Fig. 10.
Suppressing APP expression and Aβ levels allows recovery of LTP deficit in APP/tTA mice. a Experiment timeline; mice allocated to the reversibility group expressed APPSw,Ind for 3.5 weeks before being put back on the dox diet for 9–11 weeks to suppress further APPSw,Ind expression. b Aβ40 levels in hippocampal lysates of APP/tTA mice from the reversibility group were similar to control genotype levels. In comparison, shaded area shows levels of Aβ40 for age-matched APP/tTA mice from the 12 weeks-off-dox group (12 weeks-off-dox: control n = 9, APP/tTA n = 7; Reversibility study: control n = 6, APP/tTA n = 6). c Aβ42 levels in hippocampal lysates of APP/tTA mice from the reversibility group returned to control levels. Shaded area shows levels of Aβ42 for APP/tTA mice from the age-matched 12 weeks-off-dox group (12 weeks-off-dox: control n = 9, APP/tTA n = 7; Reversibility study: control n = 6, APP/tTA n = 6). d TBS-induced LTP (arrowhead) was similar between control and APP/tTA mice from the reversibility study group. e End LTP values, averaged 50–60 min after TBS, were similar between control and APP/tTA mice from the reversibility study group (control mean = 148.0 ± 16.86, n = 7; APP/tTA mean = 142.6 ± 12.24, n = 7). LTP trace shown for time points immediately before (thin line) and 60 min after (thick line) LTP induction. Scale bar calibration for LTP trace: 5 ms, 0.5 mV. f A similar input-output response was observed in the CA3-CA1 pathway of control and APP/tTA mice from the reversibility study (control n = 8, APP/tTA n = 8). Scale bar calibration for input-output trace: 5 ms, 0.5 mV. g Paired-pulse response was similar between control and APP/tTA mice from the reversibility group (control mean = 1.5 ± 0.08, n = 8; APP/tTA mean = 1.6 ± 0.12, n = 8). Scale bar calibration for paired-pulse traces: 10 ms, 0.2 mV