Hypothalamic control of innate social behaviors.

Sexual, parental, and aggressive behaviors are central to the reproductive success of individuals and species survival and thus are supported by hardwired neural circuits. The reproductive behavior control column (RBCC), which comprises the medial preoptic nucleus (MPN), the ventrolateral part of the ventromedial hypothalamus (VMHvl), and the ventral premammillary nucleus (PMv), is essential for all social behaviors. The RBCC integrates diverse hormonal and metabolic cues and adjusts an animal's physical activity, hence the chance of social encounters. The RBCC further engages the mesolimbic dopamine system to maintain social interest and reinforces cues and actions that are time-locked with social behaviors. We propose that the RBCC and brainstem form a dual-control system for generating moment-to-moment social actions. This Review summarizes recent progress regarding the identities of RBCC cells and their pathways that drive different aspects of social behaviors.

Neural circuitry for maternal oxytocin release induced by infant cries.

Oxytocin is a neuropeptide that is important for maternal physiology and childcare, including parturition and milk ejection during nursing1-6. Suckling triggers the release of oxytocin, but other sensory cues-specifically, infant cries-can increase the levels of oxytocin in new human mothers7, which indicates that cries can activate hypothalamic oxytocin neurons. Here we describe a neural circuit that routes auditory information about infant vocalizations to mouse oxytocin neurons. We performed in vivo electrophysiological recordings and photometry from identified oxytocin neurons in awake maternal mice that were presented with pup calls. We found that oxytocin neurons responded to pup vocalizations, but not to pure tones, through input from the posterior intralaminar thalamus, and that repetitive thalamic stimulation induced lasting disinhibition of oxytocin neurons. This circuit gates central oxytocin release and maternal behaviour in response to calls, providing a mechanism for the integration of sensory cues from the offspring in maternal endocrine networks to ensure modulation of brain state for efficient parenting.

Antagonistic circuits mediating infanticide and maternal care in female mice.

In many species, including mice, female animals show markedly different pup-directed behaviours based on their reproductive state1,2. Naive wild female mice often kill pups, while lactating female mice are dedicated to pup caring3,4. The neural mechanisms that mediate infanticide and its switch to maternal behaviours during motherhood remain unclear. Here, on the basis of the hypothesis that maternal and infanticidal behaviours are supported by distinct and competing neural circuits5,6, we use the medial preoptic area (MPOA), a key site for maternal behaviours7-11, as a starting point and identify three MPOA-connected brain regions that drive differential negative pup-directed behaviours. Functional manipulation and in vivo recording reveal that oestrogen receptor α (ESR1)-expressing cells in the principal nucleus of the bed nucleus of stria terminalis (BNSTprESR1) are necessary, sufficient and naturally activated during infanticide in female mice. MPOAESR1 and BNSTprESR1 neurons form reciprocal inhibition to control the balance between positive and negative infant-directed behaviours. During motherhood, MPOAESR1 and BNSTprESR1 cells change their excitability in opposite directions, supporting a marked switch of female behaviours towards the young.

Milking It for All It's Worth: The Effects of Environmental Enrichment on Maternal Nurturance, Lactation Quality, and Offspring Social Behavior.

Breastfeeding confers robust benefits to offspring development in terms of growth, immunity, and neurophysiology. Similarly, improving environmental complexity, i.e., environmental enrichment (EE), contributes developmental advantages to both humans and laboratory animal models. However, the impact of environmental context on maternal care and milk quality has not been thoroughly evaluated, nor are the biological underpinnings of EE on offspring development understood. Here, Sprague Dawley rats were housed and bred in either EE or standard-housed (SD) conditions. EE dams gave birth to a larger number of pups, and litters were standardized and cross-fostered across groups on postnatal day (P)1. Maternal milk samples were then collected on P1 (transitional milk phase) and P10 (mature milk phase) for analysis. While EE dams spent less time nursing, postnatal enrichment exposure was associated with heavier offspring bodyweights. Milk from EE mothers had increased triglyceride levels, a greater microbiome diversity, and a significantly higher abundance of bacterial families related to bodyweight and energy metabolism. These differences reflected comparable transcriptomic changes at the genome-wide level. In addition to changes in lactational quality, we observed elevated levels of cannabinoid receptor 1 in the hypothalamus of EE dams, and sex-dependent and time-dependent effects of EE on offspring social behavior. Together, these results underscore the multidimensional impact of the combined neonatal and maternal environments on offspring development and maternal health. Moreover, they highlight potential deficiencies in the use of "gold standard" laboratory housing in the attempt to design translationally relevant animal models in biomedical research.

