Area-specific regulation of gamma-aminobutyric acid type A receptor subtypes by thalamic afferents in developing rat neocortex

Targeting and innervation of the cerebral cortex by thalamic afferents is a key event in the specification of cortical areas, The molecular targets of thalamic regulation, however, have remained elusive. We now demonstrate that thalamic afferents regulate the expression of gamma-aminobutyric acid type A (GABA(A)) receptors in developing rat neocortex, leading to the area-specific expression of receptor subtypes in the primary visual (VI) and somatosensory (S1) areas, Most strikingly, the alpha 1- and alpha 5-GABA(A) receptors exhibited a reciprocal expression pattern, which precisely reflected the distribution of thalamocortical afferents at postnatal day 7, Following unilateral lesions at the birth of the thalamic nuclei innervating V1 and S1 (lateral geniculate nucleus and ventrobasal complex, respectively), profound changes in subunit expression were detected 1 week later in the deprived cortical territories (layers III-IV of V1 and S1), The expression of the alpha 1 subunit was strongly down-regulated in these layers to a level comparable to that in neighboring areas, Conversely, the alpha 5 subunit was up-regulated and areal boundaries were no longer discernible in the lesioned hemisphere, Changes similar to the alpha 5 subunit were also seen for the alpha 2 and alpha 3 subunits, These results indicate that the differential expression of GABA(A) receptor subtypes in developing neocortex is dependent on thalamic innervation, contributing to the emergence of functionally distinct areas.