Developmental alcohol exposure is exhausting: Sleep and the enduring consequences of alcohol exposure during development.

Prenatal alcohol exposure is the leading nongenetic cause of human intellectual impairment. The long-term impacts of prenatal alcohol exposure on health and well-being are diverse, including neuropathology leading to behavioral, cognitive, and emotional impairments. Additionally negative effects also occur on the physiological level, such as the endocrine, cardiovascular, and immune systems.

Homeostatic NREM sleep and salience network function in adult mice exposed to ethanol during development.

Developmental exposure to ethanol is a leading cause of cognitive, emotional and behavioral problems, with fetal alcohol spectrum disorder (FASD) affecting more than 1:100 children. Recently, comorbid sleep deficits have been highlighted in these disorders, with sleep repair a potential therapeutic target. Animal models of FASD have shown non-REM (NREM) sleep fragmentation and slow-wave oscillation impairments that predict cognitive performance.

Infant pain vs. pain with parental suppression: Immediate and enduring impact on brain, pain and affect.

Background: In the short term, parental presence while a human infant is in pain buffers the immediate pain responses, although emerging evidence suggests repeated social buffering of pain may have untoward long-term effects.

Methods/finding: To explore the short- and long-term impacts of social buffering of pain, we first measured the infant rat pup's [postnatal day (PN) 8, or 12] response to mild tail shock with the mother present compared to shock alone or no shock. Shock with the mother reduced pain-related behavioral activation and USVs of pups at both ages and reduced Fos expression in the periaqueductal gray, hypothalamic paraventricular nucleus, and the amygdala at PN12 only.

Neuroscience: Building better cognition through smell.

Developmental neural activity organizes sensory system development. New evidence in mice suggests postnatal olfactory bulb activity also modulates development of the structure and function of hippocampal-cortical circuits. Reducing cell-specific olfactory bulb output during an infant sensitive period impairs later-life cognition.

Antagonistic circuits mediating infanticide and maternal care in female mice.

In many species, including mice, female animals show markedly different pup-directed behaviours based on their reproductive state. Naive wild female mice often kill pups, while lactating female mice are dedicated to pup caring. The neural mechanisms that mediate infanticide and its switch to maternal behaviours during motherhood remain unclear.

Dynamic developmental changes in neurotransmitters supporting infant attachment learning.

Infant survival relies on rapid identification, remembering and behavioral responsiveness to caregivers' sensory cues. While neural circuits supporting infant attachment learning have largely remained elusive in children, use of invasive techniques has uncovered some of its features in rodents. During a 10-day sensitive period from birth, newborn rodents associate maternal odors with maternal pleasant or noxious thermo-tactile stimulation, which gives rise to a preference and approach behavior towards these odors, and blockade of avoidance learning.

From circuits to behavior: Amygdala dysfunction in fragile X syndrome.

Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by a repeat expansion mutation in the promotor region of the gene resulting in transcriptional silencing and loss of function of fragile X messenger ribonucleoprotein 1 protein (FMRP). FMRP has a well-defined role in the early development of the brain. Thus, loss of the FMRP has well-known consequences for normal cellular and synaptic development leading to a variety of neuropsychiatric disorders including an increased prevalence of amygdala-based disorders.

Basolateral Amygdala Hyperexcitability Is Associated with Precocious Developmental Emergence of Fear-Learning in Fragile X Syndrome.

Fragile X Syndrome is a neurodevelopmental disorder and the most common monogenic cause of intellectual disability, autism spectrum disorders, and anxiety disorders. Loss of fragile x mental retardation protein results in disruptions of synaptic development during a critical period of circuit formation in the BLA. However, it is unknown how these alterations impact microcircuit development and function.

The Neurobiology of Infant Attachment-Trauma and Disruption of Parent-Infant Interactions.

Current clinical literature and supporting animal literature have shown that repeated and profound early-life adversity, especially when experienced within the caregiver-infant dyad, disrupts the trajectory of brain development to induce later-life expression of maladaptive behavior and pathology. What is less well understood is the immediate impact of repeated adversity during early life with the caregiver, especially since attachment to the caregiver occurs regardless of the quality of care the infant received including experiences of trauma. The focus of the present manuscript is to review the current literature on infant trauma within attachment, with an emphasis on animal research to define mechanisms and translate developmental child research.