Early life oxytocin treatment improves thermo-sensory reactivity and maternal behavior in neonates lacking the autism-associated gene Magel2.

Atypical responses to sensory stimuli are considered as a core aspect and early life marker of autism spectrum disorders (ASD). Although recent findings performed in mouse ASD genetic models report sensory deficits, these were explored exclusively during juvenile or adult period. Whether sensory dysfunctions might be present at the early life stage and rescued by therapeutic strategy are fairly uninvestigated. Here we found that under cool environment neonatal mice lacking the autism-associated gene Magel2 present pup calls hypo-reactivity and are retrieved with delay by their wild-type dam. This neonatal atypical sensory reactivity to cool stimuli was not associated with autonomic thermoregulatory alteration but with a deficit of the oxytocinergic system. Indeed, we show in control neonates that pharmacogenetic inactivation of hypothalamic oxytocin neurons mimicked atypical thermosensory reactivity found in Magel2 mutants. Furthermore, pharmacological intranasal administration of oxytocin to Magel2 neonates was able to rescue both the atypical thermosensory response and the maternal pup retrieval. This preclinical study establishes for the first-time early life impairments in thermosensory integration and suggest a therapeutic potential benefit of intranasal oxytocin treatment on neonatal atypical sensory reactivity for autism.

An epigenomic shift in amygdala marks the transition to maternal behaviors in alloparenting virgin female mice.

Adults of many species will care for young offspring that are not their own, a phenomenon called alloparenting. However, in many cases, nonparental adults must be sensitized by repeated or extended exposures to newborns before they will robustly display parental-like behaviors. To capture neurogenomic events underlying the transition to active parental caring behaviors, we analyzed brain gene expression and chromatin profiles of virgin female mice co-housed with pregnant dams during pregnancy and after birth. After an initial display of antagonistic behaviors and a surge of defense-related gene expression, we observed a dramatic shift in the chromatin landscape specifically in amygdala of the pup-exposed virgin females compared to females co-housed with mother before birth, accompanied by a dampening of anxiety-related gene expression. This epigenetic shift coincided with hypothalamic expression of the oxytocin gene and the emergence of behaviors and gene expression patterns classically associated with maternal care. The results outline a neurogenomic program associated with dramatic behavioral changes and suggest molecular networks relevant to human postpartum mental health.

Effects of maternal experience on pup-induced activation of maternal neural circuits in virgin mice.

Maternal experience can promote a long-lasting increase in maternal motivation. This maintenance of caregiving behaviors, rather than avoidant or agnostic responses towards young, is advantageous for the survival of subsequent offspring. We have previously reported that maternal motivation is associated with differential immediate early gene expression in central motivation circuits and aversion circuits. Here we ask how these circuits come to differentially respond to infant cues. We used Targeted Recombination in Active Populations (TRAP) to identify cells that respond to pups in maternally hesitant TRAP2;Ai14 virgin female mice. Following an initial 60 min exposure to foster pups, virgin TRAP2;Ai14 mice were injected with 4-hydroxytamoxifen to induce recombination in c-Fos expressing cells and subsequent permanent expression of a red fluorescent reporter. We then examined whether the same cells that encode pup cues are reactivated during maternal memory retrieval two weeks later using c-Fos immunohistochemistry. Whereas initial pup exposure induced c-Fos activation exclusively in the medial preoptic area (MPOA), following repeated experience, c-Fos expression was significantly higher than baseline in multiple regions of maternal and central aversion circuits (e.g., ventral bed nucleus of the stria terminalis, nucleus accumbens, basolateral amygdala, prefrontal cortex, medial amygdala, and ventromedial nucleus of the hypothalamus). Further, cells in many of these sites were significantly reactivated during maternal memory retrieval. These data suggest that cells across both maternal motivation and central aversion circuits are stably responsive to pups and thus may form the cellular representation of maternal memory.

