Perinatal asphyxia in a nonhuman primate model.

Perinatal asphyxia is a leading cause of brain injury in neonates, occurring in 2-4 per 1,000 live births, and there are limited treatment options. Because of their similarity to humans, nonhuman primates are ideal for performing preclinical tests of safety and efficacy for neurotherapeutic interventions. We previously developed a primate model of acute perinatal asphyxia using 12-15 min of umbilical cord occlusion. Continuing this research, we have increased cord occlusion time from 15 to 18 min and extended neurodevelopmental follow-up to 9 months. The purpose of this report is to evaluate the increase in morbidity associated with 18 min of asphyxia by comparing indices obtained from colony controls, nonasphyxiated controls and asphyxiated animals. Pigtail macaques were delivered by hysterotomy after 0, 15 or 18 min of cord occlusion, then resuscitated. Over the ensuing 9 months, for each biochemical and physiologic parameters, behavioral and developmental evaluations, and structural and spectroscopic MRI were recorded. At birth, all asphyxiated animals required resuscitation with positive pressure ventilation and exhibited biochemical and clinical characteristics diagnostic of hypoxic-ischemic encephalopathy, including metabolic acidosis and attenuated brain activity. Compared with controls, asphyxiated animals developed long-term physical and cognitive deficits. This preliminary report characterizes the acute and chronic consequences of perinatal asphyxia in a nonhuman primate model, and describes diagnostic imaging tools for quantifying correlates of neonatal brain injury as well as neurodevelopmental tests for evaluating early motor and cognitive outcomes.

Vulnerability of macaque cranial nerve neurons to ethanol is time- and site-dependent.

The present study tested the hypotheses that vulnerability to ethanol depends upon (1) population-based characteristics of the neuronal progenitors and (2) the maturation of that population by examining the effects of prenatal exposure to ethanol on brainstem nuclei derived from different rhombomeres and from the alar and basal plates. Macaca nemestrina received an ethanol-containing solution 1 day per week during the first 6 (Et6) or 24 (Et24) weeks of gestation. Control animals received an equivalent volume of saline. The treatment regime for some animals included early gastrulation (gestational day [G] 19 or G20), whereas others were treated later (on G21 or G24). Brainstems were cryosectioned and stained with cresyl violet. Stereological methods were used to determine the numbers of neurons in six different nuclei: the abducens, vagal, and hypoglossal motor nuclei and sensory components of the trigeminal brainstem nuclear complex (the principal, oral, and interpolar subnuclei). There were no differences in the numbers of neurons in any of the nuclei between controls and Et6-, or controls and Et24-treated monkeys. In contrast, the number of trigeminal sensory neurons was significantly (P<.05) lower in animals treated on G19/G20 than in control. No differences between controls and monkeys treated on G21/G24 were detected. No motor nuclei exhibited an ethanol-induced change. These data together with data on the trigeminal motor nucleus show that vulnerability to ethanol (1) is greater in sensory nuclei than in motor nuclei and (2) is temporally restricted to the time of gastrulation.

Behavioral measurement of temporal contrast sensitivity development in macaque monkeys (Macaca nemestrina).

We measured the developmental time course for temporal contrast sensitivity in macaque monkeys. The animals, aged 5 weeks to 4 years, detected an unpatterned field of light sinusoidally modulated over time at frequencies ranging from 1 to 40 Hz. Young infants showed reduced sensitivity for all frequencies, and a reduced range of detectable frequencies. Sensitivity to high and low frequencies developed at different rates, but the shape of the temporal contrast sensitivity function did not change significantly with age. Temporal contrast sensitivity matures earlier than spatial contrast sensitivity. The development of high, but not low, frequency sensitivity may be limited by maturation of the magnocellular pathway.

Statistical methods for describing developmental milestones with censored data: effects of birth weight status and sex in neonatal pigtailed macaques.

