Not all rat pups are treated equally: Behavioral, neural, and (epi)genetic mechanisms mediating mother-offspring dynamics

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Mothering quality relies on the integrity of multiple physiological and behavioural systems, and on early experiences that impact how a mother mothers. This proposal focuses on the dynamics of mother-pup interactions at the behavioural, neurophysiological, and (epi)genetic levels. I hypothesize that the effects of maternal care on offspring behaviour and neurophysiology depend upon individual characteristics of both mother and offspring, and the interaction between mother and offspring. Our recent NSERC-funded studies have focused on sources of inter-individual differences in mothering. Our approach has been to explore the variety of behavioural systems and their neurophysiologies that are activated in the new mother that contribute to the quality, intensity, and timing of maternal behavior with offspring, including mother’s impulsivity, attention, reward processing, and memory, which in turn are affected by mother’s own early experiences. We have also examined hormone and neurotransmitter systems involved in the regulation of mother-pup dynamics, including corticosterone, striatal dopamine, dopamine and oxytocin receptors, brain plasticity, and genetics and gene expression dopamine and serotonin systems at transcript and protein levels in relevant brain areas. However, with the exception of our most recent study, all our previous work has focused on factors that affect the mother, and we have assumed that mother responds in a uniform fashion to different offspring. The next phase of our research extends this work by focusing on factors that regulate mothers’ DIFFERENTIAL parenting towards different pups in the litter and the differences in early experiences acquired by these individual pups that leads to differences in their subsequent development. Here we also drill down on brain areas associated with mothering and the genetic and epigenetic mechanisms that account for effects of differential mothering on the development of their subsequent mothering and associated behaviors and underlying brain mechanisms; to this end we will explore both within- and between-litter interactions between mother and pups. We will use genetic analyses in dopamine systems in outbred rats combined with epigenetic analyses and studies of pup cues and maternal factors that regulate maternal attention and nurturing in the mother rat. At the neurophysiological level, we will examine relationships between dopamine single-nucleotide polymorphism genetic and DNA methylation epigenetic variations, dopamine neurotransmitter systems and mother-pup dynamics. This research program will provide an explanation of mechanisms that mediate variations in parenting and its effects on offspring (F1 generation) at multiple levels, and inform research in human development where differential and transgenerational parenting are emerging foci of interest.