MATERNAL BRAIN

Emerging research points to a valuable role of the monoamine neurotransmitter, serotonin, in the display of maternal behaviors and reproduction-associated plasticity in the maternal brain. Serotonin is also implicated in the pathophysiology of numerous affective disorders and likely plays an important role in the pathophysiology of maternal mental illness. Therefore, the main goals of this review are to detail: 1) how the serotonin system of the female brain changes across pregnancy and postpartum; 2) the role of the central serotonergic system in maternal caregiving and maternal aggression; and 3) how the serotonin system and selective serotonin reuptake inhibitor medications (SSRIs) are involved in the treatment of maternal mental illness. Although there is much work to be done, studying the central serotonin system's multifaceted role in the maternal brain is vital to our understanding of the processes governing matrescence and the maintenance of motherhood.

Approximately 10-20% of postpartum women experience anxiety or depressive disorders, which can have extremely detrimental effects on the mother, child and family. Little is known about the neural correlates of these affective disorders when they occur in mothers, but they do have unique neural profiles during the postpartum period compared to when they occur at other times in a woman's life. Because the neural systems affected by postpartum anxiety and depression overlap and interact with the systems involved in maternal caregiving behaviors, mother-infant interactions are highly susceptible to disruption. Thus, there is an intricate interplay among maternal mental health, the mother-infant relationship, and the neurobiological mechanisms mediating them that needs to be the focus of future study.

The neural system underlying maternal caregiving has often been studied using laboratory rodents and a few other mammalian species. This research shows that the medial preoptic area (mPOA) integrates sensory cues from the young that, along with hormonal and other environmental signals, control maternal acceptance of neonates. The mPOA then activates the mesolimbic system that drives maternal motivation and caregiving activities. How components of this neural system respond to maternal experience and exposure to young in non-mammals has rarely been examined. To gain more insight into this question, virgin female Japanese quail (Coturnix japonica) were induced to be maternal through four days of continuous exposure to chicks (Maternal), or were not exposed to chicks (Non-Maternal). Chicks were removed overnight from the Maternal group and half the females from each group were then exposed to chicks for 90 minutes (Exposed), or not exposed to chicks (Non-Exposed), before euthanasia. The number of Fos-immunoreactive (Fos-ir) cells was examined as a marker of neuronal activation. As expected, repeated exposure to chicks induced caregiving behavior in the Maternal females, which persisted after the overnight separation, suggesting formation of a maternal memory. In contrast, Non-Maternal females were aggressive and rejected chicks when exposed to them. Exposed females, whether or not they were given prior experience with chicks (i.e., regardless if they accepted or rejected chicks during the exposure before euthanasia), had more Fos-ir cells in the mPOA compared to Non-Exposed females. In the nucleus accumbens (NAC), the number of Fos-ir cells was high in all Maternal females regardless of whether or not they were Exposed to chicks again before euthanasia. In the lateral bed nucleus of the stria terminalis, a site involved in general stress responding, groups did not differ in Fos-ir cells. These data indicate a conserved role for the mPOA and NAC in maternal caregiving across vertebrates, with 4 the mPOA acutely responding to the salience rather than valence of offspring cues, and the NAC showing longer-term changes in activity after a positive maternal experience even without a recent exposure.

Part of the variability in fMRI research derives from differences in the visual (infant) stimuli used across studies. For example, stimuli might differ in duration, emotive valence of facial expressions, or presentation format (pictures and video). These variations in stimulus features can affect subsequent patterns of brain response. Maternal psychology also influences the site of cerebral activity and the magnitude of activation (Barrett et al., 2012). Consequently, these factors mentioned above can potentially influence regions activated in response to the mother's own child. An enhanced maternal response to own infant's face occurs in dopaminergic brain regions, such as the SN/VTA, and subcortical nuclei, which are brain areas important for maternal attachment (Bartels & Zeki, 2004; Numan & Young, 2016). Additionally, enhanced activity has been found in the ventral striatum and nucleus accumbens, which, according to animal and human models of parenting, are regions that reinforce maternal motivation and social interaction (

With a package of 21 papers published in Science and related journals
a large interdisciplinary and international group of researchers assembled within the Cell Census Network, which is part of the US NIH
Brain Research has produced a never-before-realized brain cell atlas. Until now, brain atlases have been constructed from brain MRI images and accompanying explanatory drawings.
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Perineuronal nets (PNNs) are aggregations of extracellular matrix associated with specific neuronal populations in the central nervous system, suggested to play key roles in neural development, synaptogenesis and experience-dependent synaptic plasticity. Pregnancy and lactation are characterized by a dramatic increase in neuroplasticity. However, dynamic changes in the extracellular matrix associated with maternal circuits have been mostly overlooked. We analyzed the structure of PNNs in an essential nucleus of the maternal circuit, the medial preoptic area (mPOA), during the reproductive cycle of rats, using the Wisteria floribunda (WFA) label. PNNs associated to neurons in the mPOA start to assemble halfway through gestation and become highly organized prior to parturition, fading through the postpartum period. This high expression of PNNs during pregnancy appears to be mediated by the influence of estrogen, progesterone and prolactin, since a hormonal simulated-gestation treatmen...

