Enhanced maternal behaviors in a mouse model of congenital blindness.

In mammals, mothering is one of the most important prosocial female behavior to promote survival, proper sensorimotor, and emotional development of the offspring. Different intrinsic and extrinsic factors can initiate and maintain these behaviors, such as hormonal, cerebral, and sensory changes. Infant cues also stimulate multisensory systems and orchestrate complex maternal responsiveness. To understand the maternal behavior driven by complex sensory interactions, it is necessary to comprehend the individual sensory systems by taking out other senses. An excellent model for investigating sensory regulation of maternal behavior is a murine model of congenital blindness, the ZRDBA mice, where both an anophthalmic and sighted mice are generated from the same litter. Therefore, this study aims to assess whether visual inputs are essential to driving maternal behaviors in mice. Maternal behaviors were assessed using three behavioral tests, including the pup retrieval test, the home cage maternal behavior test, and the maternal aggression test. Our results show that blind mothers (1) took less time to retrieve their offspring inside the nest, (2) spent more time nursing and licking their offspring in the second- and third-week postpartum, and (3) exhibited faster aggressive behaviors when exposed to an intruder male, compared to the sighted counterparts. This study provides evidence that congenitally blind mothers show more motivation to retrieve the pups, care, and protection towards their pups than sighted ones, likely due to a phenomenon of sensory compensation.

Changes in maternal motivation across reproductive states in mice: A role for prolactin receptor activation on GABA neurons.

The survival of newborn offspring in mammals is dependent on sustained maternal care. Mammalian mothers are highly motivated to interact with and care for offspring, however, it is unclear how hormonal signals act on neural circuitry to promote maternal motivation during the transition to motherhood. In this study we aimed to establish methods that enable us to evaluate change in maternal motivation across the reproductive life cycle in female mice. Using two behavioural testing paradigms; a novel T-maze retrieval test and a barrier climbing test, we found that pup retrieval behaviour was low in virgin and pregnant mice compared to lactating females, indicating that maternal motivation arises around the time of parturition. Furthermore, in reproductively experienced females, maternal motivation declined over time after weaning of pups. As we have previously shown that lactogenic action mediated through the prolactin receptor (Prlr) in the medial preoptic area (MPOA) is essential for the expression of maternal behaviour, we aimed to investigate the role of lactogenic hormones in promoting pup-related motivational behaviours. With GABAergic neurons expressing Prlr in multiple brain regions important for maternal behaviour, we conditionally deleted Prlr from GABA neurons. Compared to control females, lactating GABA neuron-specific Prlr knockout mice showed slower and incomplete pup retrieval behaviour in the T-maze test. Testing of anxiety behaviour on an elevated plus maze indicated that these mice did not have increased anxiety levels, suggesting that lactogenic action on GABA neurons is necessary for the full expression of motivational aspects of maternal behaviour during lactation.

What can challenging reproductive contexts tell us about the rat's maternal behavior?

Maternal behavior in mammals encompasses a complex repertoire of activities that ensure the survival of the offspring and shape their neural and behavioral development. The laboratory rat has been employed as a classic model for investigating maternal behavior, and recently with the use of advanced techniques, the knowledge of its neural basis has been expanded significantly. However, the standard laboratory testing conditions in which rats take care of a single litter impose constraints on the study of maternal flexibility. Interestingly, the reproductive characteristics of this species, including the existence of a fertile postpartum estrus, allow us to study maternal behavior in more complex and ethologically relevant contexts, even in laboratory settings. Here we review how maternal and sexual motivations interact during the postpartum estrus, shaping the behavioral response of females according to the presence of the pups and males. Next, we describe how impregnation during the postpartum estrus creates a new reproductive context in which mothers simultaneously care for two successive litters, adapting their responses to different behavioral and physiological demands of pups. These findings illustrate the behavioral adaptability of maternal rats to pups' needs and the presence of other reinforcers, as well as its dependence on the context. In our view, future perspectives in the field, by incorporating the use of cutting-edge techniques, should analyze maternal flexibility and its neural substrates in models that incorporate complex and challenging contexts. This approach would allow a more comprehensive understanding of brain circuits involved in the adaptive and flexible nature of parenting.

Abnormal maternal behavior in mice lacking phospholipase Cß1.

