Fig. 5.

Inhibition of CaN rescues the hTau-induced memory deficits with improvement of dendritic plasticity and synaptic functions. (A) Schematics show the treatments. AAV-eGFP (Vec) or AAV-eGFP-hTau (hTau) was injected stereotaxically into the hippocampal CA3 of 2-mo-old mice. After 45 d, FK506 (10 mg⋅kg⋅d) or the vehicle was injected intraperitoneally for 1 wk. Then the cognitive behaviors and synaptic plasticity were detected. (B) The escape latency to find the hidden platform during the 6-d learning process in MWM test. (C) The representative swimming tracks during the memory test carried out on day 8 by removing the hidden platform. (D and E) The escape latency to find the platform and target platform crossings tested on day 8. (F and G) Fear conditioning was used to measure the contextual memory of the mice 1 wk after the last MWM task. (H) The representative traces of sEPSCs and sIPSCs recorded by whole-cell voltage patch-clamp on ex vivo brain slices after FK506 or vehicle treatment. (I) The average frequency and amplitude of sEPSCs or sIPSCs collected from at least 12 neurons per group. (Scale bars, 10 pA, 1 s.) (J) The IO curve of fEPSP recorded on acute hippocampal slices overexpressing hTau or the vector and treated with FK506 or the vehicle (n = 6 per group). (K) The slope of fEPSP after HFS recorded on hippocampal slices after FK506 or vehicle treatment (n = 6 per group). Arrow indicates HFS onset, the average traces fEPSPs before (thin) and after (thick) LTP induction are shown. (L) Quantitative analyses for normalized fEPSPs 60–80 min after HFS. (M and N) The spine density in hippocampal CA3 subset imaged by Golgi staining. The data were expressed as mean ± SEM, *P < 0.05, **P < 0.01, Vec vs. hTau; ^#P < 0.05, ^##P < 0.01, hTau vs. hTau plus FK506.