Higher Neuronal Facilitation and Potentiation with APOE4 Suppressed by Angiotensin II

Figures

• 

  Figure 1. Lower basal synaptic transmission but higher paired pulse facilitation with APOE4as compared to APOE3 (A) Input output (I/O) functions for E3FAD and E4FAD mice at stimulus intensities ranging from 0–200μA. Evoked fEPSP amplitudes were lower in E4FAD as compared to E3FAD mice at stimulus intensities > 75mA (p<0.05 by t-test at each stimulus intensity). (B) Two stimuli were applied to the SCCP at 20Hz and amplitudes of resulting fEPSPs were measured to assess paired pulse facilitation (PPF). The Amplitude of the first fEPSP (A1) was lower in E4FAD mice as compared to E3FAD mice (t(16)=2.45, p=0.023), (C) but the paired pulse ratio (Amplitude of the second fEPSP as a ratio of the amplitude of the first fEPSP – A2/A1) was higher in E4FAD as compared to E3FAD mice (t(16)=2.54, p=0.022). (D) There was also a significant correlation between A1 and PPF ratio in E4FAD (r=0.74, p=0.036) but not E3FAD (r=0.66, p=0.11) mice. Insets A and C show representative traces from E3FAD and E4FAD mice; calibration bars = 0.2mV, 10ms. All data expressed as mean +/− SEM. *p < 0.05 by t-test. n=7 for E3FAD mice, and n=9 for E4FAD mice.

• 

  Figure 2. Larger magnitude of response to high frequency stimulation with APOE4 compared to APOE3 (A) Time course data depicting the effect of high frequency stimulation (HFS) on the amplitude of fEPSPs in E3FAD and E4FAD mice. The arrow at 0 minute indicates induction of HFS protocol. Dashed lines between minutes 1–3 indicate post tetanic potentiation (PTP) period and dashed lines between minutes 25–30 indicate long term potentiation (LTP) period. Amplitude of fEPSPs were higher in E4FAD as compared to E3FAD mice during (B) PTP (t(8)=2.95, p=0.018), and (C)LTP (t(8)=2.77, p=0.024) time periods. Insets B and C show representative traces from E3FAD and E4FAD mice during the PTP and LTP time periods, respectively; calibration bars = 0.1mV, 10ms. All data expressed as mean +/− SEM. *p < 0.05 by t-test. n=5 for E3FAD mice, and n=5 for E4FAD mice.

• 

  Figure 3. No effect of angiotensin II on basal synaptic transmission or synaptic facilitation with APOE3 or APOE4. (A) Paired stimuli were applied to the SCCP at 20 Hz every 15s for 20 minutes to assess basal synaptic transmission and paired pulse facilitation (PPF). Time course data of the amplitude of the first response (mV) is depicted. Time 0 indicates bath application of either 10uM of angiotensin II or vehicle treatment. (B) Exogenous angiotensin II did not alter the amplitude of the first evoked fEPSP (A1) in E3FAD (t(8)=0.18, p=0.86) or E4FAD (t(8)=0.81, p=0.43) mice. Vehicle treatment also did not alter A1 in E3FAD (t(6)=0.15, p=0.88) or E4FAD (t(8)=0.27, p=0.79) mice. (C)Time course data of the paired pulse facilitation ratio (A2/A1) is depicted. (D)Exogenous angiotensin II did not alter the PPF ratio in E3FAD (t(8)=0.053, p=0.96) or E4FAD (t(8)=0.13, p=0.89) mice. Vehicle treatment also did not alter the PPF ratio in E3FAD (t(6)=0.022, p=0.98) or E4FAD (t(8)=0.30, p=0.77) mice. All data expressed as mean +/− SEM. p > 0.05 by t-test. n =4 for E3FAD vehicle, n =5 for E3FAD Ang II, n=5 for E4FAD vehicle, and n=5 for E4FAD Ang II.

• 

  Figure 4. Angiotensin II suppresses the magnitude of response to high frequency stimulation with APOE3and APOE4. (A) Time course data depicting the effect of high frequency stimulation (HFS) on the amplitude of fEPSPs in E3FAD and E4FAD mice. The arrow at 0 minute indicates induction of HFS protocol. Dashed lines between minutes 1–3 indicate post tetanic potentiation (PTP) period and dashed lines between minutes 25–30 indicate long term potentiation (LTP) period. (B) During the PTP period, amplitude of the fEPSPs were lower with the addition of 10uM angiotensin II in E3FAD and E4FAD mice (F(1,14) = 5.38, p= 0.036). (C) During the LTP period, amplitude of the fEPSPs were also lower with the addition of 10uM angiotensin II in E3FAD and E4FAD mice (F(1,14) = 11.06, p = 0.005). Insets B and C show representative control and angiotensin II traces for both the PTP and LTP periods. Calibration bars = 0.1mV, 10ms. All data expressed as mean +/− SEM. *p < 0.05 by two-way ANOVA.