GABAA receptor subunits in the human amygdala and hippocampus: Immunohistochemical distribution of 7 subunits

Abstract

GABAergic neurotransmission in the amygdala contributes to the regulation of emotional processes in anxiety, stress, reward, mnestic functions, addiction, and epilepsy. Species-specific differences in the distribution and composition of GABAA receptors may account for distinct effects and side-effects of GABAergic agents. However, data on the distribution and composition of GABAA receptors in the human amygdala are lacking. Here, the expression of GABAA receptor subunits α1, α2, α3, α5, β2, β2/3, and γ2 was studied in the human amygdala using immunohistochemistry. Hippocampi were evaluated as a reference structure. Neuronal counts and field fraction analyses were performed, and subcellular expression of GABAA receptor subunits was analyzed semiquantitatively. In the amygdala, field fraction analyses showed the highest α1 expression in the lateral nucleus (La), whereas α3 was prominent in intercalated nuclei (IC), and α5 and γ2 in the cortical nuclei, and amygdalo-hippocampal/parahippocampal-amygdala transition areas. In the hippocampus, α1 and α3 were accentuated in the dentate gyrus, CA1 region, and subiculum, whereas α5 expression was rather uniform. In both regions, α2 was homogenously distributed, and the two β subunits and γ2 showed faint immunostaining. The intensity of subunit expression also varied in the neuropil, neuronal somata, and/or cellular processes in the subregions. GABAA receptors containing subunit α1, showing the strongest expression in the La, and α3, with the strongest expression in the IC and subiculum, could be targets for treating amygdala-related disorders. Differences in GABAA receptor subunit expression between the human and rodent amygdala should be taken into consideration when developing subunit-selective drugs.