Faculty Bibliography

Long tolerated as a rite of passage into adulthood, bullying is now recognized as a major and preventable public health problem. The consequences of bullying-for those who are bullied, the perpetrators of bullying, and the witnesses-include poor physical health, anxiety, depression, increased risk for suicide, poor school performance, and future delinquent and aggressive behavior. Despite ongoing efforts to address bullying at the law, policy, and programmatic levels, there is still much to learn about the consequences of bullying and the effectiveness of various responses. In 2016, the National Academies of Sciences, Engineering, and Medicine published a report entitled Preventing Bullying Through Science, Policy and Practice, which examined the evidence on bullying, its impact, and responses to date. This article summarizes the report's key findings and recommendations related to bullying prevention.

As altricial infants gradually transition to adults, their proximate environment changes. In three short weeks, pups transition from a small world with the caregiver and siblings to a complex milieu rich in dangers as their environment expands. Such contrasting environments require different learning abilities and lead to distinct responses throughout development. Here, we will review some of the learned fear conditioned responses to threats in rats during their ontogeny, including behavioral and physiological measures that permit the assessment of learning and its supporting neurobiology from infancy through adulthood. In adulthood, odor-shock conditioning produces robust fear learning to the odor that depends upon the amygdala and related circuitry. Paradoxically, this conditioning in young pups fails to support fear learning and supports approach learning to the odor previously paired with shock. This approach learning is mediated by the infant attachment network that does not include the amygdala. During the age range when pups transition from the infant to the adult circuit (10-15 d old), pups have access to both networks: odor-shock conditioning in maternal presence uses the attachment circuit but the adult amygdala-dependent circuit when alone. However, throughout development (as young as 5 d old) the attachment associated learning can be overridden and amygdala-dependent fear learning supported, if the mother expresses fear in the presence of the pup. This social modulation of the fear permits the expression of defense reactions in life threatening situations informed by the caregiver but prevents the learning of the caregiver itself as a threat.

A major component of perception is hedonic valence: perceiving stimuli as pleasant or unpleasant. Here, we used early olfactory experiences that shape odor preferences and aversions to explore developmental plasticity in circuits mediating odor hedonics. We used 2-deoxyglucose autoradiographic mapping of neural activity to identify circuits differentially activated by biologically relevant preferred and avoided odors across rat development. We then further probed this system by increasing or decreasing hedonic value. Using both region of interest and functional connectivity analyses, we identified regions within primary olfactory, amygdala/hippocampal, and prefrontal cortical networks that were activated differentially by maternal and male odors. Although some activated regions remained stable across development (postnatal days 7-23), there was a developmental emergence of others that resulted in an age-dependent elaboration of hedonic-response-specific circuitry despite stable behavioral responses (approach/avoidance) to the odors across age. Hedonic responses to these biologically important odors were modified through diet suppression of the maternal odor and co-rearing with a male. This allowed assessment of hedonic circuits in isolation of the specific odor quality and/or intensity. Early experience significantly modified odor-evoked circuitry in an age-dependent manner. For example, co-rearing with a male, which induced pup attraction to male odor, reduced activity in amygdala regions normally activated by the unfamiliar avoided male odor, making this region more consistent with maternal odor. Understanding the development of odor hedonics, particularly within the context of altered early life experience, provides insight into the development of sensory processes, food preferences, and the formation of social affiliations, among other behaviors. SIGNIFICANCE STATEMENT: Odor hedonic valence controls approach-avoidance behaviors, but also modulates ongoing behaviors ranging from food preferences and social affiliation with the caregiver to avoidance of predator odors. Experiences can shape hedonic valence. This study explored brain circuitry involved in odor hedonic encoding throughout development using maternal and predator odors and assessed the effects of early life experience on odor hedonic encoding by increasing/decreasing the hedonic value of these odors. Understanding the role of changing brain circuitry during development and its impact on behavioral function is critical for understanding sensory processing across development. These data converge with exciting literature on the brain's hedonic network and highlight the significant role of early life experience in shaping the neural networks of highly biologically relevant stimuli.

