Fig 1: Specific elimination of a5-GABAARs from interneurons versus pyramidal neurons. A) Genetic strategies used to eliminate a5-GABAARs from interneurons (top) or pyramidal neurons (bottom). For a5-i-KO mice, Cre recombinase was driven by the interneuron-specific GAD2 promoter to target the floxed Gabra5 gene. For a5-pyr-KO mice, Cre was driven by the pyramidal neuron-specific CaMKIIa promoter. B) Western blot analysis of a5-GABAAR (55 kDa) expression in male and female WT, p-WT, a5-i-KO, and a5-gl-KO mice. Expression levels were normalized to ß-actin (42 kDa) and quantified by densitometry. Note that receptor levels were unchanged in p-WT and a5-i-KO mice versus WT mice, consistent with maintained expression in pyramidal neurons. C) Immunohistochemical analysis of a5-GABAAR expression levels in interneurons, in WT, a5-gl-KO, a5-i-KO, and a5-pyr-KO mice (ordered from top to bottom). Significant loss of a5-GABAAR staining from interneurons (GAD2-positive cells) was seen in a5-gl-KO and a5-i-KO but not a5-pyr-KO mice. (D) Quantification of punctate a5-GABAAR staining within all identified interneurons (GAD2+/DAPI+ neurons) in WT, a5-gl-KO, a5-i-KO, and a5-pyr-KO mice (N = 3 for each genotype). Expression levels were significantly reduced in a5-gl-KO and a5-i-KO mice but not in a5-pyr-KO mice.