Striatal Ionotropic Glutamate Receptor Ontogeny in the Rat

Rat striatal N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and kainate (KA) receptor staining were evaluated postnatally in the rat. Immunohistochemistry was used to detect subunit proteins of the three glutamate receptor subtypes. The glutamate receptors displayed distinct developmental expression patterns in the striatum. Morphological distributions for the NMDA R1 subunit (representative of NMDA receptors), Glu R1 and Glu R2/3 subunits (indicative of AMPA receptors), and Glu R5/6/7 subunits (demonstrating KA receptors) attained adult expression patterns and levels at different postnatal time points. The ontogenic maturation sequence of striatal glutamate receptor expression was KA, then AMPA and lastly NMDA. Staining patterns for NMDA and AMPA subunit proteins were detected initially as dense patches in the neuropil, which changed to a homogeneous stain of the striatum by the second week of life. Cellular staining for the three subtypes was intense within the highly reactive neuropil patches, but less intensely stained in neurons located outside these zones. The KA receptor subunit did not exhibit neuropil heterogeneity, but was distributed evenly at birth. All three glutamate receptor subtypes were visible within the striatal neuron populations. Populations of striatal neurons that expressed the three differential glutamate receptor subtypes overlap, exhibit different growth patterns and dendritic staining. These results support a functional emergence of different glutamate receptor activation within the striatum and provide a potential therapeutic means to isolate developmental disorders specifically associated with excitatory circuits of the basal ganglia.