Adult brain connectivity is shaped by the balance of sensory inputs in early life. In the case of pain pathways, it is less clear whether nociceptive inputs in infancy can have a lasting influence upon central pain processing and adult pain sensitivity. Here, we show that adult pain responses in the rat are 'primed' by tissue injury in the neonatal period. Rats that experience hind-paw incision injury at 3 days of age, display an increased magnitude and duration of hyperalgesia following incision in adulthood when compared with those with no early life pain experience. This priming of spinal reflex sensitivity was measured by both reductions in behavioural withdrawal thresholds and increased flexor muscle electromyographic responses to graded suprathreshold hind-paw stimuli in the 4 weeks following adult incision. Prior neonatal injury also 'primed' the spinal microglial response to adult injury, resulting in an increased intensity, spatial distribution and duration of ionized calcium-binding adaptor molecule-1-positive microglial reactivity in the dorsal horn. Intrathecal minocycline at the time of adult injury selectively prevented both the hyperalgesia and early microglial reactivity associated with prior neonatal injury. The enhanced neuroimmune response seen in neonatally primed animals could also be demonstrated in the absence of peripheral tissue injury by direct electrical stimulation of tibial nerve fibres, confirming that centrally mediated mechanisms contribute to these long-term effects. These data suggest that early life injury may predispose individuals to enhanced sensitivity to painful events.

Humans are fundamentally social creatures who are 'motivated' to be with others. In this review we examine the role of oxytocin (OT) as it relates to social motivation. OT is synthesized in the brain and throughout the body, including in the heart, thymus, gastrointestinal tract, as well as reproductive organs. The distribution of the OT receptor (OTR) system in both the brain and periphery is even more far-reaching and its expression is subject to changes over the course of development. OTR expression is also sensitive to changes in the external environment and the internal somatic world. The OT system functions as an important element within a complex, developmentally sensitive biobehavioral system. Other elements include sensory inputs, the salience, reward, and threat detection pathways, the hypothalamic-pituitary-gonadal axis, and the hypothalamic-pituitary-adrenal stress response axis. Despite an ever expanding scientific literature, key unresolved questions remain concerning the interplay of the central and peripheral components of this complex biobehavioral system that dynamically engages the brain and the body as humans interact with social partners over the course of development.

BACKGROUND Maternal-neonate separation (MNS) in mammals is a model for studying the effects of stress on the development and function of physiological systems. In contrast, for humans, MNS is a Western norm and standard medical practice. However, the physiological impact of this is unknown. The physiological stress-response is orchestrated by the autonomic nervous system and heart rate variability (HRV) is a means of quantifying autonomic nervous system activity. Heart rate variability is influenced by level of arousal, which can be accurately quantified during sleep. Sleep is also essential for optimal early brain development. METHODS To investigate the impact of MNS in humans, we measured HRV in 16 2-day-old full-term neonates sleeping in skin-to-skin contact with their mothers and sleeping alone, for 1 hour in each place, before discharge from hospital. Infant behavior was observed continuously and manually recorded according to a validated scale. Cardiac interbeat intervals and continuous electrocardiogram were recorded using two independent devices. Heart rate variability (taken only from sleep states to control for level of arousal) was analyzed in the frequency domain using a wavelet method. RESULTS Results show a 176% increase in autonomic activity and an 86% decrease in quiet sleep duration during MNS compared with skin-to-skin contact. CONCLUSIONS Maternal-neonate separation is associated with a dramatic increase in HRV power, possibly indicative of central anxious autonomic arousal. Maternal-neonate separation also had a profoundly negative impact on quiet sleep duration. Maternal separation may be a stressor the human neonate is not well-evolved to cope with and may not be benign.

The appearance of discontinuous network events and their transformation into continuous oscillatory activity are fundamental milestones in cortical circuit development. In this issue, Brockmann et al. demonstrate a protracted development of activity patterns in the prefrontal cortex in neonatal rats and a possible role for hippocampal theta bursts in the maturation of PFC connectivity.

Longitudinal effects of child maltreatment on cortisol regulation in infants from age 1 to 3 years were investigated in the context of a randomized preventive intervention trial. Thirteen-month-old infants from maltreating families (N = 91) and their mothers were randomly assigned to one of three intervention conditions: child-parent psychotherapy, psychoeducational parenting intervention, and a control group involving standard community services (CS). A fourth group of infants from nonmaltreating families (N = 52) and their mothers comprised a nonmaltreated comparison (NC) group. The two active interventions were combined into one maltreated intervention (MI) group for statistical analyses. Saliva samples were obtained from children at 10:00 a.m. before beginning a laboratory observation session with their mothers when the children were 13 months of age (preintervention), 19 months (midintervention), 26 months (postintervention), and 38 months (1-year postintervention follow-up). At the initial assessment, no significant differences among groups in morning cortisol were observed. Latent growth curve analyses examined trajectories of cortisol regulation over time. Beginning at midintervention, divergence was found among the groups. Whereas the MI group remained indistinguishable from the NC group across time, the CS group progressively evinced lower levels of morning cortisol, statistically differing from the MI and NC groups. Results highlight the value of psychosocial interventions for early child maltreatment in normalizing biological regulatory processes.

That the fear and stress of life-threatening experiences can leave an indelible trace on the brain is most clearly exemplified by post-traumatic stress disorder (PTSD). Many researchers studying the animal model of PTSD have adopted utilizing exposure to a predator as a life-threatening psychological stressor, to emulate the experience in humans, and the resulting body of literature has demonstrated numerous long-lasting neurological effects paralleling those in PTSD patients. Even though much more extreme, predator-induced fear and stress in animals in the wild was, until the 1990s, not thought to have any lasting effects, whereas recent experiments have demonstrated that the effects on free-living animals are sufficiently long-lasting to even affect reproduction, though the lasting neurological effects remain unexplored. We suggest neuroscientists and ecologists both have much to gain from collaborating in studying the neurological effects of predator-induced fear and stress in animals in the wild. We outline the approaches taken in the lab that appear most readily translatable to the field, and detail the advantages that studying animals in the wild can offer researchers investigating the "predator model of PTSD."