Neurobehavioral tests are used to assess early neonatal behavioral functioning and detect effects of prenatal and perinatal events. However, common measurement and data collection methods create specific data features requiring thoughtful statistical analysis. Assessment response measurements are often ordinal scaled, not interval scaled; the magnitude of the physical response may not directly correlate with the underlying state of developmental maturity; and a subject's assessment record may be censored. Censoring occurs when the milestone is exhibited at the first test (left censoring), when the milestone is not exhibited before the end of the study (right censoring), or when the exact age of attaining the milestone is uncertain due to irregularly spaced test sessions or missing data (interval censoring). Such milestone data is best analyzed using survival analysis methods. Two methods are contrasted: the non-parametric Kaplan-Meier estimator and the fully parametric interval censored regression. The methods represent the spectrum of survival analyses in terms of parametric assumptions, ability to handle simultaneous testing of multiple predictors, and accommodation of different types of censoring. Both methods were used to assess birth weight status and sex effects on 14 separate test items from assessments on 255 healthy pigtailed macaques. The methods gave almost identical results. Compared to the normal birth weight group, the low birth weight group had significantly delayed development on all but one test item. Within the low birth weight group, males had significantly delayed development for some responses relative to females.

Development of the primate area of high acuity, 3: temporal relationships between pit formation, retinal elongation and cone packing.

By establishing an avascular, highly elastic, region within the fetal area of high acuity (AHA), the developing primate eye has created a unique substrate on which the mechanical forces of intraocular pressure (IOP) and growth-induced retinal stretch (stretch) can act. We proposed (Springer & Hendrickson, 2004b) that these forces generate both the pit and high cone density found in the adult AHA. In this paper, we use quantitative measures to determine the temporal relationships between nasal and temporal retinal elongation, changes in pit depth, cone packing, and cone morphology over M. nemestrina retinal development. Retinal length increased rapidly to about 105 days postconception (dpc; Phase 1) and then elongation virtually ceased (Phase 2) until just after birth (180 dpc). Retinal elongation due to stretch resumed during Phase 3 until approximately 315 dpc (4-5 months), after which time the retina appeared mature (Phase 4). The pit appeared during the quiescent Phase 2, suggesting that IOP acts, in conjunction with molecular changes in the inner retina, on the highly elastic, avascular, AHA to generate a deep, narrow pit and causes inner retinal cellular displacements. Subsequently (Phase 3), the pit widened, became 50% shallower and central inner retinal lamina thinned slightly due to a small amount of retinal stretch occurring in the AHA. Centripetal movement of cones was minimal until just after birth when the pit reached 88% of its maximal depth. Accelerated cone packing during Phase 3 was temporally correlated with increased stretch.

VEGF expression by ganglion cells in central retina before formation of the foveal depression in monkey retina: evidence of developmental hypoxia.

In macaque monkeys the foveal depression forms between fetal day (Fd) 105 and birth (Fd 172 of gestation). Before this, the incipient fovea is identified by a photoreceptor layer comprising cones almost exclusively, a multilayered ganglion cell layer (GCL), and a "domed" profile. Vessels are absent from the central retina until late in development, leading to the suggestion that the GCL in the incipient fovea may be transitorily hypoxic. Vascular endothelial growth factor (VEGF), expressed by both glial and neuronal cells and mediated by the hypoxia-inducible transcription factor (HIF)-1, is the principal factor involved in blood vessel growth in the retina. We examined VEGF expression in macaque retinas between Fd 85 and 4 months postnatal. Digoxygenin-labeled riboprobes were generated from a partial-length human cDNA polymerase chain reaction fragment, detected using fluorescence confocal microscopy, and quantified using Scion Image. High levels of VEGF mRNA were detected in astrocytes associated with developing vessels. We also detected strong expression of VEGF mRNA in the GCL at the incipient fovea prior to Fd 105, with peak labeling in the incipient fovea that declined with distance in nasal and temporal directions. By Fd 152 peak labeling was in two bands associated with development of the inner nuclear layer (INL) capillary plexus: in the inner INL where Müller and amacrine cell somas are located, and in the outer INL where horizontal cells are found. The findings suggest that at the incipient fovea the GCL is hypoxic, supporting the hypothesis that the adaptive significance of the fovea centralis is in ensuring adequate oxygen supply to neuronal elements initially located within the avascular region.

