ULTRASTRUCTURAL EVIDENCE FOR PROMINENT POSTSYNAPTIC LOCALIZATION OF ALPHA(2C)-ADRENERGIC-RECEPTORS IN CATECHOLAMINERGIC DENDRITES IN THE RAT NUCLEUS LOCUS-COERULEUS

Alpha-8-adrenergic receptor (alpha(2)-AR) agonists potently inhibit th e activity of noradrenergic neurons of the locus coeruleus (LC), an ef fect that may be mediated by the A- and/or C-subtypes of alpha(2)-AR ( alpha(2A)- and alpha(2C)-AR). To gain insight into the functional sign ificance of these alpha(2)-AR subtypes in the LC, we have examined the ir ultrastructural localization by using subtype-specific antibodies. We recently demonstrated that alpha(2A)-ARs are localized prominently in axon terminals and catecholaminergic dendrites in the LC. In the pr esent study, we sought to identify the subcellular substrates underlyi ng alpha(2C)-AR actions in the LC by analyzing the ultrastructural dis tribution of alpha(2C)-AR immunoreactivity (alpha(2C)-AR-IR) in sectio ns that were dually labeled far the catecholamine-synthesizing enzyme tyrosine hydroxylase (TH). Alpha-2C-AR-IR was predominantly localized in dendrites, most of which also contained immunolabeling far TR. With in such dendrites, alpha(2C)-AR-IR was associated with the plasma memb rane and occasionally Golgi cisternae and tubulovesicles. The vast maj ority of dendrites containing alpha(2C)-AR-IR received asymmetric (exc itatory) contacts from unlabeled axon terminals that often contained d ense core vesicles. Alpha-2C-AR-IR was observed in some unmyelinated a xons and astrocytic processes that were apposed to TH-immunoreactive d endrites but was rarely associated with axon terminals. These results provide the first ultrastructural evidence that alpha(2C)-ARs (1) are localized postsynaptically in catecholaminergic neurons of the LC and (2) may be strategically situated to modulate the activation of LC neu rons by excitatory inputs. (C) 1998 Wiley-Liss, Inc.