Additional file 1 of Targeting vulnerable microcircuits in the ventral hippocampus of male transgenic mice to rescue Alzheimer-like social memory loss

Additional file 1: Materials and methods. Table S1 Virus strains and their applications. Table S2. Antibody list. Fig. S1 A realistic picture for the social memory test. Fig. S2 Schematic representation of the dissection of vCA1 and dCA1. Fig. S3 Prominent accumulation of hyper-phosphorylated tau (p-Tau, AT8) in the ventral hippocampal CA1 (vCA1) of 3xTg-AD mice. Fig. S4 Accumulation of hyper-phosphorylated tau (p-Tau) in the vCA1 of 3-month-old female P301L and 8-month-old male P301S mice. Fig. S5 Differential proteins detected in the ventral hippocampal CA1 (vCA1) and dorsal hippocampal CA1 (dCA1) in WT and P301L mice. Fig. S6 Number of differentially phosphorylated proteins/sites detected in the ventral hippocampal CA1 (vCA1) and dorsal hippocampal CA1 (dCA1) in WT and P301L mice. Fig. S7 Male 3xTg-AD and P301L mice displayed social memory deficits. Fig. S8 Injection sites of AAV-hSyn-hTau-eGFP virus into the vCA1. Fig. S9 Overexpression hTau in vCA1 has no effect on anxiety-like behaviors. Fig. S10 Tau accumulation in the dCA1 has no effect on social memory. Fig. S11 Hyper-phosphorylated tau (p-Tau) is accumulated in excitatory and PV neurons of 3xTg-AD mice. Fig. S12 hTau accumulation increases the action potential threshold of CaMKII+ and PV+ neurons in the vCA1. Fig. S13 No transmission of hTau occurs from excitatory neurons (CaMKII+) to PV neurons in vCA1-hTauCaMKII mice. Fig. S14 hTau overexpression in PV or excitatory neurons does not affect the electrophysiological properties of excitatory or PV neurons. Fig. S15 Quantitative analysis of co-location of GCaMP6f and hTau in excitatory and PV neurons. Fig. S16 Tau accumulation has no effects on eGFP signals of CaMKII and PV neurons during bouts of social interaction. Fig. S17 Accumulation of vCA1-hTauPV disinhibits excitatory neurons during novel conspecific identification. Fig. S18 Accumulation of vCA1-hTauPV has no effect on eGFP signals of CaMKII neurons during bouts of social interaction. Fig. S19 ChR2 is highly expressed in excitatory and PV neurons. Fig. S20 Photostimulation of excitatory neurons during social exploration has no improvement on social discrimination in vCA1-hTauCaMKII mice. Fig. S21 Photoactivation of excitatory and PV neurons expressing eYFP had no effects on tau-impaired social memory. Fig. S22 Photoactivation of excitatory neurons in physical condition at different rhythm has no improvements on social memory. Fig. S23 Photoactivation of PV neurons in physical condition at different rhythm has no improvements on social memory. Fig. S24 Ursolic acid (UA) at 30 μmol/L effectively reduces pathological tau without changing tau mRNA. Fig. S25 CCK-8 assay on cytotoxicity of UA in HEK293-hTau cells. Fig. S26 Low-dose UA treatment remarkably reduces tau load and ameliorates social memory deficits in vCA1-tau mice. Fig. S27 Low-dose UA treatment has no toxic effect on social memory in C57BL/6 mice. Fig. S28 Low-dose UA treatment improves the excitability of excitatory and PV neurons in vCA1-hTau mice