Timeline and design of the experiment.

<p>Sixty-five transgenic (TG) and 16 wild type (WT) male mice entered the study at the age of 2.5 months. Animals were behaviorally tested in the water maze (WM) before irradiation to determine the “baseline” performance. At the age of ~3 months they were irradiated with 0.1, 0.5, or 1.0 Gy of ~150 MeV protons. Post-irradiation, the behavioral testing consisted of the WM followed by the Barnes maze (BM). In half of the TG mice, the last behavioral testing was followed by <i>in vitro</i> electrophysiological recordings at 6 months post-irradiation. The second half of TG mice and all WT mice were electrophysiologically tested at 9 months post-irradiation. Electrophysiological protocols: (I-O) Input-Output tests; (PPF) Paired-Pulse Facilitation; (PPI) Paired-Pulse Inhibition; (LTP) Long-Term Potentiation. The grayed out methods at 6 months post-irradiation indicate the experiments that did not detect statistically significant radiation-induced changes and were not included in the manuscript. The exception was PPF (black), which showed significant age-related increase between 6 and 9 months post-irradiation. Cortices were used for Luminex cytokine assays. Immunohistochemistry (IHC) of Aβ deposition and Western blotting (WB) analyses of the presynaptic protein synaptophysin were performed at 9 months post-irradiation only.