Androgen and glucocorticoid profiles throughout extended uniparental paternal care in the eastern hellbender salamander (Cryptobranchus a. alleganiensis).

The behavioral endocrinology associated with reproduction and uniparental male care has been studied in teleosts, but little is known about hormonal correlates of uniparental male care in other ectotherms. To address this gap, we are the first to document the seasonal steroid endocrinology of uniparental male hellbender salamanders during the transition from pre-breeding to nest initiation, and through the subsequent eight months of paternal care. In doing so, we investigated the correlates of nest fate and clutch size, exploring hellbenders' alignment with several endocrinological patterns observed in uniparental male fish. Understanding the endocrinology of hellbender paternal care is also vital from a conservation perspective because high rates of nest failure were recently identified as a factor causing population declines in this imperiled species. We corroborated previous findings demonstrating testosterone and dihydrotestosterone (DHT) to be the primary androgens in hellbender reproduction, and that cortisol circulates as the most abundant glucocorticoid. However, we were unable to identify a prolactin or a "prolactin-like" peptide in circulation prior to or during parental care. We observed âˆ¼ 80 % declines in both primary androgens during the transition from pre-breeding to nest initiation, and again as paternal care progressed past its first month. In the days immediately following nest initiation, testosterone and DHT trended higher in successful individuals, but did not differ with males' clutch size. We did not observe meaningful seasonality in baseline glucocorticoids associated with breeding or nesting. In contrast, stress-induced glucocorticoids were highest at pre-breeding and through the first two months of care, before declining during the latter-most periods of care as larvae approach emergence from the nest. Neither baseline nor stress-induced glucocorticoids varied significantly with either nest fate or clutch size. Both stress-induced cortisol and corticosterone were positively correlated with total length, a proxy for age in adult hellbenders. This is consistent with age-related patterns in some vertebrates, but the first such pattern observed in a wild amphibian population. Generally, we found that nesting hellbenders adhere to some but not all of the endocrinological patterns observed in uniparental male teleosts prior to and during parental care.

Prolactin is associated with proximity to incubating partner rather than parental care in black-headed gulls.

The peptide hormone prolactin plays an important role in the expression of parental care behaviours across bird and mammal taxa. While a great deal is known about how plasma prolactin concentrations vary across the reproductive cycle, the few studies that investigate how prolactin relates to individual-level variation in parental care have reported mixed results. We argue that, since parental care is also affected by social interactions and environmental constraints, prolactin may better reflect behaviours that are indirectly related to parenting than the absolute level of care that is eventually expressed. In this study, we tested for associations between plasma prolactin and the expression of both parental care and proximity to the partner in incubating black-headed gulls, Chroicocephalus ridibundus. Baseline prolactin levels increased with calendar date but were unrelated to incubation behaviours. However, parents who showed a weaker decrease in prolactin to an acute stressor spent more time in close proximity to their incubating partner while not on the nest themselves, suggesting that individual variation in stress-induced prolactin changes reflect differences in parents' tendency to be closely associated with their partner and the joint nesting attempt. Baseline and stress-induced levels of the stress hormone corticosterone were unrelated to both prolactin levels and parental behaviours, suggesting that this hormone is not a strong moderator of parental care in black-headed gulls. One potential explanation for the link between prolactin dynamics and partner proximity is that prolactin reflects parental motivation to provide parental care or retain contact with the breeding partner, but further work is needed to directly test this hypothesis.

Father's Absence in the Mongolian gerbil (Meriones unguiculatus) is associated with alterations in paternal behavior, T, cort, presence of ERα, and AR in mPOA/ BNST.