Markovian models for the developmental study of social behavior.

Behavioral development involves changes in the probabilities of both social and nonsocial activities and the sequential pattern of activities over time. A number of methods have been offered for the analysis of these patterns of behavioral sequences. However, there continue to be problematic issues, including the analysis of nonstationary data; accommodation of changes in patterns within an observation period, or over repeated observations or age; and identification of differences in pattern changes between individuals or groups, and the factors responsible for these differences. In this work, we analyze data from 15 young monkeys (Macaca nemestrina) using classification and Markovian methods, including a new approach to nonstationary data called the double-chain Markov model (DCCM). These methods allowed us to identify differences in behavior patterns that differentiate between normal subjects and those presenting developmental anomalies.

Survival, growth, health, and reproduction following nursery rearing compared with mother rearing in pigtailed monkeys (Macaca nemestrina).

Nursery-reared primates do not experience psychological "maternal bonding" or immunological benefits of breast milk, so they are expected to be inferior to mother-raised monkeys in growth, health, survival, reproduction, and maternal abilities. Studies of nursery-reared monkeys support aspects of this prediction for infants deprived of social contact or raised in pairs. We present colony record data on 1,187 mother and 506 nursery-raised monkeys, 2-10 yr of age, living in mixed groups. We found no group differences in survival, growth, clinical treatments for disease or bite wounds, or pregnancy outcome and neonatal deaths. Nursery males given breeding opportunities produced an average of 24 offspring. In addition to 24-hr personnel present on every day of the year, we believe that three of our procedures account for differences between our results and other reports. Our infants received 1) intensive human handling, 2) daily social interaction in a playroom, and 3) success and failure experience during learning and cognitive testing. We do not advocate rearing primates without mothers, but we conclude that these procedures are sufficient for producing physical health and adaptive juvenile and adult social skills in nursery-raised monkeys.

Between-species variation in the development of hand preference among macaques.

This research examined between-species variation in the development of hand preference among Macaca. Specifically, we examined hand preference using juveniles and adults of three macaque species that differ in social and reactive tendencies in order to examine whether the correlation between temperament and handedness that has been noted within Macaca mulatta occurs between closely related species. Each of the species studied exhibited a different pattern of hand preference development. Both juvenile and adult M. mulatta exhibited group-level left-hand bias. Juvenile Macaca nemestrina were not biased towards either hand at the group-level, whereas adults exhibited a group-level left-hand bias. Neither juvenile nor adult Macaca fascicularis exhibited manual bias at the group-level. Analysis of variance indicated statistically significant main effects of species and age class on hand preference measures. Post-hoc analysis indicated greater use of the left- versus right-hand, and greater hand preference strength independent of direction, among M. mulatta and M. nemestrina than among M. fascicularis, and among adults than among juveniles. These results indicate significant between-species variation in the development of hand preference within the genus Macaca, and are inconsistent with any one single-factor theory yet offered to explain the etiology of primate laterality. We hypothesize that the relationship between handedness and temperament that has been shown within M. mulatta may generalize across closely related primate species.

Effects of experimental strabismus on the architecture of macaque monkey striate cortex.

