The organization of noradrenergic pathways from the brainstem to the paraventricular and supraoptic nuclei in the rat

Abstract

Axonal transport and immunohistochemical methods have been used to clarify the organization of pathways from noradrenergic and adrenergic cell groups in the brainstem to the paraventricular (PVH) and supraoptic (SO) nuclei of the hypothalamus. First, the location of such cells was determined with a combined retrograde tracer-immunofluorescence method. The fluorescent tracer, True Blue, was injected into the PVH or the SO, and sections through the brainstem were stained with anti(rat) DBH, a specific marker for noradrenergic and adrenergic neurons. It was found that, after injections in the PVH, doubly labeled neurons were confined almost exclusively to 3 cell groups, the A1 region of the ventral medulla, which contained a majority of such cells, the A2 region in the dorsal vagal complex, and the locus coeruleus (A6 region). After injections centered in the SO an even greater proportion of doubly labeled cells were found in the A1 region, although some were also found in the A2 and A6 regions. The topography of doubly labeled cells indicates that these projections arise primarily from noradrenergic neurons, although adrenergic cells in both the C1 and the C2 groups probably contribute as well. Because well over 80 % of the retrogradely labeled cells in these three regions were also DBH-positive, we next placed injections of [ 3H]amino acids into each of them in different groups of animals, and traced the course and distribution of the ascending (presumably DBH-positive) projections to the PVH and SO in the resulting autoradiograms. Injections centered in the A1 region labeled a substantial projection to most parts of the parvocellular division of the PVH, and was most dense in the dorsal and medial parts. In addition, terminal fields were labeled on those parts of the magnocellular division of the PVH, and of the SO, in which vasopressinergic cell bodies are concentrated. Injections centered in the A2 region also labeled a projection to the parvocellular division of the PVH that was topographically similar, but less dense, than that from the Al region. In contrast, [ 3H]amino acid injections centered in the locus coeruleus labeled a moderately dense projection to the PVH that was limited to the medialmost part of the parvocellular division. Neither the A2 nor the A6 cell groups project to the magnocellular parts of PVH, or to the SO. The autoradiographic material, and additional double-labeling experiments, were used to identify and to characterize projections that interconnect the A1, A2 and A6 regions, as well as possible projections from these cell groups to the spinal cord. These results may be summarized as follows: a substantial projection from the nucleus of the solitary tract to the Al region was identified, but this pathway does not arise from catecholaminergic neurons in the A2 cell group. DBH-stained cells in the A1 region project back to the dorsal vagal complex, as well as quite massively to the locus coeruleus (A6 region). The double-labeling method also showed that the locus coeruleus, but not the A1 or A2 groups, contributes substantially to the noradrenergic innervation of the spinal cord. These results indicate that primarily noradrenergic cells in the A1, A2 and A6 regions give rise to projections that end in specific subdivisions of the PVH and SO. These pathways may well be involved in the control of neuroendocrine responses involving both the anterior and posterior lobes of the pituitary gland, and of autonomic responses involving both parasympathetic and sympathetic mechanisms. Because the nucleus of the solitary tract, which includes the A2 cell group and which projects massively to the A1 region, receives primary visceral afferent inputs, the circuitry that we have described may play a role in the integration of hypothalamic neuroendocrine and autonomic responses to specific visceral stimuli.