Developmental Switch in the Expression of GABAA Receptor Subunits [Alpha] 1 and [Alpha] 2 in the Hypothalamus and Limbic System of the Rat

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Developmental Brain Research


GABAA receptor, pentameric ligand, brain development, genetics, hypothalamus, limbic system, amygdala, hippocampus

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The GABAA receptor is a pentameric ligand gated ion channel complex assembled from a family of at least 17 different subunits encoded by distinct genes. Two subunits, α1 and α2, exhibit age dependent expression throughout several areas of the brain. In general, the density of immunoreactive product for α1 is greatest in the adult brain, while α2 is highest in younger tissue. Since the developmental switch in α1 and α2 coincides with the end of the sensitive period for steroid-mediated sexual differentiation of the brain, we hypothesized that GABAA receptor subunit expression may be involved in this process. We have examined the age-dependent expression of α1 and α2 in discrete regions of the hypothalamus and limbic system of males and females. While we did not detect any dramatic sex differences in α1 or α2 immunoreactive density, each region exhibited a unique developmental profile. In the ventromedial nucleus of neonatal animals immunoreactivity is highest for α1, while in the adult the signal for α2 is greater; the opposite of that observed in the ventrolateral thalamus. There is no age dependent change for α1 in the preoptic area, while α2 shows a small, but significant increase. Immunoreactive densities for both subunits increase in the arcuate nucleus and the hippocampus, but decrease in the lateral amygdala. We conclude that these regional differences in subunit expression across development determine individual characteristics of brain areas and may play a role in establishing unique physiological responses to GABA.