Hormonal and non-hormonal bases of maternal behavior: The role of experience and epigenetic mechanisms
Introduction
Hormonal changes occurring during gestation serve a critical role in altering maternal physiological and neuroendocrine systems to facilitate fetal development and prepare the mother for parturition and lactation. These hormones also induce both short- and long-term changes in the maternal brain that contribute to maternal behavior during the postnatal period. Estrogen and progesterone priming with downstream consequences for prolactin and oxytocin systems have been explored extensively in the context of maternal behavior, with converging evidence from both pharmacological and genetic studies illustrating the mediating role of these hormones. However, maternal behavior can occur in the absence of hormonal priming. In a seminal paper titled “Nonhormonal Basis of Maternal Behavior in the Rat” published in Science in 1967, Jay Rosenblatt established empirical evidence for the role of exposure to pups in eliciting maternal behavior among both male and female adult rats (Rosenblatt, 1967). These findings were striking and suggestive that though hormones may influence the onset of maternal responses during the postnatal development of offspring, experience with offspring could similarly trigger these behavioral responses. These initial findings have formed the basis of many ongoing research avenues within the study of the maternal brain. In particular, recent studies of experiential effects on maternal behavior have highlighted the critical role of epigenetic mechanisms in shaping maternal responses. Here, we will describe how the ongoing study of the non-hormonal basis of maternal behavior has contributed to these research themes and the implications of this research for our understanding of variation in the parental brain.
Section snippets
Non-hormonal basis of maternal behavior
Rosenblatt (1967), expanding on the work of Weisner and Sheard (1933), demonstrated that hormonal stimulation is not required to induce the onset of maternal behavior in rats. Using an experimental design in which rats were housed continuously across consecutive days with 5–10 day old pups, maternal responses (retrieving and licking of pups, crouching over pups, nest-building) were found to emerge in both male and female adult rats within the period of 10–15 days (Rosenblatt, 1967, Weisner and
Hormonal basis of maternal behavior
Our understanding of the molecular and neural pathways through which pup exposure comes to alter maternal behavior requires consideration of the pathways through which hormones influence maternal behavior. The pattern of pregnancy hormone stimulation that primes the rodent maternal brain begins at mating when cervical stimulation initiates a twice-daily pattern of prolactin release from the anterior pituitary (for approximately 9–10 days after mating) that functions to prevent degradation of the
Interplay between hormones and epigenetics in organizing maternal responsivity
Estrogen acts through multiple cellular/molecular pathways to alter neural function and behavior (Numan, 2015, Stolzenberg and Numan, 2011, Vasudevan and Pfaff, 2008). However, the best characterized route of action involves estradiol-induced changes in gene transcription. Estradiol alters the transcription of estrogen responsive genes by binding estrogen receptors (ERα and ERβ), which are ligand-activated transcription factors. The ERα and ERβ receptor subtypes share almost 100% amino acid
Interplay between experience and epigenetics in organizing maternal responsivity
Sensitized female rats are not exposed to pregnancy hormone priming, and yet the experience of interacting with pups results in activation of neurons within the MPOA of a sensitized virgin female comparable to that observed in a lactating dam (Komisaruk et al., 2000, Numan, 2015). If pup experience does not affect circulating levels of E, how can pup exposure lead to a similar activation of MPOA neurons? Within the MPOA, intracellular signals that have been linked to the onset of mothering
Developmental origins of hormonal and non-hormonally induced maternal behavior
Though the hormonal exposures associated with pregnancy and parturition clearly facilitate maternal behavior, it is also evident that there is variation in maternal responding that can be observed in both lactating and non-lactating females. Interestingly, this variation is induced through the experience of maternal behavior itself. Virgin female rats that have experienced elevated levels of maternal care during their own postnatal development exhibit reduced latency in days to display maternal
From mother–pup interactions to epigenetics
The molecular impact of experience with pups (sensitization in adulthood) or experience of pups (effects of maternal care during development) that has been documented raises critical questions as to how these broad sensory/social experiences come to induce these downstream epigenetic consequences. These questions have yet to be systematically addressed. It is certainly the case that neuronal activation can induce epigenetic variation, and this may be a mechanism underlying neuronal plasticity
Maternal experience and the mesolimbic dopamine system
Though studies of the hormonal and non-hormonal bases of maternal behavior have focused primarily on hypothalamic regions such as the MPOA, similar to all complex behavioral phenotypes, there are contributions by a broad range of neural circuits. Particularly relevant to the motivational aspects of pup-directed behavior, the mesolimbic dopamine system plays a critical role in maternal behavior. Striatal depletion of dopamine (DA) (Hansen et al., 1991) and pharmacological antagonism of DA
Conclusions & implications
Maternal responsiveness to offspring is critical to offspring survival and development. In mammals, the hormonal changes occurring during pregnancy and at the time of parturition have been demonstrated to alter maternal behavioral and physiological functioning to promote nurturing responses. However, despite the pivotal role of hormones, experience with offspring can likewise induce maternal behavior. The study of the non-hormonal basis of maternal behavior has revealed both the unique
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