Area-specific regulation of γ-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 γ-aminobutyric acid type A (GABA(A)) receptors in developing rat neocortex, leading to the area-specific expression of receptor subtypes in the primary visual (V1) and somatosensory (S1) areas. Most strikingly, the α1- and α5-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 α1 subunit was strongly down-regulated in these layers to a level comparable to that in neighboring areas. Conversely, the α5 subunit was up-regulated and areal boundaries were no longer discernible in the lesioned hemisphere. Changes similar to the α5 subunit were also seen for the α2 and α3 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.