Testosterone (T), estrogen receptor alpha (ERα), and androgen receptor (AR) play a significant role in the regulation of paternal behavior. We determined the effects of deprivation of paternal care on alterations in paternal behavior, T concentrations in plasma, and the presence of ERα and AR in the medial preoptic area (mPOA), bed nucleus of the stria terminalis (BNST), medial amygdala (MeA), and olfactory bulb (OB), as well as the corticosterone (CORT) concentrations in plasma caused by deprivation of paternal care in the Mongolian gerbil (Meriones unguiculatus). Twenty pairs of gerbils were formed; the pups were deprived of paternal care (DPC) in 10 pairs. In another 10 pairs, the pups received paternal care (PC). Ten males raised in DPC condition and 10 males raised in PC conditions were mated with virgin females. When they became fathers, each DPC male and PC male was subjected to tests of paternal behavior on day three postpartum. Blood samples were obtained to quantify T and CORT concentrations, and the brains were removed for ERα and AR immunohistochemistry analyses. DPC males gave less care to their pups than PC males, and they had significantly lower T concentrations and levels of ERα and AR in the mPOA and BNST than PC males. DPC males also had higher CORT concentrations than PC males. These results suggest that in the Mongolian gerbil father's absence causes a decrease in paternal care in the offspring, which is associated with alterations in the neuroendocrine mechanisms that regulate it.

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.

Parental protection in fathers with negative caregiving experiences: Heightened amygdala reactivity to infant threatening situations.

Parental protection is an important, yet understudied, aspect of parenting behavior. Predictors of the quality of protection and potential underlying neural mechanisms are still unknown. In this study, we examined whether negative caregiving experiences in fathers' own childhood are related to protective behavior and neural reactivity to infant threatening situations. Paternal protective behavior was measured with self- and partner-reported protective behavior and behavioral observations in an experimental set-up (auditory startling task) in 121 first-time fathers (mean age child = 19.35 weeks, SD = 11.27). Neural activation during exposure to videos of infant-threatening (vs. neutral) situations was measured with functional magnetic resonance imaging (fMRI). We found a significant and positive association between negative caregiving experiences and amygdala reactivity to infant-threatening situations. A history of negative caregiving experiences was not significantly related to reported or observed paternal protective behavior. Our findings suggest that fathers with negative caregiving experiences show emotional hyperreactivity to cues of infant threat.

Development of the Paternal Brain in Humans throughout Pregnancy.

Previous studies have demonstrated that paternal caregiving behaviors are reliant on neural pathways similar to those supporting maternal care. Interestingly, a greater variability exists in parental phenotypes in men than in women among individuals and mammalian species. However, less is known about when or how such variability emerges in men. We investigated the longitudinal changes in the neural, hormonal, and psychological bases of expression of paternal caregiving in humans throughout pregnancy and the first 4 months of the postnatal period. We measured oxytocin and testosterone, paternity-related psychological traits, and neural response to infant-interaction videos using fMRI in first-time fathers and childless men at three time points (early to mid-pregnancy, late pregnancy, and postnatal). We found that paternal-specific brain activity in prefrontal areas distinctly develops during middle-to-late pregnancy and is enhanced in the postnatal period. In addition, among fathers, the timing of the development of prefrontal brain activity was associated with specific parenting phenotypes.

Neural basis for behavioral plasticity during the parental life-stage transition in mice.

Parental care plays a crucial role in the physical and mental well-being of mammalian offspring. Although sexually naïve male mice, as well as certain strains of female mice, display aggression toward pups, they exhibit heightened parental caregiving behaviors as they approach the time of anticipating their offspring. In this Mini Review, I provide a concise overview of the current understanding of distinct limbic neural types and their circuits governing both aggressive and caregiving behaviors toward infant mice. Subsequently, I delve into recent advancements in the understanding of the molecular, cellular, and neural circuit mechanisms that regulate behavioral plasticity during the transition to parenthood, with a specific focus on the sex steroid hormone estrogen and neural hormone oxytocin. Additionally, I explore potential sex-related differences and highlight some critical unanswered questions that warrant further investigation.

Transcriptomic analysis of paternal behaviors in prairie voles.

