Figure 1. Targeted reduction of α2 expression in CA1, CA3 or DG.
(A) Generation of the α2F/F control and α2CA1KO, α2CA3KO, α2DGKO mice. (B) Top: False color images showing the α2 staining intensity in immunohistochemically stained sections. Cooler colors = less staining. Bottom: Semi-quantitative comparisons of α2 staining. (C) α2 mRNA expression (see sample ROI’s on the right), expressed as% of α2F/F control.*p<0.05, **p<0.01, ***p<0.001 compared to corresponding α2F/F group.
Figure 1—figure supplement 1. Immunohistochemical localization of GABAAR α2 subunits in conditional knockout mice bred on a 129X1/SvJ background.
(A) False color images showing α2 staining intensity in immunohistochemically stained sections in α2F/F mice.Cooler colors = less staining. (B) Same as A for α2CA1KO, (C) Same as A for α2CA3KO, (D) Same as A for α2DGKO.
Figure 1—figure supplement 2. Expression of α1 and α5 subunits in conditional knockout mice.
(A) Top: Representative gray-scale images showing the α1 staining intensity in immunohistochemically stained sections from the hippocampus, cortex and the amygdala of α2F/F, α2CA1KO, α2CA3KO and α2DGKO mice. Bottom: Semi-quantitative comparisons of α1 staining intensity between α2F/F, α2CA1KO, α2CA3KO and α2DGKO mice in CA1, CA3, DG, cortex and the amygdala. (B) Same as A for α5.
Figure 1—figure supplement 3. Expression of α3 and α4 mRNA in conditional knockout mice.
(A) Gabra3 expression in CA1, CA3, DG, cortex and the amygdala of α2F/F, α2CA1KO, α2CA3KO and α2DGKO mice expressed as percentage of α2F/F control. (B) Same as A for Gabra4. *p<0.05 in comparison to the corresponding α2F/F control group.
Figure 1—figure supplement 4. Miniature inhibitory postsynaptic currents.
Mean ( ± S.E.M.) decay time, frequency, amplitude of mIPSCs recorded from (A) the CA1 pyramidal neurons in α2CA1KO and α2F/F sections, (B) the CA3 pyramidal neurons in α2CA3KO and α2F/F sections, (C) the DG granule cells in α2DGKO and α2F/F sections. **p<0.01, ***p<0.001. CTRL=vehicle-treated, DZP=diazepam-treated.
Figure 1—figure supplement 5. Tests of hippocampal function.
(A) Mean ( ± S.E.M.) percentage of time spent freezing during the tone 24 hr after auditory fear-conditioning using a delay (black) or trace (white) protocol.*p<0.05, ***p<0.001, different from the corresponding delay group. No significant differences were found in planned pair-wise comparisons of the genotypes within the trace-conditioned groups or within the delay-conditioned groups. (B) Mean ( ± S.E.M.) percentage of time spent freezing during re-exposure to the context 24 hr after contextual fear-conditioning. ***p<0.001, different from α2F/F. (C) Mean ( ± S.E.M.) distance to platform during probe trials. *p<0.05, ***p<0.001, different from α2F/F; gray: α2CA3KO, red: α2DGKO.