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Developmental profile of GABA A ‐receptors in the marmoset monkey: Expression of distinct subtypes in pre‐ and postnatal brain
Author(s) -
Hornung JeanPierre,
Fritschy JeanMarc
Publication year - 1996
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/(sici)1096-9861(19960408)367:3<413::aid-cne7>3.0.co;2-8
Subject(s) - forebrain , neocortex , biology , marmoset , gabaa receptor , synaptogenesis , protein subunit , basal forebrain , receptor , neuroscience , endocrinology , medicine , central nervous system , genetics , paleontology , gene
Gamma aminobutyric acid (GABA) A ‐receptors are expressed in fetal mammalian brain before the onset of synaptic inhibition, suggesting their involvement in brain development. In this study, we have analyzed the maturation of the GABA A ‐receptor in the marmoset monkey forebrain to determine whether distinct receptor subtypes are expressed at particular stages of pre‐ and postnatal ontogeny. The distribution of the subunits α1, α2, and β2,3 was investigated immunohistochemically between embryonic day 100 (6 weeks before birth) and adulthood. Prenatally, the α2‐ and β2,3‐subunit‐immunoreactivity (‐IR) was prominent throughout the forebrain, whereas the α1‐subunit‐IR appeared in selected regions shortly before birth. The α2‐subunit‐IR disappeared gradually to become restricted to a few regions in adult forebrain. By contrast, the α1‐subunit‐IR increased dramatically after birth and replaced the α2‐subunit in the basal forebrain, pallidum, thalamus, and most of the cerebral cortex. Staining for the β2,3‐subunits was ubiquitous at every age examined, indicating their association with either the α1‐ or the α2‐subunit in distinct receptor subtypes. In neocortex, the α1‐subunit‐IR was first located selectively to layers IV and VI of primary somatosensory and visual areas. Postnatally, it increased throughout the cortex, with the adult pattern being established only during the second year. The switch in expression of the α1‐ and α2‐subunits indicates that the subunit composition of major GABA A ‐receptor subtypes changes during ontogeny. This change coincides with synaptogenesis, suggesting that the emergence of α1‐GABA A ‐receptors parallels the formation of inhibitory circuits. A similar pattern has been reported in rat, indicating that the developmental regulation of GABA A ‐receptors is conserved across species, possibly including man. However, the marmoset brain is more mature than the rat brain at the onset of α1‐subunit expression, suggesting that α1‐GABA A ‐receptors are largely dispensable in utero, but may be required for information processing after birth. © 1996 Wiley‐Liss, Inc.