Figure 3. CRISPR knockdown of δ-GABA_ARs in the BLA induced behavioral deficits.

(A) A schematic of the sgRNA construct for knockdown of Gabrd and overview of viral targeting strategy in the BLA of PV/Cas9 mice. (B) Representative co-labeling for δ-GABA_ARs (DAB) and sgRNA expression (GFP) confirmed a loss of δ-GABA_ARs in GFP-positive cells. The average number of cells expressing δ-GABA_ARs in the BLA was reduced in mice injected with sgGabrd compared to controls (inset). sgGabrd mice exhibited a reduction in the total distance traveled, number of entries, and a reduction in basic movements with no change in the amount of time spent in the open arm of the elevated plus maze compared to controls (C) control n=5, sgGabrd n=13. sgGabrd mice exhibited an increase in the total time spent immobile in the forced swim test compared to controls without any change in the latency to immobility (D) control n=5, sgGabrd n=13. (E) A summary of behavioral outcomes for knockdown of δ-GABA_ARs from PV interneurons in the BLA for transparency across figures and experiments. *denotes p < 0.05, **p<0.01, ***p<0.001, ****p<0.0001 using an unpaired t-test.