The Journal of Neuroscience, December 27, 2006, ():
Deficits in Synaptic Transmission and Learning in Amyloid Precursor Protein (APP) Transgenic Mice Require C-Terminal Cleavage of APP
J. Neurosci. Saganich et al.
26: 13428
Supplemental Data
Files in this Data Supplement:
- supplemental material
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Supplemental Figure 1. D664A mutation prevents impairment of basal synaptic transmission in AD-model mice. A1-3. Impaired basal synaptic transmission in PDAPP(J20) animals (open circles) compared to nontransgenic littermates (closed squares). A1-A2. Average fEPSP slope (A1) and fiber volley (A2) measured at increasing stimulus intensity. The average fEPSP slope for PDAPP(J20) was significantly reduced at all stimulus levels; in contrast, no significant change was seen in fiber volley amplitude. A3. Scatter plot of the fEPSP slope versus fiber volley of every recording in PDAPP(J20) (grey circles, grey line) (n= 378 recordings, 24 slices, 9 animals) and nontransgenic control (n=253 recordings, 16 slices, 7 animals) (black squares, black line) lines, fit by linear regression. PDAPP(J20) mice showed a reduction by 45% in the slope of the fitted data. B1-B2. D664A(B21) mice showed no difference in average fEPSP slope (B1) or fiber volley amplitude (B2). B3. Linear regression analysis demonstrated no significant change in the slope of the fitted data (nontransgenic: n= 326 recordings, 22slices, 7 animals; D664A(B21): n=262 recordings,18 slices, 9 animals). C1-C2. D664A(B254) mice showed no significant change in fEPSP slope or fiber volley amplitude. Scatter plot of all D664A(B254) data (circle) and control (square) plotted as a function of fEPSP slope and fiber volley amplitude (C3). D664A(B254) showed a small (approximately 12%) but non-significant decrease in basal synaptic transmission, which was determined by the slope of fitted data. (nontransgenic: n=390 recordings, 30 slices, 9 animals; D664A(B254): n= 371 recordings, 27 slices; 9 animals).
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Supplemental Figure 2. PDAPP(J20) animals showed no change in paired-pulse ratio or AMPA/NMDA ratio. A. Paired-pulse facilitation at the Schaffer-collateral CA1 synapse was measured by dividing the amplitude of the second fEPSP by the amplitude of the first elicited by a pair of two 50ms spaced stimuli. No significant change was observed, indicating that the observed deficits in PDAPP(J20) mice were unlikely to be a result of a change in presynaptic release probability. (Scale bar = 0.25mV, 50ms) B. AMPA/NMDA ratio was measured using whole-cell patch clamp method. Whole cell EPSCs (average of 20 responses) were recorded at a holding potential of +40mV in the absence and presence of the NMDA antagonist d-APV. The AMPA component was defined as the peak current remaining following 50μM d-APV application (black traces). The NMDA component (grey traces) was determined by digital subtraction of the APV insensitive current from the total current. No significant change in AMPA/NMDA ratio was observed (n=6 animals/group). (Scale bar = 50pA, 50s).
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Supplemental Figure 3. Visible platform task at 8-12 months in PDAPP(J20) and D664A(B21) mice. A-B. There were no significant differences between PDAPP (J20) mice and their nontransgenic littermates, or between D664A (B21) mice and their nontransgenic littermates, indicating that the ability to use visual clues is not deficient in any of the lines of mice.
