Laminar segregation of the cortical plate during corticogenesis is accompanied by changes in glutamate receptor expression

We tested the hypothesis that subtypes of glutamate receptors (GluRs) are differentially expressed during corticogenesis. The neocortex of fetal sheep (term = approximately 145 days) was evaluated by immunoblotting and immunohistochemistry to determine the protein expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (GluR1, GluR2/GluR3 GluR2/3], and GluR4), kainate (KA) receptors (GluR6/GluR7 GluR6/7]), and a metabotropic GluR (mGluR5). AMPA/KA receptors and mGluR5 were expressed in neocortex by midgestation. GluR1 and mGluR5 expression increased progressively, with expression being maximal just before birth and then decreasing postnatally. GluR2/3 and GluR6/7 levels increased progressively during corticogenesis to reach adult levels near term. GluR4 was expressed at low levels during corticogenesis and in adult neocortex. The localizations of GluRs in the developing neocortex were distinct. Each GluR had a differential localization within the marginal zone, cortical plate, and subplate. GluR subtypes were expressed in laminar patterns before major cytoarchitectonic segregation occurred based on Nissl staining, although connectional patterns were emergent by midgestation based on labeling of corticostriatal projections with DiI. The GluR localizations changed during cortical plate segregation, resulting in highly differential distributions in the neocortex at term. AMPA/KA receptors were expressed transiently in proliferative zones and in developing white matter. Oligodendrocytes in fetal brain expressed AMPA receptors. The expression of ion channel and metabotropic GluR subtypes is dynamic during corticogenesis, with subtype- and subunit-specific regulation occurring during the laminar segregation of the cortical plate and differentiation of the neocortex.