Neuromuscular Maturation Research Articles

Slow development of vocal sequences through ontogeny in wild chimpanzees (Pan troglodytes verus).

The development of the unique, hierarchical, and endless combinatorial capacity in a human language requires neural maturation and learning through childhood. Compared with most non-human primates, where combinatorial capacity seems limited, chimpanzees present a complex vocal system comprising hundreds of vocal sequences. We investigated how such a complex vocal system develops and the processes involved. We recorded 10,929 vocal utterances of 98 wild chimpanzees aged 0-55 years, from Taï National Park, Ivory Coast. We developed customized Generalized non-Linear Models to estimate the ontogenetic trajectory of four structural components of vocal complexity: utterance length, diversity, probability of panting (requiring phonation across inhalation and exhalation), and probability of producing two adjacent panted units. We found chimpanzees need 10 years to reach adult levels of vocal complexity. In three variables, the steepest increase coincided with the age of first non-kin social interactions (2-5 years), and plateaued in sub-adults (8-10 years), as individuals integrate into adult social life. Producing two adjacent panted units may require more neuromuscular coordination of the articulators, as its emergence and steepest increase appear later in development. These results suggest prolonged maturational processes beyond those hitherto thought likely in species that do not learn their vocal repertoire. Our results suggest that multifaceted ontogenetic processes drive increases in vocal structural complexity in chimpanzees, particularly increases in social complexity and neuro-muscular maturation. As humans live in a complex social world, empirical support for the "social complexity hypothesis" may have relevance for theories of language evolution. RESEARCH HIGHLIGHTS: Chimpanzees need around 10 years to develop the vocal structural complexity present in the adult repertoire, way beyond the age of emergence of every single vocal unit. Multifaceted ontogenetic processes may drive increases in vocal structural complexity in chimpanzees, particularly increases in social complexity and neuro-muscular maturation. Non-linear increases in vocal complexity coincide with social developmental milestones. Vocal sequences requiring rapid articulatory change emerge later than other vocal sequences, suggesting neuro-muscular maturational processes continue through the juvenile years.

Trabecular bone ontogeny tracks neural development and life history among humans and non-human primates

Trabecular bone-the spongy bone inside marrow cavities-adapts to its mechanical environment during growth and development. Trabecular structure can therefore be interpreted as a functional record of locomotor behavior in extinct vertebrates. In this paper, we expand upon traditional links between form and function by situating ontogenetic trajectories of trabecular bone in four primate species into the broader developmental context of neural development, locomotor control, and ultimately life history. Our aim is to show that trabecular bone structure provides insights into ontogenetic variation in locomotor loading conditions as the product of interactions between increases in body mass and neuromuscular maturation.Our results demonstrate that age-related changes in trabecular bone volume fraction (BV/TV) are strongly and linearly associated with ontogenetic changes in locomotor kinetics. Age-related variation in locomotor kinetics and BV/TV is in turn strongly associated with brain and body size growth in all species. These results imply that age-related variation in BV/TV is a strong proxy for both locomotor kinetics and neuromuscular maturation. Finally, we show that distinct changes in the slope of age-related variation in bone volume fraction correspond to the age of the onset of locomotion and the age of locomotor maturity.Our findings compliment previous studies linking bone development to locomotor mechanics by providing a fundamental link to brain development and life history. This implies that trabecular structure of fossil subadults can be a proxy for the rate of neuromuscular maturation and major life history events like locomotor onset and the achievement of adult-like locomotor repertoires.

Growth and development of trabecular structure in the calcaneus of Japanese macaques (Macaca fuscata) reflects locomotor behavior, life history, and neuromuscular development.

