Hormonal and non-hormonal bases of maternal behavior: The role of experience and epigenetic mechanisms

doi:10.1016/j.yhbeh.2015.07.005

Hormones and Behavior

Volume 77, January 2016, Pages 204-210

https://doi.org/10.1016/j.yhbeh.2015.07.005 Get rights and content

Highlights

•
In the absence of hormones, experience induces maternal behavior.
•
Epigenetic mechanisms mediate effects of experience on maternal responses.
•
Individual differences emerge in maternal neural circuits via epigenetic mechanisms.

Abstract

This article is part of a Special Issue “Parental Care”. Though hormonal changes occurring throughout pregnancy and at the time of parturition have been demonstrated to prime the maternal brain and trigger the onset of mother–infant interactions, extended experience with neonates can induce similar behavioral interactions. Sensitization, a phenomenon in which rodents engage in parental responses to young following constant cohabitation with donor pups, was elegantly demonstrated by Rosenblatt (1967) to occur in females and males, independent of hormonal status. Study of the non-hormonal basis of maternal behavior has contributed significantly to our understanding of hormonal influences on the maternal brain and the cellular and molecular mechanisms that mediate maternal behavior. Here, we highlight our current understanding regarding both hormone-induced and experience-induced maternal responsivity and the mechanisms that may serve as a common pathway through which increases in maternal behavior are achieved. In particular, we describe the epigenetic changes that contribute to chromatin remodeling and how these molecular mechanisms may influence the neural substrates of the maternal brain. We also consider how individual differences in these systems emerge during development in response to maternal care. This research has broad implications for our understanding of the parental brain and the role of experience in the induction of neurobiological and behavior changes.

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

References (86)

V.M. Afonso et al.
Previous maternal experience affects accumbal dopaminergic responses to pup-stimuli
Brain Res.
(2008)
V.M. Afonso et al.
Hormones that increase maternal responsiveness affect accumbal dopaminergic responses to pup- and food-stimuli in the female rat
Horm. Behav.
(2009)
V.M. Afonso et al.
Accumbal dopamine function in postpartum rats that were raised without their mothers
Horm. Behav.
(2011)
R.S. Bridges
Long-term effects of pregnancy and parturition upon maternal responsiveness in the rat
Physiol. Behav.
(1975)
J.R. Brown et al.
A defect in nurturing in mice lacking the immediate early gene fosB
Cell
(1996)
F.A. Champagne et al.
Variations in maternal care in the rat as a mediating influence for the effects of environment on development
Physiol. Behav.
(2003)
B.M. Colquitt et al.
Dnmt3a regulates global gene expression in olfactory sensory neurons and enables odorant-induced transcription
Neuron
(2014)
J. Cortes-Mendoza et al.
Shaping synaptic plasticity: the role of activity-mediated epigenetic regulation on gene transcription
Int. J. Dev. Neurosci.
(2013)
A.I. Csapo et al.
Prevention of implantation by antiprogesterone
J. Steroid Biochem.
(1979)
A.I. Csapo et al.
Induction of preterm labor in the rat by antiprogesterone
Am. J. Obstet. Gynecol.
(1979)

M.N. Edelmann et al.

Epigenetic impact of simulated maternal grooming on estrogen receptor alpha within the developing amygdala

Brain Behav. Immun.

(2011)

A.L. Giordano et al.

Nuclear estrogen receptor binding in microdissected brain regions of female rats during pregnancy: implications for maternal and sexual behavior

Physiol. Behav.

(1991)

S. Hansen et al.

The effects of 6-OHDA-induced dopamine depletions in the ventral or dorsal striatum on maternal and sexual behavior in the female rat

Pharmacol. Biochem. Behav.

(1991)

S. Hansen et al.

Interaction with pups enhances dopamine release in the ventral striatum of maternal rats: a microdialysis study

Pharmacol. Biochem. Behav.

(1993)

S.H. Jin et al.

Cyclic AMP response element-binding protein is required for normal maternal nurturing behavior

Neuroscience

(2005)

S.E. Keer et al.

Dopamine receptor blockade in the nucleus accumbens inhibits maternal retrieval and licking, but enhances nursing behavior in lactating rats

Physiol. Behav.

(1999)

B.R. Komisaruk et al.

Combined c-fos and 14C-2-deoxyglucose method to differentiate site-specific excitation from disinhibition: analysis of maternal behavior in the rat

Brain Res.

(2000)

K.O. Kuroda et al.

ERK-FosB signaling in dorsal MPOA neurons plays a major role in the initiation of parental behavior in mice

Mol. Cell. Neurosci.

(2007)

M. Numan et al.

Medial preoptic area interactions with dopamine neural systems in the control of the onset and maintenance of maternal behavior in rats

Front. Neuroendocrinol.

(2009)

M. Numan et al.

Medial preoptic area interactions with the nucleus accumbens-ventral pallidum circuit and maternal behavior in rats

Behav. Brain Res.

(2005)

C.L. Peterson et al.

Histones and histone modifications

Curr. Biol.

(2004)

E. Putignano et al.

Developmental downregulation of histone posttranslational modifications regulates visual cortical plasticity

Neuron

(2007)

J.S. Rosenblatt et al.

Hormonal basis during pregnancy for the onset of maternal behavior in the rat

Psychoneuroendocrinology

(1988)

K.M. Seip et al.

Exposure to pups influences the strength of maternal motivation in virgin female rats

Physiol. Behav.

(2008)

H.I. Siegel et al.

Estrogen-induced maternal behavior in hysterectomized–overiectomized virgin rats

Physiol. Behav.

