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. 2021 Mar 10;11:5552. doi: 10.1038/s41598-021-84943-x

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Animals lacking RXRγ exhibit impaired performance in a spatial version of a novel object recognition task, but normal performance in non-spatial object recognition, Morris water maze learning, and contextual fear conditioning. (A) Plot of average percent of time spent freezing ± SEM during 2 min of pre-shock exposure to a conditioning chamber as well as the first 2 min of each 10 min re-exposure to that environment on each of the following 9 days for 18 RXRγ KO animals and 16 wild type siblings revealed no differences in baseline freezing (T-test: t = 0.2340, P = 0.8165), conditioned fear response at 24 h (T-test: t = 0.7031, P = 0.4871), or extinction of conditioned fear response (2-way RM-ANOVA: F(8,256) = 21.97, P < 0.0001 for effect of trial, F(1,32) = 0.1310, P = 0.7198 for genotype). (B) Plot of average latency to reach escape platform ± SEM over 4 trials per day during the visible platform, hidden platform, and reversal phases of a Morris water maze task for 17 RXRγ KO animals and 17 wild type siblings revealed no differences between groups (2-way RM-ANOVA: F(1,32) = 0.1200, P = 0.7313, F(1,32) = 2.116, P = 0.1555, and F(1,32) = 1.195, P = 0.2825 for genotype during visible, hidden and reversal stages respectively). (C) Histograms of average percent time ± SEM spent in each of 4 quadrants of the water maze during 1 min probe trials conducted at the end of day H5 (probe 1) and R5 (probe 2) of the water maze task shown in B revealed no significant difference between RXRγ KO animals (gray) and wild type siblings (black) (2-way RM-ANOVA: F(3,96) = 128.9, P < 0.0001 for quadrant, and F(1,32) = 1.336, P = 0.2563 for genotype for probe 1; and F(3,96) = 123.5, P < 0.0001 for quadrant, and F(1,32) = 0.2819, P = 0.5991 for genotype for probe 2). (D) Histogram of average percent of time ± SEM spent exploring two familiar objects (object 1 and center object) and one novel object during a non-spatial novel object recognition test revealed no differences between RXRγ KO animals (N = 17) and wild type siblings (N = 20) (2-way ANOVA shows significant effect of object (F(2,70) = 23.77, P < 0.0001) but not genotype (F(1,35) = 1.094, P = 0.3028). Tukey’s post-hoc test reveals significant differences in exploration time for object 1 vs. novel object (P = 0.0051 for WT and 0.0088 for KO). (E) Histogram of average percent time ± SEM spent exploring two familiar objects (object 1 and center object) and one novel object during a spatial version of a novel object recognition test revealed significant differences between RXRγ KO animals (N = 12) and wild type siblings (N = 12). 2-way ANOVA shows significant object × genotype interaction (F(2,44) = 4.102, P = 0.0233). Tukey’s post-hoc test reveals significant differences in exploration time for object 1 vs. novel object for wild type (P = 0.0046), but not RXRγ KO animals (P = 0.8940). Data were plotted using Prism (https://www.graphpad.com/scientific-software/prism/) and the figure assembled using Affinity Designer (https://affinity.serif.com/en-gb/designer/) software.