A serotonergic innervation of noradrenergic neurons in nucleus locus coeruleus: demonstration by immunocytochemical localization of the transmitter specific enzymes tyrosine and tryptophan hydroxylase.

Immunocytochemical localization of the neurotransmitter synthesizing enzymes, tyrosine and tryptophan hydroxylase, was used to determine whether the noradrenergic neurons in the nucleus locus coeruleus of the rat are innervated by serotonergic (5-HT) neurons. Specific antibodies were prepared to tyrosine hydroxylase, purified from the bovine adrenal medulla, and tryptophan hydroxylase, purified from rat midbrain. These were localized by both light and electron microscopy by the use of the peroxidase-antiperoxidase method. In the nucleus locus coeruleus, tyrosine hydroxylase was contained in the cytoplasm, proximal axons, and dendrites of intrinsic neurons. Tryptophan hydroxylase, on the other hand, was only contained within processes surrounding the perikarya and dendrites of the catecholaminergic neurons. The processes labeled with tryptophan hydroxylase were unmyelinated, ranged in size from 0.1 to 1.4 micron, and consisted of terminal varicosities separated by intervaricose segments. Although in close approximation to noradrenergic neurons, these processes, presumably axons, rarely formed synatic contacts with thickened membrane specializations. In processes, tryptophan hydroxylase was associated with subcellular organelles which had size and distribution of microtubules, and small and large synaptic vesicles. These observations provide a morphological basis to support the hypothesis that the activity of noradrenergic neurons may be modulated by a direct action of 5-HT neurons.