Expression and distribution of metabotropic GABA receptor subtypes GABABR1 and GABABR2 during rat neocortical development

To understand the possible contribution of metabotropic gamma-aminobutyric acid receptors (GABA(B) R) in cortical development, we investigated the expression pattern and the cellular and subcellular localization of the GABA(B) R1 and GABA(B) R2 subtypes in the rat neocortex from embryonic day 14 (E14) to adulthood. At the light microscopic level, both GABA(B) R1 and GABA(B) R2 were detected as early as E14. During prenatal development, both subtypes were expressed highly in the cortical plate. Using double immunofluorescence, GABA(B) R1 colocalized with GABA(B) R2 in neurons of the marginal zone and subplate, indicating that these proteins are coexpressed and could be forming functional GABA(B) Rs during prenatal development in vivo . In contrast, only GABA(B) R1 but not GABA(B) R2 was detected in the tangentially migratory cells in the lower intermediate zone. During postnatal development, immunoreactivity for GABA(B) R1 and GABA(B) R2 was distributed mainly in pyramidal cells. Discrete GABA(B) R1-immunopositive cell bodies of interneurons were present throughout the neocortex. In addition, GABA(B) R1 but not GABA(B) R2 was found in identified Cajal-Retzius cells in layer I. At the electron microscopic level, immunoreactivity for GABA(B) R1 and GABA(B) R2 was found in dendritic spines and dendritic shafts at extrasynaptic and perisynaptic sites throughout postnatal development. We further demonstrated the presynaptic localization of GABA(B) R1 and GABA(B) R2, as well as the association of the receptors with asymmetrical synaptic junctions. These results indicate potentially important roles for the GABA(B) Rs in the regulation of migratory processes during corticogenesis and in the modulation of synaptic transmission during early development of cortical circuitry.