Organization of central adrenergic pathways: I. Relationships of ventrolateral medullary projections to the hypothalamus and spinal cord

Abstract

We studied the organization of projections from the C1 adrenergic and A1 noradrenergic cell groups in the ventrolateral medulla (VLM) to the hypothalamus and the spinal cord by using a combination of retrograde transport of fluorescent tracers and immunocytochemistry. Three issues were addressed. Neurons in the VLM that stain immunohistochemically for phenylethanolamine N-methyltransferase (PNMT) have been assumed to be adrenergic. However, the presence of PNMT-immunoreactive neurons in the hypothalamus that do not stain for tyrosine hydroxylase (TH) prompted us to re-evaluate the VLM by an elution-restaining immunohistochemical procedure. We confirmed that nearly all of the rostral medullary PNMT-immunoreactive neurons also stained for TH. By contrast, in the caudal medulla, very few TH-positive neurons stained for PNMT. Neurons of the C1 group in the rostral VLM project both to the thoracic spinal cord and to the hypothalamus. To determine whether individual C1 neurons send collaterals to the hypothalamus and spinal cord, we injected different-colored fluorescent dyes (diamidino yellow or fast blue) into the thoracic spinal gray matter and either the median preoptic (MnPO) or paraventricular (PVH) nuclei of the hypothalamus. Very few double-labeled neurons were found in the VLM, indicating that hypothalamic and spinal cord projections arise from almost completely independent populations of cells. Approximately half of the neurons projecting to the spinal cord from rostral VLM were not immunoreactive for TH or PNMT, indicating that a substantial part of this projection is noncatecholaminergic. The MnPO and the PVH both receive extensive catecholaminergic inputs from the VLM. We also used fluorescent retrograde tracers to determine whether individual VLM neurons send collaterals to both hypothalamic sites. Approximately 20% of neurons projecting to the MnPO in the rostral two thirds of the VLM also sent collaterials to the PVH, nearly all of these neurons being TH-positive. The collateralization of the VLM catecholaminergic projection to the hypothalamus may provide an anatomical substrate for integration of fore-brain participation in cardiovascular regulation. In contrast, the adrenergic projection from the VLM to the intermediolateral column of the spinal cord arises from a separate population of neurons.