Strabismus, a misalignment of the eyes, results in a loss of binocular visual function in humans. The effects are similar in monkeys, where a loss of binocular convergence onto single cortical neurons is always found. Changes in the anatomical organization of primary visual cortex (V1) may be associated with these physiological deficits, yet few have been reported. We examined the distributions of several anatomical markers in V1 of two experimentally strabismic Macaca nemestrina monkeys. Staining patterns in tangential sections were related to the ocular dominance (OD) column structure as deduced from cytochrome oxidase (CO) staining. CO staining appears roughly normal in the superficial layers, but in layer 4C, one eye's columns were pale. Thin, dark stripes falling near OD column borders are evident in Nissl-stained sections in all layers and in immunoreactivity for calbindin, especially in layers 3 and 4B. The monoclonal antibody SMI32, which labels a neurofilament protein found in pyramidal cells, is reduced in one eye's columns and absent at OD column borders. The pale SMI32 columns are those that are dark with CO in layer 4. Gallyas staining for myelin reveals thin stripes through layers 2-5; the dark stripes fall at OD column centers. All these changes appear to be related to the loss of binocularity in cortical neurons, which has its most profound effects near OD column borders.

Distribution and development of short-wavelength cones differ between Macaca monkey and human fovea.

Macaca monkey and humans have three cone types containing either long-wavelength (L), medium-wavelength (M), or short-wavelength (S)-specific opsin. The highest cone density is found in the fovea, which mediates high visual acuity. Most studies agree that the adult human fovea has a small S cone-free area, but data are conflicting concerning S-cone numbers in the adult Macaca monkey fovea, and little evidence exists for how either primate fovea develops its characteristic cone pattern. Single- and double-label in situ hybridization and immunocytochemistry have been used to determine the pattern of foveal S cones in both the fetal and adult Macaca and human. Both labels find a clear difference at all ages between monkey and human. Adult humans have a distinct but variable central zone about 100 microm wide that lacks S cones and is surrounded by a ring in which the S-cone density is 8%. This S cone-free zone is detectable at fetal week 15.5 (Fwk15.5), shortly after S opsin is expressed, and is similar to the adult by Fwk20.5. Adult monkey foveas have an overall S-cone foveal density of 10%, with several areas lacking a few S cones that are not coincident with the area of highest cone density. A surrounding zone at 200-microm eccentricity has an S-cone density averaging 25%, but, by 800 microm, this has decreased to 11%. Fetal day 77-135 monkeys all have a distribution and density of foveal S cones similar to adults, although the high-density ring is not obvious in fetal retinas. Estimates of the numbers of S cones missing in the fetal human fovea range from 234 to 328, whereas no more than 40 are missing in the fetal monkey. These results show that, in these two trichromatic primates, S-cone distribution and the developmental mechanisms determining S-cone topography are markedly different from the time that S cones are first detected.

A longitudinal study of the growth pattern of the maxillary sinus in the pig-tailed macaque (Macaca nemestrina).

The ontogeny of sexual dimorphism in maxillary sinus size in a nonhuman primate was studied longitudinally for a period of 8 years in 25 female and 25 male Macaca nemestrina via lateral cephalograms. The maxillary sinus was traced and its area digitized. The growth of female maxillary sinuses was described with a Gompertz model; the best fit to the male data was obtained by the logistic model. Growth curves and confidence intervals revealed that the sinuses grew in a similar fashion for 3-4 years in both sexes. After this, female sinuses achieved a plateau in their development while male sinuses continued to grow. Confidence intervals suggested that size dimorphism appeared at the age of 6.3 years. Lowess regression indicated growth spurts in both sexes. Females experienced an earlier and smaller spurt than males. Sexual dimorphism in maxillary sinus size seems to represent a combination of differences in velocity and length of growth. This study indicates that growth of the maxillary sinus follows closely the growth in body size. Nevertheless, due to the variation in sinus size in Macaca, it is questionable if body size is the main determinant of maxillary sinus size. It is suggested that Macaca, with its wide geographic range and different environments, is an especially appropriate genus to use to test hypotheses about the evolution of skull pneumatization in primates.

Social development in nursery-reared pigtailed macaques (Macaca nemestrina).

