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1.
Science ; 382(6669): 399-404, 2023 10 27.
Article in English | MEDLINE | ID: mdl-37883550

ABSTRACT

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.


Subject(s)
Hypothalamus , Social Behavior , Animals , Aggression/physiology , Hypothalamus/cytology , Hypothalamus/physiology , Sexual Behavior/physiology , Male , Female , Maternal Behavior/physiology , Paternal Behavior/physiology , Consummatory Behavior
2.
Nature ; 621(7980): 788-795, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37730989

ABSTRACT

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.


Subject(s)
Maternal Behavior , Neural Pathways , Neurons , Oxytocin , Vocalization, Animal , Animals , Female , Mice , Cues , Hypothalamus/cytology , Hypothalamus/physiology , Maternal Behavior/physiology , Neurons/metabolism , Oxytocin/metabolism , Photometry , Thalamic Nuclei/physiology , Vocalization, Animal/physiology , Wakefulness
3.
Nature ; 618(7967): 1006-1016, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37286598

ABSTRACT

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.


Subject(s)
Infanticide , Maternal Behavior , Preoptic Area , Animals , Female , Mice , Lactation , Maternal Behavior/physiology , Neural Pathways/physiology , Preoptic Area/cytology , Preoptic Area/physiology , Thalamus/cytology , Thalamus/physiology
4.
Mol Psychiatry ; 28(1): 483-496, 2023 01.
Article in English | MEDLINE | ID: mdl-36476733

ABSTRACT

Infant avoidance and aggression are promoted by activation of the Urocortin-3 expressing neurons of the perifornical area of hypothalamus (PeFAUcn3) in male and female mice. PeFAUcn3 neurons have been implicated in stress, and stress is known to reduce maternal behavior. We asked how chronic restraint stress (CRS) affects infant-directed behavior in virgin and lactating females and what role PeFAUcn3 neurons play in this process. Here we show that infant-directed behavior increases activity in the PeFAUcn3 neurons in virgin and lactating females. Chemogenetic inhibition of PeFAUcn3 neurons facilitates pup retrieval in virgin females. CRS reduces pup retrieval in virgin females and increases activity of PeFAUcn3 neurons, while CRS does not affect maternal behavior in lactating females. Inhibition of PeFAUcn3 neurons blocks stress-induced deficits in pup-directed behavior in virgin females. Together, these data illustrate the critical role for PeFAUcn3 neuronal activity in mediating the impact of chronic stress on female infant-directed behavior.


Subject(s)
Lactation , Urocortins , Animals , Female , Male , Mice , Aggression , Hypothalamus , Maternal Behavior , Neurons
5.
J Reprod Infant Psychol ; 41(3): 301-318, 2023 07.
Article in English | MEDLINE | ID: mdl-34672887

ABSTRACT

BACKGROUND: This study explores maternal looking - the unidirectional looking by a mother at her newborn - as a precursor to mother-infant gaze. METHODS: Phase 1 used video as a means of detailed and disciplined observation to examine how mothers look at their newborns (n = 13). Using an iterative design, intensive analysis identified and categorised patterns of looking and looking-related behaviours. This resulted in a typology of looking. Phase 2 subjected the typology to inter-rater reliability testing, with midwives as multiple raters (n = 24), using the typology to rate standardised tapes of mothers and newborns (n = 10). RESULTS: Phase 1 generated a one-page clinical tool (Maternal Looking Guide). This tool enables the assessment of mothers' looking behaviour over six constructs and allocation to one of three overall categories of looking: those women who are doing well (comfortable), those who need a referral to an expert perinatal service (worrisome) and those to whom something extra could be offered (uncomfortable). In Phase 2 the Maternal Looking Guide achieved moderate reliability. CONCLUSIONS: The Maternal Looking Guide is a practical, moderately reliable, clinical tool that can assist midwives and other perinatal workers identify those mothers who may need extra support at this critical perinatal window of opportunity. .


