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

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 GABA(A) receptors may account for distinct effects and side-effects of GABAergic agents. However, data on the distribution and composition of GABA(A) receptors in the human amygdala are lacking. Here, the expression of GABA(A) receptor subunits 1, 2, 3, 5, 2, 2/3, and 2 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 GABA(A) receptor subunits was analyzed semiquantitatively. In the amygdala, field fraction analyses showed the highest 1 expression in the lateral nucleus (La), whereas 3 was prominent in intercalated nuclei (IC), and 5 and 2 in the cortical nuclei, and amygdalo-hippocampal/parahippocampal-amygdala transition areas. In the hippocampus, 1 and 3 were accentuated in the dentate gyrus, CA1 region, and subiculum, whereas 5 expression was rather uniform. In both regions, 2 was homogenously distributed, and the two subunits and 2 showed faint immunostaining. The intensity of subunit expression also varied in the neuropil, neuronal somata, and/or cellular processes in the subregions. GABA(A) receptors containing subunit 1, showing the strongest expression in the La, and 3, with the strongest expression in the IC and subiculum, could be targets for treating amygdala-related disorders. Differences in GABA(A) receptor subunit expression between the human and rodent amygdala should be taken into consideration when developing subunit-selective drugs.