Sensitive Periods Of Development Research Articles

Transient exposure to ethanol during zebrafish embryogenesis results in defects in neuronal differentiation: an alternative model system to study FASD.

BackgroundThe exposure of the human embryo to ethanol results in a spectrum of disorders involving multiple organ systems, including the impairment of the development of the central nervous system (CNS). In spite of the importance for human health, the molecular basis of prenatal ethanol exposure remains poorly understood, mainly to the difficulty of sample collection. Zebrafish is now emerging as a powerful organism for the modeling and the study of human diseases. In this work, we have assessed the sensitivity of specific subsets of neurons to ethanol exposure during embryogenesis and we have visualized the sensitive embryonic developmental periods for specific neuronal groups by the use of different transgenic zebrafish lines.Methodology/Principal FindingsIn order to evaluate the teratogenic effects of acute ethanol exposure, we exposed zebrafish embryos to ethanol in a given time window and analyzed the effects in neurogenesis, neuronal differentiation and brain patterning. Zebrafish larvae exposed to ethanol displayed small eyes and/or a reduction of the body length, phenotypical features similar to the observed in children with prenatal exposure to ethanol. When neuronal populations were analyzed, we observed a clear reduction in the number of differentiated neurons in the spinal cord upon ethanol exposure. There was a decrease in the population of sensory neurons mainly due to a decrease in cell proliferation and subsequent apoptosis during neuronal differentiation, with no effect in motoneuron specification.ConclusionOur investigation highlights that transient exposure to ethanol during early embryonic development affects neuronal differentiation although does not result in defects in early neurogenesis. These results establish the use of zebrafish embryos as an alternative research model to elucidate the molecular mechanism(s) of ethanol-induced developmental toxicity at very early stages of embryonic development.

Programming of formalin-induced nociception by neonatal LPS exposure: Maintenance by peripheral and central neuroimmune activity

The immune and nociceptive systems are shaped during the neonatal period where they undergo fine-tuning and maturation. Painful experiences during this sensitive period of development are known to produce long-lasting effects on the immune and nociceptive responses. It is less clear, however, whether inflammatory pain responses are primed by neonatal exposure to mild immunological stimuli, such as with lipopolysaccharide (LPS). Here, we examine the impact of neonatal LPS exposure on inflammatory pain responses, peripheral and hippocampal interleukin-1β (IL-1β), as well as mast cell number and degranulation in preadolescent and adult rats. Wistar rats were injected with LPS (0.05mg/kg IP, Salmonella enteritidis) or saline on postnatal days (PNDs) 3 and 5 and later subjected to the formalin test at PNDs 22 and 80-97. At both time-points, and one-hour after formalin injection, blood and hippocampus were collected for measuring circulating and central IL-1β levels using ELISA and Western blot, respectively. Paw tissue was also isolated to assess mast cell number and degree of degranulation using Toluidine Blue staining. Behavioural analyses indicate that at PND 22, LPS-challenged rats displayed enhanced flinching (p<.01) and licking (p<.01) in response to formalin injection. At PNDs 80-97, LPS-challenged rats exhibited increased flinching (p<.05), an effect observed in males only. Furthermore, neonatal LPS exposure enhanced circulating IL-1β and mast cell degranulation in preadolescent but not adult rats following formalin injection. Hippocampal IL-1β levels were increased in LPS-treated adult but not preadolescent rats in response to formalin injection. These data suggest neonatal LPS exposure produces developmentally regulated changes in formalin-induced behavioural responses, peripheral and central IL-1β levels, as well as mast cell degranulation following noxious stimulation later in life. These findings highlight the importance of immune activation during the neonatal period in shaping immune response and pain sensitivity later in life. This is of clinical relevance given the high prevalence of bacterial infection during the neonatal period, particularly in the vulnerable population of preterm infants admitted to neonatal intensive care units.

The effects of child maltreatment on the developing brain.

