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. 2017 Feb 15;42(7):1435–1446. doi: 10.1038/npp.2017.7

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Copyright © 2017 The Author(s)

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/

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MIA offspring display ASD core behavioral deficits but not motor coordination deficits. (a) MIA offspring generated distinct patterns of total vocalizations. There was no significant main effect of sex F_1,46=0.006, P=0.94. There was a significant main effect of postnatal days, F_4,90=4 8.340, P<0.001, and a significant postnatal day x condition interaction, F_4,90=2.718, P=0.035. Examinations of individual postnatal days using one-way ANOVA indicated that compared to control offspring, MIA offspring emitted a significantly lower number of USVs on postnatal days 6 and 8, F_1,75=5.560, P=0.021 and F_1,75=4.988, P=0.029, respectively. MIA offspring emitted significantly more vocalizations on postnatal day 10 F_1,75=7.665, P=0.007, as determined by one-way ANOVA based on postnatal day x condition interaction. (b) P40 MIA and control offspring were assessed for repetitive behavior by marble burying assay. MIA offspring (male, n=17 and female, n=18) displayed higher marble burying than control offspring male (n=16) and female (n=18) with main effects of sex (F_1,65=4.7, P=0.03) and prenatal condition (F_1,65=19.59, P<0.0001) but no significant sex x prenatal condition interaction (F_1,65=0.0138, P=0.9). (c) MIA offspring display abnormal social interaction behaviors. Adult MIA (n=9) and control (n=9) offspring were repeatedly paired with the same partner for 3 sessions and a different partner in a fourth session. Arrows point to sessions with novel mouse pairing. There was a significant session x prenatal condition interaction, F_3,14=5.144, P=0.013. Post hoc one way ANOVA comparisons of individual sessions showed that the control group had a significantly longer interaction time compared to the MIA group during session 1, F_1,16=5.353, P=0.034. In the control mice there was no significance between session 1 and 4, but there was a significant decrease in the amount of time spent interacting from session 1 to 2, t(8)=3.451, P=0.009. MIA offspring showed an increase in interaction across sessions, with session 4 showing a significant increase in social behavior compared to session 1, t(8)=2.519, P=0.036. (d) Females showed better motor coordination and there was a significant main effect of sex (F_{1, 40}=5.268, P=0.027). The main prenatal condition effect was not significant, F_1,40=2.552, P=0.118, nor the sex × prenatal condition interaction, F(1, 40)=1.575, P=0.217. (e and f) To determine if MIA offspring display increased motor learning, mice were tested on additional trials at 4–40 r.p.m. and 8–79 r.p.m. There was no main effect of sex (F_1,40=2.135, P=0.152) therefore both sexes were pooled. Although there was a significant main effect of trials for both the 4–40 r.p.m. trials (F_{5, 210}=29, P<0.0001) and the 8–79 r.p.m. trials (F_5,210=2.691, P=0.22), there was no significant main effect of prenatal condition (F_{1, 42}=0.1479, P=0.702) and (F_{1, 42}=1.391, P=0.24) for the 4–40 and the 8–79 r.p.m. trials respectively as determined by RM two-way ANOVA. *p<0.05, **p<0.01.