Article Figures & Data
Figures
- Figure 1.
Expression of APP and Aβ in critical period-age APP/PS1 mice. A–C, Fractionated brain homogenates from a P28 APP/PS1 mouse (lanes 1–3) and a nontransgenic litter mate (lanes 4–6). Brain homogenates were sequentially fractionated in TBS (lanes 1 and 4), 1% Triton X-100 (lanes 2 and 5), and 2% SDS (lanes 3 and 6). Immunoprecipitation with human APP/Aβ antibody 6E10 was performed with each fraction. Samples were run on a 10–20% SDS polyacrylamide gel, blotted, and probed with 6E10 (A, B), then stripped and reprobed with anti-N-terminal Aβ antibody 82E1 (C). Secreted, α secretase-cleaved APP is present in lane 1 (>98 kDa; labeled *). Membrane-bound, full-length human APP is present in lanes 2 and 3 (>98 kDa; labeled #). Membrane-bound, BACE-cleaved, APP (termed C99; 16 kDa band) is present in lane 2 (arrowhead). A 4 kDa band representing soluble, monomeric Aβ is present in lane 1 upon longer exposure of blot to film (arrow; B), and upon stripping and reprobing with 82E1 (arrow; C). D, E, Coronal sections of P26 cerebral cortex from transgenic (D) or nontransgenic (E) litter mates are immunostained for APP and Aβ (6E10; red). Cortical layers 2–4 are shown. Most cortical neurons express human APP. Nuclei are labeled with DAPI (blue). Scale bar, 50 μm.
- Figure 2.
Ocular dominance plasticity defect in APP/PS1 mice following 4 d monocular visual deprivation. A–F, Coronal sections of visual cortex showing the pattern of Arc mRNA induction following stimulation of one eye. The laminar and areal pattern of induction is indistinguishable in nontransgenic (A, B) and APP/PS1 (C, D) mice in the absence of deprivation. Following a 4 d period of eye lid suture (P28–P32), nontransgenic mice demonstrate a normal expansion in the width of visual cortex responsive to input driven by the ipsilateral, nondeprived eye (E), whereas APP/PS1 mice do not demonstrate this expansion (F). Arrowheads denote medial and lateral edges of responding visual cortex ipsilateral to stimulated eye. The right edges of A and C are medial and the left edges of B and D–F are medial. Cortical layers are labeled in E. Scale bar, 400 μm. G, Quantitation of the results demonstrated in B–F. n = 7–13 mice per group. Error bars denote SD. ***p < 0.0001, t test.
- Figure 3.
Critical period ODP defect in APP-expressing mice following a 10 d period (P22–P32) of ME. A, B, The expansion in the domain of Arc mRNA induction in visual cortex ipsilateral to the remaining, open eye in nontransgenic mice (A) does not occur in APP/PS1 (B) mice. Arrows denote medial and lateral limits of the domain of Arc-expressing layer 2/3 neurons. Medial is to the left in each image. Scale bar, 400 μm. C, Fold-change in the width of the domain of Arc mRNA induction in visual cortex ipsilateral to the remaining, open eye following a 10 d period of ME compared with normally reared nontransgenic litter mates and transgenic mice which express APPswe and PS1dE9 (APP/PS1), APPswe alone (APP), or PS1dE9 alone (PS1). n = 6–17 mice per group. Error bars denote SD. ***p < 0.0001, t test comparing width of Arc induction domain following 10 d ME to that of normally reared mice of the same genotype and age.
- Figure 4.
In vivo imaging indicates normal retinotopic acuity in awake APP/PS1 mice. A, Experimental timeline. Cranial window and headpost installation was performed on P22–P24, followed by optical imaging 5–6 d later. B, Visual responses in nontransgenic mice to a local visual stimulus presented to the contralateral eye at ∼10° eccentricity (Values are percent change in fluorescence, % dF/F; see Materials and Methods). Dark regions indicate responses in areas V1, LM, and AL (anterolateral). A 500-μm-wide strip along the V1/LM axis was constructed, and smoothed maximum responses along this strip were used to generate spatial response profiles (see Materials and Methods). Image dimensions: 3 mm × 3 mm. C, Response profiles (left) to contralateral-eye stimulation in this mouse at three retinotopic positions (Stim1–3; right) illustrate retinotopic progression of peak response location (dashed blue vertical lines). D, Retinotopic progression of peak responses from Stim2 to Stim1 location. Top, Peak response locations for all individual mice (at ∼P28). Bottom, Average shifts in peak location from Stim2 to Stim1. Shifts did not differ significantly between nontransgenic and APP/PS1 mice (two-tailed rank sum test, p > 0.28). E, Top, Normalized response cross-sections (Stim1), centered at peak response. Bottom, Average estimates of full-width at half-maximum (see green arrow in C) did not differ significantly between nontransgenic and APP/PS1 mice (two-tailed rank sum test, p > 0.4).
- Figure 5.
In vivo imaging indicates that OD plasticity is decreased in APP/PS1 mice. A, Experimental timeline. Following imaging at P27–P29, MD was performed, animals experienced MD for 4 d, then the sutured eyes were reopened and mice were reimaged. B, Example of OD plasticity following 4 d of MD in a nontransgenic mouse. Left, Spatial response profiles for deprived, contralateral eye (contra; black lines) and nondeprived, ipsilateral eye (ipsi; gray lines) stimulation at three retinotopic locations, and average response (bottom) across all stimulus locations. Right, Responses from the same region of cortex, following MD. C, Summary of binocular zone responses to ipsi and contra eye stimulation across nontransgenic (black) and APP/PS1 (red) mice pre- and post-MD. The average responses 100–350 μm from the V1/LM border were used (violet rectangles in B; see Materials and Methods). D, Top, Response bias to contra eye stimuli was computed as ODI = (contra − ipsi)/(contra + ipsi) for each experimental session. Indices from the same mouse pre-MD and post-MD are connected by a line. Bottom, Average ODI across all sessions. ODI values were significantly decreased by MD in nontransgenic mice (**p < 0.01) but not in APP/PS1 mice (p = 0.27). We also noted a significant decrease in ODI before MD, in APP/PS1 mice (*p < 0.05). Error bars denote SEM.
