Fig. 4

Circuit mechanism of WT1 action. a Scheme of WT1 depletion effect on corticohippocampal input to CA1. Left panel (wild type animal): normally, activation of both the direct temporoammonic pathway (blue) and the trisynaptic pathway (green) are required for LTP induction at the Schaffer collateral (SC) → CA1 synapse. Right panel (WT1 knock-down animal): in WT1-depleted hippocampus, enhanced basal efficiency of SC → CA1 signaling and/or CA1 excitability enable trisynaptic pathway activity alone to induce LTP. EC = entorhinal cortex; DG = dentate gyrus; TA = temporoammonic pathway. b Theta burst stimulation (TBS, delivered at arrow) of the SC induced stable LTP in slices from rats injected with SC-ODN only when combined with phase-delayed TBS at the TA pathway (left and right panels). Conversely, in slices from WT1-AS-injected hippocampi, the same TBS of SC alone induced LTP, which did not differ from that induced by dual-pathway TBS (center and right panels). Representative fEPSPs show superimposed traces recorded during baseline and 60 min post-TBS. Calibrations: 0.5 mV/10 ms. Data are expressed as mean fEPSP ± s.e.m. Statistical analysis by two-way ANOVA RM: SC stimulation comparing SC-ODN vs WT1-AS ODNs: F_(1,10) = 6.931, *p = 0.0250; SC-ODN comparing SC stimulation vs SC + TA: F_(1,9) = 7.112, *p = 0.0258. No significant effect was observed when comparing WT1-AS SC vs WT1-AS SC + TA: F_(1,10) = 1.437, p = 0.2582