Maternal behavior modulates X-linked inheritance of behavioral coping in the defensive burying test

Abstract

Background: Complex behavioral traits such as coping strategies in response to stress are usually formed by genetic and environmental influences.

Methods: By exploiting the phenotypic and genotypic differences between the Wistar Kyoto (WKY) and Fischer 344 (F344) inbred rat strains, we recently identified three X chromosome-linked quantitative trait loci contributing to differences in coping strategies in the defensive burying (DB) paradigm. In this article we study the influence of postnatal maternal environment in these behaviors by characterizing the maternal behavior of these strains and the effect of cross-fostering on DB behavior of male offspring from reciprocal crossing (F1).

Results: Maternal behavior of WKY rats can be quantitatively characterized by less contact and more periods of neglect of their F1 pups. In contrast, F344 mothers engaged in more active behaviors such as licking/grooming and arched-back nursing. Cross-fostering male F1 pups at birth did not influence the latency to bury measure in DB; however, duration of burying and prod approaches were influenced by both genotype and maternal environment in an additive manner.

Conclusions: These results demonstrate that different measures of behavioral coping in the DB paradigm are influenced by maternal environment to differing degrees and in addition by genetic factors.

Figure 1

Schematic showing the reciprocal cross/matings and the cross-fostering design employed in this study. (A) Reciprocal crosses between F344 and WKY inbred strains produce male F1 rats that are heterozygous on all autosomal loci and contain the X chromosome from the maternal strain. (B) The cross-fostering design consisted of transferring 2 male F1 pups from a WKY mother (white) to be raised by a F344 foster mother, while simultaneously fostering 2 F1 males from a F344 (gray) to a WKY litter. In addition, 2 native control pups from each litter were identified at the time of cross-fostering. All 4 experimental animals (2 native, and 2 cross-fostered) are marked with an X in the schematic. In all, 100 animals were analyzed: 25 pups from each group (F344 native, F344 foster, WKY native, WKY foster), 25 native pups from a F344 biological mother raised by its own F344 mother [F ₁(F X W)/F344], 25 cross-fostered pups from a WKY biological mother raised by a F344 foster mother [F₁(W X F)/F344], 25 native pups from a WKY biological mother raised by the WKY mother [F₁(W X F)/WKY], and 25 cross-fostered pups from an F344 biological mother raised by a WKY foster mother [F₁(F X W)/WKY]. F344, Fischer 344; WKY, Wistar Kyoto; F1, first-generation.

Figure 2

Strain differences and effect of cross-fostering on maternal behavior. Means ± SEM for maternal behaviors of arched-back nursing (ABN), licking/grooming (LG), no contact (NC), and neglect (Neg) for regular F344 mothers (F344 raising [F₁(F X W)], n = 7) as compared with F344 foster mothers (F344 raising [F₁(W X F)], n = 5) and for regular WKY mothers (WKY raising [F₁(W X F)], n = 8) as compared with WKY foster mothers (WKY raising [F₁(F X W)], n = 5) during postnatal days 1–10. There were no differences between foster mothers and regular mothers of either strain. Each behavior is represented as the mean percentage of the total number of observations. F344, Fischer 344; WKY, Wistar Kyoto.

Figure 3

Effect of cross-fostering on body weight of pups at weaning (21 days of age, n = 25 pups/group) and adulthood (4 months of age, n = 25 adults/group). (A) Means ± SEM for body weight at weaning, separated by cross and the maternal environment in which the pups were raised. There was a significant main effect of environment, with offspring raised by WKY weighing more at weaning than offspring raised by F344, p < .001. Importantly, fostering status did not affect body weight of pups. That is, foster pups and native pups raised by WKY mothers (and foster pups and native pups raised by F344 mothers) weighed the same. (B) Body weight at 4 months of age is not significantly different in any of the conditions, irrespective of genotype or environment. F344, Fischer 344; WKY, Wistar Kyoto.

Figure 4

Means + SEM of coping behaviors of adult rats by X chromosomal genotype and pre-weaning postnatal maternal environment. (A) Latency to bury: significant main effect of genotype, p < .001. B) Duration of burying: significant effect of genotype, p < .001, as well as a significant effect of maternal environment, p < .01; asterisk indicates significant difference from F₁(F X W) raised by F344. (C) Prod Approaches: significant main effect of maternal environment, p < .05; number sign indicates significant difference (main effect) from offspring raised by F344. F1, first-generation; F344, Fischer 344.