The social development of 240 nursery-reared pigtailed macaques (Macaca nemestrina) was studied from postnatal weeks 4 to 32. The objectives of the study were to document developmental trends and evaluate social behavior in laboratory-reared M. nemestrina raised at the University of Washington Infant Primate Laboratory, and to identify husbandry factors that might affect early social development. Only infants who had not undergone invasive postnatal experimental manipulation and had no chronic illness or injuries were included in the study. Infants were separated from their mothers and housed singly, but had access to peers for 30 min a day, 5 days a week, in a large playroom. Play and social behaviors emerged early in development, increased during the developmental period studied and occupied a large portion of the infants' time budgets. Although disturbance behaviors occurred with some frequency and duration early in development, they occupied a very small portion of the infants' time budget at 8 months of age. Weaning from infant formula at 16-19 weeks retarded development of play behavior. Permanent removal of a cloth comforter (diaper) during weeks 20-24 had no long-term behavioral effects. It was concluded that at 8 months of age these infants showed relatively normal species-typical behavioral repertoires.

Heterochrony and sexual dimorphism in the pigtailed macaque (Macaca nemestrina).

Somatic growth is not a simple linear process with a constant rate of growth. The most successful attempts to quantify growth as a function of age or size have employed nonlinear techniques. Sexual dimorphism of primate growth, weight vs. age, was examined using nonlinear models with Sirianni and Swindler's ([1985] Growth and Development of the Pigtailed Macaque, Boca Raton, FL: CRC Press) growth data on the pigtailed macaque (Macaca nemestrina). The best fit of several exponential growth models was the Gompertz curve: Weight = a*e-b*e-K*age Different multiple phase models were also fit, where each phase represents a distinct exponential component. The two-phase models proved to be the best (R2 = .0.84 for females, 0.91 for males), suggesting that there are two growth spurts, one in infancy and one at puberty. The timing of the beginning and end of the first spurt is the same in males and females, but the rate, and value of the asymptote for this phase, is greater in males. The timing of the second spurt is earlier, and the rate of growth for this spurt is smaller in females than males. The sexual dimorphism in these species is not a simple rate change, but a complex interaction of timing and rate over the entire period of growth. It would be impossible to separate these entities with a linear, polynomial, or single-phase model of the data. While these data and results complement much of the existing work on adult dimorphism, they also emphasize the vital role that ontogenetic data have in elucidating the underlying evolutionary mechanisms that generate sexual dimorphism.

Pre- and postnatal development of GABA receptors in Macaca monkey visual cortex.

GABA is a putative inhibitory neurotransmitter in adult mammalian visual cortex but also has been implicated as playing a crucial role in cortical information processing during development. In order to understand better the role of GABA during primate visual cortex development, we have examined the time course of GABAA and GABAB receptor ontogenesis in 18 Macaca nemestrina monkeys ranging from fetal day 61 (F61d) to adulthood. The GABA and benzodiazepine binding sites of the GABAA receptor were detected by 3H-muscimol (3H-MS) and 3H-flunitrazepam (3H-FZ), respectively. GABAB receptors were detected by 3H-baclofen (3H-BA). All ligands were visualized by in vitro autoradiography. Quantitative analysis of film density was done to compare laminar changes during pre- and postnatal development. Saturation binding experiments were done for MS and FZ binding sites to determine receptor number (Bmax) and affinity (Kd) at selected pre- and postnatal ages. Both MS and FZ binding sites were present at F61d-72d throughout the cortical plate and marginal zone. FZ binding sites were more dense than MS binding sites over the cortical plate at young ages and were especially dense over the marginal zone. FZ binding sites also were present in lesser amounts over the subplate and intermediate zone, but not over the subventricular zone. By F119d-126d, layer 4 could be distinguished by its higher density for both ligands. The basic adult laminar pattern was established for both MS and BZ binding sites by birth (birth = F165d-170d). After birth, MS density increases dramatically in all layers, but layer 4C remains most dense to adulthood. FZ labeling is heavy in both layers 4 and 3 at birth but after 4 weeks after birth (P4 wk) it declines somewhat in the supragranular layers so that layer 4C now predominates. Labeling in layers 5/6 virtually disappears after birth. BA binding sites were present at F126d, at which time layer 4 was slightly lighter than the remainder of striate cortex; this laminar pattern remained basically the same throughout our series to adulthood. Competitive binding of agonist and antagonists for the GABAA receptor showed that MS binding characteristics were similar at F126d and P8.5 years (yr). MS binding site Bmax was about 8% of adult values at F72d, 24% by F126d, and 56% at F152d. Bmax then rose rapidly after birth to peak at P18wk at 169% of adult values, and then declined to P1yr. A second peak of 143% was found around P3.5yr, with adult values reached by P8.5yr.(ABSTRACT TRUNCATED AT 400 WORDS)