Subject(s)
Midwifery , Mothers , Pregnancy , Infant, Newborn , Infant , Female , Humans , Reproducibility of Results , Parturition , Maternal Behavior
6.
Psicol. ciênc. prof ; 43: e253659, 2023.
Article in Portuguese | LILACS, INDEXPSI | ID: biblio-1448943

ABSTRACT

Partindo da pergunta "Como tem sido ser mulher e mãe em tempos de pandemia?", o presente estudo convidou mulheres que são mães, em redes sociais virtuais, a partilhar um relato de suas experiências com a readaptação parental em função do distanciamento social causado pela pandemia de covid-19. O objetivo foi refletir sobre a experiência de ser mulher e mãe em tempos de covid-19 e distanciamento social, apontando algumas ressonâncias do cenário pandêmico na subjetividade dessas mulheres. O estudo teve como base o referencial psicanalítico, tanto na construção da pesquisa e análise dos relatos quanto na sua discussão. A análise dos cerca de 340 relatos coletados, os quais variaram de uma breve frase a longos parágrafos, apontou para uma série de questionamentos, pontos de análise e reflexões. A pandemia, e o decorrente distanciamento social, parece ter colocado uma lente de aumento sobre as angústias das mulheres que são mães, evidenciando sentimentos e sofrimentos sempre presentes. Destacaram-se, nos relatos, a sobrecarga das mulheres com as tarefas de cuidado dos filhos e da casa, a culpa, a solidão, a exaustão, e o sentimento de que não havia espaço nesse contexto para "ser mulher", sendo isso entendido especialmente a questões estéticas e de vaidade.(AU)


Starting from the question "How does it feel to be a woman and a mother in pandemic times?", this study invited women who are mothers, in virtual social networks, to share their experiences regarding parental adaptations due to social distancing caused by the COVID-19 pandemic. The objective was to reflect on the experience of being a woman and a mother in the context of COVID-19 and of social distancing, pointing out some resonances of the pandemic scenario in the subjectivity of these women. The study was based on the psychoanalytical framework, both in the construction of the research and analysis of the reports and in their discussion. The analysis of about 340 collected reports, which ranged from a brief sentence to long paragraphs, pointed to a series of questions, analysis topics, and reflections. The pandemic, and the resulting social distancing, seems to have placed a magnifying glass over the anguish of women who are mothers, showing ever-present feelings and suffering. The reports highlighted women's overload with child and house care tasks, the guilt, loneliness, exhaustion, and the feeling that there was no space in this context to "be a woman," and it extends to aesthetic and vanity related questions especially.(AU)


A partir de la pregunta "¿cómo te sientes siendo mujer y madre en tiempos de pandemia?", este estudio invitó por las redes sociales a mujeres que son madres a compartir un relato de sus experiencias sobre la readaptación parental en función del distanciamiento social causado por la pandemia del covid-19. Su objetivo fue reflexionar sobre la experiencia de ser mujer y madre en tiempos del covid-19 y el distanciamiento social, señalando algunas resonancias del escenario pandémico en la subjetividad de estas mujeres. Este estudio se basó en el marco psicoanalítico, tanto en la construcción de la investigación y análisis de los informes como en su discusión. El análisis de los casi 340 relatos, que variaron de una pequeña frase a largos párrafos, generó en las investigadoras una serie de cuestionamientos y reflexiones. La pandemia y el consecuente distanciamiento social parece haber agrandado las angustias de las mujeres que son madres, evidenciando sentimientos y sufrimientos siempre presentes. En los relatos destacan la sobrecarga de las mujeres con las tareas de cuidado de los hijos y del hogar, la culpa, la soledad, el cansancio, así como el sentimiento de que no hay espacio em este contexto para "ser mujer", relacionado principalmente a cuestiones estéticas y de vanidad.(AU)


