Abstract:
γ-Aminobutyric acidA (GABAA) receptors (GABAAR) are inhibitory heteropentameric chloride ion channels comprising a variety of subunits and are localized at postsynaptic sites within the central nervous system. In this study we present the first detailed immunohistochemical investigation on the regional, cellular, and subcellular localisation of α1, α2, α3, β2,3, and γ2 subunits of the GABAAR in the human substantia nigra (SN). The SN comprises two major regions, the SN pars compacta (SNc) consisting of dopaminergic projection neurons, and the SN pars reticulata (SNr) consisting of GABAergic parvalbumin-positive projection neurons. The results of our single- and double-labeling studies demonstrate that in the SNr GABAA receptors contain α1, α3, β2,3, and γ2 subunits and are localized in a weblike network over the cell soma, dendrites, and spines of SNr parvalbumin-positive nonpigmented neurons. By contrast, GABAARs on the SNc dopaminergic pigmented neurons contain predominantly α3 and γ2 subunits; however there is GABAAR heterogeneity in the SNc, with a small subpopulation (6.5%) of pigmented SNc neurons additionally containing α1 and β2,3 GABAAR subunits. Also, in the SNr, parvalbumin-positive terminals are adjacent to GABAAR on the soma and proximal dendrites of SNr neurons, whereas linear arrangements of substance P-positive terminals are adjacent to GABAA receptors on all regions of the dendritic tree. These results show marked GABAAR subunit hetereogeneity in the SN, suggesting that GABA exerts quite different effects on pars compacta and pars reticulata neurons in the human SN via GABAA receptors of different subunit configurations.