Motherhood goes through preparation, onset and maintenance phases until the natural weaning. A variety of changes in hormonal/neurohormonal systems and brain circuits are involved in the maternal behavior. Hormones, neuropeptides, and neurotransmitters involved in maternal behavior act via G-protein-coupled receptors, many of which in turn activate plasma membrane enzymes including phospholipase C (PLC) ß isoforms. In this study, we examined the effect of PLCß1 knockout (KO) on maternal behavior. There was little difference between PLCß1-KO and wild-type (WT) dams in the relative time spent in maternal behavior during the period between 24 h prepartum and 12 h postpartum (-24 h ∼ PPH 12). After PPH 18, however, PLCß1-KO dams neglected their pups so that they all died in 2-3 days. In the pup retrieval test, latency was not different during the period within PPH 12, but after PPH 18, PLCß1-KO dams could not finish pup retrieval in a given time. During both periods, FosB expression in the nucleus accumbens (NAcc) of PLCß1-KO dams was significantly lower than WT, but not different in the medial preoptic area (mPOA). Given that mPOA activity is required for initiation of maternal behavior, and that NAcc is known to be involved in maternal motivation and maintenance of maternal behavior, our results suggest that PLCß1 signaling is essential for transition from the onset to maintenance phase of maternal behavior.

High social motivation induces deficits in maternal behaviour but not plasticity of the subventricular zone in Japanese quail (Coturnix japonica).

Maternal behaviour develops differently depending on the characteristics of an individual, such as age or emotional reactivity. Social motivation, defined as the propensity to establish social contact, has received little attention in relation to maternal behaviour in birds. In addition, the transition to motherhood is a time of plasticity in the brain of the new mother in mammals. However, it remains to be determined how maternal brain plasticity is affected in avian species. The present study investigated how a the social motivation of a mother alters maternal behaviour and brain plasticity of the Japanese quail (Coturnix japonica). Adult females from lines selected for high and low social motivation were exposed to chicks for 11 days. After maternal care testing, and at matched time points in controls, the brains of females were perfused for assessment of doublecortin-immunoreactive staining, a marker of neurogenesis, in the subventricular zone (SVZ), a neurogenic niche. The results obtained showed that high socially motivated female quail spent significantly less time performing maternal behaviour when exposed to chicks compared to low socially motivated females. Moreover, the warming of chicks by high socially motivated females involved less covering postures and mothers were more rejecting of chicks. Interestingly, the plasticity indicators in the SVZ did not differ between low and high socially motivated females and were not associated with differences in maternal caregiving when using doublecortin-immunoreactive staining. Thus, high social motivation in this avian species does not favour maternal behaviour and this level of motivation to the mother is not related to changes in neuroplasticity in the SVZ of the female quail.

More than reproduction: Central gonadotropin-releasing hormone antagonism decreases maternal aggression in lactating rats.

Gonadotropin-releasing hormone (GnRH) is a major regulator and activator of the hypothalamic-pituitary-gonadal axis. Many studies have demonstrated the importance of GnRH in reproduction and sexual behaviour. However, to date, only a single study shows an involvement of GnRH in maternal behaviour where a 30% reduction of GnRH neurones abolishes a mother's motivation to retrieve pups. On this basis, we aimed to investigate the effects of acute central GnRH receptor blockade in lactating rats on maternal care under non-stress and stress conditions, maternal motivation in the pup retrieval test, maternal anxiety on the elevated plus maze, and maternal aggression in the maternal defence test. We found that acute central infusion of a GnRH antagonist ([d-Phe2,6 ,Pro3 ]-luteinising hormone-releasing hormone; 0.5 ng 5 µL-1 ) impaired a mother's attack behaviour against a female intruder rat during the maternal defence test compared to vehicle controls. However, in contrast to the previous study on reduced GnRH neurones, acute central GnRH antagonism did not affect pup retrieval, nor any other parameter of maternal behaviour or maternal anxiety. Taken together, GnRH receptor activation is mandatory for protection of the offspring. These findings shed new light on GnRH as a neuropeptide acting not exclusively on the reproductive axis but, additionally, on maternal behaviour including pup retrieval and maternal aggression.

Once and Again : History of Rearing Experiences and Psychosocial Parenting Resources at Six Months in Primiparous Mothers.