Postnatal development of thalamic recipient neurons in the monkey striate cortex: I. Comparison of spine acquisition and dendritic growth of layer 4C alpha and beta spiny stellate neurons.

A quantitative study has been made from Golgi impregnations of the maturation of dendrites and their spines on spiny stellate neurons in the macaque monkey primary visual cortex. The neurons studied lay within either the alpha or the beta division of lamina 4C; previous workers have shown the alpha division neurons to be contacted by thalamic axon terminals arising from the magnocellular division of the lateral geniculate nucleus (LGN) of the thalamus and the beta division neurons to be contacted by parvocellular LGN inputs. Most thalamic terminals and perhaps the majority of other type 1 (Colonnier, '81), presumed excitatory, inputs to these cells make synaptic contacts on the tips of their dendritic spines. Measurement was made of relative changes in the total number of spines on these alpha and beta spiny neurons over age by measuring both spine density along the dendrites and dendritic arbor size in single 90-microns sections from Golgi rapid preparations. Our previous work (Lund et al., '77; Boothe et al., '79) showed a marked proliferation and attrition of spines and dendritic branches to occur in the early postnatal weeks; Rakic et al. ('86) have since proposed that there is a cortexwide synchrony of synapse acquisition and loss during this same period. However, different visual capacities channelled via the magnocellular and parvicellular geniculate relays show different maturational rates (Harwerth et al., '86). This study indicates that the anatomical maturation of spines on the alpha and beta neurons is not temporally coincident from birth to 30 weeks. During this period, phases of spine acquisition and loss on alpha neurons precedes similar phases on beta neurons. The alpha neurons carry a peak spine population at 5-8 weeks postnatal, whereas the beta neurons carry their peak spine populations between 8 and 24 weeks postnatal. At all ages prior to 30 weeks, the two sets of neurons carry quite different total spine populations. Close to 30 weeks of age, the total spine coverage has fallen on both sets of neurons and becomes identical between the alpha and beta neurons. In animals aged 30 weeks to adult, spine coverage per neuron is maintained at a common figure for the alpha and beta neurons despite further growth and disparate dendritic arbor sizes and different local spine densities in the two groups; this suggests that some common sampling paradigm between pre- and postsynaptic elements is adopted by the alpha and beta neurons and also suggests the development of a close functional correlation between the two sets of neurons.

Postnatal development of thalamic recipient neurons in the monkey striate cortex: II. Influence of afferent driving on spine acquisition and dendritic growth of layer 4C spiny stellate neurons.