BACKGROUND: The importance of fathers' engagement in care and its critical role in the offspring's cognitive and emotional development is now well established. Yet, little is known on the underlying neurobiology due to the lack of appropriate animal models. In the socially monogamous and bi-parental prairie vole (Microtus ochrogaster), while 60-80% of virgin males show spontaneous paternal behaviors (Paternal), others display pup-directed aggression (Attackers). Here we took advantage of this phenotypic dichotomy and used RNA-sequencing in three important brain areas to characterize gene expression associated with paternal behaviors of Paternal males and compare it to experienced Fathers and Mothers. RESULTS: While Paternal males displayed the same range and extent of paternal behaviors as experienced Fathers, we observed structure-specific transcriptomic differences between parental behaviors phenotypes. Using differential expression, gene set expression, as well as co-expression network analyses, we found that phenotypic differences between Paternal males and Attackers were mainly reflected by the lateral septum (LS), and to a lower extent, the nucleus accumbens (NAc), transcriptomes. In the medial preoptic area (MPOA), the profiles of gene expression mainly reflected differences between females and males regardless of their parental behaviors phenotype. Functional enrichment analyses of those gene sets associated with Paternal males or Attackers in the LS and the NAc revealed the involvement of processes related to the mitochondria, RNA translation, protein degradation processes, as well as epigenetic regulation of gene expression. CONCLUSIONS: By leveraging the natural phenotypic differences in parental behaviors in virgin male prairie voles alongside fathers and mothers, we identified a marked structure- and phenotype-specific pattern of gene expression associated with spontaneous paternal behaviors independently from fatherhood and pair-bonding. The LS transcriptome related to the mitochondria, RNA translation, and protein degradation processes was thus highlighted as a primary candidate associated with the spontaneous display of paternal behaviors. Altogether, our observations further characterize the behavioral and transcriptomic signature of parental behaviors in the socially monogamous prairie vole and lay the groundwork to further our understanding of the molecular underpinnings of paternal behavior.

Prolactin Action Is Necessary for Parental Behavior in Male Mice.

Parental care is critical for successful reproduction in mammals. Recent work has implicated the hormone prolactin in regulating male parental behavior, similar to its established role in females. Male laboratory mice show a mating-induced suppression of infanticide (normally observed in virgins) and onset of paternal behavior 2 weeks after mating. Using this model, we sought to investigate how prolactin acts in the forebrain to regulate paternal behavior. First, using c-fos immunoreactivity in prolactin receptor (Prlr) Prlr-IRES-Cre-tdtomato reporter mouse sires, we show that the circuitry activated during paternal interactions contains prolactin-responsive neurons in multiple sites, including the medial preoptic nucleus, bed nucleus of the stria terminalis, and medial amygdala. Next, we deleted Prlr from three prominent cell types found in these regions: glutamatergic, GABAergic, and CaMKIIα. Prlr deletion from CaMKIIα, but not glutamatergic or GABAergic cells, had a profound effect on paternal behavior as none of these KO males completed the pup-retrieval task. Prolactin was increased during mating, but not in response to pups, suggesting that the mating-induced secretion of prolactin is important for establishing the switch from infanticidal to paternal behavior. Pharmacological blockade of prolactin secretion at mating, however, had no effect on paternal behavior. In contrast, suppressing prolactin secretion at the time of pup exposure resulted in failure to retrieve pups, with exogenous prolactin administration rescuing this behavior. Together, our data show that paternal behavior in sires is dependent on basal levels of circulating prolactin acting at the time of interaction with pups, mediated through Prlr on CaMKIIα-expressing neurons.SIGNIFICANCE STATEMENT Parental care is critical for offspring survival. Compared with maternal care, however, the neurobiology of paternal care is less well understood. Here we show that the hormone prolactin, which is most well known for its female-specific role in lactation, has a role in the male brain to promote paternal behavior. In the absence of prolactin signaling specifically during interactions with pups, father mice fail to show normal retrieval behavior of pups. These data demonstrate that prolactin has a similar action in both males and females to promote parental care.

