GLUTAMATE-RECEPTOR EXPRESSION IN RAT STRIATUM - EFFECT OF DEAFFERENTATION

The cerebral cortex is the primary source of glutamatergic afferents t o the neostriatum. We used in situ hybridization to examine the effect of removal of the glutamatergic input to the striatum by unilateral f rontal cortical ablation on the expression of genes encoding subunits from three families of glutamate receptors: N-methyl-D-aspartate recep tors (NMDAR1, NMDAR2A, and NMDAR2B); pha-amino-3-hydroxy-5-methyl-4-is oxazolepropionate (AMPA) receptors (GluR1-4, flip and flop splice vari ants); and metabotropic receptors (mGluR1-5). Significant changes were restricted to the dorsolateral quadrant of the ipsilateral striatum, the main projection area of the sensorimotor cortex. The expression of those messages which are normally abundant, NMDAR1, NMDAR2A, GluR1-4 flop and mGluR1, 3 and 5, was decreased in the deafferented dorsolater al striatum by 10-39% at 3 days after cortical ablation and subsequent ly increased to 120-165% of control at 15 and 60 days. mRNAs encoding the flip isoforms of GluR1-4, mGluR2 and 4, and an alternatively splic ed region of NMDAR1 (Insertion I) which are undetectable or present at low levels in the striatum were not induced by cortical ablation. In contrast, both glial fibrillary acid protein and p-actin mRNA expressi on were; markedly enhanced at 3 and 15 days, returning to near normal at 60 days. Striatal NMDA, AMPA and metabotropic type 1 ligand binding sites were increased as early as 3 days after cortical ablation, reac hed a peak at 15 days and remained increased for up to 60 days, while metabotropic type 2 binding was slightly but significantly reduced at 3 and 15 days and [H-3]kainate binding did not change significantly. T hese results demonstrate that cortical ablation, and subsequent loss o f glutamatergic afferents to the striatum, results in alterations in t he expression of genes encoding glutamate receptor subunits in striata l neurons. The regulation of these genes appears to be coordinate, so that the relative abundance of the different messages is preserved.