Journal of Neuroscience, Vol 15, 1150-1161, Copyright © 1995 by Society for Neuroscience
3-Hydroxyanthranilic acid oxygenase-containing astrocytic processes surround glutamate-containing axon terminals in the rat striatum
RC Roberts, KE McCarthy, F Du, OP Ottersen, E Okuno and R Schwarcz
Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore 21228.
Glutamate, the major transmitter of the corticostriatal pathway, is present
in abundance in the striatum. 3-Hydroxyanthranilic acid oxygenase (3HAO) is
the biosynthetic enzyme for quinolinic acid, an endogenous agonist of the
NMDA glutamate receptor subtype and a potent neurotoxin. In order to
explore the anatomical basis of possible functional interactions between
glutamate and quinolinic acid in the rat striatum, pre- and postembedding
immunocytochemical methods were used to localize 3HAO immunoreactivity (-i)
and glutamate-i at the electron microscopic 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 and symmetric. Glutamate-i was heavily
deposited (3-13-fold higher gold particle density than tissue average) in
axon terminals forming asymmetric synapses with spines and, occasionally,
dendrites. In contrast, terminals forming symmetric synapses, dendrites,
neuronal somata, and glial cells contained significantly less labeling than
terminals forming asymmetric synapses. In double-labeled material, 3HAO-i
was observed in glial processes that partially surrounded or were adjacent
to glutamate-labeled terminals forming asymmetric synapses. 3HAO-labeled
glial processes were also adjacent to unlabeled terminals forming symmetric
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 neurotransmission in the
rat striatum.