Ontogeny and distribution of GABA A receptors in rat brainstem and rostral brain regions

Abstract

Previous studies from our laboratory and others have shown that there are major age-related differences in brainstem neuronal function. Since GABA A receptors are major targets for GABA-mediated inhibitory modulation and play a key role in regulating cardiorespiratory function, especially during O 2 deprivation, we examined differences in GABA A receptor density and distribution during postnatal development. Using quantitative receptor autoradiography, the present study was performed to examine the postnatal expression of GABA A receptors in the rat brainstem and rostral brain areas at five ages, i.e. postnatal day 1 (P1), P5, P10, P21 and P120. Ten-micrometer brain sections at different brain levels were labelled with [ 3H]muscimol in Tris-citrate buffer. We found that (i) GABA A receptors appeared very early in almost all the brainstem as well as rostral areas; (ii) at P1, the brainstem had a higher GABA A receptor binding density than rostral areas and its density peaked at P5 or P10; and (iii) receptor densities of the cerebellum and rostral brain areas such as cortex, thalamus and dentate gyrus increased with age, especially between P10 and P21, but most other subcortical areas like caudate-putamen and hippocampal CA1 area did not increase remarkably after birth. We conclude that: (i) GABA A receptors exist in most brain areas at birth; (ii) there are several patterns of postnatal development of GABA A receptors in the CNS with dramatic differences between the brainstem and cortex; (iii) brainstem functions rely more on GABA A receptors in early postnatal life than at more mature stages. We speculate that GABA A receptors develop earlier in phylogenetically older structures (such as brainstem) than in newer brain regions (such as cortex).