Spatial working memory deficits were evaluated using the spontaneous Y-maze alternation task, which relies on the natural tendency of mice to alternate the choice of maze arms. At 8 weeks of age this natural tendency was not as pronounced or working memory ability was not fully matured, because the group-housed fGluN1 controls alternated less at 8 weeks old than at 12 weeks old (Figure S2A in Supplement 1). Thus we tested KO animals at 12 weeks old. At this age, group-housed KO mice displayed a reduction in alternation which was exacerbated by PWSI (Figure 2D), suggesting a spatial working memory deficit and echoing the results of our previous study (15). Notably, chronic oral APO administration for 10 weeks increased the alternation index of PWSI KO mice to a similar level as the PWSI control (Figure 2D).