Estudio piloto: contacto padre-hijo(a) y oxitocina en varones preparados especialmente para el nacimiento / Pilot study: father-child contact and oxytocin in males with a special education for childbirth

INTRODUCCÍON: Los padres se han involucrado cada vez más en el embarazo y el nacimiento de sus hijos, pero aún se requieren intervenciones paternas que permitan reubicar al padre en su rol de corresponsabilidad en la crianza. OBJETIVO: Observar el comportamiento-actitud paterna hacia el/la hijo(a) y la cantidad de oxitocina (OT) secretada en el nacimiento, en padres preparados de un modo especial para el parto. Método: Estudio piloto de 8 meses, parte de una investigación mayor cuali-cuantitativa de dos fases. La fase cualitativa inicial desarrolló una intervención preparatoria de padres para el nacimiento, con énfasis en la vinculación padre-hijo(a). La fase cuantitativa correspondió al piloto de la intervención paterna antenatal. RESULTADOS: Los padres presenciaron activamente el momento del expulsivo y el encuentro madre-hijo(a). Posteriormente, todos optaron por el contacto físico piel-piel con su hijo(a). La OT paterna experimentó un aumento (no significativo) durante el contacto padre-hijo(a) en comparación con la OT basal (momento inmediato al nacimiento). CONCLUSIONES: Padres preparados, sensibilizados y vinculados con su hijo(a) desde el embarazo experimentarían variaciones de la cantidad de OT cuando realizan contacto piel-piel con su hijo(a) en el nacimiento. Se requiere investigación experimental con una muestra mayor de participantes para concluir de manera categórica.

INTRODUCTION: Fathers have been increasingly involved in the pregnancy and birth of their children, but paternal interventions are still required to relocate the father in his role of co-responsibility in parenting. OBJECTIVE: To observe the paternal behavior-attitude towards the child and the amount of oxytocin (OT) secreted at birth in parents prepared (in a special way) for childbirth. METHOD: Pilot study of 8 months, part of a larger qualitative-quantitative research of two phases. The initial qualitative phase developed a male preparatory intervention for the birth, with emphasis on the father-child bonding. The quantitative phase corresponded to the pilot of the antenatal paternal intervention. RESULTS: Fathers actively witnessed the moment of delivery and the mother-child attachment. Subsequently, all of them opted for physical skin-to-skin contact with their child. Paternal OT experienced a (non-significant) increase during father-child contact, compared to baseline OT (immediately after birth). CONCLUSIONS: Males prepared, sensitized and involved with their child since pregnancy would experience variations in the amount of OT when they make father-child skin-to-skin contact at childbirth. Experimental research with a larger sample of participants is required to categorically reach a conclusion.

Motivational increase of androgens and behavior by infant distress calls in highly responsive common marmoset fathers, Callithrix jacchus.

Common marmoset fathers are highly involved in care of their infants. However, variability exists in their response to infant behavior even in paternally experienced fathers. Using infant distress cries as a motivation test, we investigated: 1. the differences in paternally experienced fathers' motivation to search for the infant vocalization stimuli; 2. the relationship between a father's motivation to search for the source of the infant cries and testosterone levels; and 3. if there is a rapid steroidogenesis pathway leading to increased testosterone and estradiol in the peripheral circulation. Only 44% of the paternally experienced fathers showed a high frequency of searching for the source of the infant distress cries. Through the use of multisteroid analysis, we found high responsive fathers had significantly higher levels of progesterone and testosterone in response to infant distress cries compared to a control stimulus with progesterone and androstenedione correlating with testosterone, while no differences were seen in low responders. The frequency to search for the infant stimuli was positively correlated with higher testosterone compared to control vocal levels. These results suggest that searching for the source of infant cries represents a motivation behavior for fathers that is activated by testosterone and reflects rapid circulating testosterone.

