alpha2A-adrenergic receptors in the rat nucleus locus coeruleus: subcellular localization in catecholaminergic dendrites, astrocytes, and presynaptic axon terminals

Abstract

To define the anatomic substrates subserving the inhibitory actions of alpha2-adrenergic receptors (alpha2-ARs) in the locus coeruleus (LC), we used dual-label immunoelectron microscopy with antibodies directed against the A-subtype of alpha2-AR (alpha2A-AR) and the catecholamine-synthesizing enzyme tyrosine hydroxylase (TH). Of the profiles containing peroxidase labeling for alpha2A-AR (alpha2A-AR-IR) in the LC (n=735), most were dendrites ( approximately 50%), glial processes ( approximately 30%), and axon terminals ( approximately 15%). alpha2A-AR-IR was also observed in unmyelinated axons and perikarya. Within dendrites, alpha2A-AR-IR was associated with nonsynaptic regions of the plasma membrane and subsurface cisternae. Approximately 60% of dendrites with alpha2A-AR-IR were dually labeled for TH. Fifty percent of the axon terminals contacting alpha2A-AR-immunoreactive dendrites formed asymmetric (excitatory) synaptic contacts. Axon terminals with alpha2A-AR-IR were not dually labeled for TH and generally formed asymmetric synapses with TH-immunoreactive dendrites that contained or lacked alpha2A-AR-IR. Astrocytic processes exhibiting alpha2A-AR-IR were closely apposed to TH-labeled dendrites. These results extend previous ultrastructural observations of alpha2A-ARs in the LC and suggest that the inhibitory actions of norepinephrine and epinephrine in this region may be mediated by postsynaptic alpha2A-ARs on catecholaminergic dendrites and presynaptic alpha2A-ARs on excitatory inputs to catecholaminergic dendrites. In addition, the localization of alpha2A-AR-IR in astrocytic processes apposed to TH-immunoreactive dendrites suggests a role for alpha2A-ARs in functional interactions between catecholaminergic dendrites and neighboring astrocytes.