Fig. 6: Adgrl2 deletion from MEC layer III neurons impairs reversal spatial learning.

(A) Adgrl2fl/fl mice were crossed with Adgrl2fl/fl;pOxr1-Cre mice to generate offspring that were homozygous Adgrl2fl/fl without (control) or with the pOxr1-Cre allele (KO). Sex matched control/KO pairs were used for subsequent behavior experiments. (B) Summary graphs of open field locomotor/exploration test. (Left) total distance traversed during the open field task, (middle) distance traversed in the periphery of the open field, (right) average speed across the open field task. (C) Summary graph of novel object discrimination. (D–F) Barnes maze spatial learning/memory tests. (D) Barnes Maze experimental design. Mice were trained 5 times a day for 4 days with memory test 1 the following day after training and memory test 2 at 14 days after the final training. (E) Summary graphs of maze training. Plotted is average time spent to find the target hole across 5 training trials conducting on days 1–4. (F) Summary graphs of time spent to find target hole on memory test 1 (left) and test 2 (right). (G, H) Alternating water T-maze cognitive flexibility task. (G) Experimental schematic. Mice were trained 4 days with individual trials consisting of a 2-swim protocol (5trials/day). First swim consists of randomized placement of escape platform in either left or right arm of a 1-arm maze. Second swim occurs after a 30 s delay, with mice exposed to an opened 2-arm open maze with escape platform placed on opposite arm from the first swim. (H) Summary plots of time to platform during 2-arm swim test trials. Statistical analyses were performed using repeated-measure ANOVA with post hoc comparisons, finding learning effect by trial (p < 0.0001) and between genotypes (p = 0.014). (I) Summary graphs of time to platform averaged across 5 trials/day during 2-arm swim test. Plots and graphs shown are means +/− SEM. Statistical analysis were performed using Student’s t-test (***p < 0.001). n = 12 control/KO mice pairs (3 male, 9 female pairs), P60-90.