Characterization of glutamate receptor interacting protein-immunopositive neurons in cerebellum and cerebral cortex of the albino rat

Glutamate receptor interacting protein (GRIP) binds to the C-terminus of th e glutamate receptor 2 (GluR2) subunit of alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionate (AMPA) receptors in vitro and may play an important rol e in the synaptic organization of these receptors. To determine the distrib ution of GRIP in vivo, GRIP was localized immunocytochemically in cerebellu m and cerebral cortex of adult Sprague-Dawley rats. In the cerebellar corte x, GRIP staining was prominent in perikarya and proximal dendrites of Purki nje cells, whereas Golgi cells were stained more weakly. Double labeling re vealed that GRIP and GluR2 were colocalized in Purkinje cells but not in Go lgi cells. In the cerebral cortex, GRIP-stained dendrites and somata of non pyramidal neurons were scattered throughout cortical layers, whereas pyrami dal cells were only weakly immunopositive. GRIP was especially prominent in a subset of GluR2-containing cells that also expressed a high level of Glu R1. The large majority of strongly GRIP-positive cells in neocortex were im munopositive for gamma-aminobutyric acid (GABA), including the overwhelming majority of calbindin-positive cells in superficial cortical layers, most of the parvalbumin-positive cells, and half of the calretinin-positive inte rneurons. Staining in the neuropil became more punctate after antigen was u nmasked with proteinase K. Electron microscopic localization in the cerebra l cortex by postembedding immunogold showed that somatic GRIP was associate d with rough endoplasmic reticulum and Golgi apparatus. GRIP was seen over the postsynaptic density of axospinous and axodendritic asymmetric synapses and at high levels in dendrites of GABA-positive neurons. The present data support a role for GRIP in anchoring AMPA receptors and suggest that GRIP trafficking may be especially active in GABAergic neurons. (C) 1999 Wiley-L iss, Inc.