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. 2004 Sep 30;23(20):4096–4105. doi: 10.1038/sj.emboj.7600415

Figure 4.

Figure 4

Functional neuronal deficits: decreased LTP in Tg mAPP/RAGE mice. (A) BST was reduced in the CA1 region of slices from 3–5-month-old Tg mAPP/RAGE (APP/RAGE) mice (*P<0.05) and Tg mAPP (APP) littermates compared with nonTg littermates (male animals were used throughout in electrophysiologic studies). A greater reduction in BST was observed in 10-month-old Tg mAPP/RAGE mice and Tg mAPP littermates (**P<0.01). Single Tg RAGE (RAGE) mice showed normal values of BST at both ages. The responsiveness of CA1 cells to increasing afferent fiber stimulation (slope of input–output (i/o) relation) was measured to assess BST strength. Results from 3–5-month-old animals were based on recordings in 16 slices from five male Tg mAPP/RAGE mice, 19 slices from six Tg mAPP mice, 16 slices from six Tg RAGE mice, and 19 slices from seven nonTg mice. Results from 8–10-month-old mice were based on recordings in 12 slices from five Tg mAPP/RAGE mice; 10 slices from four Tg mAPP mice; 15 slices from six Tg RAGE; and 12 slices from six nonTg mice. Insets show representative fEPSP for a nonTg mouse and a Tg mAPP/RAGE mouse, illustrating that far higher stimulation strengths are required to elicit synaptic responses in 10-month-old Tg mAPP/RAGE mice. Scale: 0.2 mV; 5 ms. (B) LTP was normal in the CA1 region of slices from 3–5-month-old Tg mice (all genotypes) and their nonTg littermates. Theta-burst stimulation indicated by the three arrows was delivered after recording a 15-min baseline (n=16 slices from five Tg mAPP/RAGE mice, n=19 slices from six male Tg mAPP mice, n=16 slices from six male Tg RAGE mice, and n=19 slices from seven male nonTg mice). Insets show traces taken 1 min before and 60 min after LTP induction on 3–5-month-old nonTg and Tg mAPP/RAGE mice. Scale: 0.1 mV (nonTg), 0.05 mV (Tg mAPP/RAGE mice); 2.5 ms. (C) LTP was reduced in the CA1 region of slices from 8–10-month-old double Tg mAPP/RAGE mice, whereas Tg mAPP, Tg RAGE, and nonTg mice showed normal potentiation (n=12 slices from five Tg mAPP/RAGE mice; n=10 slices from four Tg mAPP mice; n=15 slices from six Tg RAGE mice; and n=12 slices from six nonTg mice; *P<0.05). Insets show traces taken 1 min before and 60 min after LTP induction on 8–10-month-old nonTg and Tg mAPP/RAGE mice. Scale: 0.1 mV (nonTg), 0.03 mV (Tg mAPP/RAGE mice); 2.5 ms. (D) LTP was still reduced in double Tg mAPP/RAGE mice after enhancement of the theta-burst strength (n=7 slices from four Tg mAPP/RAGE mice; and n=8 slices from four nonTg mice; *P<0.05).