The Neural Basis of Human Fatherhood: A Unique Biocultural Perspective on Plasticity of Brain and Behavior.

With the growing involvement of fathers in childrearing and the application of neuroscientific tools to research on parenting, there is a need to understand how a father's brain and neurohormonal systems accommodate the transition to parenthood and how such neurobiological changes impact children's mental health, sociality, and family functioning. In this paper, we present a theoretical model on the human father's brain and the neural adaptations that take place when fathers assume an involved role. The neurobiology of fatherhood shows great variability across individuals, societies, and cultures and is shaped to a great extent by bottom-up caregiving experiences and the amount of childrearing responsibilities. Mechanisms of mother-father coparental brain coordination and hormonal correlates of paternal behavior are detailed. Adaptations in the father's brain during pregnancy and across the postpartum year carry long-term implications for children's emotion regulation, stress management, and symptom formation. We propose a new conceptual model of HEALthy Father Brain that describes how a father's brain serves as a source of resilience in the context of family adversity and its capacity to "heal", protect, and foster social brain maturation and functionality in family members via paternal sensitivity, attunement, and support, which, in turn, promote child development and healthy family functioning. Father's brain provides a unique model on neural plasticity as sustained by committed acts of caregiving, thereby affording a novel perspective on the brain basis of human affiliation.

Paternal Cocaine in Mice Alters Social Behavior and Brain Oxytocin Receptor Density in First Generation Offspring.

It is well established that the damaging effects of drugs of abuse, such as cocaine, can extend beyond the user to their offspring. While most preclinical models of the generational effects of cocaine abuse have focused on maternal effects, we, and others, report distinct effects on offspring sired by fathers treated with cocaine prior to breeding. However, little is known about the effects of paternal cocaine use on first generation (F1) offspring's social behaviors. Here, we expand upon our model of oral self-administered paternal cocaine use to address the idea that paternal cocaine alters first generation offspring social behaviors through modulation of the oxytocin system. F1 cocaine-sired males displayed unaltered social recognition vs. non-cocaine sired controls but showed increased investigation times that were not related to altered olfaction. Paternal cocaine did not alter F1 male-aggression behavior or depression-like behaviors, but cocaine-sired males did display decreased anxiety-like behaviors. Female F1 behavior was similarly examined, but there were no effects of paternal cocaine. Cocaine-sired male mice also exhibited localized oxytocin receptor expression differences vs. controls in several brain regions regulating social behavior. These results provide evidence for effects of paternal cocaine exposure on social behaviors in male offspring with associated alterations in central oxytocin transmission.

Dopaminergic modulation of the circadian activity and sociability: Dissecting parental inheritance versus maternal styles as determinants of epigenetic influence.

In mammalians, social life and circadian rhythms find their neurobiological basis in a network that includes the dopaminergic system. The malfunctioning of dopamine pathways can lead to various disorders such as Attention-Deficit/Hyperactivity and Obsessive/compulsive disorders. A useful research approach is to exploit animal models that carry a functional silencing of SLC6A3 gene, encoding the dopamine transporter (DAT). Hyperactivity, working memory deficits, and asocial tendencies are core features in truncated-DAT rats, for example. We investigated how inheritance and maternal caring style influence circadian rhythms and social behaviours in DAT heterozygous (HET) rats, belonging to four groups: Mat-P, Mat-M, Mix-P, and Mix-M (Mat label stands for care from wild-type dam, Mix label stands for care by heterozygous dam; M label stands for maternal wild-DAT and P label stands for paternal wild-DAT). In Experiment 1, we monitored 24/7 the spontaneous locomotor activity of peri-adolescent subjects. Hyperactivity occurred only in P-asset subjects (with maternal-origin truncated-DAT allele) at specific bins of the day. In Experiment 2, we observed social interactions of the same rats. Mix-M subjects (raised by HET dams and/or inheriting the wild-DAT allele from mothers) tend to interact with all rats; Mat-P (cared by WT dams and/or inheriting the truncated-DAT allele from mothers) seem to be ignored, when acting as stimulus subjects. Overall, results confirm complex modulations for circadian cycle and social life: flexible DAT expression in HET subjects depends on epigenetic combinations of parental inheritance and early experiential factors. Once confirmed, these data could shed light on trans-generational contributions to dopaminergic-related disorders.