Lasting effects of child abuse and neglect are well recognised. Apart from physical effects resulting from injuries and neglect, the effects are on behaviour, emotional well-being, interpersonal relationships and cognitive functioning. These psychological aspects are now known to have their counterparts in brain structure, chemistry and function. The growing knowledge of brain development has shed new light on our understanding of the processes by which especially early abuse and neglect may have a profound effect on the child's later adjustment. The brain undergoes its greatest growth and development in the first years of life, (with a second phase in adolescence). While the sequence of development within the brain is genetically determined, the nature of this development is determined to a considerable extent on the young child's experiences. The absence of some experiences, such as extreme deprivation during sensitive periods of development may mean that certain functions will not develop. For most functions, the nature of experience will shape brain development. Negative experiences and certain ways of interaction will be incorporated into the brain's connectivity. While learning and new experiences continue throughout life, and their effects continue to be incorporated into brain structure and functioning, previous patterns cannot be erased, only added on to and more slowly. As we know from our adult experiences, learning is far faster in childhood. A further aspect of child maltreatment which has a profound effect on brain development is the significant neurobiological stress which the young, maltreated, child experiences. It is interesting to learn that secure attachment organisation protects the developing brain from the worst effects of the stress response. The effects of the experiences interact with the child's genetic resilience or vulnerability.

Adolescent but not adult-born neurons are critical for susceptibility to chronic social defeat

Recent evidence implicates adult hippocampal neurogenesis in regulating behavioral and physiologic responses to stress. Hippocampal neurogenesis occurs across the lifespan, however the rate of cell birth is up to 300% higher in adolescent mice compared to adults. Adolescence is a sensitive period in development where emotional circuitry and stress reactivity undergo plasticity establishing life-long set points. Therefore neurogenesis occurring during adolescence may be particularly important for emotional behavior. However, little is known about the function of hippocampal neurons born during adolescence. In order to assess the contribution of neurons born in adolescence to the adult stress response and depression-related behavior, we transiently reduced cell proliferation either during adolescence, or during adulthood in GFAP-Tk mice. We found that the intervention in adolescence did not change adult baseline behavioral response in the forced swim test, sucrose preference test or social affiliation test, and did not change adult corticosterone responses to an acute stressor. However following chronic social defeat, adult mice with reduced adolescent neurogenesis showed a resilient phenotype. A similar transient reduction in adult neurogenesis did not affect depression-like behaviors or stress induced corticosterone. Our study demonstrates that hippocampal neurons born during adolescence, but not in adulthood are important to confer susceptibility to chronic social defeat.

Development of echolocation calls and neural selectivity for echolocation calls in the pallid bat.

Studies of birdsongs and neural selectivity for songs have provided important insights into principles of concurrent behavioral and auditory system development. Relatively little is known about mammalian auditory system development in terms of vocalizations or other behaviorally relevant sounds. This review suggests echolocating bats are suitable mammalian model systems to understand development of auditory behaviors. The simplicity of echolocation calls with known behavioral relevance and strong neural selectivity provides a platform to address how natural experience shapes cortical receptive field (RF) mechanisms. We summarize recent studies in the pallid bat that followed development of echolocation calls and cortical processing of such calls. We also discuss similar studies in the mustached bat for comparison. These studies suggest: (1) there are different developmental sensitive periods for different acoustic features of the same vocalization. The underlying basis is the capacity for some components of the RF to be modified independent of others. Some RF computations and maps involved in call processing are present even before the cochlea is mature and well before use of echolocation in flight. Others develop over a much longer time course. (2) Normal experience is required not just for refinement, but also for maintenance, of response properties that develop in an experience independent manner. (3) Experience utilizes millisecond range changes in timing of inhibitory and excitatory RF components as substrates to shape vocalization selectivity. We suggest that bat species and call diversity provide a unique opportunity to address developmental constraints in the evolution of neural mechanisms of vocalization processing.

Postnatal overfeeding promotes early onset and exaggeration of high-fat diet-induced nonalcoholic fatty liver disease through disordered hepatic lipid metabolism in rats

Exposure to overnutrition in critical or sensitive developmental periods may increase the risk of developing obesity and metabolic syndrome in adults. Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome, but the relationship among postnatal nutrition, lipid metabolism, and NAFLD progression during development remains poorly understood. Here we investigated in a rat model whether postnatal overfeeding increases susceptibility to NAFLD in response to a high-fat diet. Litters from Sprague-Dawley dams were culled to three (small litters) or ten (normal litters) pups and then weaned onto a standard or high-fat diet at postnatal day 21 to generate normal-litter, small-litter, normal-litter/high-fat, and small-litter/high-fat groups. At age 16weeks, the small-litter and both high-fat groups showed obesity, dyslipidemia, and insulin resistance. Hepatic disorders appeared earlier in the small-litter/high-fat rats with greater liver mass gain and higher hepatic triglycerides and steatosis score versus normal-litter/high-fat rats. Hepatic acetyl-CoA carboxylase activity and mRNA expression were increased in small-litter rats and aggravated in small-litter/high-fat rats but not in normal-litter/high-fat rats. The high expression in small-litter/high-fat rats coincided with high sterol regulatory element-binding protein-1c mRNA and protein expression. However, mRNA expression of enzymes involved in hepatic fatty acid oxidation (carnitine palmitoyltransferase 1) and output (microsomal triglyceride transfer protein) was decreased under a high-fat diet regardless of litter size. In conclusion, overfeeding related to small-litter rearing during lactation contributes to the NAFLD phenotype when combined with a high-fat diet, possibly through up-regulated hepatic lipogenesis.