Bone structure dynamically adapts to its mechanical environment throughout ontogeny by altering the structure of trabecular bone, the three‐dimensional mesh‐like structure found underneath joint surfaces. Trabecular structure, then, can provide a record of variation in loading directions and magnitude; and in ontogenetic samples, it can potentially be used to track developmental shifts in limb posture. We aim to broaden the analysis of trabecular bone ontogeny by incorporating interactions between ontogenetic variation in locomotor repertoire, neuromuscular maturation, and life history. We examine the associations between these variables and age‐related variation in trabecular structure in the calcaneus of Japanese macaques (Macaca fuscata). We used high‐resolution micro‐computed tomography scanning to image the calcaneus in a cross‐sectional sample of 34 juvenile M. fuscata aged between 0 and 7 years old at the Primate Research Institute, Japan. We calculated whole bone averages of standard trabecular properties and generated whole‐bone morphometric maps of bone volume fraction and Young’s modulus. Trabecular structure becomes increasingly heterogeneous in older individuals. Bone volume fraction (BV/total volume [TV]) decreases during the first month of life and increases afterward, coinciding with the onset of independent locomotion in M. fuscata. At birth, primary Young’s modulus is oriented orthogonal to the ossification center, but after locomotor onset bone structure becomes stiffest in the direction of joint surfaces and muscle attachments. Age‐related variation in bone volume fraction is best predicted by an interaction between the estimated percentage of adult brain size, body mass, and locomotor onset. To explain our findings, we propose a model where interactions between age‐related increases in body weight and maturation of the neuromuscular system alter the loading environment of the calcaneus, to which the internal trabecular structure dynamically adapts. This model cannot be directly tested based on our cross‐sectional data. However, confirmation of the model by longitudinal experiments and in multiple species would show that trabecular structure can be used both to infer behavior from fossil morphology and serve as a valuable proxy for neuromuscular maturation and life history events like locomotor onset and the achievement of an adult‐like gait. This approach could significantly expand our knowledge of the biology and behavior of fossil species.

Emergence of Different Gaits in Infancy: Relationship Between Developing Neural Circuitries and Changing Biomechanics.

How does gait-specific pattern generation evolve in early infancy? The idea that neural and biomechanical mechanisms underlying mature walking and running differ to some extent and involve distinct spinal and supraspinal neural circuits is supported by various studies. Here we consider the issue of human gaits from the developmental point of view, from neonate stepping to adult mature gaits. While differentiating features of the walk and run are clearly distinct in adults, the gradual and progressive developmental bifurcation between the different gaits suggests considerable sharing of circuitry. Gaits development and their biomechanical determinants also depend on maturation of the musculoskeletal system. This review outlines the possible overlap in the neural and biomechanical control of walking and running in infancy, supporting the idea that gaits may be built starting from common, likely phylogenetically conserved elements. Bridging connections between movement mechanics and neural control of locomotion could have profound clinical implications for technological solutions to understand better locomotor development and to diagnose early motor deficits. We also consider the neuromuscular maturation time frame of gaits resulting from active practice of locomotion, underlying plasticity of development.

Neuromuscular maturation in the neonate: Combined electroneurographic and ultrasonographic study

BackgroundThe combined electroneurography and muscle ultrasound examination (ENG-USM) in adult patients showed a correlation between the compound motor action potential (CMAP) and muscular thicknesses (MT). No similar studies exist regarding the neonatal period. AimTo evaluate the correlations between the maximum compound muscle action potential (CMAP) and maximum muscle thickness (MT) in term and premature newborns versus a group of young adults, as measured by combined electroneurography-ultrasonography (ENG-USM) to assess the stages. Study designObservational cohort study. SubjectsWe studied 36 subjects (14 premature and 11 term infants, and 11 young adults), who underwent ENG-USM of the tibialis anterioris (TA) muscle. Outcome measuresWe measured: 1) Onset-Peak (O-P) and Peak-to-Peak (P-P) maximum CMAP; 2) maximum MT; and 3) MT at the detected maximum CMAP. ResultsThe maximum CMAP in term newborns studied was about 1/3 of the mean value measured in the adults; the differences between O-P and P-P values of the term versus premature infants were not significant. We did not find a good correlation between maximum MT and maximum CMAP in the term (r = 0.63) newborns, contrary to what was found in preterms (r = 0.95) and in young adults (r = 0.98). ConclusionOur ENG-USM study shows that in newborns, the site of innervation of the neuromuscular plaque does not correspond to MT since muscle growth is related to the period of development, and depends on the progression of the nerve terminal branches that go to innervate the same muscle.