Animal and human studies suggest that parenting style is transmitted from one generation to the next. The hypotheses of this study were that (1) a mother's rearing experiences (G1) would predict her own parenting resources (G2) and (2) current maternal mood, motivation to care for her offspring, and relationship with her parents would underlie this association. In a subsample of 201 first-time mothers participating in the longitudinal Maternal Adversity, Vulnerability and Neurodevelopment project, we assessed a mother's own childhood maltreatment and rearing experiences (G1) using the Childhood Trauma Questionnaire and the Parental Bonding Instrument. At 6 months postpartum, mothers completed questionnaires on parenting stress (G2), symptoms of depression, maternal motivation, and current relationship with their own parents. The sample consisted of mostly high socioeconomic status mothers recruited from Montréal (n = 135) or Hamilton (n = 66), Canada, with an age range from 18 to 43 years (M = 29.41, SD = 4.85 years). More severe maltreatment and less supportive rearing by the mother's parents (G1) predicted increased parenting stress at 6 months (G2). These associations were mediated through distinct psychosocial pathways: maltreatment (G1) on parenting stress (G2) through symptoms of depression (Z = 2.297; p = .022); maternal rearing (G1) on parenting stress (G2) through maternal motivation (Z = -2.155; p = .031) and symptoms of depression (Z = -1.842; p = .065); and paternal rearing (G1) on parenting stress (G2) through current relationship with the father (Z = -2.617; p = .009). Maternal rearing experiences predict a mother's own parenting resources though distinct psychosocial pathways, including depressed mood, maternal motivation, and social support.

Dissecting maternal care: Patterns of maternal parenting in a prospective cohort study.

Parental care has a strong impact on neurodevelopment and mental health in the offspring. Although numerous animal studies have revealed that the parental brain is a highly complex system involving many brain structures and neuroendocrine systems, human maternal parenting as a multidimensional construct with cognitive, emotional, and behavioural components has not been characterised comprehensively. This unique multi-method analysis aimed to examine patterns of self-reported and observed parenting from 6 to 60 months postpartum in a cohort of 496 mothers (mean maternal age = 32 years). Self-report questionnaires assessed motivational components of mothering, parenting stress, parenting-related mood, maternal investment, maternal parenting style, mother-child relationship satisfaction, and mother-child bonding at multiple time points. Observed parenting variables included the Ainsworth Sensitivity Scales at 6 and 18 months, the Behavioral Evaluation Strategies Taxonomies at 6 months, an Etch-A-Sketch cooperation task at 48 months, and the Parent-Child Early Relationship Assessment at 60 months. To examine whether different latent constructs underlie these measures of maternal parenting, we conducted an exploratory factor analysis. Self-report measures of parenting correlated only weakly with behavioural observations. Factor analysis on a subsample (n = 197) revealed four latent factors that each explained from 7% to 11% of the variance in the data (32% total variance explained). Based on the loadings of the instruments, the factors were interpreted as: Supportive Parenting, Self-Enjoyment Parenting, Overwhelmed Parenting, and Affectionate Parenting. These factor scores showed specific associations with maternal education and depressive symptoms, as well as with child outcomes, including maternally reported internalising and externalising behavioural problems, school readiness, and child-reported symptoms of mental health. These findings parallel the complexity of the parental brain, suggesting that maternal parenting consists of multiple components, each of which is associated with different maternal characteristics and child outcomes.

Brain vasopressin signaling modulates aspects of maternal behavior in lactating rats.

The brain vasopressin system mediates various social behaviors as has been studied mostly in males. Only recently, advances in social neuroscience revealed that central vasopressin signaling via its V1a and V1b receptors also facilitates female social behavior, including maternal behavior. In this review, we show how maternal care, maternal motivation and maternal aggression of lactating rat mothers are modulated in a V1 receptor subtype- and brain region-specific manner. Measuring local release pattern of vasopressin via intracerebral microdialysis in the behaving rat mother as well as using pharmacological approaches to activate or block vasopressin receptors with subsequent behavioral observation provide detailed insight into the functional role of the vasopressin system in maternal behavior. In this context, the complementary rat animal model of high (HAB) and low anxiety-related behavior (LAB) is particularly helpful due to the genetically determined high activity of the vasopressin gene in HAB rats, which also underlies their high levels of maternal behavior. Furthermore, first studies in humans indicate that the vasopressin system in general and the V1a receptor in more particular might mediate mothering.

Dopaminergic activity mediates pups' over male preference of postpartum estrous rats.