Vocal motor changes beyond the sensitive period for song plasticity.

Behavior is critically shaped during sensitive periods in development. Birdsong is a learned vocal behavior that undergoes dramatic plasticity during a sensitive period of sensorimotor learning. During this period, juvenile songbirds engage in vocal practice to shape their vocalizations into relatively stereotyped songs. By the time songbirds reach adulthood, their songs are relatively stable and thought to be "crystallized." Recent studies, however, highlight the potential for adult song plasticity and suggest that adult song could naturally change over time. As such, we investigated the degree to which temporal and spectral features of song changed over time in adult Bengalese finches. We observed that the sequencing and timing of song syllables became more stereotyped over time. Increases in the stereotypy of syllable sequencing were due to the pruning of infrequently produced transitions and, to a lesser extent, increases in the prevalence of frequently produced transitions. Changes in song tempo were driven by decreases in the duration and variability of intersyllable gaps. In contrast to significant changes to temporal song features, we found little evidence that the spectral structure of adult song syllables changed over time. These data highlight differences in the degree to which temporal and spectral features of adult song change over time and support evidence for distinct mechanisms underlying the control of syllable sequencing, timing, and structure. Furthermore, the observed changes to temporal song features are consistent with a Hebbian framework of behavioral plasticity and support the notion that adult song should be considered a form of vocal practice.

Naturalistic rodent models of chronic early-life stress.

A close association between early-life experience and cognitive and emotional outcomes is found in humans. In experimental models, early-life experience can directly influence a number of brain functions long-term. Specifically, and often in concert with genetic background, experience regulates structural and functional maturation of brain circuits and alters individual neuronal function via large-scale changes in gene expression. Because adverse experience during sensitive developmental periods is often associated with neuropsychiatric disease, there is an impetus to create realistic models of distinct early-life experiences. These can then be used to study causality between early-life experiential factors and cognitive and emotional outcomes, and to probe the underlying mechanisms. Although chronic early-life stress has been linked to the emergence of emotional and cognitive disorders later in life, most commonly used rodent models of involve daily maternal separation and hence intermittent early-life stress. We describe here a naturalistic and robust chronic early-life stress model that potently influences cognitive and emotional outcomes. Mice and rats undergoing this stress develop structural and functional deficits in a number of limbic-cortical circuits. Whereas overt pathological memory impairments appear during adulthood, emotional and cognitive vulnerabilities emerge already during adolescence. This naturalistic paradigm, widely adopted around the world, significantly enriches the repertoire of experimental tools available for the study of normal brain maturation and of cognitive and stress-related disorders including depression, autism, post-traumatic stress disorder, and dementia.

Transient inactivation of the ventral hippocampus in neonatal rats impairs the mesolimbic regulation of prefrontal glutamate release in adulthood

Cognitive deficits in schizophrenia (SZ) reflect maturational disruptions within a neural system that includes the ventral hippocampus (VH), nucleus accumbens (NAc), basal forebrain, and prefrontal cortex (PFC). A better understanding of these changes may reveal drug targets for more efficacious cognition enhancers. We have utilized an animal model in which the above distributed system is altered, during a sensitive period of development, by transiently inactivating the VH and its efferent projections. We determined the ability of NAc shell activation to evoke prefrontal glutamate release in adult male Wistar rats that had received saline (Sal) or tetrodotoxin (TTX) as neonates (PD7) or as adolescents (PD32). The nucleus accumbens shell (NAcSh) was activated by NMDA infusions (0.05–0.30 μg/0.5 μL). Basal and evoked glutamate levels were measured amperometrically using a glutamate-sensitive microelectrode. There were no differences in basal glutamate levels among the groups tested (overall 1.41 ± 0.26 uM). However, the dose-related stimulation of prefrontal glutamate levels seen in control rats treated with saline on PD7 (4.31 ± 0.22 μM after 0.15 μg) was markedly attenuated in rats treated with TTX on PD7 (0.45 ± 0.12 μM after 0.15 μg). This effect was age-dependent as infusions of TTX on PD32 did not alter the NMDA-induced increases in glutamate release (4.10 ± 0.37 μM after 0.15 μg). Collectively, these findings reveal that transient inactivation of VH transmission, during a sensitive period of development, leads to a functional mesolimbic-cortical disconnection that produces neurochemical and ultimately cognitive impairments resembling those seen in SZ.

