Identification of distinct GABAA-receptor subtypes in cholinergic and parvalbumin-positive neurons of the rat and marmoset medial septum-diagonal band complex.

GABAA-receptor heterogeneity is based on a multiplicity of subunits (alpha 1-6, beta 1-4, gamma 1-4, delta, rho 1-2) encoded by distinct genes. Flexibility in GABAergic signal transduction and allosteric modulation is expected to arise from the differential assembly of subunits into receptor subtypes. The aim of the present study was to investigate the potential diversity of receptor subtypes expressed by defined neuron populations, as identified by their neurotransmitter phenotype. To this end we have determined immunohistochemically the subunit repertoire of cholinergic and GABAergic neurons in the basal forebrain of rat and marmoset monkey, focusing on the medial septum-diagonal band complex. Co-localization of the GABAA-receptor subunits alpha 1, alpha 3, beta 2, beta 3, and gamma 2 with markers of cholinergic and GABAergic neurons (choline acetyltransferase and parvalbumin, respectively) was assessed by double- and triple immunofluorescence staining. The results reveal that cholinergic neurons in the rat basal forebrain are typically characterized by the subunit combination alpha 3/beta 3/gamma 2, whereas most of the parvalbumin-positive GABAergic neurons express either the subunit combination alpha 1/beta 2/gamma 2 or the combination alpha 1/alpha 3/beta 2/gamma 2. A similar pattern was observed in marmoset monkey, with GABAA-receptors containing the alpha 1-subunit being associated with parvalbumin-positive cells, but never with cholinergic neurons. Thus, the expression of distinct subunit repertoires by cholinergic and GABAergic neurons points to a functional specialization which is conserved across species. These subunit combinations are likely to correspond to different receptor subtypes, and may reflect the engagement of cholinergic and GABAergic neurons in distinct neuronal circuits in the basal forebrain.