Clinical characteristics of premature infants who orally feed on continuous positive airway pressure

BackgroundBetween 32 and 34 weeks postconceptional age (PCA), premature infants typically achieve neuromuscular maturation to initiate the coordination of a nutritive suck triad. Many premature infants also require intubation, which has been associated with dysphagia in adults and infants. At our institution, despite these factors, some infants have been noted to tolerate oral feeds while on continuous positive airway pressure (CPAP). AimsCompare the clinical characteristics and duration of intubation in infants that initiate oral feedings on CPAP to infants that did not begin oral feeding on CPAP. Study designRetrospective case control study. SubjectsInfants with gestational age < 32 weeks who required CPAP at 32 weeks PCA. Outcome measuresOral feeding was defined as any oral feed ≥5 ml. Duration of intubation was defined as the number of intubated days prior to 32 weeks PCA. ResultsOf the 243 infants on CPAP at 32 weeks PCA, 31% (n = 76) began oral feeding on CPAP. Infants who initiated oral feeding on CPAP were of younger gestational age at birth (median 26 versus 27 weeks, p < 0.001) and remained intubated for longer (median 10.5 versus 2 days, p < 0.001). ConclusionsInfants who began oral feeding on CPAP had lower gestational age and longer duration of intubation than infants who started oral feeding off CPAP.

Skeletal Maturation, Body Size, and Motor Coordination in Youth 11-14 Years.

The objective of this study is to estimate the relative contribution of biological maturation to variance in the motor coordination (MC) among youth and to explore gender differences in the associations. Skeletal maturation (Tanner-Whitehouse 3), stature, body mass, and MC (Körperkoordinationstest für Kinder) were assessed in 613 youths, 284 boys and 329 girls 11-14 yr of age. Standardized residuals of skeletal age on chronological age were used as the estimate of skeletal maturity status independent of chronological age. Hierarchical multiple regression analyses were used to analyse associations between skeletal maturity status and MC. Skeletal maturity status by itself, i.e., standardized residuals of skeletal age on chronological age (step 3) explained a maximum of 8.1% of the variance in MC in boys (ΔR3 in the range of 0.0%-8.1%) and 2.8% of the variance in girls (ΔR3 in the range of 0.0%-2.8%), after controlling for stature, body mass and interactions of the standardized residuals of skeletal age on chronological age with stature and body mass. Corresponding percentages for the interactions of the standardized residuals of skeletal age and stature and body mass, after adjusting for stature and body mass (step 2) were 8.7% in boys (ΔR2 in the range of 0.3%-8.7%) and 7.1% in girls (ΔR2 in the range of 0.1%-7.1%). Chow tests suggested structural changes in β-coefficients in the four MC tests among boys and girls, 12-13 yr. The percentage of variance in the four MC tests explained by skeletal maturation was relatively small, but the relationships differed between boys and girls. By inference, other factors, e.g., neuromuscular maturation, specific instruction and practice, sport participation, and others may influence MC at these ages.

Gait Transitions in Human Infants: Coping with Extremes of Treadmill Speed.

