GABAA-receptor subtypes in developing brain. Actors or spectators?

Abstract

Distinct GABAA-receptor subtypes, differing in subunit composition, physiology, and pharmacology, are expressed in fetal, neonatal, and adult brain. Their developmental schedule, evidenced by the differential maturation of the GABAA-receptor subunits alpha 1, alpha 2, and alpha 5, is similar in rodents and primates, indicating that the regulation of receptor subtypes is conserved across species. "Adult" GABAA-receptors, characterized by the alpha 1-subunit immunoreactivity, are largely absent from fetal brain. They appear, however, before the onset of functional inhibitory connections, suggesting that GABAA-receptors may play an active role in the formation of GABAergic synapses. In neocortex, the maturation of GABAA-receptor subtypes is governed by an intrinsic program, leading to an area- and lamina-specific distribution as early as E20 in rats. In primary somatosensory and visual areas, this pattern is influenced postnatally by the ingrowing thalamocortical projection, a process that can be prevented experimentally by lesioning the thalamus at birth. Altogether, the expression of GABAA-receptor subtypes in developing brain reflects the changing functional needs of neurons during differentiation, the formation of inhibitory circuits, and the emergence of functionally distinct brain compartments.