Approximately 10-20% of postpartum women experience anxiety or depressive disorders, which can have extremely detrimental effects on the mother, child and family. Little is known about the neural correlates of these affective disorders when they occur in mothers, but they do have unique neural profiles during the postpartum period compared to when they occur at other times in a woman's life. Because the neural systems affected by postpartum anxiety and depression overlap and interact with the systems involved in maternal caregiving behaviors, mother-infant interactions are highly susceptible to disruption. Thus, there is an intricate interplay among maternal mental health, the mother-infant relationship, and the neurobiological mechanisms mediating them that needs to be the focus of future study.

It is becoming clear that the female brain has an inherent plasticity that is expressed during reproduction. The changes that occur benefit the offspring, which in turn secures the survival of the mother's genetic legacy. Thus, the onset of maternal motivation involves basic mechanisms from genetic expression profiles, to hormone release, to hormone-neuron interactions, all of which fundamentally change the neural architectureand for a period of time that extends, interestingly, beyond the reproductive life of the female. Although multiple brain areas involved in maternal responses are discussed, this review focuses primarily on plasticity in the maternal hippocampus during pregnancy, the postpartum period and well into aging as it pertains to changes in cognition. In addition, the effects of prolonged and repeated stress on these dynamic responses are considered. The maternal brain is a marvel of directed change, extending into behaviors both obvious (infant-directed) and less obvious (predation, cognition). In sum, the far-reaching effects of reproduction on the female nervous system provide an opportunity to investigate neuroplasticity and behavioral flexibility in a natural mammalian model.

Females usually display low levels of aggressiveness; however, during lactation, the aggressive behavior against intruders to the nest area is an important component of the maternal behavioral repertoire. The present study aimed to analyze the influence of progesterone (P4) on the maternal aggressive behavior in rats. Lactating rat were ovariectomized on the first day after delivery and, on the 6th postpartum day, aggressive behaviors against a male intruder were recorded. Also in the 6th PPD, the effects of a P4 receptor antagonist (RU 486) as well as of finasteride-which inhibits the conversion of P4 to its metabolite allopregnanolone-on the aggressive behavior of non-ovariectomized lactating rats were analyzed. Finally, plasma concentration of prolactin was measured on the 8th PPD. This study shows, for the first time, that ovariectomy just after parturition reduces some aspects of the maternal behavior (frequency of licking) and the aggressive behavior and increased plasma prolactin. On the other hand, the administration of RU486 induced a marked increase in the aggressiveness of lactating females. No changes were detected after finasteride injection. Gonadal hormones after parturition seem necessary for the development of maternal aggressive behavior. Furthermore, our results suggest that the increase in P4 levels throughout the postpartum period could be one of the causes for the natural reduction of the aggressive behavior in lactating rats.

In pregnancy and the postpartum period, many women have emotional instability and some suffer from depression. The ovarian steroid hormone milieu is markedly changed during these periods, and this hormonal change may be an important cause of peripartum emotional instability. The amygdala is a central region of emotion, and the bed nucleus of the stria terminalis (BNST), which is considered to be the extended amygdala, is also involved in the emotional response. The amygdala and BNST are well characterized as target brain regions for ovarian steroid hormones, and this suggests that the functional response of neurons in these regions to hormonal fluctuation is affected in the peripartum period. In this study, we investigated the neuronal morphology in the central (CeA) and basolateral (BLA) nucleus of the amygdala and BNST on gestational days 15 (G15) (mid-gestation) and 20 (G20) (late gestation) and 4days after delivery (P4) (early postpartum) in rat. Golgi staining showed that the d...

Emerging research points to a valuable role of the monoamine neurotransmitter, serotonin, in the display of maternal behaviors and reproduction-associated plasticity in the maternal brain. Serotonin is also implicated in the pathophysiology of numerous affective disorders and likely plays an important role in the pathophysiology of maternal mental illness. Therefore, the main goals of this review are to detail: 1) how the serotonin system of the female brain changes across pregnancy and postpartum; 2) the role of the central serotonergic system in maternal caregiving and maternal aggression; and 3) how the serotonin system and selective serotonin reuptake inhibitor medications (SSRIs) are involved in the treatment of maternal mental illness. Although there is much work to be done, studying the central serotonin system's multifaceted role in the maternal brain is vital to our understanding of the processes governing matrescence and the maintenance of motherhood.