Spinal pattern generators in quadrupedal animals can coordinate different forms of locomotion, like trotting or galloping, by altering coordination between the limbs (interlimb coordination). In the human system, infants have been used to study the subcortical control of gait, since the cerebral cortex and corticospinal tract are immature early in life. Like other animals, human infants can modify interlimb coordination to jump or step. Do human infants possess functional neuronal circuitry necessary to modify coordination within a limb (intralimb coordination) in order to generate distinct forms of alternating bipedal gait, such as walking and running? We monitored twenty-eight infants (7–12 months) stepping on a treadmill at speeds ranging between 0.06–2.36 m/s, and seventeen adults (22–47 years) walking or running at speeds spanning the walk-to-run transition. Six of the adults were tested with body weight support to mimic the conditions of infant stepping. We found that infants could accommodate a wide range of speeds by altering stride length and frequency, similar to adults. Moreover, as the treadmill speed increased, we observed periods of flight during which neither foot was in ground contact in infants and in adults. However, while adults modified other aspects of intralimb coordination and the mechanics of progression to transition to a running gait, infants did not make comparable changes. The lack of evidence for distinct walking and running patterns in infants suggests that the expression of different functional, alternating gait patterns in humans may require neuromuscular maturation and a period of learning post-independent walking.

Effects of Nitric Oxide on Neuromuscular Properties of Developing Zebrafish Embryos

Nitric oxide is a bioactive signalling molecule that is known to affect a wide range of neurodevelopmental processes. However, its functional relevance to neuromuscular development is not fully understood. Here we have examined developmental roles of nitric oxide during formation and maturation of neuromuscular contacts in zebrafish. Using histochemical approaches we show that elevating nitric oxide levels reduces the number of neuromuscular synapses within the axial swimming muscles whilst inhibition of nitric oxide biosynthesis has the opposite effect. We further show that nitric oxide signalling does not change synapse density, suggesting that the observed effects are a consequence of previously reported changes in motor axon branch formation. Moreover, we have used in vivo patch clamp electrophysiology to examine the effects of nitric oxide on physiological maturation of zebrafish neuromuscular junctions. We show that developmental exposure to nitric oxide affects the kinetics of spontaneous miniature end plate currents and impacts the neuromuscular drive for locomotion. Taken together, our findings implicate nitrergic signalling in the regulation of zebrafish neuromuscular development and locomotor maturation.

Gait selection and the ontogeny of quadrupedal walking in squirrel monkeys (Saimiri boliviensis)

Locomotor researchers have long known that adult primates employ a unique footfall sequence during walking. Most mammals use lateral sequence (LS) gaits, in which hind foot touchdowns are followed by ipsilateral forefoot touchdowns. In contrast, most quadrupedal primates use diagonal sequence (DS) gaits, in which hind foot touchdowns are followed by contralateral forefoot touchdowns. However, gait selection in immature primates is more variable, with infants and juveniles frequently using LS gaits either exclusively or in addition to DS gaits. I explored the developmental bases for this phenomenon by examining the ontogeny of gait selection in juvenile squirrel monkeys walking on flat and simulated arboreal substrates (i.e., a raised pole). Although DS gaits predominated throughout development, the juvenile squirrel monkeys nonetheless utilized LS gaits in one-third of the ground strides and in one-sixth of pole strides. Multiple logistic regression analyses showed that gait selection within the juvenile squirrel monkey sample was not significantly associated with either age or body mass per se, arguing against the oft-cited argument that general neuromuscular maturation is responsible for ontogenetic changes in preferred footfall sequence. Rather, lower level biomechanical variables, specifically the position of the whole-body center of mass and the potential for interference between ipsilateral fore and hindlimbs, best explained variation in footfall patterns. Overall, results demonstrate the promise of developmental studies of growth and locomotor development to serve as "natural laboratories" in which to explore how variability in morphology is, or is not, associated with variability in locomotor behavior.

Esophageal disease in pediatrics

The following on esophageal disease in pediatrics contains commentaries on acquisition of neuromuscular maturation; physiology of esophageal peristaltic and sphincteric reflexes; implications for clinical practice; and conditions that predispose to severe gastroesophageal reflux disease (GERD) in children with potential risk for esophageal cancer.