Prolactin-mediated restraint of maternal aggression in lactation.

Aggressive behavior is rarely observed in virgin female mice but is specifically triggered in lactation where it facilitates protection of offspring. Recent studies demonstrated that the hypothalamic ventromedial nucleus (VMN) plays an important role in facilitating aggressive behavior in both sexes. Here, we demonstrate a role for the pituitary hormone, prolactin, acting through the prolactin receptor in the VMN to control the intensity of aggressive behavior exclusively during lactation. Prolactin receptor deletion from glutamatergic neurons or specifically from the VMN resulted in hyperaggressive lactating females, with a marked shift from intruder-directed investigative behavior to very high levels of aggressive behavior. Prolactin-sensitive neurons in the VMN project to a wide range of other hypothalamic and extrahypothalamic regions, including the medial preoptic area, paraventricular nucleus, and bed nucleus of the stria terminalis, all regions known to be part of a complex neuronal network controlling maternal behavior. Within this network, prolactin acts in the VMN to specifically restrain male-directed aggressive behavior in lactating females. This action in the VMN may complement the role of prolactin in other brain regions, by shifting the balance of maternal behaviors from defense-related activities to more pup-directed behaviors necessary for nurturing offspring.

Maternal behavior, novelty confrontation, and subcortical c-Fos expression during lactation period are shaped by gestational environment.

The environmental context during gestation may modulate the postpartum variations in maternal behaviors observed within different animal species. Most of our experimental knowledge on this phenomenon and its physiological effects have been gained by confronting the pregnant mother with stressful situations, with the consensual results indicating a reduced maternal behavior and a hyper reactivity of stress-related neural paths. Here, in contrast, by exposing nulliparous rats strictly during pregnancy to a standard laboratory environment (STD) or a highly stimulating sensory and social environment (EE), we investigated the hypothesis that subjects frequently exposed to social stimuli and novel situations during pregnancy will show postpartum changes in subcortical brain areas' activity related to the processing of social stimuli and novelty, such that there will be modifications in maternal behavior. We found that EE mothers doubled the levels of licking and grooming, and active hovering over pups during the first postpartum week than STD dams, without a difference in the time of contact with the pups. Associated with these behaviors, EE dams showed increased c-Fos immunoreaction in hypothalamic nuclei and distinct responses in amygdalar nuclei, than STD dams. In the maternal defensive test, EE dams tripled the levels of aggressive behaviors of the STD rats. Additionally, in two different tests, EE mothers showed lower levels of postpartum anxiety-like behaviors when confronted with novel situations. Our results demonstrate that the activity of brain areas related to social behavior is adaptable by environmental circumstances experienced during gestation, presumably to prepare the progeny for these particular conditions.

Opium Effect in Pregnancy on the Dynamics of Maternal Behavior: Testing a Neurochemical Model.