Subject(s)
Humans , Female , Pregnancy , Psychoanalysis , Women , Parenting , Pandemics , COVID-19 , Anxiety , Parent-Child Relations , Paternal Behavior , Paternity , Prenatal Care , Psychology , Psychology, Social , Relaxation , Self Care , Self Concept , Social Adjustment , Social Responsibility , Socialization , Socioeconomic Factors , Stereotyping , Stress, Physiological , Stress, Psychological , Women's Rights , Work Hours , Body Image , Burnout, Professional , Activities of Daily Living , Pregnancy , Adaptation, Biological , Family , Marriage , Child , Child Development , Child Rearing , Quarantine , Hygiene , Mental Health , Family Health , Immunization , Sex Characteristics , Universal Precautions , Employment, Supported , Cost of Illness , Confusion , Feminism , Self Efficacy , Affect , Culture , Parturition , Depression , Postpartum Period , Educational Status , Ego , Employment , Fear , Femininity , Sexism , Work-Life Balance , Frailty , Occupational Stress , Androcentrism , Freedom , Self-Neglect , Frustration , Body Dissatisfaction , Psychological Distress , Social Comparison , Teleworking , Physical Distancing , Gender Equity , Family Support , Family Structure , Guilt , Health Promotion , Household Work , Identification, Psychological , Identity Crisis , Income , Individuation , Anger , Leisure Activities , Loneliness , Love , Maternal Behavior , Maternal Welfare , Mothers
7.
Psicol. ciênc. prof ; 43: e255195, 2023.
Article in Portuguese | LILACS, INDEXPSI | ID: biblio-1529228

ABSTRACT

A pandemia de covid-19 provocou intensas mudanças no contexto do cuidado neonatal, exigindo dos profissionais de saúde a reformulação de práticas e o desenvolvimento de novas estratégias para a manutenção da atenção integral e humanizada ao recém-nascido. O objetivo deste artigo é relatar a atuação da Psicologia nas Unidades Neonatais de um hospital público de Fortaleza (CE), Brasil, durante o período de distanciamento físico da pandemia de covid-19. Trata-se de estudo descritivo, do tipo relato de experiência, que ocorreu no período de março a agosto de 2020. No contexto pandêmico, o serviço de Psicologia desenvolveu novas condutas assistenciais para atender às demandas emergentes do momento, como: atendimento remoto; registro e envio on-line de imagens do recém-nascido a seus familiares; visitas virtuais; e reprodução de mensagens de áudio da família para o neonato. Apesar dos desafios encontrados, as ações contribuíram para a manutenção do cuidado centrado no recém-nascido e sua família, o que demonstra a potencialidade do fazer psicológico.(AU)


The COVID-19 pandemic brought intense changes to neonatal care and required health professionals to reformulate practices and develop new strategies to ensure comprehensive and humanized care for newborn. This study aims to report the experience of the Psychology Service in the Neonatal Units of a public hospital in Fortaleza, in the state of Ceará, Brazil, during the social distancing period of the COVID-19 pandemic. This descriptive experience report study was conducted from March to August 2020. During the pandemic, the Psychology Service developed new care practices to meet the emerging demands of that moment, such as remote care, recordings and online submission of newborns' pictures and video images for their family, virtual tours, and reproduction of family audio messages for the newborns. Despite the challenges, the actions contributed to the maintenance of a care that is centered on the newborns and their families, which shows the potential of psychological practices.(AU)


La pandemia de la COVID-19 ha traído cambios intensos en el contexto de la atención neonatal, que requieren de los profesionales de la salud una reformulación de sus prácticas y el desarrollo de nuevas estrategias para asegurar una atención integral y humanizada al recién nacido. El objetivo de este artículo es reportar la experiencia del Servicio de Psicología en las Unidades Neonatales de un hospital público de Fortaleza, en Ceará, Brasil, durante el periodo de distanciamiento físico en la pandemia de la COVID-19. Se trata de un estudio descriptivo, un reporte de experiencia, que se llevó a cabo de marzo a agosto de 2020. En el contexto pandémico, el servicio de Psicología desarrolló nuevas conductas asistenciales para atender a las demandas emergentes del momento, tales como: atención remota; grabación y envío em línea de imágenes del recién nacido; visitas virtuales; y reproducción de mensajes de audio de la familia para el recién nacido. A pesar de los desafíos encontrados, las acciones contribuyeron al mantenimiento de la atención centrada en el recién nacido y su familia, lo que demuestra el potencial de la práctica psicológica.(AU)


