GABAA-receptor subtypes in developing brain. Actors or spectators?
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.
Institute of Pharmacology, University of Zurich, Switzerland.
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Paysan
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Fritschy
D000818:Animals; D001921:Brain / Q000254:growth & development* / Q000378:metabolism* / Q000502:physiology; D002454:Cell Differentiation; D006801:Humans; D009474:Neurons / Q000378:metabolism; D020033:Protein Isoforms / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D011963:Receptors, GABA-A / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*
D020033:Protein Isoforms; D011963:Receptors, GABA-A