GABAA receptor alpha 1 subunit, an early marker for area specification in developing rat cerebral cortex

Abstract

Changes in the expression of neurotransmitter receptors in developing cerebral cortex may be related to the functional maturation of distinct areas. In the present study, we have tested whether GABAA receptor expression in neonatal rats reflects the differentiation of cortical areas. Specifically, the alpha 1 subunit, one of the most prevalent GABAA receptor subunits in adult cerebral cortex, is up-regulated postnatally, suggesting a link with the establishment of inhibitory circuits. Using immunohistochemistry with a subunit-specific antiserum, we observed a striking area- and lamina-specific increase in staining for GABAA receptors containing the alpha 1 subunit (alpha 1-GABAA receptors), from low levels in neonates to an intense and uniform staining in adults. Already at birth, the alpha 1-subunit immunoreactivity selectively demarcated the boundaries of certain cortical areas. In particular, the primary somatosensory (S1) and visual (V1) areas were distinctly delineated with a band of alpha 1-subunit immunoreactivity located in the developing layers III and IV. The staining ended abruptly at the presumptive boundaries of S1 and V1, adjacent areas being unstained at this age. Around postnatal day 3, clusters of alpha 1-subunit positive cells were seen in layers III-IV of S1 and V1 extending their dendrites up to layer I, where they arborized profusely. In addition, the distribution of alpha 1-GABAA receptors in S1 revealed in detail the differentiation of the barrel field during early postnatal development. Although staining was observed in all areas by postnatal day 6, differences in the laminar distribution of alpha 1-GABAA receptors persisted for at least 1 more week. Our results provide evidence for the existence of area-specific boundaries in neocortex of newborn rats before layers III-IV are fully differentiated and innervated by cortical afferents. Furthermore, the area- and lamina-specific maturation of alpha 1-GABAA receptor staining demonstrates the value of this marker for investigating the cytoarchitectonic differentiation of cortical areas during development.