HIPPOCAMPAL ALPHA(2A)-ADRENERGIC RECEPTORS ARE LOCATED PREDOMINANTLY PRESYNAPTICALLY BUT ARE ALSO FOUND POSTSYNAPTICALLY AND IN SELECTIVE ASTROCYTES

Alpha-adrenergic receptor, subtype 2A(alpha(2A)-AR), activation is one of the primary modes of action for norepinephrine (NE) in the rat hip pocampal formation. In this study, alpha(2A)-AR immunoreactivity (alph a(2A)-AR-I) was localized by light and electron microscopy in the rat hippocampus and dentate gyrus by using a previously characterized anti body to the rat alpha(2A)-AR. BY light microscopy, dense alpha(2A)-AR- I was observed in the pyramidal and granule cell layers. Diffuse and s lightly granular alpha(2A)-AR-I was found in the neuropil in all other laminae, notably stratum lacunosum-moleculare. Ultrastructurally, alp ha(2A)-AR-I was found in neuronal cytoplasm associated with large mult ivesicular-like organelles and with clusters adjacent to endoplasmic r eticula and/or plasmalemma. The distribution of alpha(2A)-AR-I in the strata oriens, radiatum, and lacunosum-moleculare of hippocampal CA1 a nd CA3 regions and in the molecular layer of the dentate gyrus was rem arkably similar (n > 2,000 profiles examined): alpha(2A)-AR-I was foun d in axons and terminals (similar to 40%), glia (similar to 30%), dend ritic spines (similar to 25%), and dendritic shafts (similar to 5%). T his mixed pre-and postsynaptic distribution was not seen in the stratu m lucidum of the CA3 region and the dentate hilar region, where most a lpha(2A)-AR-I was found in axons (similar to 60%) and glia (similar to 30%). Alpha-2A-AR-labeled axons were small and unmyelinated; labeled terminals usually formed asymmetric synapses on unlabeled spines; and labeled dendritic spines were morphologically similar to pyramidal or granule cells. Dual labeling studies demonstrated that some axons cont ained alpha(2A)-AR-I and tyrosine hydroxylase (TH), the catecholaminer gic synthesizing enzyme, and that some TH-labeled terminals were in cl ose proximity to alpha(2A)-AR-labeled spines and glia. These studies d emonstrate that hippocampal alpha(2A)-AR-I is localized (1) presynapti cally in both noncatecholaminergic and catecholaminergic terminals, (2 ) postsynaptically in the dendritic spines of pyramidal and granule ce lls near catecholaminergic terminals, and (3) in some glial processes. These results suggest several sites for NE to exert its effects on hi ppocampal alpha(2A)-ARs. (C) 1998 Wiley-Liss. Inc.