(1975)

H.I. Siegel et al.

Progesterone inhibition of estrogen-induced maternal behavior in hysterectomized–ovariectomized virgin rats

Horm. Behav.

(1975)

H.I. Siegel et al.

Duration of estrogen stimulation and progesterone inhibition of maternal behavior in pregnancy-terminated rats

Horm. Behav.

(1978)

D.S. Stolzenberg et al.

Hypothalamic interaction with the mesolimbic DA system in the control of the maternal and sexual behaviors in rats

Neurosci. Biobehav. Rev.

(2011)

D.S. Stolzenberg et al.

Dopamine D(1) receptor activation of adenylyl cyclase, not phospholipase C, in the nucleus accumbens promotes maternal behavior onset in rats

Horm. Behav.

(2010)

D.S. Stolzenberg et al.

Experience-facilitated improvements in pup retrieval; evidence for an epigenetic effect

Horm. Behav.

(2012)

J. Terkel et al.

Male copulatory behavior triggers nightly prolactin surges resulting in successful pregnancy in rats

Horm. Behav.

(1978)

C. Teyssier et al.

Requirement for multiple domains of the protein arginine methyltransferase CARM1 in its transcriptional coactivator function

J. Biol. Chem.

(2002)

N. Vasudevan et al.

Non-genomic actions of estrogens and their interaction with genomic actions in the brain

Front. Neuroendocrinol.

(2008)

G.G. Wozniak et al.

Hitting the ‘mark’: interpreting lysine methylation in the context of active transcription

Biochim. Biophys. Acta

(2014)

T. Zakar et al.

Progesterone withdrawal: key to parturition

Am. J. Obstet. Gynecol.

(2007)

E. Abraham et al.

Father's brain is sensitive to childcare experiences

Proc. Natl. Acad. Sci. U. S. A.

(2014)

V.M. Afonso et al.

Distal pup cues evoke dopamine responses in hormonally primed rats in the absence of pup experience or ongoing maternal behavior

J. Neurosci.

(2013)

K.I. Ansari et al.

Histone methylases MLL1 and MLL3 coordinate with estrogen receptors in estrogen-mediated HOXB9 expression

Biochemistry

(2011)

R. Bridges et al.

Differences in maternal responsiveness between lactating and sensitized rats

Dev. Psychobiol.

(1972)

F. Champagne et al.

Naturally occurring variations in maternal behavior in the rat are associated with differences in estrogen-inducible central oxytocin receptors

Proc. Natl. Acad. Sci. U. S. A.

(2001)

F.A. Champagne et al.

Natural variations in maternal care are associated with estrogen receptor alpha expression and estrogen sensitivity in the medial preoptic area

Endocrinology

(2003)

F.A. Champagne et al.

Variations in nucleus accumbens dopamine associated with individual differences in maternal behavior in the rat

J. Neurosci.

(2004)

F.A. Champagne et al.

Maternal care associated with methylation of the estrogen receptor-alpha1b promoter and estrogen receptor-alpha expression in the medial preoptic area of female offspring

Endocrinology

(2006)

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Hormonal and non-hormonal bases of maternal behavior: The role of experience and epigenetic mechanisms

Highlights

Abstract

Introduction

Section snippets

Non-hormonal basis of maternal behavior

Hormonal basis of maternal behavior

Interplay between hormones and epigenetics in organizing maternal responsivity

Interplay between experience and epigenetics in organizing maternal responsivity

Developmental origins of hormonal and non-hormonally induced maternal behavior

From mother–pup interactions to epigenetics

Maternal experience and the mesolimbic dopamine system

Conclusions & implications

Brain Res.

Horm. Behav.

Horm. Behav.

Physiol. Behav.

Cell

Physiol. Behav.

Neuron

Int. J. Dev. Neurosci.

J. Steroid Biochem.

Am. J. Obstet. Gynecol.

Brain Behav. Immun.

Physiol. Behav.

Pharmacol. Biochem. Behav.

Pharmacol. Biochem. Behav.

Neuroscience

Physiol. Behav.

Brain Res.

Mol. Cell. Neurosci.

Front. Neuroendocrinol.

Behav. Brain Res.

Curr. Biol.

Neuron

Psychoneuroendocrinology

Physiol. Behav.

Physiol. Behav.

Horm. Behav.

Horm. Behav.

Neurosci. Biobehav. Rev.

Horm. Behav.

Horm. Behav.

Horm. Behav.

J. Biol. Chem.

Front. Neuroendocrinol.

Biochim. Biophys. Acta

Am. J. Obstet. Gynecol.

Father's brain is sensitive to childcare experiences

Proc. Natl. Acad. Sci. U. S. A.

Distal pup cues evoke dopamine responses in hormonally primed rats in the absence of pup experience or ongoing maternal behavior

J. Neurosci.

Histone methylases MLL1 and MLL3 coordinate with estrogen receptors in estrogen-mediated HOXB9 expression

Biochemistry

Differences in maternal responsiveness between lactating and sensitized rats

Dev. Psychobiol.

Naturally occurring variations in maternal behavior in the rat are associated with differences in estrogen-inducible central oxytocin receptors

Proc. Natl. Acad. Sci. U. S. A.

Natural variations in maternal care are associated with estrogen receptor alpha expression and estrogen sensitivity in the medial preoptic area

Endocrinology

Variations in nucleus accumbens dopamine associated with individual differences in maternal behavior in the rat

J. Neurosci.

Maternal care associated with methylation of the estrogen receptor-alpha1b promoter and estrogen receptor-alpha expression in the medial preoptic area of female offspring

Endocrinology