Sensitive periods of amygdala development: The role of maltreatment in preadolescence

The amygdala is vulnerable to stress-dependent disruptions in neural development. Animal models have shown that stress increases dendritic arborization leading to larger amygdala volumes. Human studies of early stress and amygdala volume, however, remain inconclusive. This study compared amygdala volume in adults with childhood maltreatment to that in healthy controls. Eighteen participants from a longitudinal cohort and 33 cross-sectional controls (17 M/34 F, 25.5±3.1years) completed a structural magnetic resonance imagining scan and the Maltreatment and Abuse Chronology of Exposure scale. Random forest regression with conditional trees was used to assess relative importance of exposure to adversity at each age on amygdala, thalamic or caudate volume. Severity of exposure to adversity across age accounted for 27% of the variance in right amygdala volume. Peak sensitivity occurred at 10–11years of age, and importance of exposure at this time was highly significant based on permutation tests (p=0.003). The regression model showed that exposure during this sensitive period resulted in steep dose–response function with maximal response to even modest levels of exposure. Subjects in the highest exposure quartile (MACE-11, range=11–54) had a 9.1% greater right amygdala volume than subjects in the lowest exposure quartile (MACE-11, ≤3.5). No associations emerged between age of exposure and volume of the left amygdala or bilateral caudate or thalamus. Severity of adversity experienced at age 10–11 contributed to larger right but not left amygdala volume in adulthood. Results provide preliminary evidence that the amygdala may have a developmental sensitive period in preadolescence.

Development of neural responsivity to vocal sounds in higher level auditory cortex of songbirds.

Like humans, songbirds learn vocal sounds from "tutors" during a sensitive period of development. Vocal learning in songbirds therefore provides a powerful model system for investigating neural mechanisms by which memories of learned vocal sounds are stored. This study examined whether NCM (caudo-medial nidopallium), a region of higher level auditory cortex in songbirds, serves as a locus where a neural memory of tutor sounds is acquired during early stages of vocal learning. NCM neurons respond well to complex auditory stimuli, and evoked activity in many NCM neurons habituates such that the response to a stimulus that is heard repeatedly decreases to approximately one-half its original level (stimulus-specific adaptation). The rate of neural habituation serves as an index of familiarity, being low for familiar sounds, but high for novel sounds. We found that response strength across different song stimuli was higher in NCM neurons of adult zebra finches than in juveniles, and that only adult NCM responded selectively to tutor song. The rate of habituation across both tutor song and novel conspecific songs was lower in adult than in juvenile NCM, indicating higher familiarity and a more persistent response to song stimuli in adults. In juvenile birds that have memorized tutor vocal sounds, neural habituation was higher for tutor song than for a familiar conspecific song. This unexpected result suggests that the response to tutor song in NCM at this age may be subject to top-down influences that maintain the tutor song as a salient stimulus, despite its high level of familiarity.

Commentary: Paternal and maternal influences on offspring phenotype: the same, only different

Commentary: Paternal and maternal influences on offspring phenotype: the same, only different

Functional Connectivity Density in Congenitally and Late Blind Subjects

Visual deprivation during different developmental periods leads to different structural and functional alterations in the brain; however, the effects of visual deprivation on the spontaneous functional organization of the brain remain largely unknown. In this study, we used voxel-based functional connectivity density (FCD) analyses to investigate the effects of visual deprivation during different developmental periods on the spontaneous functional organization of the brain. Compared with the sighted controls (SC), both the congenitally blind (CB) and the late blind (LB) exhibited decreased short- and long-range FCDs in the primary visual cortex (V1) and decreased long-range FCDs in the primary somatosensory and auditory cortices. Although both the CB and LB exhibited increased short-range FCD in the dorsal visual stream, the CB exhibited greater increases in the short- and long-range FCDs in the ventral visual stream and hippocampal complex compared with the LB. Moreover, the short-range FCD of the left V1 exhibited a significant positive correlation with the duration of blindness in the LB. Our findings suggest that visual deprivation before the developmental sensitive period can induce more extensive brain functional reorganization than does visual deprivation after the sensitive period, which may underlie an enhanced capacity for processing nonvisual information in the CB.