Neuroimaging researchers commonly assume that the brain of a mother is comparable to that of a nulliparous woman. However, pregnancy leads to pronounced gray matter volume reductions in the mother’s brain, which have been associated with maternal attachment towards the baby. Beyond two years postpartum, no study has explored whether these brain changes are maintained or instead return to pre-pregnancy levels. The present study tested whether gray matter volume reductions detected in primiparous women are still present six years after parturition. Using data from a unique, prospective neuroimaging study, we compared the gray matter volume of 25 primiparous and 22 nulliparous women across three sessions: before conception (n = 25/22), during the first months of postpartum (n = 25/21), and at six years after parturition (n = 7/5). We found that most of the pregnancy-induced gray matter volume reductions persist six years after parturition (classifying women as having been pregnant or n...

Previous work from our laboratory has shown that there is a much higher level of bFGF and GFAP immunoreactivity in area 2 of the cingulate cortex (Cg2) of rats on day 16 of lactation than in cycling or late pregnant females. To examine the time course of this change, in the first of the current studies, we compared bFGF and GFAP immunoreactivity in the brains of lactating females on postpartum day 4 (PP4), day 10 (PP10), day 16 (PP16), and day 24 (PP24) with that of cycling and ovariectomized (OVX) females. In the second study, we investigated whether the maintenance of these changes in bFGF and GFAP depended on suckling stimulation by removing litters on day 1 or day 16 postpartum and examining the brains of the dams on day 4 (Pr4) or day 24 (Pr24) postpartum, respectively. bFGF and GFAP immunoreactivity within Cg2 and the medial preoptic area (MPOA) were measured. In both experiments astrocytic bFGF and GFAP surface density in the Cg2 varied significantly across groups. All postpartum rats, regardless of stage of lactation or presence of the litter, had significantly higher levels of bFGF and GFAP immunoreactivity than cycling animals. Thus, the maintenance of this upregulation in bFGF and GFAP immunoreactivity does not depend on suckling stimulation. Consistent with our previous report, astrocytic bFGF was also elevated in the MPOA of PP16 animals. These data suggest a robust, long-lasting, postpartum change in bFGF and GFAP immunoreactivity in Cg2 and a role for this area of the cortex in the physiological and behavioral adaptations that accompany reproductive experience.

During pregnancy, maternal brain neuroplasticity indicates vast neurofunctional and neuroanatomical changes. Recent findings documented a similarly massive readjustment after pregnancy. Currently, these brain changes are interpreted as preparation for and adjustment of the maternal brain to motherhood. Yet, this perspective leaves many questions unsolved. Neuroscientific studies have not yet been conducted to determine the brain areas that function during natural childbirth even though physiological birth is the natural process of women who have reproduced successfully throughout two million years of evolution of the genus Homo. It is rational to believe that the female brain is an active and crucial actor during birth and that birth, itself, is a process that requires brain neuroplasticity. Lack of studies of the birthing brain and brain preparation for birth is a significant lacuna in neuroscience research. I demonstrate theoretically that a new hypothesis for complementary interpretation of maternal brain neuroplasticity is reasonable: Certain maternal brain changes during pregnancy can be interpreted as brain preparation for birth and certain maternal brain changes after birth can be interpreted as brain recovery after the tremendous event of birth. This essay can be a starting point for new directions in neuroscience studies.

Prolactin (PRL), an anterior pituitary hormone with neurogenic properties associated with pregnancy, has been implicated in oligodendrocyte proliferation during gestation, contributing to increased myelination in the maternal brain. However, PRL is elevated during lactation as well, suggesting that the postpartum (PP) period may contribute to additional gliogenesis in lactating females. In the present study, we assessed oligodendrocyte number in the corpus callosum (CC) of female Sprague-Dawley rats near the end of gestation, and at two weeks postpartum in both lactating and non-lactating dams, and in virgins. Though pregnant females did not differ significantly from any other group, lactating females had significantly more oligodendrocytes in the CC than virgins (p = .01), and in medial regions of the CC than non-lactating dams (p < .02). Oligodendrocyte number in the CC of pregnant and PP females correlated positively with the number of pups in their litter (r 2 = .68, p < .005). These results suggest that the gestational period contributes to oligodendrocyte proliferation or survival, likely mediated by an endocrine hormone whose concentration varies with the size of the litter. The PP period also contributes to increases in CC oligodendrocyte number, though it is unclear whether endocrine influences and/or pup-interaction underlie the differences in myelination between lactating and non-lactating groups. Further investigation is required in order to confirm whether the effects observed are mediated by members of the PRL-family, experience, and/or other gestational/ PP endocrine hormones.