Neurobiology of Parental Regulation of the Infant and Its Disruption by Trauma Within Attachment.

The complex process of regulating physiological functions and homeostasis during external and internal disruptions develops slowly in altricial species, with parental care functioning as a co-regulator of infant physiological and emotional homeostasis. Here, we review our current understanding of the infant's use of parental behaviors for neurobehavioral regulation and its disruption with harsh parental care. Taking a cross-species view, we briefly review the human developmental literature that highlights the importance of the caregiver in scaffolding the child's physiological and emotional regulation, especially under threat and stress.

The Added Value of Crosstalk Between Developmental Circuit Neuroscience and Clinical Practice to Inform the Treatment of Adolescent Anxiety.

Significant advances have been made in recent years regarding the developmental trajectories of brain circuits and networks, revealing links between brain structure and function. Emerging evidence highlights the importance of developmental trajectories in determining early psychiatric outcomes. However, efforts to encourage crosstalk between basic developmental neuroscience and clinical practice are limited.

Basolateral amygdala to posterior piriform cortex connectivity ensures precision in learned odor threat.

Odor perception can both evoke emotional states and be shaped by emotional or hedonic states. The amygdala complex plays an important role in recognition of, and response to, hedonically valenced stimuli, and has strong, reciprocal connectivity with the primary olfactory (piriform) cortex. Here, we used differential odor-threat conditioning in rats to test the role of basolateral amygdala (BLA) input to the piriform cortex in acquisition and expression of learned olfactory threat responses.

Bidirectional control of infant rat social behavior via dopaminergic innervation of the basolateral amygdala.

Social interaction deficits seen in psychiatric disorders emerge in early-life and are most closely linked to aberrant neural circuit function. Due to technical limitations, we have limited understanding of how typical versus pathological social behavior circuits develop. Using a suite of invasive procedures in awake, behaving infant rats, including optogenetics, microdialysis, and microinfusions, we dissected the circuits controlling the gradual increase in social behavior deficits following two complementary procedures-naturalistic harsh maternal care and repeated shock alone or with an anesthetized mother.

Infant Attachment and Social Modification of Stress Neurobiology.

Decades of research have informed our understanding of how stress impacts the brain to perturb behavior. However, stress during development has received specific attention as this occurs during a sensitive period for scaffolding lifelong socio-emotional behavior. In this review, we focus the developmental neurobiology of stress-related pathology during infancy and focus on one of the many important variables that can switch outcomes from adaptive to maladaptive outcome: caregiver presence during infants' exposure to chronic stress.

Oxytocin neurons enable social transmission of maternal behaviour.

Maternal care, including by non-biological parents, is important for offspring survival. Oxytocin, which is released by the hypothalamic paraventricular nucleus (PVN), is a critical maternal hormone. In mice, oxytocin enables neuroplasticity in the auditory cortex for maternal recognition of pup distress.

Maternal continuous oral oxycodone self-administration alters pup affective/social communication but not spatial learning or sensory-motor function.

Background: The broad use/misuse of prescription opioids during pregnancy has resulted in a surge of infants with Neonatal Opioid Withdrawal Syndrome (NOWS). Short-term irritability and neurological complications are its hallmarks, but the long-term consequences are unknown.

Methods: A newly-developed preclinical model of oxycodone self-administration enables adult female rats to drink oxycodone (∼10/mg/kg/day) before and during pregnancy, and after delivery, and to maintain normal liquid intake, titrate dosing, and avoid withdrawal.

Elevated infant cortisol is necessary but not sufficient for transmission of environmental risk to infant social development: Cross-species evidence of mother-infant physiological social transmission.

Environmental adversity increases child susceptibility to disrupted developmental outcomes, but the mechanisms by which adversity can shape development remain unclear. A translational cross-species approach was used to examine stress-mediated pathways by which poverty-related adversity can influence infant social development. Findings from a longitudinal sample of low-income mother-infant dyads indicated that infant cortisol (CORT) on its own did not mediate relations between early-life scarcity-adversity exposure and later infant behavior in a mother-child interaction task.