BACKGROUND: Investigations into neurochemical mechanisms of opioid addiction are difficult due to the complexity of behavior and multiplicity of involved neurotransmitter and hormonal systems. The aim of this study was to examine the benefits of structured analysis of these mechanisms using the framework of the neurochemical model Functional Ensemble of Temperament (FET) and the example of maternal behavior under the condition of opium consumption in pregnancy. The FET differentiates between (a) endurance, (b) speed of integration, and (c) emotionality aspects of behavior suggesting that these systems are differentially regulated by (a) serotonin-neuropeptides-brain-derived neurotrophic factor (BDNF), (b) dopamine-GABA, and (c) opioid receptor systems, correspondingly. The FET also suggests that mu-opioid receptors (MORs) binding the endorphines (including opium's ingredient morphine) have a stronger association with regulation endurance, whereas delta-OR have a stronger association with integration of behavior and kappa-OR - with the perceptual mobilization seen in anxiety. To test the predictions of this model, we compared the impact of massive MOR dysregulation on 3 behavioral aspects of behavior and on serotonin, BDNF, and corticosterone levels. METHODS: The study used 24 female white Wistar rats which were randomly divided into (1) control group: pregnant rats without any intervention; (2) opium-exposed group: animals that were exposed to opium during pregnancy and after the delivery until the end of the study. At the end of the study, the levels of BDNF, serotonin (5-HT) in the hippocampus of the mother's brain, and serum corticosterone, as well as 12 aspects of the maternal behavior were evaluated. The differences between control and experimental groups were assessed using the t test for independent samples. RESULTS: The BDNF and serotonin concentrations in the hippocampus of the mother rats which were exposed to opium were lower than in the control group; the mean corticosterone in exposed mothers was higher than in the control group. Behaviorally, opium-consuming mothers showed lower endurance in 4 distinct behavioral categories (nesting, feeding, grooming, and retrieval) than the mothers in the control group. Ease of integration of behavior was affected to a lesser degree, showing a significant effect only in 1 out of 5 applied measures. Self-grooming, seen as an emotionality-related aspect of behavior, was not affected. CONCLUSION: Opium exposure during pregnancy in our experiment primarily reduced the endurance of rat's maternal behavior, but the speed of integration of behavioral acts was less affected. This negative impact of opium on endurance was associated with a decrease of BDNF and serotonin levels in the hippocampus and an increase in corticosterone level in opium-consuming mothers. There is no effect of opium exposure on self-grooming behavior. This pattern supports the FET hypothesis about the role of 5-HT and BDNF in endurance, differential regulation of endurance, integrative and emotionality aspects of behavior, and differential association of the MOR system with endurance aspects, in comparison with kappa- and delta opioid receptors.

Reported maternal childhood maltreatment experiences, amygdala activation and functional connectivity to infant cry.

Maternal childhood maltreatment experiences (CMEs) may influence responses to infants and affect child outcomes. We examined associations between CME and mothers' neural responses and functional connectivity to infant distress. We hypothesized that mothers with greater CME would exhibit higher amygdala reactivity and amygdala-supplementary motor area (SMA) functional connectivity to own infant's cries. Postpartum mothers (N = 57) assessed for CME completed an functional magnetic resonance imaging task with cry and white-noise stimuli. Amygdala region-of-interest and psychophysiological interaction analyses were performed. Our models tested associations of CME with activation and connectivity during task conditions (own/other and cry/noise). Exploratory analyses with parenting behaviors were performed. Mothers with higher CME exhibited higher amygdala activation to own baby's cries vs other stimuli (F1,392 = 6.9, P < 0.01, N = 57) and higher differential connectivity to cry vs noise between amygdala and SMA (F1,165 = 22.3, P < 0.001). Exploratory analyses revealed positive associations between both amygdala activation and connectivity and maternal non-intrusiveness (Ps < 0.05). Increased amygdala activation to own infant's cry and higher amygdala-SMA functional connectivity suggest motor responses to baby's distress. These findings were associated with less intrusive maternal behaviors. Follow-up studies might replicate these findings, add more granular parenting assessments and explore how cue processing leads to a motivated maternal approach in clinical populations.

Perinatal dietary omega-3 fatty acid deficiency reduces maternal nurturing behavior in rats: dissociation from elevated pro-inflammatory signaling.

