β-Adrenergic receptors: Astrocytic localization in the adult visual cortex and their relation to catecholamine axon terminals as revealed by electron microscopic immunocytochemistry

It has long been recognized that noradrenaline, the most abundant catecholamine within the visual cortex, plays important roles in modulating the sensitivity of cortical neurons to visual stimuli. However, whether or not these noradrenaline effects are confined to a discrete synaptic specialization or mediated by diffuse modulation of a group of synapses has remained an issue open for debate. The aim of this study was to examine the cellular basis for noradrenaline action within the visual cortex of adult rats and cats. To this end, I used electron microscopic immunocytochemistry to examine the relationship between (1) catecholamine axon terminals and β-adrenergic receptors (βAR), which, together, may define the effective sphere of noradrenaline modulation; and then (2) these putative sites for catecholamine modulation and axospinous asymmetric junctions where excitatory neurotransmission is likely to dominate. Antibodies against βAR were used at light and electron microscopic levels on the visual cortex of rat and cat. Rat visual cortex was also labeled simultaneously for βAR and the catecholamine-synthesizing enzyme, tyrosine hydroxylase (TH), to determine the ultra structural relationships between catecholamine terminals and βAR. Immunoperoxidase labeling revealed that βAR404, a polyclonal antibody directed against the C-terminal tail of hamster lung βAR (β₂-type), recognized astrocytic processes predominantly. In contrast, βAR248, a polyclonal antibody directed against the third cytoplasmic loop, recognized neuronal perikarya as observed in previous studies. Dual labeling for βAR404 and TH revealed that catecholamine axon terminals that contained numerous vesicles formed direct contacts with astrocytic processes exhibiting βAR404 immunoreactivity. However, some catecholamine axon terminals that lacked dense clusters of vesicles were positioned away from βAR404-immunoreactive astrocytes. Frequently, βAR-immunoreactive astrocytic processes surrounded asymmetric axospinous junctions while also contacting catecholamine axon terminals. These observations support the possibility that, through activation of astrocytic βAR, noradrenaline modulates astrocytic uptake mechanism for excitatory amino acids, such as L-glutamate. Astrocytic βAR might also define the effective sphere of catecholamine modulation through alterations in the morphology of distal astrocytic processes and the permeability of gap junctions formed between astrocytes.