Caregiver-associated cues, including those learned in abusive attachment, provide a sense of safety and security to the child. Here, we explore how cues associated with abusive attachment, such as maternal odor, can modify the enduring neurobehavioral effects of early-life abuse. Two early-life abuse models were used: a naturalistic paradigm, where rat pups were reared by an abusive mother; and a more controlled paradigm, where pups underwent peppermint odor-shock conditioning that produces an artificial maternal odor through engagement of the attachment circuit. Animals were tested for maternal odor preference in infancy, forced swim test (FST), social behavior, and sexual motivation in adulthood-in the presence or absence of maternal odors (natural or peppermint). Amygdala odor-evoked local field potentials (LFPs) via wireless electrodes were also examined in response to the maternal odors in adulthood. Both early-life abuse models induced preference for the maternal odors in infancy. In adulthood, these early-life abuse models produced FST deficits and decreased social behavior, but did not change sexual motivation. Presentation of the maternal odors rescued FST and social behavior deficits induced by early-life abuse and enhanced sexual motivation in all animals. In addition, amygdala LFPs from both abuse animal models showed unique activation within the gamma frequency (70-90 Hz) bands in response to the specific maternal odor present during early-life abuse. These results suggest that attachment-related cues learned during infancy have a profound ability to rescue neurobehavioral dysregulation caused by early-life abuse. Paradoxically, abuse-associated cues seem to acquire powerful and enduring antidepressive properties and alter amygdala modulation.

The bonding and early life attachment between the infant and caregiver is a dynamic, bidirectional process involving caregiver nurturing of the infant, as well as complementary infant behavior that elicits parental care. Attachment appears to have a dual function. The first function is to ensure the infant remains close to the caregiver in order to receive necessary care for survival. Interestingly, animal research has shown that both nurturing and painful stimuli associated with the caregiver support attachment. Secondly, the quality of attachment and its associated sensory stimuli organize the brain to define the infant's cognitive and emotional development. Specifically, the patterning and quality of care regulate the infant's brain function and behavioral expression that determines long-term emotional regulation. These issues, presented within an historical view of infant attachment, highlight the importance of integrating human and animal research in understanding infant care.

We review recent findings related to the neurobiology of infant attachment, emphasizing the role of parenting quality in attachment formation and emotional development. Current findings suggest that the development of brain structures important for emotional expression and regulation (amygdala, prefrontal cortex, hippocampus) is deeply associated with the quality of care received in infancy, with sensitive caregiving providing regulation vital for programming these structures, ultimately shaping the development of emotion into adulthood. Evidence indicates that without sensitive caregiving, infants fail to develop mechanisms needed for later-life emotion and emotion regulation. Research suggests that a sensitive period exists in early life for parental shaping of emotional development, although further cross-species research is needed to discern its age limits, and thus inform interventions.

Children reared in impoverished environments are at risk for enduring psychological and physical health problems. Mechanisms by which poverty affects development, however, remain unclear. To explore one potential mechanism of poverty's impact on social-emotional and cognitive development, an experimental examination of a rodent model of scarcity-adversity was conducted and compared to results from a longitudinal study of human infants and families followed from birth (N = 1,292) who faced high levels of poverty-related scarcity-adversity. Cross-species results supported the hypothesis that altered caregiving is one pathway by which poverty adversely impacts development. Rodent mothers assigned to the scarcity-adversity condition exhibited decreased sensitive parenting and increased negative parenting relative to mothers assigned to the control condition. Furthermore, scarcity-adversity reared pups exhibited decreased developmental competence as indicated by disrupted nipple attachment, distress vocalization when in physical contact with an anesthetized mother, and reduced preference for maternal odor with corresponding changes in brain activation. Human results indicated that scarcity-adversity was inversely correlated with sensitive parenting and positively correlated with negative parenting, and that parenting fully mediated the association of poverty-related risk with infant indicators of developmental competence. Findings are discussed from the perspective of the usefulness of bidirectional-translational research to inform interventions for at-risk families.

Childhood maltreatment is associated with adverse brain development and later life psychiatric disorders, with maltreatment from the caregiver inducing a particular vulnerability to later life psychopathologies. Here we review two complementary rodent models of early life abuse, which are used to examine the infant response to trauma within attachment and the developmental trajectories that lead to later life neurobehavioral deficits. These rodent models include being reared with an abusive mother, and a more controlled attachment-learning paradigm using odor-shock conditioning to produce a new maternal odor. In both of these rodent models, pups learn a strong attachment and preference to the maternal odor. However, both models produce similar enduring neurobehavioral deficits, which emerge with maturation. Importantly, cues associated with our models of abuse serve as paradoxical safety signals, by normalizing enduring neurobehavioral deficits following abuse. Here we review these models and explore implications for human interventions for early life maltreatment.

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.

When animals and their offspring are threatened, parents switch from self-defense to offspring protection. How self-defense is suppressed remains elusive. We postulated that suppression of the self-defense response, freezing, is gated via oxytocin acting in the centro-lateral amygdala (CeL). We found that rat dams conditioned to fear an odor, froze when tested alone, whereas if pups were present, they remained in close contact with them or targeted the threat. Furthermore, blocking oxytocin signaling in the CeL prevented the suppression of maternal freezing. Finally, pups exposed to the odor in the presence of the conditioned dam later froze when re-exposed alone. However, if oxytocin signaling in the dam had been blocked, pups failed to learn. This study provides a functional role for the well-described action of oxytocin in the central amygdala, and demonstrates that self-defense suppression allows for active pup protection and mother-pup interactions crucial for pup threat learning.DOI: http://dx.doi.org/10.7554/eLife.24080.001

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.