GABAA receptors in the basal ganglia of the rat, baboon and the human brain

Abstract

The regional, cellular and subcellular distribution of GABAA receptors was investigated in the striatum and globus pallidus of the rat, baboon and human brain using receptor autoradiography, and multiple immunohistochemical labelling techniques at the light, confocal and electron microscopic levels using antibodies to the α1, α2, α3, β2,3 and γ2-subunits of the GABAA receptor complex. The results demonstrated that GABAA receptors in the striatum showed considerable subunit heterogeneity in their regional (primate brain) and cellular distribution (rodent and primate brain). At the regional level in the baboon and human brain, GABAA receptors in the striosome compartment contained the α2, α3, β2,3 and γ2-subunits while receptors in the matrix compartment contained the α1, α2, α3, β2,3 and γ2-subunits In general terms in both the rodent and the primate brain, up to six different types of neurons were identified in the striatum. There was considerable species diversity in the cell types. Two main types of neurons (type 1 and type 2) immunoreactive for the subunits α1,β2,3,γ2 were identified in the striatum. They were GAD positive and were classified according to their cellular morphology and staining properties; rat type 1 neurons were GAD positive only, while human type 1 neurons were GAD and parvalbumin positive. Type 2 neurons were identified in both the rat (GAD positive only) and in human (GAD and calretinin positive). All three mammalian species showed the presence of type 3 neurons which were large neurons with few spines and immunoreactive for subunits α1,3,β2,3,γ2. Type 4 neurons were calbindin positive and immunoreactive for subunits α2,3,β2,3,γ2. The remaining neurons were immunoreactive for ChAT and the α3-subunit (type 5), or immunoreactive for neuropeptide Y with no GABAA receptor subunit immunoreactivity (type 6). The globus pallidus contained three types of neurons; type 1 neurons contained parvalbumin and type 2 contained parvalbumin and calretinin and both were immunoreactive for subunits α1,β2,3, γ2 while type 3 neurons were medium-sized calretinin neurons immunoreactive for the subunits α1,β2,3,γ2 At the ultrastructural level in the globus pallidus, α1 and β2,3-subunits were localised on large neurons (types 1 and 2) and were found at three types of synaptic terminals. These results show that the subunit composition of GABAA receptors displays considerable regional and cellular variation in the striatum, but is more homogeneous in the globus pallidus.