Fig. 4

Tau accumulation disrupts the discharge of excitatory and PV neurons. a Timeline of the experimental procedures. b Schematic of AAV-CaMKII-hTau-mCherry injection into the vCA1 of C57BL/6 mice. c Representative traces of action potentials of CaMKII⁺ neurons from the control and vCA1-hTau^CaMKII groups following the injection of currents. Ctrl: n = 19 neurons from 4 mice; vCA1-hTau^CaMKII: n = 22 neurons from 5 mice. d Schematic of AAV-DIO-hTau-mCherry injection into the vCA1 of PV-Cre mice. e Representative traces of action potentials of PV neurons from the control and vCA1-hTau^PV groups following the injection of currents. Ctrl: 21 neurons from 5 mice; vCA1-hTau^PV: 24 neurons from 5 mice. Representative image of GCaMP6f expression in CaMKII-hTau⁺ (f) and PV-hTau⁺ (g) neurons in the vCA1. The arrows indicate colabelled cells. Scale bar = 100 μm. h Representative traces of GCaMP6f signals in the control and vCA1-hTau^CaMKII groups. i Per-bout stacked plots of CaMKII-GCaMP6f signals were aligned to the start of the interaction event. The presence of “#” indicates a significant increase in the average calcium signals during the social exploration period (the first 2 s) compared to the baseline period (2 s before social exploration). n = 8 per group. j Quantitative analysis of peak dF/F of Ca²⁺ signals in CaMKII⁺ neurons during the social memory test. k Representative traces of GCaMP6f signals in the control and vCA1-hTau^PV groups. l Per-bout stacked plots of PV-GCaMP6f signals aligned to the start of the interaction event. The presence of “#” indicates a significant increase in the average calcium signals during the social exploration period (the first 2 s) compared to those during the baseline period (2 s before social exploration). n = 6 per group. m Quantitative analysis of peak dF/F of Ca²⁺ signals in PV⁺ neurons during the social memory test. n = 6 mice per group. ^*P < 0.05; ^**P < 0.01, as determined by two-way ANOVA, two-way repeated ANOVA, two-tailed unpaired t test or two-tailed t test. The data are presented as the mean ± SEM. IHC immunohistochemistry, CaMKII calcium/calmodulin-dependent protein kinase II, PV parvalbumin, vCA1 ventral hippocampal CA1, GCaMP6f genetically encoded calcium indicators, hTau human tau