title: Ultrastructural evidence for convergence of enkephalin and adrenaline-containing axon terminals on common targets and their presynaptic associations in the rat nucleus locus coeruleus.
abstract: The endogenous opioid peptide, enkephalin, and epincphrine are distributed in varicose processes throughout the nucleus locus coeruleus (LC) in the dorsolateral tegmentum of the rat brain. In this brain region, micro-opioid and alpha-2-adrenergic receptors have been shown to share the same potassium channel suggesting that they may be co-localized in the same terminal or that they may be present in terminals that innervate the same target neuron. However, this has not been demonstrated at the ultrastructural level. Thus, the present study combined the immunocytochemical localization of the opioid peptide leucine5-enkephalin (ENK) and the epinephrine synthesizing enzyme, phenylethanolamine-N-methyltransferase (PNMT) in the same section of tissue within the LC at the electron microscopic level. At the light microscopic level, both ENK and PNMT varicose processes were dense and overlapped the region known to contain the noradrenergic cell bodies and dendrites of the LC. However, the morphological features of the two immunolabeled fiber types appeared different in 30-microns thick coronal sections. PNMT-labeled process were thin, beaded and ramified within the coronal plane. ENK-immunoreactive fibers, however, were more punctate in appearance and processes joining these puncta were not often evident in the frontal plane examined. Varicose fibers immunolabeled for either ENK or PNMT were confirmed to be axons and axon terminals by electron microscopy. Both types contained small clear as well as large dense core vesicles and formed heterogeneous types of synaptic specializations with postsynaptic targets. A common feature encountered in dually labeled tissue sections was convergence of the separately labeled axon terminals on common targets. Another common feature was the apposition of PNMT-labeled axon terminals with ENK-immunoreactive axon terminals that formed synaptic contacts in the plane of section examined. Although numerous ENK and PNMT-labeled axon terminals were identified in similar regions of the neuropil, few terminals were found to contain both labels. These findings indicate that the opioid peptide ENK and epinephrine may elicit concerted actions on common noradrenergic neurons in the LC via separate sets of afferents.
authors.affiliation: Department of Neurology and Neuroscience, Cornell University Medical College, New York, NY 10021, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Van Bockstaele
authors.forename: J
authors.initials: J
authors.lastname: Chan
authors.forename: A
authors.initials: A
authors.lastname: Biswas
mesh_terms: D000818:Animals; D004743:Enkephalin, Leucine / Q000378:metabolism / Q000502:physiology*; D004837:Epinephrine / Q000378:metabolism / Q000502:physiology*; D007150:Immunohistochemistry; D008125:Locus Coeruleus / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure*; D008297:Male; D008854:Microscopy, Electron; D009434:Neural Pathways / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D010625:Phenylethanolamine N-Methyltransferase / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017661:Receptors, Presynaptic / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure*
chemical_list: D017661:Receptors, Presynaptic; D004743:Enkephalin, Leucine; D010625:Phenylethanolamine N-Methyltransferase; D004837:Epinephrine