function, and the A5 group on sympathetic function.

Gene Therapy for the Nervous System: Challenges and New Strategies

“…In addition, it is also possible that this small level of mistargeting could be due to transactivation from the AAV2 inverted terminal repeat, which has promoter activity in the brain [158,159], and at sufficiently high vector doses may become detectable. A similar finding of low percentage mistargeting was reported for an AAV vector carrying an artificial dopamine beta-hydroxylase (PRSx8) promoter [160] to drive GFP expression in noradrenergic neurons in locus coeruleus for tracing of axonal projections [161].…”

Neuropathic and inflammatory pain are modulated by tuberoinfundibular peptide of 39 residues

“…None of these criteria are definitive. We do not know the effective diffusion distance of the secreted PTH2R antagonist, and the relative contribution of brainstem noradrenergic nuclei to spinal antinociception varies between reports, likely due to species or strain differences (21,22). However, the A7 group is unlikely to mediate TIP39 effects because there are very few PTH2Rs in its vicinity.…”

“…However, the A7 group is unlikely to mediate TIP39 effects because there are very few PTH2Rs in its vicinity. The A5 group contains PTH2Rs and TIP39 fibers, but its major projection is to the intermediolateral cell column and its fibers do not reach the lumbar spinal cord where sciatic nerve afferents synapse (22). The LC is influenced by projections from more rostral areas that affect nociception including the periaqueductal gray (23) and amygdala (24)(25)(26).…”

Orexins and the cardiovascular events of awakening

“…69 Increases in the activity of the hypothalamic orexin neurons lagged behind, but occurred still before the onset of electroencephalographic desynchronization, which marks awakening. 68 The projections from the locus coeruleus to the sympathetic 70 and pre-sympathetic 71 neurons are relatively limited. Chemical stimulation of the locus coeruleus reportedly decreases ABP mainly because of skeletal muscle and kidney vasodilation.…”