Subject(s)
Humans , Female , Pregnancy , Infant, Newborn , Infant , Psychology , Teleworking , COVID-19 , Neonatology , Anxiety , Oxygen Inhalation Therapy , Apgar Score , Patient Care Team , Patient Discharge , Pediatrics , Perinatology , Phototherapy , Prenatal Care , Quality of Health Care , Respiration, Artificial , Skilled Nursing Facilities , Survival , Congenital Abnormalities , Unconscious, Psychology , Visitors to Patients , Obstetrics and Gynecology Department, Hospital , Health Care Levels , Brazil , Breast Feeding , Case Reports , Infant, Newborn , Infant, Premature , Cardiotocography , Health Behavior , Intensive Care Units, Pediatric , Intensive Care Units, Neonatal , Child Development , Child Health Services , Infant Mortality , Maternal Mortality , Cross Infection , Risk , Probability , Vital Statistics , Health Status Indicators , Life Expectancy , Women's Health , Neonatal Screening , Nursing , Enteral Nutrition , Long-Term Care , Parenteral Nutrition , Pregnancy, High-Risk , Pliability , Comprehensive Health Care , Low Cost Technology , Pregnancy Rate , Life , Creativity , Critical Care , Affect , Crying , Humanizing Delivery , Uncertainty , Pregnant Women , Continuous Positive Airway Pressure , Disease Prevention , Humanization of Assistance , User Embracement , Information Technology , Child Nutrition , Perinatal Mortality , Resilience, Psychological , Fear , Feeding Methods , Fetal Monitoring , Patient Handoff , Microbiota , Integrality in Health , Ambulatory Care , Neurodevelopmental Disorders , Maternal Health , Neonatal Sepsis , Pediatric Emergency Medicine , Psychosocial Support Systems , Survivorship , Mental Status and Dementia Tests , Access to Essential Medicines and Health Technologies , Family Support , Gynecology , Hospitalization , Hospitals, Maternity , Hyperbilirubinemia , Hypothermia , Immune System , Incubators , Infant, Newborn, Diseases , Length of Stay , Life Change Events , Love , Maternal Behavior , Maternal Welfare , Medicine , Methods , Nervous System Diseases , Object Attachment , Obstetrics
8.
EMBO J ; 41(24): e111648, 2022 12 15.
Article in English | MEDLINE | ID: mdl-36341708

ABSTRACT

The ability to care for the young is innate and readily displayed by postpartum females after delivery to ensure offspring survival. Upon pup exposure, rodent virgin (nulliparous) females also develop parental behavior that over time becomes displayed at levels equivalent to parenting mothers. Although maternal behavior in postpartum females and the associated neurocircuits are well characterized, the neural mechanisms underlying the acquisition of maternal behavior without prior experience remain poorly understood. Here, we show that the development of maternal care behavior in response to first-time pup exposure in virgin females is initiated by the activation of the anterior cingulate cortex (ACC). ACC activity is dependent on feedback excitation by Vglut2+ /Galanin+ neurons of the centrolateral nucleus of the thalamus (CL), with their activity sufficient to display parenting behaviors. Accordingly, acute bidirectional chemogenetic manipulation of neuronal activity in the ACC facilitates or impairs the attainment of maternal behavior, exclusively in virgin females. These results reveal an ACC-CL neurocircuit as an accessory loop in virgin females for the initiation of maternal care upon first-time exposure to pups.


Subject(s)
Maternal Behavior , Postpartum Period , Humans , Animals , Mice , Female , Postpartum Period/physiology , Neurons/physiology , Thalamus , Prefrontal Cortex , Behavior, Animal
9.
Subj. procesos cogn ; 26(2): 123-132, nov. 28, 2022.
Article in Spanish | LILACS, UNISALUD, BINACIS | ID: biblio-1402002

ABSTRACT

Medir el empuje que transmite la voz materna es casi inconcebible, (Didier-Weill,1998) ya que la estructura de su discurso primordial incluye una paradoja. ¿De qué manera entonces medir un espacio de encuentro que está en construcción? Este estudio explora la distancia afectiva en la díada madre-bebé desde una perspectiva intersubjetiva, durante la emisión del fenómeno sonoro denominado "tono maternés". Como parte de los avances de la investigación en curso, se destaca el valor de la interdisciplina para la obtención de los datos y el modo en que su procesamiento conduce a una posible categorización de su objeto de estudio. La consulta a expertos (del campo de la fonoaudiología y la psicomotricidad) permitió abordar un "único cuerpo suficientemente complejo"(Bernardi,2000)y de este modo cercar la realidad compartida. Se acuerda con Winnicott (1989) en la idea de que, si distintos observadores llegan a conclusiones semejantes, probablemente signifique que se ocupan de cosas reales(AU)