Neurobiology of Infant Fear and Anxiety: Impacts of Delayed Amygdala Development and Attachment Figure Quality.

Anxiety disorders are the most common form of mental illness and are more likely to emerge during childhood compared with most other psychiatric disorders. While research on children is the gold standard for understanding the behavioral expression of anxiety and its neural circuitry, the ethical and technical limitations in exploring neural underpinnings limit our understanding of the child's developing brain. Instead, we must rely on animal models to build strong methodological bridges for bidirectional translation to child development research.

Defining Immediate Effects of Sensitive Periods on Infant Neurobehavioral Function.

During a sensitive period associated with attachment, the infant brain has unique circuitry that enables the specialized adaptive behaviors required for survival in infancy. This infant brain is not an immature version of the adult brain. Within the attachment relationship, the infant remains close (proximity seeking) to the caregiver for nurturing and survival needs, but the caregiver also provides the immature infant with the physiological regulation interaction needed before self-regulation matures.

Adverse caregiving in infancy blunts neural processing of the mother.

The roots of psychopathology frequently take shape during infancy in the context of parent-infant interactions and adversity. Yet, neurobiological mechanisms linking these processes during infancy remain elusive. Here, using responses to attachment figures among infants who experienced adversity as a benchmark, we assessed rat pup cortical local field potentials (LFPs) and behaviors exposed to adversity in response to maternal rough and nurturing handling by examining its impact on pup separation-reunion with the mother.

Enhancing Executive Functions Through Social Interactions: Causal Evidence Using a Cross-Species Model.

It has long been theorized that humans develop higher mental functions, such as executive functions (EFs), within the context of interpersonal interactions and social relationships. Various components of social interactions, such as interpersonal communication, perspective taking, and conforming/adhering to social rules, may create important (and perhaps even necessary) opportunities for the acquisition and continued practice of EF skills. Furthermore, positive and stable relationships facilitate the development and maintenance of EFs across the lifespan.

Early Life Trauma Has Lifelong Consequences for Sleep And Behavior.

Sleep quality varies widely across individuals, especially during normal aging, with impaired sleep contributing to deficits in cognition and emotional regulation. Sleep can also be impacted by a variety of adverse events, including childhood adversity. Here we examined how early life adverse events impacted later life sleep structure and physiology using an animal model to test the relationship between early life adversity and sleep quality across the life span.

Corticosterone administration targeting a hypo-reactive HPA axis rescues a socially-avoidant phenotype in scarcity-adversity reared rats.

It is well-established that children from low-income, under-resourced families are at increased risk of altered social development. However, the biological mechanisms by which poverty-related adversities can "get under the skin" to influence social behavior are poorly understood and cannot be easily ascertained using human research alone. This study utilized a rodent model of "scarcity-adversity," which encompasses material resource deprivation (scarcity) and reduced caregiving quality (adversity), to explore how early-life scarcity-adversity causally influences social behavior via disruption of developing stress physiology.

During infant maltreatment, stress targets hippocampus, but stress with mother present targets amygdala and social behavior.

Infant maltreatment increases vulnerability to physical and mental disorders, yet specific mechanisms embedded within this complex infant experience that induce this vulnerability remain elusive. To define critical features of maltreatment-induced vulnerability, rat pups were reared from postnatal day 8 (PN8) with a maltreating mother, which produced amygdala and hippocampal deficits and decreased social behavior at PN13. Next, we deconstructed the maltreatment experience to reveal sufficient and necessary conditions to induce this phenotype.

Parental presence switches avoidance to attraction learning in children.

Attachment-related learning (that is, forming preferences for cues associated with the parent) defies the traditional rules of learning in that it seems to occur independently of apparent reinforcement-young children prefer cues associated with their parent, regardless of valence (rewarding or aversive), despite the diversity of parenting styles. This obligatory attraction for parental cues keeps the child nearby and safe to explore the environment; thus, it is critical for survival and sets the foundation for normal human cognitive-emotional behaviour. Here we examined the learning underlying this attraction in preschool-age children.