Fig. 6: Knockdown of TARP-γ8 in excitatory neurons in the ventral hippocampus blocks the antidepressant effects of ketamine.

a Immunofluorescence results showing TARP-γ8 (green) was mainly expressed in CaMKIIα (purple)-expressing neurons rather than GAD67 (purple)-expressing neurons. Scale bar = 30 μm (two bars on the left), 50 μm (two bars on the right). DAPI (blue). Experiments were repeated independently 3 times with similar results. b AAV-expressing constructs with CaMKIIα promoter encoding GFP and shRNAs targeting TARP-γ8. c Timeline of experimental procedure. d Preference for sucrose in the SPT (n = 8 samples per group). e Immobility time in the FST (n = 8, 8, 9, and 10 in Vehicle-Scr-shRNA, Vehicle-Cacng8-shRNA, Ketamine-Scr-shRNA and Ketamine-Cacng8-shRNA, respectively). f Total distance in the OFT (n = 8, 9, 10 and 10 in Vehicle-Scr-shRNA, Vehicle-Cacng8-shRNA, Ketamine-Scr-shRNA and Ketamine-Cacng8-shRNA, respectively). g Representative traces of AMPARs-mediated mEPSC recordings from excitatory neurons in the ventral hippocampus. h Quantification of cumulative probability and amplitude and frequency of mEPSCs (n = 10 cells from 4 mice in Vehicle-Scr-shRNA, n = 9 cells from 4 mice in Vehicle-Cacng8-shRNA, n = 7 cells from 4 mice in Ketamine-Scr-shRNA and n = 8 cells from 4 mice in Ketamine-Cacng8-shRNA). Comparisons were performed by two-way ANOVA analysis followed by Bonferroni’s multiple comparisons test. Data are presented as mean ± SEM. All numbers (n) are biologically independent experiments. Source data are provided as a Source Data file.