RhoE Deficiency Produces Postnatal Lethality, Profound Motor Deficits and Neurodevelopmental Delay in Mice

Rnd proteins are a subfamily of Rho GTPases involved in the control of actin cytoskeleton dynamics and other cell functions such as motility, proliferation and survival. Unlike other members of the Rho family, Rnd proteins lack GTPase activity and therefore remain constitutively active. We have recently described that RhoE/Rnd3 is expressed in the Central Nervous System and that it has a role in promoting neurite formation. Despite their possible relevance during development, the role of Rnd proteins in vivo is not known. To get insight into the in vivo function of RhoE we have generated mice lacking RhoE expression by an exon trapping cassette. RhoE null mice (RhoE gt/gt) are smaller at birth, display growth retardation and early postnatal death since only half of RhoE gt/gt mice survive beyond postnatal day (PD) 15 and 100% are dead by PD 29. RhoE gt/gt mice show an abnormal body position with profound motor impairment and impaired performance in most neurobehavioral tests. Null mutant mice are hypoactive, show an immature locomotor pattern and display a significant delay in the appearance of the hindlimb mature responses. Moreover, they perform worse than the control littermates in the wire suspension, vertical climbing and clinging, righting reflex and negative geotaxis tests. Also, RhoE ablation results in a delay of neuromuscular maturation and in a reduction in the number of spinal motor neurons. Finally, RhoE gt/gt mice lack the common peroneal nerve and, consequently, show a complete atrophy of the target muscles. This is the first model to study the in vivo functions of a member of the Rnd subfamily of proteins, revealing the important role of Rnd3/RhoE in the normal development and suggesting the possible involvement of this protein in neurological disorders.

Growth Diagrams for Grip Strength in Children

Grip strength dynamometers often are used to assess hand function in children. The use of normative grip strength data at followup is difficult because of the influence of growth and neuromuscular maturation. As an alternative, infant welfare centers throughout the world use growth diagrams to observe normative growth. The aim of this study was to develop similar growth diagrams for grip strength in children. We measured the grip strength, hand dominance, gender, height, and weight of 225 children, 4 to 12 years old. We developed separate statistical models for both hands of boys and girls for drawing growth curves. Grip strength increased with age for both hands. For the whole group, the dominant hand produced higher grip strength than the nondominant hand and boys were stronger than girls. The grip strength of boys and girls differed between 2 and 19 N for the different age groups. Because grip strength measurements are accompanied by a rather large variance, the growth diagrams (presenting a continuum in grip strength) make it possible to better observe grip strength development with time corresponding to a more exact age. Depending on the accuracy needed, the use of one combined diagram could be considered. Level of Evidence: Level II, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.

Organisation structurale, moléculaire, formation et maturation de la jonction neuromusculaire

The neuromuscular junction is made up of the apposition of highly differentiated domains of three types of cell: the motor neuronal ending, the terminal Schwann cell and the muscle postsynaptic membrane. These three components are surrounded by a basal lamina, dedicated to molecular signal exchanges controlling neuromuscular formation, maturation and maintenance. This functional and structural differentiated complex conducts synaptic neurotransmission to the skeletal muscle fiber. Nerve and muscle have distinct roles in synaptic compartment differentiation. The initial steps of this differentiation and the motor endplate formation require several postsynaptic molecular agents including agrin, the tyrosine kinase receptor MuSK. Neuregulin is essentially involved in Schwann cell survival and guidance for axonal growth.