Measuring the drive transmitted by the maternal voice is almost inconceivable (Didier-Weill 1998). This statement is based on the idea that the primordial discourse structure is paradoxical. How then, to measure a meeting space that is under construction. One of the objectives of this psychoanalytic thesisis to explore the affective distance present in the dyad, while she emits the sound phenomenon 'babytalk'. As part of the progress, the author presents some moments of the investigation. This paper highlights the value of interdisciplinary approach to obtain the data and presents a possible categorization of the affective distance present in the early relationship.To study the real movements for the psychical constitution, it was required the dialogue with experts (from the areas of phonology and psychomotricity) to border a shared reality and address a "single sufficiently complex body (Bernardi, 2000). In agreement with Winnicott (1989), if different observers arrive at a similar conclusion, it possibly implies that they are dealing with real things(AU)


Subject(s)
Humans , Male , Female , Infant , Adult , Psychoanalysis , Psychological Distance , Voice , Affect , Maternal Behavior/psychology , Mother-Child Relations/psychology , Play Therapy , Interdisciplinary Research , Interpersonal Relations
10.
eNeuro ; 9(4)2022.
Article in English | MEDLINE | ID: mdl-35995560

ABSTRACT

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.


Subject(s)
Milk , Social Behavior , Animals , Female , Humans , Hypothalamus/metabolism , Lactation , Maternal Behavior/physiology , Rats , Rats, Sprague-Dawley
11.
J Pediatr ; 248: 46-50.e1, 2022 09.
Article in English | MEDLINE | ID: mdl-35660492

ABSTRACT

OBJECTIVE: To evaluate patterns of mother-infant sleeping behaviors among US-based mothers who received care from midwives and breastfed their infants the majority of time at 6 weeks postpartum. STUDY DESIGN: Infant sleep locations were reported for 24 915 mother-infant dyads followed through 6 weeks postpartum, following midwife-led singleton births. Using data derived from medical records, we used multinomial logistic regression to identify predictors of sleep location. RESULTS: The median maternal age was 31 years (IQR, 27-34 years). The majority were White (84.5%), reported having a partner or spouse (95%), had a community birth (87%), and reported bedsharing with their infant for part (13.2%) or most of the night (43.8%). In the adjusted analysis, positive predictors of always bedsharing included increasing maternal age (OR, 1.17; 95% CI, 1.13-1.21; per 5 years), cesarean birth (OR, 1.49; 95% CI, 1.18-1.86), Medicaid eligibility (OR, 1.76; 95% CI, 1.62-1.91), and maternal race/ethnicity (Black OR, 1.40 [95% CI, 1.09-1.79]; Latinx OR, 1.53 [95% CI, 1.35-1.74]; multiracial OR, 1.69 [95% CI, 1.39-2.07]). Negative predictors of bedsharing included having a partner/spouse (OR, 0.66; 95% CI, 0.56-0.77) and birth location in hospitals (OR, 0.56; 95% CI, 0.49-0.64) or birthing centers (OR, 0.48; 95% CI, 0.44-0.51). Partial breastfeeding dyads were less likely to bedshare than those who were exclusively breastfeeding (always bedsharing OR, 0.48 [95% CI, 0.41-0.56]; sometimes bedsharing OR 0.69 [95% CI, 0.56-0.83]). CONCLUSIONS: These data suggest that cosleeping is common among US families who choose community births, most of whom exclusively breastfeed through at least 6 weeks.


Subject(s)
Midwifery , Adult , Breast Feeding , Child, Preschool , Female , Humans , Infant , Maternal Behavior , Postpartum Period , Pregnancy , Prevalence , Sleep
12.
Neuropsychopharmacology ; 47(11): 1901-1912, 2022 10.
Article in English | MEDLINE | ID: mdl-35396500

ABSTRACT

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.


