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. 2021 Aug 2;11(3):1091–1115. doi: 10.3233/JPD-212566

Fig. 3.

Fig. 3

Performance in the water maze. A) Schematic of the water maze paradigm used at 3 mpi (left) and 6 mpi (right). Animals were trained to locate a hidden platform over the course of 5 days (2 sessions per day). At 3 mpi, the escape platform was located in the SW Quadrant for days 1-5 and in the NE Quadrant for days 6-7; at 6 mpi, the escape platform was located in the SE Quadrant. On the last day at each time point, a visible cue was placed on the platform. Probe trials were performed in the morning to assess spatial memory. B, C) Cumulative distance to the target platform at 3 mpi (B, pre-ASO) and 6 mpi (C, post-ASO). Mono-injected animals had a lower cumulative distance to the target compared to PFF-injected animals during training for the hidden platforms across both time points (F(1,29) = 6.638, p < 0.05). Additionally, a time-by-PFF interaction suggests that PFF animals had impaired learning over time compared to Mono animals (F(8.472,245.702) = 2.025, p < 0.05), and a time-by-ASO interaction suggests altered learning before and after ASO delivery compared to Scramble-treated animals (F(8.472,245.702) = 2.626, p < 0.01). A time by ASO interaction was found when visible platform location was analyzed, indicating that ASO treatment significantly impaired task performance compared to the prior time point (F(1.521,43.853) = 5.078, p = 0.017). D) Average cumulative distance to the target for the distinct platform locations at 3 and 6 mpi, and average visible cumulative distance to the target. PFF animals had a higher overall cumulative distance to the target during the hidden sessions (F(1,29) = 6.638, p < 0.05) compared to Mono animals. No differences were detected during the visible sessions, and no effects of ASO were detected. E) Change in water maze performance, calculated by subtracting the last session from the first session for a given platform location. PFF mice had a smaller change in water maze performance during the hidden platform locations compared to Mono mice (F(1,29) = 4.159, p < 0.05), indicating impaired learning from the first to last sessions. During the visible sessions, ASO animals showed a negative change that was significantly different than Scramble-treated animals (F(1,29) = 7.049, p < 0.05), indicating worse performance at 6 mpi (post-treatment) compared to 3 mpi (pre-treatment). F) Cumulative distance to the target location during probe trials at 3 mpi and 6 mpi. PFF mice did not show improvement over time, in contrast to the Mono mice (F(4.283,124.217) = 3.257, p < 0.05). Mono-Scramble and Mono-ASO mice swam closer to the target location than PFF-Scramble and PFF-ASO across all probe trials (F(1,29) = 9.372, p < 0.05). G) Percent time spent in the target quadrant during probe trials. PFF mice spent less time in the target quadrants across all probe trials (F(1,29) = 8.043, p = 0.008). Additionally, PFF mice showed a slower improvement in memory, indicated by a time by PFF interaction (F(7,203) = 3.535, p = 0.001). We also found a time by ASO interaction, where Scramble-injected animals continued to improve after ICV delivery, but ASO animals did not (F(7,203) = 2.083, p = 0.047). *p < 0.05, PFF vs. Mono; **p < 0.01, PFF vs. Mono; &p < 0.05, ASO vs. Scramble.