Pups have greater incentive value than males for rats during the postpartum estrus (PPE); a period when females are both maternally and sexually motivated. Mesolimbic dopaminergic system has been proposed as a general motivational circuit; however in the literature it has been more related to the control of the motivational aspects of maternal than sexual motivation of females. Therefore, we aimed to assess the effect of antagonizing dopaminergic neurotransmission of PPE females on their preference for pups over a male. To achieve this objective we tested PPE rats in a Y-maze with three-choice chambers (one containing eight pups, the other a male and the last one no stimulus) after the systemic administration of the dopaminergic antagonist haloperidol (0.0; 0.025 or 0.05 mg/kg). Furthermore, to determine if this dopaminergic antagonist differentially affects maternal and sexual motivations when pups and male are not competing, we evaluated the effect of haloperidol in the preference of females for pups vs. a non-receptive female and for a male vs. a non-receptive female. In the preference test for pups vs. male, both doses of haloperidol decreased the time that females spent in pups' chamber while increased the time that they spent in male's chamber, resulting in a lack of preference between both incentives. Besides, haloperidol reduced the effort -attempts to get access to the stimuli- made by the females to obtain the pups. Conversely, 0.05 mg/kg of haloperidol did not affect the preference for both incentives when they were confronted to a non-receptive female. Together, these results indicate that the dopaminergic activity mediates pups' preference over male during the PPE and point toward a more relevant role of this system in females' behavioral output when incentives are competing.

Incentive value of newborn pups relative to juveniles for mother rats raising overlapping litters.

In rats, successful mating during the postpartum estrus results in the temporal overlapping of successive litters within the maternal nest. Mothers with two overlapping-litters (OLM) simultaneously take care of neonate and juvenile pups; however, they mostly direct their attention to the neonates. We hypothesized that these differences reflect an adaptation to the specific characteristics and needs of the two litters and not a lack of interest in the juveniles. To test this hypothesis, we assessed the relative incentive value of newborns and juveniles for OLM in a preference test and compared it with that exhibited by mothers in early (EPM) and late (LPM) postpartum, which were raising only newborns or only juveniles, respectively. Results showed that OLM spent similar time in the newborns and juveniles compartments and did not prefer the newborns as did the EPM, however, similarly to them, OLM made more attempts to get access to the newborns than the juveniles. On the other hand, OLM and LPM did not exhibit a clear preference between the stimuli. These results indicate that both neonates and juveniles have incentive value for OLM, although these mothers invest more effort in the newborns. These results point out to a unique behavioral profile of OLM, which shows similarities with EPM and LPM on different behavioral measures. They also support the idea that motivational processes underlying maternal behavior are complex and dynamic, adapting the response of the mother to pups' needs and the context.

Behavioral, pharmacological and neuroanatomical analysis of serotonin 2C receptor agonism on maternal behavior in rats.

As a highly motivated social behavior, maternal behavior in rats has been routinely used to study psychoactive drugs for clinical, neuroscience and pharmacological purposes. Recent evidence indicates that acute activation of serotonin 2C (5-HT2C) receptors causes a disruption of rat maternal behavior. The present study was designed to elucidate the behavioral, pharmacological mechanisms and neuroanatomical basis of this 5-HT2C effect. First, we replicated the finding that acute MK212 injection (2.0mg/kg, a highly selective 5-HT2C agonist) disrupts maternal behavior, especially on pup retrieval. Interestingly, this disruption was significantly attenuated by 4-h pup separation (a procedure putatively increased maternal motivation). MK212 also suppressed food retrieval, indicating that it has a general effect on motivated behaviors. Second, we showed that MK212 disrupts maternal behavior by specifically activating 5-HT2C receptor, as pretreatment with a 5-HT2C receptor antagonist SB242084 (0.6 and 1.0mg/kg) alleviated MK212-induced disruption on pup retrieval. Third, we microinjected MK212 into various brain regions implicated in the regulation of maternal behavior: nucleus accumbens shell (25, 75, 250ng/0.5µl/side), medial prefrontal cortex (25 and 250ng, 1, 2 and 5µg/0.5µl/side), and medial preoptic area (MPOA, 75ng, 1 and 5µg/0.5µl/side). Pup retrieval and other maternal responses were not affected by any of these manipulations. Finally, we used c-Fos immunohistochemistry to identify the central mechanisms of the acute and repeated MK212 effects on maternal behavior. Acute MK212 (2.0mg/kg) disrupted pup retrieval and concurrently decreased c-Fos expression in the ventral part of lateral septal nucleus (LSv), MPOA, dentate gyrus (DG) and dorsal raphe (DR), but increased it in the central amygdala (CeA). Five days of repeated MK212 (2.0mg/kg) treatment produced a persistent disruption of pup retrieval and only decreased c-Fos expression in the DR. These findings not only confirm a role of 5-HT2C receptor in rat maternal behavior, but also suggest that the coordinated 5-HT2C activity in various limbic (e.g., LSv, DG, CeA), hypothalamic regions (e.g., MPOA) and brainstem areas (e.g. DR), is likely involved in the mediation of important psychological processes (e.g. motor function, motivation) necessary for the normal expression of maternal behavior.