Objectives: Maternal-pup nurturing behavior has previously been shown to impact offspring neurodevelopment independent of diet. Here we investigated the effects of perinatal maternal n-3 fatty acid deficiency on maternal-pup nurturing behavior and potential associations with pro-inflammatory signaling.Methods: Eight-week-old virgin female Long-Evans hooded rats were randomized to a control diet containing alpha-linolenic acid (ALA, 18:3n-3) (CON, n = 10) or an ALA-free diet (Deficient, DEF, n = 11) 30 d prior to mating. On postnatal day 2 (P2) litters were culled to eight per dam. On P3, P6, and P9 dams and their litters were video recorded and maternal nurturing behaviors, including licking/grooming of pups and arched-back nursing, were scored by a blinded rater. Following weaning on P21, dam postmortem central (prefrontal cortex, PFC) and peripheral (red blood cell, RBC) fatty acid composition and central (PFC IL-1ß, IL-2, IL-6, TNFα, cPLA2, COX-2 mRNA) and peripheral (plasma IL-1ß, IL-2, IL-6, TNFα, CRP) pro-inflammatory biostatus assessed.Results: DEF dams exhibited significantly lower RBC (p ≤ 0.0001) and PFC (p ≤ 0.0001) docosahexaenoic acid (DHA) levels compared with CON dams. Irrespective of diet dams exhibited significantly lower RBC, but not PFC, DHA levels compared with non-parous rats. DEF dams exhibited less licking/grooming (p = 0.008), arched-back nursing (p ≤ 0.0001) and blanket nursing (p = 0.003), and exhibited more passive nursing (p = 0.003) but not time off pups (p = 0.1), compared with CON dams. PFC and plasma inflammatory measures did not differ significantly between groups.Discussion: Perinatal dietary n-3 fatty acid deficiency reduces maternal nurturing behavior and this effect is not associated with enduring elevations in pro-inflammatory signaling.

Maternal responsiveness to suckling is modulated by time post-nursing: A behavioural and c-Fos/oxytocin immunocytochemistry study in rabbits.

Doe rabbits nurse once/day for approximately 3 minutes, with circadian periodicity, inside the nest box. The amount of suckling received at each bout regulates this behaviour because reducing the litter size to four kits or less disrupts nursing circadian periodicity and increases suckling bout duration. Additionally, the likelihood that does will nurse kits at a given time of day depends on the time elapsed since the last suckling episode and the litter size nursed then. We hypothesised that the time elapsed since the last nursing would impact the number of c-Fos immunoreactive (IR) cells observed after suckling five kits and also that observed before the next nursing ("no kits"). Suckling significantly increased, relative to "no kits", the number of c-Fos-IR cells in the medial preoptic area and lateral septum but not in the bed nucleus of the stria terminalis (BNST), suprachiasmatic nucleus or ventromedial hypothalamus in does nursing at 18 or 24 hours after the previous bout. No effects of suckling were observed in mothers nursing at 6 hours. Does given kits at 3 hours post last suckling refused to nurse but, in the remaining three groups, all does nursed normally. At "no kits", more c-Fos-IR cells were seen (in all regions except the BNST) in does given kits at 24 hours after the last nursing and killed 1 hour later (ie, 4 hours after lights on) than in those killed earlier. The percentage of oxytocinergic (OT) cells co-expressing c-Fos was not modified by nursing in the paraventricular or supraoptic nuclei but, in the latter, the largest number of total OT-IR cells occurred at 18 and 24 hours post-last nursing. In conclusion, the responsiveness of particular forebrain regions involved in regulating circadian rhythms, lactation, and maternal behaviour is modulated by suckling and time of day.

Identification of hypothalamic genes in associating with food intake during incubation behavior in domestic chicken.

The molecular mechanism underlying in the onset and maintenance of incubation behavior are not fully understood, and it is still unknown the reason why White Leghorn, a layer strain, hens never display incubation behavior. Therefore, to explore specific hypothalamic genes regulating incubation behavior, cap analysis of gene expression (CAGE) were applied to comparison between incubating Silkie and laying White Leghorn hens. In addition, mRNA expression of some differentially expressed genes (DEGs) and melanocortinergic appetite genes including agouti-related peptide (AgRP) and pro-opiomelanocortin (POMC) was also analyzed on Silkie hens under natural anorexia and starvation. The CAGE identified 217 hypothalamic DEGs in incubating Silkie hens, and that of two, transthyretin (TTR) and prolactin-releasing peptide (PrRP), suggested as appetite gene, were markedly up- and down-regulated in incubating hens, respectively. In addition, AgRP and POMC expression also increased in incubating bird. mRNA expression of TTR, PrRP, and appetite genes were not differed significantly by starvation, although TTR mRNA expression was relatively high in fasting hens. Consequently, transcriptome by CAGE identified a number of hypothalamic genes differentially expressed by incubation behavior in Silkie hens. Of these, it is suggested that TTR and PrRP may, at least in part, be related to adaptation to natural anorexia in incubating Silkie chickens.

