CELLULAR, SUBCELLULAR, AND SUBSYNAPTIC DISTRIBUTION OF AMPA-TYPE GLUTAMATE-RECEPTOR SUBUNITS IN THE NEOSTRIATUM OF THE RAT

Glutamate released in the basal ganglia is involved in the expression of clinical symptoms of neurodegenerative diseases like Parkinson's or Huntington's. Neostriatal neurons are the targets of glutamatergic in puts derived from the cortex and the thalamus acting via AMPA-type as well as other glutamate receptors. To determine the location of subuni ts of the AMPA subclass of glutamate receptors (GluR) in the rat neost riatum, we applied multiple immunocytochemical techniques using anti-p eptide antibodies against the GluR1, GluR2/3, and GluR4 subunits at bo th the light and electron microscopic levels. All medium spiny efferen t neurons, some of which were identified as striatonigral neurons, dis played immunoreactivity for GluR1 and GluR2/3 subunits. Double immunof luorescence revealed that at least 70-90% of parvalbumin-immunopositiv e GABAergic interneurons were immunoreactive for each of GluR1, GluR2/ 3, or GluR4 subunits and that at least 40% of choline acetyltransferas e-immunopositive cholinergic interneurons were immunopositive for GluR 1 or GluR4 subunits. The majority of nitric oxide synthase-immunoposit ive neurons had no detectable immunoreactivity for any of the AMPA rec eptor subunits. Electron microscopic analysis confirmed the presence o f immunoreactivity for GluR1 and GluR2/3 in the perikarya of spiny neu rons and interneurons and GluR4 in perikarya of interneurons only. Glu R1 and GluR2/3 subunits were detected in dendrites and spines. A signi ficant population of extrasynaptic receptors was revealed by pre-embed ding immunogold labeling along the plasma membranes of perikarya, dend rites, and spines. Receptors were concentrated in the postsynaptic mem brane specialization of asymmetrical synapses, as revealed by the post embedding immunogold method. Quantitative analysis demonstrated that i mmunoreactivity for the GluR1 and GluR2/3 subunits is higher at the pe riphery than at the middle of the postsynaptic membrane specialization . Our results demonstrate that AMPA receptor subunits are distributed widely and heterogeneously among striatal neurons and are concentrated on the postsynaptic membrane of asymmetrical synaptic specializations , although extrasynaptic receptors are also present.