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Figure 1.

Natural Abeta oligomer solution and injection.

A) Blot image showing the presence of Abeta monomers, dimers, trimers, and tetramers in the Abeta solution. The 6E10 antibody was used for detection of Abeta oligomers that were removed from the Abeta solution using immunoprecipitation with A/G beads and 4G8 antibody (IP1, IP2, IP3: oligomers bound to beads used for first, second, and third immunoprecipitation). No oligomers were detected after three rounds of immunoprecipitation, which confirmed the absence of Abeta oligomers in the control solution (see “Materials and Methods” for a detailed description of how Abeta and control solutions were generated). B) Diagram showing the location of the guide cannula (green) and the injector cannula (red) in a Nissl-stained coronal section of the mouse brain [38]. The tip of the guide cannula stopped just above the corpus callosum. The tip of the injection cannula extended into the lateral ventricle.

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Figure 2.

Experiment 1: repeated Abeta injection.

Top) Diagram showing the design of experiment 1. Separate groups of mice were injected three times with either control or Abeta solution. Bottom) Graphs showing average freezing scores during fear conditioning on day 1 and the two retrieval trials on day 2 (see “Materials and Methods: Analysis of freezing behavior” for explanation of intervals on the X axis). Mice injected with the Abeta solution (n = 5) had significantly lower freezing scores during the context fear retrieval trial as compared with mice injected with the control solution (n = 6). Error bars are standard errors of means. * P<0.05.

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Figure 2 Expand

Figure 3.

Experiment 2: single Abeta injection 1 hour before fear conditioning.

Top) Diagram showing the design of experiment 2. Separate groups of mice were injected one time with either control or Abeta solution 1 hour before fear conditioning. Bottom) Graphs showing average freezing scores during fear conditioning on day 1 and the two retrieval trials on day 2. Mice injected with the Abeta solution (n = 8) had significantly lower freezing scores during the context fear retrieval trial as compared with mice injected with the control solution (n = 10). Error bars are standard errors of means. * P<0.05.

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Figure 3 Expand

Figure 4.

Experiment 3: single Abeta injection 2 hours before fear conditioning.

Top) Diagram showing the design of experiment 3. Separate groups of mice were injected one time with either control or Abeta solution 2 hours before fear conditioning. Bottom) Graphs showing average freezing scores during fear conditioning on day 1 and the two retrieval trials on day 2. There was no difference during any of the intervals analyzed between mice injected with the Abeta solution (n = 10) and mice injected with the control solution (n = 8). Error bars are standard errors of means.

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Figure 4 Expand