Prenatal Adversity Modulates the Quality of Maternal Care Via the Exposed Offspring.

Adversities in pregnancy, including poor diet and stress, are associated with increased risk of developing both metabolic and mental health disorders later in life, a phenomenon described as fetal programming or developmental origins of disease. Predominant hypotheses proposed to explain this relationship suggest that the adversity imposes direct changes to the developing fetus which are maintained after birth resulting in an increased susceptibility to ill health. However, during pregnancy the mother, the developing fetus, and the placenta are all exposed to the adversity. The same adversities linked to altered offspring outcome can also result in suboptimal maternal care, which is considered an independent adverse exposure for the offspring. Recent key experiments in mice reveal the potential of prenatal adversity to drive alterations in maternal care through abnormal maternal-pup interactions and via alterations in placental signaling. Together, these data highlight the critical importance of viewing fetal programming holistically paying attention to the intimate, bidirectional, and reiterative relationship between mothers and their offspring.

Functional Ontogeny of Hypothalamic Agrp Neurons in Neonatal Mouse Behaviors.

Hypothalamic Agrp neurons regulate food ingestion in adult mice. Whether these neurons are functional before animals start to ingest food is unknown. Here, we studied the functional ontogeny of Agrp neurons during breastfeeding using postnatal day 10 mice. In contrast to adult mice, we show that isolation from the nursing nest, not milk deprivation or ingestion, activated Agrp neurons. Non-nutritive suckling and warm temperatures blunted this effect. Using in vivo fiber photometry, neonatal Agrp neurons showed a rapid increase in activity upon isolation from the nest, an effect rapidly diminished following reunion with littermates. Neonates unable to release GABA from Agrp neurons expressed blunted emission of isolation-induced ultrasonic vocalizations. Chemogenetic overactivation of these neurons further increased emission of these ultrasonic vocalizations, but not milk ingestion. We uncovered important functional properties of hypothalamic Agrp neurons during mouse development, suggesting these neurons facilitate offspring-to-caregiver bonding.

Access to a high resource environment protects against accelerated maturation following early life stress: A translational animal model of high, medium and low security settings.

Early life exposure to a low security setting, characterized by a scarcity of resources and limited food access, increases the risk for psychiatric illness and metabolic dysfunction. We utilized a translational rat model to mimic a low security environment and determined how this manipulation affected offspring behavior, metabolism, and puberty. Because food insecurity in humans is associated with reduced access to healthy food options the "low security" rat manipulation combined a Western diet with exposure to a limited bedding and nesting manipulation (WD-LB). In this setting, dams were provided with limited nesting materials during the pups' early life (P2-P10). This manipulation was contrasted with standard rodent caging (SD) and environmental enrichment (EE), to model "medium security" and "high security" environments, respectively. To determine if transitioning from a low to high security environment improved outcomes, some juvenile WD-LB offspring were exposed to EE. Maternal care was impacted by these environments such that EE dams engaged in high quality care when on the nest, but spent less time on the nest than SD dams. Although WD-LB dams excessively chased their tails, they were very attentive to their pups, perhaps to compensate for limited resources. Offspring exposed to WD-LB only displayed subtle changes in behavior. However, WD-LB exposure resulted in significant metabolic dysfunction characterized by increased body weight, precocious puberty and alterations in the hypothalamic kisspeptin system. These negative effects of WD-LB on puberty and weight regulation were mitigated by EE exposure. Collectively, these studies suggest that both compensatory maternal care and juvenile enrichment can reduce the impact of a low security environment. Moreover, they highlight how utilizing diverse models of resource (in)stability can reveal mechanisms that confer vulnerability and resilience to early life stress.

Effects of pre-reproductive maternal enrichment on maternal care, offspring's play behavior and oxytocinergic neurons.

