THE PARAFASCICULAR THALAMIC NUCLEUS MODULATES MESSENGER-RNA ENCODING GLUTAMATE-DECARBOXYLASE-67 IN RAT STRIATUM

We investigated whether the parafascicular thalamostriatal pathway, on e of the major excitatory inputs to the striatum, regulates the expres sion in rat striatum of isoforms of glutamate decarboxylase (mel. wt 6 7,000: glutamate decarboxylase 67 and mel. wt 65,000: glutamate decarb oxylase 65). Acute (one day) and chronic (14 days) electrolytic lesion s of the parafascicular nucleus resulted in 58% and 23% decreases in g lutamate decarboxylase 67 messenger RNA expression, respectively, as d etermined by northern blot analysis. Glutamate decarboxylase 65 messen ger RNA was not modified by either lesion. Sections of sham- and acute -lesioned striata were processed for in situ hybridization histochemis try al the single cell level with an RNA probe for glutamate decarboxy lase 67. Labelling of glutamate decarboxylase 67 messenger RNA was dec reased in both types of cells known to be present in the striatum, i.e . the lightly and the very densely-labelled neurons. The frequency dis tribution of glutamate decarboxylase 67 labelling per neuron in the le sioned striata, in fact, was shifted to the left and its median was lo wer than in the sham-lesioned striata. In view of the excitatory natur e of the thalamostriatal pathway, we examined the subtype of glutamate receptors modulating the glutamate decarboxylase 67 gene expression. The N-methyl-D-aspartate-type receptor antagonist, dizocilpine, at 0.1 -0.5 mg/kg i.p., produced a marked and persistent reduction in striata l glutamate decarboxylase 67 messenger RNA. The non-N-methyl-D-asparta te receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione (12 nmol/side , i.c.v.) had no such effect. The results provide evidence that excita tory thalamostriatal afferents selectively modulate the gene expressio n of glutamate decarboxylase 67, probably through the N-methyl-D-aspar tate subtype of glutamate receptors. (C) 1997 IBRO. Published by Elsev ier Science Ltd.