Figure 6. Upregulation of α5-GABA_A receptors in the dentate granule cells of 5xFAD animals.

(a) Dentate granule cells in WT animals (left) showed a small component of tonic current that was sensitive to the inverse agonist L-655,708 (100 nM) specific for α5-GABA_A-Rs, but L-655,708 blocked the majority of tonic current in the dentate granule cells of 5xFAD animals (right). 5 μM GABA was included in the bath solution to increase the tonic current. (c) CA1 pyramidal neurons showed similar L-655,708-sensitive tonic currents between WT and 5xFAD animals. (b & d) Quantified data showing increased tonic current mediated by the α5-GABA_A-Rs in dentate granule cells of 5xFAD animals. (e, f) Double immunostaining of the α5 subunit (red) and GAD65 (green) in the dentate gyrus revealed a significant increase of α5 puncta in the dentate granule cells of 5xFAD mice. Inset showing the majority of α5 puncta were extrasynaptic, not colocalizing with presynaptic GAD65 puncta. Scale bar = 20 μm. (g, h) Quantified data showing increased α5 puncta number, but not GAD65, in the DG of 5xFAD mice (n = 6 mice for WT and 9 mice for 5xFAD group). No differences were found in CA1 or CA3 regions between WT and 5xFAD mice. Data are presented as mean ± s.e.m., *** P < 0.001, Student’s t test.