Potentiating social, cognitive, and sensorimotor stimulations the Environmental Enrichment (EE) increases levels of novelty and complexity experienced by individuals. Growing evidence demonstrates that parental EE experience, even occurring in the pre-reproductive phase, affects behavioral and neural developmental trajectories of the offspring. To discover how the accumulation of early maternal complex experiences may inform and shape the social behavior of the following generation, we examined the effects of pre-reproductive enrichment of dams (post-natal days 21-72) on the play performances of their male and female adolescent offspring. Furthermore, we examined the effects of pre-reproductive enrichment on maternal behavior (during post-partum days 1-10) and male intruder aggression (on post-partum day 11). Since oxytocin modulates maternal care, social bonding, and agonistic behavior, the number of oxytocinergic neurons of the paraventricular (PVN) and supraoptic (SON) nuclei was examined in both dams and offspring. Results revealed that enriched females exhibited higher levels of pup-oriented behaviors, especially Crouching, and initiated pup-retrieval more quickly than standard females after the maternal aggression test. Such behavioral peculiarities were accompanied by increased levels of oxytocinergic neurons in PVN and SON. Moreover, pre-reproductive maternal EE cross-generationally influenced the offspring according to sex. Indeed, male pups born to enriched females exhibited a reduced play fighting associated with a higher number of oxytocinergic neurons in SON in comparison to male pups born to standard-housed females. In conclusion, pre-reproductive EE to the mothers affects their maternal care and has a cross-generational impact on the social behavior of their offspring that do not directly experiences EE. This article is part of the Special Issue entitled "Neurobiology of Environmental Enrichment".

Understanding Placentophagy.

OBJECTIVE: To evaluate the knowledge, attitudes, and beliefs of women during pregnancy and the postpartum period related to placentophagy. DESIGN: Mixed methods study (cross-sectional survey and online discussions). SETTING: We used social media to advertise the study to mother/parenting groups. Online discussion groups were conducted through Google Groups. PARTICIPANTS: Women during pregnancy and in the postpartum period and placenta encapsulation specialists with Internet access. METHODS: We summarized descriptive data and analyzed subgroups with the use of chi-square tests. We conducted a binary logistic regression to compare placentophagy with demographic variables and used constant comparative analysis to analyze online discussion group themes. RESULTS: Overall, 271 of 1,088 (24.9%) respondents consumed their placentas. Canadian respondents and those who experienced pregnancy/birth-related complications were significantly (p < .05) less likely to consume their placentas than respondents from the United States (odds ratio = 0.48, 95% confidence interval [0.28, 0.82]) and those who had no complications (odds ratio = 0.56, 95% confidence interval [0.37, 0.85]). Increased iron stores (521/1,030, 50.6%), prevention of postpartum depression (519/1,030, 50.4%), and increased energy/decreased fatigue (460/1,030, 44.7%) were the most commonly listed perceived benefits. Infection and improper handling/preparation of the placenta were important concerns, and hospital policy was noted as a barrier to placentophagy. CONCLUSION: Respondents who engaged in placentophagy were primarily motivated by unproven benefits, such as the prevention of postpartum depression and anemia, for which there are other management alternatives. Although placentophagy is gaining popularity, it remains unregulated, and safety and efficacy data are limited. A safe, standardized preparation process is needed to minimize potential harm before further efficacy studies can be done. Targeted educational material surrounding placentophagy is needed to improve woman-centered care.

A Hypothalamic Midbrain Pathway Essential for Driving Maternal Behaviors.

Maternal behaviors are essential for the survival of the young. Previous studies implicated the medial preoptic area (MPOA) as an important region for maternal behaviors, but details of the maternal circuit remain incompletely understood. Here we identify estrogen receptor alpha (Esr1)-expressing cells in the MPOA as key mediators of pup approach and retrieval. Reversible inactivation of MPOAEsr1+ cells impairs those behaviors, whereas optogenetic activation induces immediate pup retrieval. In vivo recordings demonstrate preferential activation of MPOAEsr1+ cells during maternal behaviors and changes in MPOA cell responses across reproductive states. Furthermore, channelrhodopsin-assisted circuit mapping reveals a strong inhibitory projection from MPOAEsr1+ cells to ventral tegmental area (VTA) non-dopaminergic cells. Pathway-specific manipulations reveal that this projection is essential for driving pup approach and retrieval and that VTA dopaminergic cells are reliably activated during those behaviors. Altogether, this study provides new insight into the neural circuit that generates maternal behaviors.