Subject(s)
Autistic Disorder , Hypesthesia , Maternal Behavior , Oxytocin , Proteins , Administration, Intranasal , Age Factors , Animals , Antigens, Neoplasm/genetics , Antigens, Neoplasm/metabolism , Autism Spectrum Disorder/complications , Autistic Disorder/complications , Autistic Disorder/genetics , Autistic Disorder/metabolism , Central Nervous System Agents/administration & dosage , Central Nervous System Agents/metabolism , Female , Hypesthesia/etiology , Hypesthesia/genetics , Hypesthesia/metabolism , Hypothalamus/drug effects , Hypothalamus/metabolism , Maternal Behavior/physiology , Mice , Oxytocin/administration & dosage , Oxytocin/metabolism , Proteins/genetics , Proteins/metabolism , Social Behavior
13.
PLoS One ; 17(2): e0263632, 2022.
Article in English | MEDLINE | ID: mdl-35192674

ABSTRACT

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.


Subject(s)
Amygdala/metabolism , Behavior, Animal/physiology , Epigenesis, Genetic , Maternal Behavior/physiology , Nerve Tissue Proteins/genetics , Oxytocin/genetics , Animals , Animals, Newborn , Anxiety/psychology , Chromatin/chemistry , Chromatin/metabolism , Female , Gene Expression Profiling , Gene Regulatory Networks , Hypothalamus/metabolism , Maternal Behavior/psychology , Mice , Nerve Tissue Proteins/classification , Nerve Tissue Proteins/metabolism , Oxytocin/metabolism , Pregnancy , Sexual Abstinence
14.
Horm Behav ; 141: 105129, 2022 05.
Article in English | MEDLINE | ID: mdl-35168026

ABSTRACT

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.


Subject(s)
Maternal Behavior , Preoptic Area , Animals , Female , Humans , Hypothalamus/metabolism , Maternal Behavior/physiology , Mice , Nucleus Accumbens/metabolism , Preoptic Area/metabolism , Proto-Oncogene Proteins c-fos/metabolism
15.
Proc Natl Acad Sci U S A ; 119(6)2022 02 08.
Article in English | MEDLINE | ID: mdl-35131854

ABSTRACT

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.


Subject(s)
Aggression/physiology , Lactation/metabolism , Prolactin/metabolism , Animals , Female , Hypothalamus/metabolism , Male , Maternal Behavior/physiology , Mice , Mice, Inbred C57BL , Neurons/metabolism , Paraventricular Hypothalamic Nucleus/metabolism , Preoptic Area/metabolism , Receptors, Prolactin/metabolism , Thalamus/metabolism , Ventromedial Hypothalamic Nucleus/metabolism
16.
Article in English | MEDLINE | ID: mdl-34896909

ABSTRACT

INTRODUCTION: Perinatal women often experience mood disorders and postpartum depression due to the physical load and the rapid changes in hormone levels caused by pregnancy, childbirth, and nursing. When the mother's emotions become unstable, their parental behavior (maternal behavior) may decline, the child's attachment may weaken, and the formation of mother-child bonding can become hindered. As a result, the growth of the child may be adversely affected. The objective of this study was to investigate the effect of ω3 fatty acid deficiency in the perinatal period on maternal behavior and the oxytocin concentration and fatty acid composition in brain tissue. MATERIALS AND METHODS: Virgin female C57BL/6 J mice fed a ω3 fatty acid-deficient (ω3-Def) or adequate (ω3-Adq) diet were mated for use in this study. To assess maternal behavior, nest shape was evaluated at a fixed time from gestational day (GD) 15 to postpartum day (PD) 13, and a retrieval test was conducted on PD 3. For neurochemical measurement, brains were removed from PD 1-6 dams and hippocampal fatty acids and hypothalamic oxytocin concentrations were assessed. RESULTS: Peripartum nest shape scores were similar to those reported previously (Harauma et al., 2016); nests in the ω3-Def group were small and of poor quality whereas those in the ω3-Adq group were large and elaborate. The inferiority of nest shape in the ω3-Def group continued from PD 0-7. In the retrieval test performed on PD 3, dams in the ω3-Def group took longer on several parameters compared with those in the ω3-Adq group, including time to make contact with pups (sniffing time), time to start retrieving the next pup (interval time), and time to retrieve the last pup to the nest (grouping time). Hypothalamic oxytocin concentrations on PD 1-6 were lower in the ω3-Def group than in the ω3-Adq group. DISCUSSION: Our data show that ω3 fatty acid deficiency reduces maternal behavior, a state that continued during pup rearing. This was supported by the observed decrease in hypothalamic oxytocin concentration in the ω3-Def group. These results suggest that ω3 fatty acid supplementation during the perinatal period is not only effective in delivering ω3 fatty acids to infants but is also necessary to activate high-quality parental behavior in mothers.


