Journal of Neuroscience, Vol 12, 3162-3174, Copyright © 1992 by Society for Neuroscience
Robust enkephalin innervation of the locus coeruleus from the rostral medulla
G Drolet, EJ Van Bockstaele and G Aston-Jones
Department of Mental Health Sciences, Hahnemann University, Philadelphia, Pennsylvania 19102-1192.
Substantial evidence indicates that the noradrenergic nucleus locus
coeruleus (LC) is a key target of endogenous opioid neurons, and an
important structure in mediating opiate effects. However, the detailed
distribution of opioid fibers and terminals in the LC, and the sources of
its opioid innervation are unknown. In the present study, the enkephalin
innervation of the LC was investigated in the rat using an antibody
directed against the extended enkephalin peptide Met-
enkephalin-Arg6-Gly7-Leu8 (ENK), which is derived exclusively from the
enkephalin precursor proenkephalin A. An antibody directed against tyrosine
hydroxylase (TH), the synthetic enzyme for catecholaminergic neurons, was
also applied to the same tissue sections to delineate LC neurons and their
dendrites. Enkephalin fibers in the LC were dense and highly varicose. In
horizontal sections, ENK-like-immunoreactive (ENK- ir) fibers of
considerable length coursed throughout the rostrocaudal orientation of the
LC proper, whereas in frontal sections ENK-ir processes appeared punctate,
suggesting a rostrocaudal orientation. Dense ENK-ir fibers were also
identified in the rostromedial and caudal juxtaependymal pericoerulear
regions where extranuclear dendrites of LC neurons are extensive. As
previously reported, there were no ENK-ir neurons in the LC nucleus proper,
but such cells were present in neighboring structures such as the
parabrachial, sphenoid, and Barrington's nuclei as well as in the central
gray and in the subcoeruleus area. ENK-ir neurons were also present in
nuclei of the rostral medulla reported to be major afferents of the LC, the
nucleus prepositus hypoglossi (PrH), and the nucleus paragigantocellularis
(PGi). In the dorsomedial medulla, numerous ENK-ir neurons were identified
in the medial aspect of the PrH and along the medial longitudinal
fasciculus in the perifascicular reticular formation. In the ventrolateral
medulla, ENK-ir neurons were distributed in a conical caudorostral column
throughout the PGi. Retrograde transport of a WGA- colloidal gold conjugate
(WGA-apoHRP-Au) from LC, combined with immunohistochemistry for ENK in the
same tissue sections, revealed that LC afferents in the PGi and PrH were
interdigitated with ENK-ir neurons. Furthermore, an unexpectedly high
incidence of doubly labeled neurons were identified in both PGi and PrH.
Overall, 57% and 56% of the LC-projecting neurons in PGi and PrH,
respectively, were also immunoreactive for ENK, suggesting that
enkephalinergic neurons of PGi and PrH are major afferents to noradrenergic
LC neurons.
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