This study uses Golgi-impregnated material to examine the effects of altering the nature of afferent driving on the maturation of spines and dendrites on thalamic recipient spiny stellate neurons in layers 4C alpha and beta of the monkey striate cortex. These two laminae receive input from different sets of thalamic afferents with different functional properties. The development of dendritic spine and dendritic branch populations on these neurons in experimental animals is compared to the same features on similar groups of neurons in a series of normal animals described in the preceding study (Lund and Holbach, '91). Three conditions of rearing were used to alter afferent driving from normal: complete darkness (with in some cases return to normal diurnal light-dark cycle), bilateral eye lid suture, and monocular eye lid suture. Some of the normal and dark-reared infant monkeys were examined behaviorally for visual capacity in an earlier study (Regal et al., '76). All conditions of abnormal afferent driving caused changes from the normal developmental patterns of spine and dendritic arbor growth in these first-order neurons of the cortex and each condition differed in the nature of change produced. Major findings of this study are: 1. Vigorous spine acquisition and dendritic growth occurs under all conditions of visual deprivation on alpha and beta neurons. Eventual spine and dendritic attrition occurs under at least conditions of bilateral or monocular lid suture to produce a rather constant adult morphology. We assume, therefore, that visually driven activity is a modulator or shaper of the developmental process for thalamic recipient neurons of visual cortex, rather than being an initiator, terminator, or driving force for their maturation. 2. An innate "clock," whose nature is unknown but is apparently not driven by visual input, initiates and terminates a period of growth of the thalamic recipient neurons between birth and 30-32 weeks of age. 3. Factors controlling dendritic arbor growth and retraction are different from those controlling spine synapse addition or attrition. 4. Whereas the alpha and beta neurons normally show quite different early growth patterns between birth and 30 weeks of age, when both eyes are simultaneously deprived of vision, an early temporal and numerical convergence occurs in patterns of spine population development on the two groups of neurons. This convergent pattern assumes a different form in dark-reared and lid-sutured animals.(ABSTRACT TRUNCATED AT 400 WORDS)

Postnatal development of thalamic recipient neurons in the monkey striate cortex: III. Somatic inhibitory synapse acquisition by spiny stellate neurons of layer 4C.

The development of type 2 (Colonnier, '81) synapses on the cell bodies of thalamic recipient spiny stellate neurons in layers 4C alpha and 4C beta of primary visual cortex neurons was examined over the first 36 postnatal weeks and in the adult monkey. The type 2 synapses, known to be GABAergic (Ribak, '78) and therefore presumed to be inhibitory, developed faster on the alpha neurons than the beta neurons. Both neuron groups show a marked increase and then decline in the percentage of the somatic membrane covered by type 2 synaptic appositions during this 36-week time period. The time course of the type 2 synapses development is compared to that of the spine synapse development described in previous studies (Lund and Holbach, '91; Lund et al., '91), and it is clear that on both neuron groups this inhibitory synapse population is put in place and refined later than the spine synapses. These findings suggest that each cortical neural circuit has a unique time course for its early development within an overall time window (Rakic et al., '86), or sensitive period (Hubel and Wiesel, '70). Visual deprivation, although causing the alpha and beta neurons to adopt a more similar temporal and numerical developmental pattern than normal, did not prevent acquisition and loss phases of type 2 synapses or the assumption of a normal numerical loading by 36 weeks of age.

Postnatal growth and skeletal maturation of experimental preterm macaques (Macaca nemestrina).

The growth and skeletal maturation of nine preterm female pigtailed macaques (Macaca nemestrina) obtained by C-section at less than or equal to 155 postconceptional days were followed through six months of age. At C-section they were of normal size and maturation for gestational age. Compared with 50 normal females born at term (mean = 173 +/- 6.4 postconceptional days), preterm infants were also of normal size at term, but delayed in skeletal maturation, requiring about one month to achieve the standard.

Macaque anteroventral cochlear nucleus: developmental anatomy.

The development of the anteroventral cochlear nucleus (AVCN) in fetal and infant monkeys (Macaca nemestrina) was analyzed for gross morphologic changes together with growth-related modifications in constituent cell size and cell distribution. Rapid and extensive prenatal volumetric changes were followed by slow and limited postnatal volumetric changes. The time course of packing density and cell size changes paralleled the volumetric changes. At each age the packing density along the rostrocaudal axis of the AVCN was constant except in the youngest specimens (mid- to late-fetal), where local variations occurred. Similarly, the size of AVCN cells along the rostrocaudal axis remained approximately constant at any given age. In comparison with the human and mouse, the macaque exhibits relatively less pronounced postnatal change in overall volume and cellular growth features.