Uncovering the Sex-Specific Endocrine Responses to Reproduction and Parental Care.

Hormones mediate physiological and behavioral changes in adults as they transition into reproduction. In this study, we characterize the circulating levels of five key hormones involved in reproduction in rock doves (Columba livia): corticosterone, progesterone, estradiol, testosterone, and prolactin using univariate and multivariate approaches. We show similar patterns as previous studies in the overall patterns in circulating levels of these hormones, i.e., testosterone (males) and estradiol (females) high during nest-building or egg-laying, prolactin increasing at mid-incubation and peaking at hatching (both sexes), and elevated corticosterone levels in later incubation and early nestling development. In our investigation of hormone co-variation, we find a strong correlation between prolactin and corticosterone across sampling stages and similarities in earlier (early to mid-incubation) compared to later (late incubation to nestling d9) sampling stages in males and females. Finally, we utilized experimental manipulations to simulate nest loss or altered caregiving lengths to test whether external cues, internal timing, or a combination of these factors contributed most to hormone variation. Following nest loss, we found that both males and females responded to the external cue. Males generally responded quickly following nest loss by increasing circulating testosterone, but this response was muted when nest loss occurred early in reproduction. Similar treatment type, e.g., removal of eggs, clustered similarly in hormone space. These results suggest internal drivers limited male response early in reproduction to nest loss. In contrast, circulating levels of these hormones in females either did not change or decreased following nest manipulation suggesting responsiveness to external drivers, but unlike males, this result suggests that reproductive processes were decreasing.

Turn taking is not restricted by task specialisation but does not facilitate equality in offspring provisioning.

Sexual conflict arises when two individuals invest in their common offspring because both individuals benefit when their partner invests more. Conditional cooperation is a theoretical concept that could resolve this conflict. Here, parents are thought to motivate each other to contribute to provisioning visits by following the rules of turn taking, which results in equal and efficient investment. However, parents have other tasks besides provisioning, which might hinder taking turns. To investigate restrictions by other care tasks and whether turn taking can be used to match investment, we manipulated brooding duration in female blue tits (Cyanistes caeruleus) during the early nestling phase by changing nest box temperature. As expected, females subjected to cold conditions brooded longer than females under warm conditions. Yet, contrary to our prediction, females had similar visit rates in both treatments, which suggests that females in the cold treatment invested more overall. In addition, the females' turn taking level was higher in the more demanding cold condition (and the calculated randomised turn taking levels of females did not differ), hence females don't seem to be restricted in their turn taking strategy by other care tasks. However, males did not seem to match the females' turn taking levels because they did not adjust their visit rates. Thus, level of turn taking was not restricted by an other sex-specific task in females and did not facilitate a greater investment by their male partners.

Paternal and infanticidal behavior in the Mongolian gerbil (Meriones unguiculatus): An approach to neuroendocrine regulation.