Ovariectomy (OVX) has been widely used to explore the effect of ovarian hormones on brain regions. It has been observed that estrogen in OVX rats increases the dopaminergic function in nucleus accumbens (NAcc). To determine whether absence or presence of estradiol changes the dendritic structure of some dopaminergic neurons, we investigated the consequences of a daily injection for 2 weeks of 17-beta estradiol (E2) on the dendritic morphology of NAcc neurons in two groups of rats, immediately or 10 weeks administered after OVX. The structure of dendrites was measured by using the Golgi-Cox procedure followed by a Sholl analysis. We found a reduction in the number of spiny dendrites of the medium spiny neurons of the NAcc in animals in which E2 was administrated without delay after OVX. However, when the same treatment was administered 10 weeks after OVX, not any difference was observed. Independently of the hormone treatment, rats from the group of 10 weeks after OVX showed a reduction in the number of spiny dendrites of the medium spiny neurons when compared with their counterparts at 2 weeks. Data suggest that estrogens or their absence regulate synaptogenesis in the NAcc.

The peripartum period is accompanied by dramatic changes in hormones and a host of new behaviours in response to experience with offspring. Both maternal experience and maternal hormones can have a significant impact upon the brain and behaviour. This review outlines recent studies demonstrating modifications in hippocampal plasticity across the peripartum period, as well as the putative hormonal mechanisms underlying these changes and their modulation by stress. In addition, the impact of reproductive experience upon the ageing hippocampus is discussed. Finally, we consider how these changes in hippocampal structure may play a role in postpartum cognitive function and mood disorders, as well as age-related cognitive decline.

As any new parent knows, having a baby provides opportunities for enrichment, learning and stress -experiences known to change the adult brain. Yet surprisingly little is known about the effects of maternal experience, and even less about the effects of paternal experience, on neural circuitry not directly involved in parenting. Here we discuss how caregiving and the accompanying experiential and hormonal changes influence the hippocampus and prefrontal cortex, brain regions involved in cognition and mood regulation. A better understanding of how parenting impacts the brain is likely to help in devising strategies for treating parental depression, a condition that can have serious cognitive and mental health consequences for children.

Among the suite of adaptations displayed by seasonally-breeding rodents, individuals of most species display reproductive regression and concomitant decreases in gonadal steroids during the winter. In addition, some species display increased aggression in short "winter-like" days compared with long "summer-like" day lengths. For example, male Syrian and Siberian hamsters held in short days express heightened levels of aggression that are independent of gonadal steroids. Virtually nothing is known, however, regarding seasonal aggression in female Siberian hamsters (Phodopus sungorus). Studies were undertaken to determine female levels of aggression in long and short days as well as the role of gonadal steroids in mediating this behavior. In Experiment 1, females were housed in long or short days for 10 weeks and resident-intruder aggression was assessed. Prior to testing, estrous cycle stages were determined by vaginal cytology and females were tested during both Diestrus I and Proestrus. In Experiment 2, hormone levels were experimentally manipulated; long-day females were ovariectomized (OVx) or given sham surgeries whereas short-day females were implanted with capsules containing 17β-estradiol (E 2 ) or Progesterone (P). In Experiment 3, both longand short-day females were ovariectomized and implanted with either an exogenous E 2 or blank capsule, or given a sham surgery. Short-day hamsters displayed increased aggression relative to long-day females. Aggression was not affected by estrous stage. There was no difference in aggression between long-day OVx and sham animals. Furthermore, neither exogenous E 2 nor P had any significant effect on aggression. These results support previous findings of increased non-breeding aggression and suggest that short-day aggression is not likely mediated by circulating levels of gonadal steroids. These results also suggest that the endocrine regulation of seasonal aggression may be similar between the sexes.

Motherhood modifies the biology and behavior of the female, a process which prepares the mother's cognitive systems that are needed for nurturance. It has recently been shown that motherhood enhances hippocampal-mediated spatial learning and synaptic plasticity. Deleterious and long-term effects of a stress experienced during gestation have been demonstrated on progeny. Surprisingly little is known about the effect of such stress on mothers. Here, we investigated the effect of gestational stress on the adaptive changes due to motherhood. Female rats were mated and stressed during the last week of gestation. Two weeks after weaning, they were submitted to behavioral tests or electrophysiological study. A group of females were then kept for 16 months after motherhood experience to study the long-term effect of gestational stress and motherhood on memory when they were 22 months old. We confirm that a single motherhood experience selectively increases hippocampal-mediated spatial memory during the entire lifespan of female rats and protects them from age-associated memory impairments. However, we demonstrate that a stressful experience during gestation totally abolishes the positive effects of motherhood both on spatial memory and on hippocampal synaptic plasticity (long-term potentiation). Environmental factors that induce biological vulnerability have negative effects even for fundamental biological behaviors.