Subject(s)
Diet/methods , Dietary Supplements , Fatty Acids, Omega-3/administration & dosage , Maternal Behavior/drug effects , Oxytocin/biosynthesis , Paraventricular Hypothalamic Nucleus/metabolism , Parturition/metabolism , Postpartum Period/metabolism , Signal Transduction/drug effects , Animals , Animals, Newborn/metabolism , Female , Gestational Age , Hippocampus/chemistry , Male , Mice , Mice, Inbred C57BL , Parturition/drug effects , Postpartum Period/drug effects , Pregnancy
17.
Nutrients ; 13(12)2021 Dec 05.
Article in English | MEDLINE | ID: mdl-34959919

ABSTRACT

Racial, ethnic, and socioeconomic disparities in childhood obesity in the United States (U.S.) originate in early life. Maternal sugar-sweetened beverage (SSB) consumption is an early life risk factor for later offspring obesity. The goal of this study was to test the effects of policy-relevant messages delivered by text messages mobile devices (mHealth) on maternal SSB consumption. In this three-arm 1-month randomized controlled trial (RCT), pregnant women or mothers of infants in predominantly Hispanic/Latino New York City neighborhoods were randomized to receive one of three text message sets: graphic beverage health warning labels, beverage sugar content information, or attention control. The main outcome was change in maternal self-reporting of average daily SSB consumption from baseline to one month. Among 262 participants, maternal SSB consumption declined over the 1-month period in all three arms. No intervention effect was detected in primary analyses. In sensitivity analyses accounting for outliers, graphic health warning labels reduced maternal SSB consumption by 28 kcal daily (95% CI: -56, -1). In this mHealth RCT among pregnant women and mothers of infants, graphic health warning labels and beverage sugar content information did not reduce maternal SSB consumption.


Subject(s)
Consumer Behavior/statistics & numerical data , Eating/psychology , Food Labeling , Maternal Behavior/psychology , Sugar-Sweetened Beverages/adverse effects , Text Messaging , Adolescent , Adult , Female , Food Analysis , Humans , Infant , New York City , Pregnancy , Sugar-Sweetened Beverages/analysis , Sugars/analysis , Young Adult
18.
Int J Mol Sci ; 22(18)2021 Sep 12.
Article in English | MEDLINE | ID: mdl-34576011

ABSTRACT

Both the detrimental effect of prenatal exposure to di-(2-ethylhexyl)-phthalate (DEHP) and the beneficial effects of physical exercise on brain functions have been reported. The oxytocin pathway has been implicated in the onset of maternal behaviors. Epigenetic modification of the oxytocin receptor gene (OXTR) through DNA methylation has been associated with the pathogenesis of neuropsychiatric disorders. The purpose of this study was to investigate the effects of prenatal DEHP exposure on oxytocin-regulated maternal behaviors and to examine the protective effect of exercise. Pregnant rats (F0) were fed with vehicle or DEHP during gestation and the offspring females (F1) were assessed for their maternal behaviors by pup retrieval test at postpartum. The results showed that reduced pup retrieval activities without significant alteration of stress responses were observed in the prenatally DEHP-exposed females. Prenatal DEHP exposure decreased the expressions of oxytocin, Oxtr mRNA, and oxytocin receptor, and increased Oxtr methylation in the hypothalamus of postpartum female rats. There were no significant effects of exercise on behavioral, biochemical, and epigenetic measurements. These results suggest that prenatal DEHP exposure has a long-term adverse effect on maternal behaviors; Oxtr hyper-methylation may be a potential epigenetic mechanism for this alteration, which cannot be prevented by physical exercise during childhood.