Vasopressin V1a, but not V1b, receptors within the PVN of lactating rats mediate maternal care and anxiety-related behaviour.

The brain neuropeptide arginine-vasopressin (AVP) mediates a wide range of social behaviours via its V1a (V1aR) but also its V1b receptor (V1bR). With respect to maternal behaviour, V1bR are still less investigated, whereas V1aR have been shown repeatedly to trigger maternal behaviour, depending on the brain region. Here, we aimed to study the role of both V1aR and V1bR within the hypothalamic paraventricular nucleus (PVN), a major source of AVP, in maternal care (lactation day (LD) 1), maternal motivation in the pup retrieval test (LD 3) and anxiety-related behaviour on the elevated plus maze (EPM; LD 5) by acute local infusion of receptor subtype-specific antagonists for V1aR (d(CH2)5Tyr(Me)(2)AVP) or V1bR (SSR149415). Furthermore, we compared V1bR expression in the PVN of virgin versus lactating rats (LD 4). Our results demonstrate that within the PVN neither V1bR mRNA (qPCR) nor protein (Western Blot) content differed between virgin and lactating rats. Regarding behaviour, acute antagonism of V1aR, but not of V1bR, decreased the occurrence of nursing as well as anxiety-related behaviour as reflected by higher percentage of time spent on and of entries into the open arms of the EPM. Maternal motivation was not affected by any treatment. In summary, we demonstrate subtype-specific involvement of V1 receptors within the PVN in mediating various maternal behaviours. The lack of effects after V1bR blockade reveals that AVP acts mainly via V1aR in the PVN, at least in lactating rats, to mediate maternal care and anxiety.

Previous and recent maternal experiences modulate pups' incentive value relative to a male without affecting maternal behavior in postpartum estrous rats.

This study extends the behavioral analysis of the postpartum estrus (PPE) which represents a unique period in the female rat's lifetime when maternal and sexual motivations co-exist. The aim of this study was to explore how previous and recent maternal experiences influence the maternal responses to pups when confronted with a male in a preference test or when they are presented independently in the home cage. To achieve this objective, we firstly compared the maternal behavior in the home cage and the preference for pups or a male in a Y-maze of primiparous and multiparous females approximately twelve hours after delivery. No differences were observed in the active and passive components of the maternal behavior of primiparous and multiparous rats; however second-time mothers made more efforts to gain access to the pups and tended to spend more time with them in the Y-maze than maternally inexperienced dams. In a second experiment, we assessed the influence of recent maternal experience with pups on PPE females' behavior by comparing pups vs. male preference and maternal behavior of females that had experienced continuous or limited (approximately two hours) interaction with their litters after parturition was completed. PPE rats subjected to reduced interaction with their pups preferred the male, while females continuously exposed to pups chose them over the male. This change in females' preference was not accompanied by significant alterations of maternal performance in the home cage, although anogenital licking tended to decrease in females with limited mother-litter interaction. Together, the results of these experiments indicate that previous and recent maternal experiences influence the motivational responses of PPE females, and that these effects are more evident when both motivations compete.

Preoptic inputs and mechanisms that regulate maternal responsiveness.

The preoptic area is a well-established centre for the control of maternal behaviour. An intact medial preoptic area (mPOA) is required for maternal responsiveness because lesion of the area abolishes maternal behaviours. Although hormonal changes in the peripartum period contribute to the initiation of maternal responsiveness, inputs from pups are required for its maintenance. Neurones are activated in different parts of the mPOA in response to pup exposure. In the present review, we summarise the potential inputs to the mPOA of rodent dams from the litter that can activate mPOA neurones. The roles of potential indirect effects through increased prolactin levels, as well as neuronal inputs to the preoptic area, are described. Recent results on the pathway mediating the effects of suckling to the mPOA suggest that neurones containing the neuropeptide tuberoinfundibular peptide of 39 residues in the posterior thalamus are candidates for conveying the suckling information to the mPOA. Although the molecular mechanism through which these inputs alter mPOA neurones to support the maintenance of maternal responding is not yet known, altered gene expression is a likely candidate. Here, we summarise gene expression changes in the mPOA that have been linked to maternal behaviour and explore the idea that chromatin remodelling during mother-infant interactions mediates the long-term alterations in gene expression that sustain maternal responding.