CEREBELLAR GRAFTS PARTIALLY REVERSE AMINO-ACID RECEPTOR CHANGES OBSERVED IN THE CEREBELLUM OF MICE WITH HEREDITARY ATAXIA - QUANTITATIVE AUTORADIOGRAPHIC STUDIES

We used quantitative autoradiography of [H-3]CNQX (200 nM), [H-3]musci mol (13 nM), and [H-3]flunitrazepam (10 nM) binding to study the distr ibution of non-NMDA and GABA, receptors in the cerebellum of pcd mutan t mice with unilateral cerebellar grafts, Nonspecific binding was dete rmined by incubation with 1 mM Glu, 200 mu M GABA, or 1 mu M clonazepa m, respectively, Saturation parameters were defined in wild-type and m utant cerebella, In mutants, non-NMDA receptors were reduced by 38% in the molecular layer and by 47% in the granule cell layer, The reducti on of non-NMDA receptors in the pcd cerebellar cortex supports their l ocalization on Purkinje cells, [H-3] CNQX binding sites were visualize d at higher density in grafts that had migrated to the cerebellar cort ex of the hosts (4.1 and 11.0 pmol/mg protein, respectively, at 23 and 37 days after grafting) than in grafts arrested intraparenchymally (2 .6 and 6.2 pmol/mg protein, respectively, at 23 and 37 days after graf ting), The pattern of expression of non-NMDA receptors in cortical vs, parenchymal grafts suggests a possible regulation of their levels by transacting elements from host parallel fibers, GABA(A) binding levels in the grafts for both Ligands used were similar to normal molecular layer, Binding was increased in the deep cerebellar nuclei of pcd muta nts: the increase in [H-3]muscimol binding over normal was 215% and th e increase in [H-3]flunitrazepam binding was 89%, Such increases in th e pcd deep cerebellar nuclei may reflect a denervation-induced superse nsitivity subsequent to the loss of Purkinje axon terminal innervation , In the deep nuclei of pcd mutants with unilateral cerebellar grafts, [H-3]muscimol binding was 31% lower in the grafted side than in theno ngrafted side at 37 days after transplantation; [H-3]flunitrazepam bin ding was also lower in the grafted side by 15% compared to the nongraf ted side, Such changes in GABA(A) receptors suggest a significant, alb eit partial, normalizing trend of cerebellar grafts on the state of po stsynaptic supersensitive receptors in the host cerebellar nuclei. (C) 1997 Elsevier Science Inc.