Tempo máximo de fonação de crianças pré-escolares

Pesquisas sobre o tempo máximo de fonação (TMF) em crianças obtiveram diferentes resultados, constatando que tal medida pode refletir o controle neuromuscular e aerodinâmico da produção vocal, podendo ser utilizada como indicador para outras formas de avaliação, tanto qualitativas quanto objetivas. OBJETIVO: Verificar as medidas de TMF de 23 crianças pré-escolares, com idades entre quatro e seis anos e oito meses. MATERIAL E MÉTODO: O processo de amostragem contou com questionário enviado aos pais, triagem auditiva e avaliação perceptivo-auditiva vocal, por meio da escala RASAT. A coleta de dados constou dos TMF. DESENHO DO ESTUDO: Prospectivo de corte transversal. RESULTADOS: Os TMF /a/, /s/ e /z/ médios foram 7,42s, 6,35s e 7,19s; os TMF /a/ aos seis anos, foram significativamente maiores do que aos quatro anos; à medida que a idade aumentou, todos os TMF também aumentaram; e a relação s/z para todas as idades foi próxima de um. CONCLUSÕES: Os valores de TMF mostraram-se superiores aos verificados em pesquisas nacionais e inferiores aos verificados em pesquisa internacionais. Além disso, pode-se concluir que as faixas etárias analisadas no presente estudo encontram-se num período de maturação nervosa e muscular, sendo a imaturidade mais evidente na faixa etária dos quatro anos.

Maximum phonation time in pre-school children

SummaryPast studies on the maximum phonation time (MPT) in children have shown different results in duration. This factor may reflect the neuromuscular and aerodynamic control of phonation in patients; such control might be used as an indicator of other evaluation methods on a qualitative and quantitative basis.Aimto verify measures of MPT and voice acoustic characteristics in 23 children aged four to six year and eight months.MethodThe sampling process comprised a questionnaire that was sent to parents, followed by auditory screening and a voice perceptive-auditory assessment based on the R.A.S.A.T. scale. Data collection included the MPT.Studya prospective and cross-sectional study.ResultsThe MPT was 7.42s, 6.35s and 7.19s; as age increased, the MPT also increase significantly; the s/z relation at all ages was close to one.ConclusionsThe results mostly agree with the medical literature. MPT values, however, were higher than in other Brazilian studies. It may be concluded that the ages that were analyzed are going through neuromuscular maturation; lack of structural maturity and neuromuscular control was more evident in chidlren aged four years.

Timing of fetal exposure to stress hormones: Effects on newborn physical and neuromuscular maturation

The purpose of the study was to determine the specific periods during pregnancy in which human fetal exposure to stress hormones affects newborn physical and neuromuscular maturation. Blood was collected from 158 women at 15, 19, 25, and 31 weeks' gestation. Levels of placental corticotropin-releasing hormone (CRH) and maternal cortisol were determined from plasma. Newborns were evaluated with the New Ballard Maturation Score. Results indicated that increases in maternal cortisol at 15, 19, and 25 weeks and increases in placental CRH at 31 weeks were significantly associated with decreases in infant maturation among males (even after controlling for length of gestation). Results also suggested that increases in maternal cortisol at 31 weeks were associated with increases in infant maturation among females, although these results were not significant after controlling for length of gestation. Findings suggest that stress hormones have effects on human fetal neurodevelopment that are independent of birth outcome.

Developmental aspects of infant’s cry melody and formants

This paper deals with the analysis of cry melodies (time variations of the fundamental frequency) as well as vocal tract resonance frequencies (formants) from infant cry signals. The increase of complexity of cry melodies is a good indicator for neuro-muscular maturation as well as for the evaluation of pre-speech development. The variation of formant frequencies allows an estimation of articulatory activity during pre-speech vocalization. Subjects are three pairs of healthy identical twins (monocygozity determined by DNA-fingerprint). Spontaneous cries of these six children were recorded at different ages: 8th–9th week, 15th–17th week and 23rd–24th week. Analysis of 136 cry melodies and intensity contours was made using KAY-CSL 4300/MDVP. For formant estimation a spectral parametric technique was applied, which was based on autoregressive models (Digital spectral analysis with applications, 1987) whose order is adaptively estimated on subsequent signal frames by means of a new method (Med. Eng. Phys. 20 (1998) 432; Utras. Med. Biol. 21 (1995) 793). Cry melodies exhibited an increasing complexity during the observation period. Beginning with the second observation period (15th–17th week) an increasing coupling and tuning between melody and resonance frequencies was observed, which was interpreted as “intentional” articulatory activity. Possible applications are in cry diagnosis as well as in the evaluation of pre-speech development.

