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. 2021 Oct 1;118(40):e2108239118. doi: 10.1073/pnas.2108239118

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Copyright © 2021 the Author(s). Published by PNAS.

This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).

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Fig. 7. — Learning and memory after AAV-Id2–induced MF rewiring. (Statistical tests are two-way ANOVA unless stated otherwise.) (A) Novel object recognition. Left to right: experiment design, DI (AAV-EGFP versus AAV-Id2, training P = 0.87, test *P = 0.021). (B) T-maze. Left to right: experiment design, alteration (Mann–Whitney U test, P = 0.33), and choice latency (AAV-EGFP versus AAV-Id2, trial 1, P = 0.87, trial 2, P = 0.66, trial 3, P = 0.31, trial 4, **P = 0.0048, trial 5, *P = 0.011, trial 6, ****P < 0.0001). (C) Morris water maze. Left to right: experiment design, escape latency [F_Day (4, 84) = 13, P < 0.0001; F_Treatment (1, 21) = 0.056, P = 0.82; F_Treatment × _Day (4, 84) = 1.4, P = 0.23], quadrant time (adjacent versus target, first probe trial, AAV-EGFP: *P = 0.017, AAV-Id2: *P = 0.014; second probe trial, AAV-EGFP: P = 0.82, AAV-Id2: **P = 0.0026), swim path length parallel to walls (acquisition versus reversal, AAV-EGFP: **P = 0.0025, AAV-Id2: P = 0.45), and number of wall approaches (acquisition versus reversal, AAV-EGFP: **P = 0.0079, AAV-Id2: P = 0.57). (D) Barnes maze. Left to right: experiment design, primary path length [F_Day (4, 88) = 6.6, P = 0.0001; F_Treatment (1, 22) = 0.4, P = 0.52; F_Treatment × _Day (4, 88) = 0.3, P = 0.85], primary errors (Mann–Whitney U test, **P = 0.0038), poke ratio in probe trial after acquisition (AAV-EGFP versus AAV-Id2, angle = 0°: ****P < 0.0001, angle = 18°: P = 0.52, angle = 36°: P = 0.54, angle = 54°: P = 0.98, angle > 72°: P = 0.72), and average strategy used during acquisition and reversal AAV-EGFP versus AAV-Id2: direct, P = 0.31, serial, **P = 0.0047, mixed P = 0.059). (E) Eight-arm radial maze. Left to right: experiment design, memory errors per consumed baits over days [F_Day (2, 44) = 9.0, P = 0.0005; F_Treatment (1, 22) = 2.8, P = 0.11; F_Treatment × _Day (2, 44) = 0.53, P = 0.59], memory errors per consumed bait (AAV-EGFP versus AAV-Id2: bait 1 to 4, P = 0.88, bait 5 to 6, P = 0.86, bait 7 to 8, **P = 0.0029), preferred angle [F_Angle (2, 44) = 16, P < 0.0001; F_Treatment (1, 22) = 0.056, P = 0.81; F_Treatment × _Angle (2, 44) = 2.6, P = 0.086], and choices performed at preferred angle (AAV-EGFP, days 1 to 2 versus 3 to 8, **P = 0.0071, days 1 to 2 versus 9 to 10, *P = 0.020, day 3 to 8 versus 9 to 10, P = 0.68; AAV-Id2, days 1 to 2 versus 3 to 8, **P = 0.0049, days 1 to 2 versus 9 to 10, ****P < 0.0001, days 3 to 8 versus 9 to 10, *P = 0.026). (F) Contextual and cued fear conditioning. Left to right: experiment design, freezing during context retention (AAV-EGFP versus AAV-Id2: baseline, P = 0.60, context, ****P < 0.0001), freezing during cue retention (AAV-EGFP versus AAV-Id2: pretone, P = 0.58, tone, P = 0.032, q = 0.064; does not meet FDR criterion), and freezing during extinction (AAV-EGFP versus AAV-Id2: baseline, P = 0.24, first tone, P = 0.38, last tone, P = 0.73).