Reinforcement sensitivity, sensation seeking, and counter-productive behaviour at secondary schools

Behavioural approach and behavioural inhibition as well as sensation seeking have been postulated important determinants of impulsive and risky decision making, or, the pursuit of long-term goals. Adolescence has been described a particularly sensitive developmental period, as an imbalance of these factors may result in risk-taking and counter-productive behaviour. In the current study, we assessed sensitivity to reward, sensitivity to punishment, and sensation-seeking in a cross-sectional sample of adolescents at secondary schools. The battery also included experimental paradigms to assess different forms delay and probability discounting, risk-taking behaviour and gambling as well as a capacity measure of intelligence. As outcome variables, we assessed counter-productive behaviour, substance consumption, and scholastic achievement. The presentation will focus on an imbalance of motivational approach and avoidance tendencies as predictors of risk-taking behaviour and will end with a brief discussion of the behavioural paradigms.

Dopamine and serotonin signaling during two sensitive developmental periods differentially impact adult aggressive and affective behaviors in mice

Pharmacologic blockade of monoamine oxidase A (MAOA) or serotonin transporter (5-HTT) has antidepressant and anxiolytic efficacy in adulthood. Yet, genetically conferred MAOA or 5-HTT hypoactivity is associated with altered aggression and increased anxiety/depression. Here we test the hypothesis that increased monoamine signaling during development causes these paradoxical aggressive and affective phenotypes. We find that pharmacologic MAOA blockade during early postnatal development (P2-P21) but not during peri-adolescence (P22-41) increases anxiety- and depression-like behavior in adult (>P90) mice, mimicking the effect of P2-21 5-HTT inhibition. Moreover, MAOA blockade during peri-adolescence, but not P2-21 or P182-201, increases adult aggressive behavior, and 5-HTT blockade from P22-P41 reduced adult aggression. Blockade of the dopamine transporter, but not the norepinephrine transporter, during P22-41 also increases adult aggressive behavior. Thus, P2-21 is a sensitive period during which 5-HT modulates adult anxiety/depression-like behavior, and P22-41 is a sensitive period during which DA and 5-HT bi-directionally modulate adult aggression. Permanently altered DAergic function as a consequence of increased P22-P41 monoamine signaling might underlie altered aggression. In support of this hypothesis, we find altered aggression correlating positively with locomotor response to amphetamine challenge in adulthood. Proving that altered DA function and aggression are causally linked, we demonstrate that optogenetic activation of VTA DAergic neurons increases aggression. It therefore appears that genetic and pharmacologic factors impacting dopamine and serotonin signaling during sensitive developmental periods can modulate adult monoaminergic function and thereby alter risk for aggressive and emotional dysfunction.

Remodelling at the calyx of Held–MNTB synapse in mice developing with unilateral conductive hearing loss

Structure and function of central synapses are profoundly influenced by experience during developmental sensitive periods. Sensory synapses, which are the indispensable interface for the developing brain to interact with its environment, are particularly plastic. In the auditory system, moderate forms of unilateral hearing loss during development are prevalent but the pre- and postsynaptic modifications that occur when hearing symmetry is perturbed are not well understood. We investigated this issue by performing experiments at the large calyx of Held synapse. Principal neurons of the medial nucleus of the trapezoid body (MNTB) are innervated by calyx of Held terminals that originate from the axons of globular bushy cells located in the contralateral ventral cochlear nucleus. We compared populations of synapses in the same animal that were either sound deprived (SD) or sound experienced (SE) after unilateral conductive hearing loss (CHL). Middle ear ossicles were removed 1week prior to hearing onset (approx. postnatal day (P) 12) and morphological and electrophysiological approaches were applied to auditory brainstem slices taken from these mice at P17-19. Calyces in the SD and SE MNTB acquired their mature digitated morphology but these were structurally more complex than those in normal hearing mice. This was accompanied by bilateral decreases in initial EPSC amplitude and synaptic conductance despite the CHL being unilateral. During high-frequency stimulation, some SD synapses displayed short-term depression whereas others displayed short-term facilitation followed by slow depression similar to the heterogeneities observed in normal hearing mice. However SE synapses predominantly displayed short-term facilitation followed by slow depression which could be explained in part by the decrease in release probability. Furthermore, the excitability of principal cells in the SD MNTB had increased significantly. Despite these unilateral changes in short-term plasticity and excitability, heterogeneities in the spiking fidelity among the population of both SD and SE synapses showed similar continuums to those in normal hearing mice. Our study suggests that preservations in the heterogeneity in spiking fidelity via synaptic remodelling ensures symmetric functional stability which is probably important for retaining the capability to maximally code sound localization cues despite moderate asymmetries in hearing experience.