This study aimed to provide evidence on estrogen and androgen pathways regulating the Mongolian gerbil's paternal and infanticidal behaviors (Meriones unguiculatus). We analyzed estrogen receptor alpha (ERα) and androgen receptor (AR) distribution in the medial preoptic area (mPOA), the bed nucleus of stria terminalis (BNST), as well as the anterior hypothalamic nucleus (AHN), the ventromedial hypothalamus nucleus (VMH), and the periaqueductal gray area (PAG) nuclei activated when males interact paternally or aggressively with the pups, respectively. Twenty aggressive males towards the pups and 10 paternal were selected through a screen paternal behavior test. Three groups of 10 males each were formed: paternal males (PAT), males with testosterone (T)-induced paternal behavior (T-PAT), and aggressive males (AGG). Male gerbils could interact with a pup for a few minutes, and their brains were removed and dissected for ERα and AR immunoreactivity (ir). The results showed that in T-PAT and PAT males, the number of ERα-ir and AR-ir cells in the mPOA/BNST was significantly higher than in AGG males. In AGG males, the number of ERα-ir and AR-ir cells in the AHN/VMH/PAG was significantly higher than PAT and T-PAT males. This difference in the presence of ERα and AR in nuclei activated in paternal interactions in the Mongolian gerbil supports the idea that these receptors participate in regulating paternal behavior. Also, these results suggest, for the first time, that they could be involved in the infanticidal behavior in this rodent.

Involvement of the dopamine system in paternal behavior induced by repeated pup exposure in virgin male ICR mice.

Like mothers, fathers play a vital role in the development of the brain and behavior of offspring in mammals with biparental care. Unlike mothers, fathers do not experience the physiological processes of pregnancy, parturition, or lactation before their first contact with offspring. Whether pup exposure can induce the onset of paternal behavior and the underlying neural mechanisms remains unclear. By using Slc:ICR male mice exhibiting maternal-like parental care, the present study found that repeated exposure to pups for six days significantly increased the total duration of paternal behavior and shortened the latency to retrieve and care for pups. Repeated pup exposure increased c-Fos-positive neurons and the levels of dopamine- and TH-positive neurons in the nucleus accumbens (NAc). In addition, inhibition of dopamine projections from the ventral tegmental area to the NAc using chemogenetic methods reduced paternal care induced by repeated pup exposure. In conclusion, paternal behavior in virgin male ICR mice can be initiated by repeated pup exposure via sensitization, and the dopamine system may be involved in this process.

Paraventricular Nucleus Oxytocin Subsystems Promote Active Paternal Behaviors in Mandarin Voles.

Paternal care plays a critical role in the development of brain and behaviors in offspring in monogamous species. However, the neurobiological mechanisms, especially the neuronal circuity, underlying paternal care is largely unknown. Using socially monogamous male mandarin voles (Microtus mandarinus) with high levels of paternal care, we found that paraventricular nucleus of the hypothalamus (PVN) to ventral tegmental area (VTA) or nucleus accumbens (NAc) oxytocin (OT) neurons are activated during paternal care. Chemogenetic activation/inhibition of the PVN OT projection to VTA promoted/decreased paternal care, respectively. Chemogenetic inhibition of the PVN to VTA OT pathway reduced dopamine (DA) release in the NAc of male mandarin voles during licking and grooming of pups as revealed by in vivo fiber photometry. Optogenetic activation/inhibition of the VTA to NAc DA pathway possibly enhanced/suppressed paternal behaviors, respectively. Furthermore, chemogenetic activation/inhibition of PVN to NAc OT circuit enhanced/inhibited paternal care. This finding is a first step toward delineating the neuronal circuity underlying paternal care and may have implications for treating abnormalities in paternal care associated with paternal postpartum depression or paternal abuse.SIGNIFICANCE STATEMENT Paternal behavior is essential for offspring survival and development in some mammalian species. However, the circuit mechanisms underlying the paternal brain are poorly understood. We show that manipulation of paraventricular nucleus of the hypothalamus (PVN) to ventral tegmental area (VTA) oxytocin (OT) projections as well as VTA to nucleus accumbens (NAc) DA projections promote paternal behaviors. Inhibition the PVN to VTA OT pathway reduces DA release in the NAc during pup licking and grooming. PVN to NAc OT circuit is also essential for paternal behaviors. Our findings identify two new neural circuits that modulate paternal behaviors.