3-HYDROXYANTHRANILIC ACID OXYGENASE-CONTAINING ASTROCYTIC PROCESSES SURROUND GLUTAMATE-CONTAINING AXON TERMINALS IN THE RAT STRIATUM

Glutamate, the major transmitter of the corticostriatal pathway, is pr esent in abundance in the striatum. 3-Hydroxyanthranilic acid oxygenas e (3HAO) is the biosynthetic enzyme for quinolinic acid, an endogenous agonist of the NMDA glutamate receptor subtype and a potent neurotoxi n. In order to explore the anatomical basis of possible functional int eractions between glutamate and quinolinic acid in the rat striatum, p re- and postembedding immunocytochemical methods were used to localize 3HAO immunoreactivity (-i) and glutamate-i at the electron microscopi c level. In accordance with previous light microscopic and biochemical studies, 3HAO-i was detected exclusively in astrocytes throughout the striatum. Notably, 3HAO-i was present in fine-caliber glial processes that often surrounded or abutted synaptic profiles, both asymmetric a nd symmetric. Glutamate-i was heavily deposited (3-13-fold higher gold particle density than tissue average) in axon terminals forming asymm etric synapses with spines and, occasionally, dendrites. In contrast, terminals forming symmetric synapses, dendrites, neuronal somata, and glial cells contained significantly less labeling than terminals formi ng asymmetric synapses. In double-labeled material, 3HAO-i was observe d in glial processes that partially surrounded or were adjacent to glu tamate-labeled terminals forming asymmetric synapses. 3HAO-labeled gli al processes were also adjacent to unlabeled terminals forming symmetr ic synapses. Since quinolinic acid is known to enter the extracellular compartment readily, these results suggest that astrocytic quinolinic acid may participate in the regulation of glutamatergic neurotransmis sion in the rat striatum.