The regional and cellular distribution of GABAA receptor subunits in the human amygdala

Abstract

GABAergic neurotransmission in the amygdala plays a crucial role in mediating emotional learning, fear, and memory. In this study, expression of five major GABAA receptor subunits (α1, α2, α3, β2,3, and γ2) was investigated in the normal human amygdala using immunohistochemistry. At the regional level, the amygdala contains a highly heterogeneous distribution of all the subunits investigated. The most intense staining for α1, α2, β2,3, and γ2 subunits was present in the lateral nucleus (LA), and α3 in the intercalated nuclei (ICM). Six distinct cell populations that express GABAA receptor subunits were identified throughout the amygdala: type 1 aspiny cells in the basolateral nuclear group (BLNG) and superficial cortical-like nuclear region (SCLR) express α1, β2,3, and γ2; type 2 larger aspiny cells in the paralaminar nucleus (PL) express α1, β2,3, and γ2; type 3 aspiny cells in the BLNG express α1, β2,3, and γ2 as well as calcium-binding proteins including parvalbumin (PV), calbindin (CB), and calretinin (CR); type 4 pyramidal cells in the BLNG and SCLR express α2, α3, β2,3, and γ2 subunits at high levels on proximal specialised spines; type 5 cells in the central nucleus (CE) express α2, α3, and β2,3; type 6 cells are found closely packed in the intercalated cell masses (ICM) and express α3 and β2,3. The α1 subunit rarely co-labelled with α2 and α3 in the same cell population, while the α2 and α3 were often expressed within the same type 4 or 5 cell though not at always at the same puncta. The predominant GABAA receptor subunit combinations expressed in the human amygdala are the α1β2,3γ2 and α2β2,3γ2. Cells classified as interneuron types (types 1–3) contained GAD and principally expressed α1β2,3γ2. The major projection neurons of the BLNG (type 4) are non-GABAergic and mainly express α2β2,3γ2. The α3 subunit was found intracellularly in type 5 cells and decorating the surface of type 6 cells but rarely co-labelled with the subunits investigated. The results reveal a complex and heterogeneous distribution of GABAA receptor subtypes throughout the amygdala as well as on a variety of cell types through which inhibitory processing is carried out to maintain emotional responses, and control anxiety and fear responses in the brain.