Pavlovian fear or threat conditioning, where a neutral stimulus takes on aversive properties through pairing with an aversive stimulus, has been an important tool for exploring the neurobiology of learning. In the past decades, this neurobehavioral approach has been expanded to include the developing infant. Indeed, protracted postnatal brain development permits the exploration of how incorporating the amygdala, prefrontal cortex and hippocampus into this learning system impacts the acquisition and expression of aversive conditioning. Here we review the developmental trajectory of these key brain areas involved in aversive conditioning and relate it to pups' transition to independence through weaning. Overall, the data suggests that adult-like features of threat learning emerge as the relevant brain areas become incorporated into this learning. Specifically, the developmental emergence of the amygdala permits cue learning and the emergence of the hippocampus permits context learning. We also describe unique features of learning in early life that block threat learning and enhance interaction with the mother or exploration of the environment. Finally, we describe the development of a sense of time within this learning and its involvement in creating associations. Together these data suggest that the development of threat learning is a useful tool for dissecting adult-like functioning of brain circuits, as well as providing unique insights into ecologically relevant developmental changes.

It has been long recognized that parents exert profound influences on child development. Dating back to at least the seventeenth-century Enlightenment, the ability for parents to shape child behavior in an enduring way has been noted. Twentieth-century scholars developed theories to explain how parenting histories influence psychological development, and since that time, the number of scientific publications on parenting influences in both human and nonhuman animal fields has grown at an exponential rate, reaching numbers in the thousands by 2015. This special issue describes a symposium delivered by Megan Gunnar, Regina Sullivan, Mar Sanchez, and Nim Tottenham in the Fall of 2014 at the Society for Social Neuroscience. The goal of the symposium was to describe the emerging knowledge on neurobiological mechanisms that mediate parent-offspring interactions across three different species: rodent, monkey, and human. The talks were aimed at designing testable models of parenting effects on the development of emotional and stress regulation. Specifically, the symposium aimed at characterizing the special modulatory (buffering) effects of parental cues on fear- and stress-relevant neurobiology and behaviors of the offspring and to discuss examples of impaired buffering when the parent-infant relationship is disrupted.

Social buffering, which is the attenuation of stress hormone release by a social partner, occurs in many species throughout the lifespan. Social buffering of the infant by the caregiver is particularly robust, and animal models using infant rodents are uncovering the mechanisms and neural circuitry supporting social buffering. At birth, the hypothalamic-pituitary-adrenal (HPA) stress system is functional but is suppressed via extended social buffering by the mother: the profound social buffering effects of the mother can last for one to two hours when pups are removed from the mother. At 10 days of age, pups begin to mount a stress response immediately when separated from the mother. The stimuli from the mother supporting social buffering are broad, for tactile stimulation, milk, and an anesthetized mother (no maternal behavior) all sufficiently support social buffering. The mother appears to produce social buffering by blocking norepinephrine (NE) release into the hypothalamic paraventricular nucleus (PVN), which blocks HPA activation. Since the infant amygdala relies on the presence of corticosterone (CORT), this suggests that social buffering of pups by the mother attenuates the neurobehavioral stress response in infancy and prevents pups from learning about threat within mother-infant interactions.

Children form a strong attachment to their caregiver-even when that caretaker is abusive. Paradoxically, despite the trauma experienced within this relationship, the child develops a preference for trauma-linked cues-a phenomenon known as trauma bonding. Although infant trauma compromises neurobehavioral development, the mechanisms underlying the interaction between infant trauma bonding (i.e., learned preference for trauma cues) and the long-term effects of trauma (i.e., depressive-like behavior, amygdala dysfunction) are unknown. We modeled infant trauma bonding by using odor-shock conditioning in rat pups, which engages the attachment system and produces a life-long preference for the odor that was paired with shock. In adulthood, this trauma-linked odor rescues depressive-like behavior and amygdala dysfunction, reduces corticosterone (CORT) levels, and exerts repair-related changes at the molecular level. Amygdala microarray after rescue implicates serotonin (5-HT) and glucocorticoids (GCs), and a causal role was verified through microinfusions. Blocking amygdala 5-HT eliminates the rescue effect; increasing amygdala 5-HT and blocking systemic CORT mimics it. Our findings suggest that infant trauma cues share properties with antidepressants and safety signals and provide insight into mechanisms by which infant trauma memories remain powerful throughout life.