Subject(s)
Diethylhexyl Phthalate/toxicity , Hypothalamus/drug effects , Maternal Behavior/drug effects , Physical Conditioning, Animal , Prenatal Exposure Delayed Effects , Animals , DNA Methylation , Female , Hypothalamus/metabolism , Pregnancy , Rats, Sprague-Dawley , Receptors, Oxytocin/genetics
19.
Environ Health Perspect ; 129(8): 87003, 2021 08.
Article in English | MEDLINE | ID: mdl-34383603

ABSTRACT

BACKGROUND: The effects of endocrine-disrupting chemicals (EDCs) on fertility and reproductive development represent a rising concern in modern societies. Although the neuroendocrine control of sexual maturation is a major target of EDCs, little is known about the potential role of the hypothalamus in puberty and ovulation disruption transmitted across generations. OBJECTIVES: We hypothesized that developmental exposure to an environmentally relevant dose of EDC mixture could induce multi- and/or transgenerational alterations of sexual maturation and maternal care in female rats through epigenetic reprograming of the hypothalamus. We investigated the transmission of a disrupted reproductive phenotype via the maternal germline or via nongenomic mechanisms involving maternal care. METHODS: Adult female Wistar rats were exposed prior to and during gestation and until the end of lactation to a mixture of the following 13 EDCs: di-n-butyl phthalate (DnBP), di(2-ethylhexyl) phthalate (DEHP), bisphenol A (BPA), vinclozolin, prochloraz, procymidone, linuron, epoxynaxole, dichlorodiphenyldichloroethylene, octyl methoxynimmate, 4-methylbenzylidene camphor (4-MBC), butylparaben, and acetaminophen. Perinatally exposed offspring (F1) were mated with unexposed males to generate germ cell (F2) and transgenerationally exposed (F3 and F4) females. Sexual maturation, maternal behavior, and hypothalamic targets of exposure were studied across generations. RESULTS: Germ cell (F2) and transgenerationally (F3) EDC-exposed females, but not F1, displayed delayed pubertal onset and altered folliculogenesis. We reported a transgenerational alteration of key hypothalamic genes controlling puberty and ovulation (Kiss1, Esr1, and Oxt), and we identified the hypothalamic polycomb group of epigenetic repressors as actors of this mechanism. Furthermore, we found a multigenerational reduction of maternal behavior (F1-F3) induced by a loss in hypothalamic dopaminergic signaling. Using a cross-fostering paradigm, we identified that the reduction in maternal phenotype was normalized in EDC-exposed pups raised by unexposed dams, but no reversal of the pubertal phenotype was achieved. DISCUSSION: Rats developmentally exposed to an EDC mixture exhibited multi- and transgenerational disruption of sexual maturation and maternal care via hypothalamic epigenetic reprogramming. These results raise concerns about the impact of EDC mixtures on future generations. https://doi.org/10.1289/EHP8795.


Subject(s)
Endocrine Disruptors , Hypothalamus/drug effects , Maternal Behavior/drug effects , Prenatal Exposure Delayed Effects , Animals , Endocrine Disruptors/toxicity , Epigenesis, Genetic , Female , Pregnancy , Prenatal Exposure Delayed Effects/chemically induced , Rats , Rats, Wistar , Sexual Maturation
20.
Elife ; 102021 08 23.
Article in English | MEDLINE | ID: mdl-34423776

ABSTRACT

While recent studies have uncovered dedicated neural pathways mediating the positive control of parenting, the regulation of infant-directed aggression and how it relates to adult-adult aggression is poorly understood. Here we show that urocortin-3 (Ucn3)-expressing neurons in the hypothalamic perifornical area (PeFAUcn3) are activated during infant-directed attacks in males and females, but not other behaviors. Functional manipulations of PeFAUcn3 neurons demonstrate the role of this population in the negative control of parenting in both sexes. PeFAUcn3 neurons receive input from areas associated with vomeronasal sensing, stress, and parenting, and send projections to hypothalamic and limbic areas. Optogenetic activation of PeFAUcn3 axon terminals in these regions triggers various aspects of infant-directed agonistic responses, such as neglect, repulsion, and aggression. Thus, PeFAUcn3 neurons emerge as a dedicated circuit component controlling infant-directed neglect and aggression, providing a new framework to understand the positive and negative regulation of parenting in health and disease.


Subject(s)
Aggression , Behavior, Animal , Hypothalamus/metabolism , Maternal Behavior , Neurons/metabolism , Paternal Behavior , Urocortins/metabolism , Animals , Female , Male , Mice, 129 Strain , Mice, Inbred C57BL , Mice, Transgenic , Neural Pathways/metabolism , Optogenetics , Sex Factors , Urocortins/genetics
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