Показники силової витривалості школярів різних медичних груп

Purpose: to found the peculiarities of the natural development of certain physical properties of middle school age students of various medical groups. Material: the testing conducted in 1414 16 students of secondary schools in Ukraine secondary school age (10-16 years), including 761 youth, 653 girls. Results: a period of accelerating the development of strength endurance of the abdominal muscles of students was founded. With a decrease in the level of health a sensitive period of development of an effective strength endurance gradually shifted to 1–2 years. Conclusions: periods of accelerating the development of strength endurance in children with poor health were already, the growth rate is significantly lower than in healthy peers.

Body Mass Index and Height From Infancy to Adulthood and Carotid Intima-Media Thickness at 60 to 64 Years in the 1946 British Birth Cohort Study

Atherosclerosis begins early in life and obesity is a key determinant. We investigated the role of body mass index (BMI) and height from infancy to adulthood in presenting with high adulthood carotid intima-media thickness. Odds ratios of BMI, and height Z scores at 2, 4, 6, 7, 11, 15, and 20 years, and changes between 2 and 4, 4 and 7, 7 and 15, and 15 and 20 years, for carotid intima-media thickness at 60 to 64 years in the upper quartile were estimated for 604 men and 669 women. Confounding by early-life environments, mediating by body size and cardiometabolic measures at 60 to 64 years, and effect modification were investigated. In men, there was positive association of BMI at 4 years (odds ratio, 1.256; 95% confidence interval, 1.026-1.538) and 20 years (1.282; 1.022-1.609), negative association of height at 4 years (0.780; 0.631-0.964), and negative association of height growth between 2 and 4 years (0.698; 0.534-0.913) with high carotid intima-media thickness. The childhood estimates were robust, but the estimate for BMI at 20 years was attenuated by adjustment for BMI at 60 to 64 years. The protective influence of greater early childhood height was strongest in those with the lowest systolic blood pressure at 60 to 64 years. In women, there was no pattern of association and all confidence intervals crossed 1. Early childhood in men might be a sensitive developmental period for atherosclerosis, in which changes in BMI and height represent 2 distinct biological mechanisms. The maintenance of healthy weight in men from adolescence onward may be a useful strategy to avoid the atherosclerotic complications of adiposity tracking.

Stress and the healthy adolescent brain: Evidence for the neural embedding of life events

Little is known about the long-term neural consequences of adverse life events for healthy adolescents, and this is particularly the case for events that occur after a putative stress-sensitive period in early childhood. In this functional magnetic resonance imaging study of healthy adolescents, we found that prior exposure to severe adverse life events was associated with current anxiety and with increased amygdala reactivity to standardized emotional stimuli (viewing of fearful faces relative to calm ones). Conjunction analyses identified multiple regions, including the amygdala, insula, and prefrontal cortex, in which reactivity to emotional faces covaried with life events as well as with current anxiety. Our morphometric analyses suggest systemic alterations in structural brain development with an association between anxiety symptoms and global gray matter volume. No life events were reported for the period before 4 years of age, suggesting that these results were not driven by exposure to stress during an early sensitive period in development. Overall, these data suggest systemic effects of traumatic events on the dynamically developing brain that are present even in a nonclinical sample of adolescents.

Programming Physical Activity in Young Infants At-Risk for Early Onset of Obesity

The purpose of this article is to discuss the growing problem of very early onset of obesity occurring before two years of age and to review infant motor development, physical activity, and effective pediatric disability motor interventions that may offer potential strategies to help reduce this growing problem earlier in life. Based on the review of physical activity interventions used with infants with a disability, we will propose strategies to consider to program early physical activity exposures into nondisabled young infants who are at risk for obesity. These proposed physical activity strategies will need to be combined with successful public health approaches to reducing early onset of obesity during infancy. Lucas (1991) conceived the termprogrammingreferring to permanent or extended effects of an environmental exposure occurring during a sensitive developmental period. In this paper, we propose that a very sensitive period for early onset of obesity is the first six months of postnatal life. If innovative strategies to increase the frequency of daily exposures to physical activity in young infants can be identified, these strategies could be combined with current public health approaches to preventing obesity in women before, during, and following pregnancy. Given the complexity of the obesity problem, no single strategy for prevention should be expected to be very successful.