Survival motor neuron (SMN) protein: role in neurite outgrowth and neuromuscular maturation during neuronal differentiation and development

Childhood spinal muscular atrophy (SMA) is a common neuromuscular disorder caused by absent or deficient full-length survival motor neuron (SMN) protein. Clinical studies and animal models suggest that SMA is a developmental defect in neuromuscular interaction; however, the role of SMN in this process remains unclear. In the present study, we have determined the subcellular localization of SMN during retinoic-acid-induced neuronal differentiation of mouse embryonal teratocarcinoma P19 cells as well as in skeletal muscle during the critical period of neuromuscular maturation. We demonstrate, for the first time, SMN accumulation in growth-cone- and filopodia-like structures in both neuronal- and glial-like cells, identifying SMN as a new growth cone marker. Indeed, SMN was present at the leading edge of neurite outgrowths, suggesting that SMN may play a role in this process. In addition, SMN was detected as small dot-like particles within the cytoplasm of skeletal muscle during the first 2 weeks after birth, but their number peaked by P6. Intense SMN staining in neuromuscular junctions was observed throughout the entire postnatal period examined. Taken together, these results suggest that SMN may indeed fulfill neuronal- and muscle-specific functions, providing a more plausible mechanism explaining motor neuron degeneration and associated denervation atrophy of skeletal muscles in SMA. The primary SMA pathology most likely initiates in the peripheral axon--the result of deficient neurite outgrowth and/or neuromuscular maturation.

Effects of pre- and postnatal exposure to 3,3′,4,4′,5-pentachlorobiphenyl on physical development, neurobehavior and xenobiotic metabolizing enzymes in rats

An experiment was conducted to study the effects of the coplanar non-ortho-chlorinated congener 3,3′,4,4′,5-pentachlorobiphenyl (PCB-126) in rats exposed during fetal development and postnatal suckling period. Two groups of eight dams were administered by gavage six doses of 10 and 20 μg/kg body weight of PCB-126 dissolved in corn oil every second day from days 9 to 19 of gestation. The corresponding control rats were treated with corn oil only. The physical development of the offspring was observed. From age 5 to 18 weeks, 12 randomly selected pups from each group were tested daily for visual discrimination with successively more demanding tasks in Skinner boxes. The effects of PCB-126 on hepatic xenobiotic metabolizing enzyme activities and the concentrations of PCB in the liver and brain were investigated in samples from pups of different age and from their mothers. The litter size, the body weights, and the survival of the exposed sucklings were reduced, and the onset of spontaneous movement and neuromuscular maturation were delayed, whereas the development of reflexes was not affected, as compared to controls The body weight was still reduced in a dose-related manner up to 18 weeks postpartum. Also, the postpartum body weight of the PCB-exposed mothers was reduced as compared to controls, but the difference disappeared at weaning. The hepatic enzyme activities of cytochrome P450 1A1 examined by ethoxyresorufin O-deethylase (EROD) and glutathione S-transferase (GST) toward 1-chloro-2,4-dinitrobenzene (CDNB) were increased in both the exposed pups and their mothers, and the relative liver weight was increased in the exposed pups. The behavior training in Skinner boxes did not reveal PCB effects on the learning performance or the activity level Hepatic PCB-126 residues were detected in samples collected throughout the experiment, whereas no detectable concentration was found in the brain We conclude that exposure of this PCB congener in utero and through lactation showed fetotoxic effects, delayed physical maturation, and induced liver xenobiotic metabolizing enzymes without causing neurobehavioral effects