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. Author manuscript; available in PMC: 2023 Feb 1.
Published in final edited form as: Alzheimers Dement. 2021 Jun 20;18(2):222–239. doi: 10.1002/alz.12398

Figure 4. Development of cognition decline in aging GluN3A KO mice.

Figure 4.

Cognitive function was tested in WT and Glu N3A KO mice at ages of 5 to 12-month old. A. Spatial learning and memory ability was tested using the Morris water maze test. At adult ages of 5–6-month old, GluN3A KO mice started to show slower learning ability during the 5 day trial protocol, yet the bar graphs indicates that, one day after the training, GluN3A KO mice did not have difficulties in memorizing the location of the platform. B. GluN3A KO mice of 7–9-month old developed slower learning activity during the 5-day training. The time spent and travel distances in the platform quarter of these animals were significantly less compared to WT mice. C. The water maze test was performed in mice at ages of 10–12-month old. GluN3A KO mice suffered significant difficulties in the spatial memory shown as a flat learning curve during the last 3 days of the training period. The bar graphs show marked deteriorations in identifying the platform quarter one day after training compared to WT mice (5–6m: n=12 in WT and n=12 in KO; 7–9m: n=12 in WT and n=9 in KO; 10–12m: n=14 in WT and n=7 in KO; *P<0.05, **P<0.01, ***P<0.001 vs. WT controls; Two-way ANOVA for training curve and Student’s t-test for memory recall test). D. In the novel object test, the mouse was allowed to explore 2 identical objects. On the test day, one of the training objects was replaced with a novel object. WT mice sniffed significantly more on the novel object at 1 hr after training, suggesting memory of previous object. GluN3A KO mice showed no preference on these objects (5–6m: n=8 in WT and n=8 in KO; 7–9m: n=8 in WT and n=8 in KO; 10–12m: n=9 in WT and n=8 in KO; *P<0.05, **P<0.01 vs. familiar object; Two-way ANOVA). E. In the context test, the test mouse was reintroduced to the conditioning chamber and recorded for 3 min without stimulation to evaluate the contextual fear. Comparing to age-matched WT mice, GluN3A KO mice aged at 5–9-month old showed significantly less freeze behavior during the first 2 min. Elderly GluN3A KO mice, moreover, had much less freeze behavior during the whole 3-min period. (5–6m: n=11 in WT and n=9 in KO; 7–9m: n=11 in WT and n=13 in KO; 10–12m: n=10 in WT and n=12 in KO; *P<0.05, **P<0.01, ***P<0.001 vs. WT controls; Two-way ANOVA. The main factor of genetic background (WT vs. KO) is significantly different across the three age groups). F. In the cued text, the test mice were introduced to a new chamber with different context background for 3 min, followed by the 30s tone cue (US). The cued fear was accessed by evaluating the freeze behavior after US. GluN3A KO mice aged at 5–12m showed significant less freezing for 2 minutes after US compared to age-matched WT ones. Thus, GluN3A KO mice developed poorer contextual and cued conditioning fear memory (5–6m: n=7 in WT and n=5 in KO; 7–9m: n=8 in WT and n=6 in KO; 10–12m: n=4 in WT and n=9 in KO; *P<0.05, **P<0.01, ***P<0.001 vs. WT controls; Two-way ANOVA and main factor of genetic background (WT vs. KO) is significantly different across the three age groups).