Spatiotemporal variations of magnetic susceptibility in the deep gray matter nuclei from 1 month to 6 years: A quantitative susceptibility mapping study.

BACKGROUND: Quantitative susceptibility mapping (QSM) is emerging as a technique that quantifies the paramagnetic nonheme iron in brain tissue. Brain iron quantification during early development provides insights into the underlying mechanism of brain maturation. PURPOSE: To quantify the spatiotemporal variations of brain iron-related magnetic susceptibility in deep gray matter nuclei during early development by using QSM. STUDY TYPE: Retrospective. SUBJECTS: Eighty-seven infants and children aged 1 month to 6 years. FIELD STRENGTH/SEQUENCE: Enhanced T2 *-weighted angiography using a 3D gradient-echo sequence at 3.0T. ASSESSMENT: QSM was calculated by modified sophisticated harmonic artifact reduction for phase data and sparse linear equations and sparse least squares-based algorithm. Means of susceptibility in deep gray matter nuclei (caudate nucleus, putamen, globus pallidus, thalamus) relative to that in splenium of corpus callosum were measured. STATISTICAL TESTS: Relationships of mean susceptibility with age and referenced iron concentration were tested by Pearson correlation. Differences of mean susceptibility between the selected nuclei in each age group were compared by one-way analysis of variance (ANOVA) and Fisher's Linear Significant Difference (LSD) test. RESULTS: Positive correlations of susceptibility with both referenced iron concentration and age were found (P < 0.0001); particularly, globus pallidus showed the highest correlation with age (correlation coefficient, 0.882; slope, 1.203; P < 0.001) and greatest susceptibility (P < 0.05) among the selected nuclei. DATA CONCLUSION: QSM allows the feasible quantification of iron deposition in deep gray matter nuclei in infants and young children, which exhibited gradual accumulation at different speeds. The fastest and highest iron accumulation was observed in the globus pallidus with increasing age during early development. LEVEL OF EVIDENCE: 4 Technical Efficacy:Stage 2 J. Magn. Reson. Imaging 2018.

Early-life decline in neurogenesis markers and age-related changes of TrkB splice variant expression in the human subependymal zone.

Neurogenesis in the subependymal zone (SEZ) declines across the human lifespan, and reduced local neurotrophic support is speculated to be a contributing factor. While tyrosine receptor kinase B (TrkB) signalling is critical for neuronal differentiation, maturation and survival, little is known about subependymal TrkB expression changes during postnatal human life. In this study, we used quantitative PCR and in situ hybridisation to determine expression of the cell proliferation marker Ki67, the immature neuron marker doublecortin (DCX) and both full-length (TrkB-TK+) and truncated TrkB receptors (TrkB-TK-) in the human SEZ from infancy to middle age (n = 26-35, 41 days to 43 years). We further measured TrkB-TK+ and TrkB-TK- mRNAs in the SEZ from young adulthood into ageing (n = 50, 21-103 years), and related their transcript levels to neurogenic and glial cell markers. Ki67, DCX and both TrkB splice variant mRNAs significantly decreased in the SEZ from infancy to middle age. In contrast, TrkB-TK- mRNA increased in the SEZ from young adulthood into ageing, whereas TrkB-TK+ mRNA remained stable. TrkB-TK- mRNA positively correlated with expression of neural precursor (glial fibrillary acidic protein delta and achaete-scute homolog 1) and glial cell markers (vimentin and pan glial fibrillary acidic protein). TrkB-TK+ mRNA positively correlated with expression of neuronal cell markers (DCX and tubulin beta 3 class III). Our results indicate that cells residing in the human SEZ maintain their responsiveness to neurotrophins; however, this capability may change across postnatal life. We suggest that TrkB splice variants may differentially influence neuronal and glial differentiation in the human SEZ.

Trait positive affect is associated with hippocampal volume and change in caudate volume across adolescence.

Trait positive affect (PA) in childhood confers both risk and resilience to psychological and behavioral difficulties in adolescence, although explanations for this association are lacking. Neurodevelopment in key areas associated with positive affect is ongoing throughout adolescence, and is likely to be related to the increased incidence of disorders of positive affect during this period of development. The aim of this study was to prospectively explore the relationship between trait indices of PA and brain development in subcortical reward regions during early to mid-adolescence in a community sample of adolescents. A total of 89 (46 male, 43 female) adolescents participated in magnetic resonance imaging assessments during both early and mid-adolescence (mean age at baseline = 12.6 years, SD = 0.45; mean follow-up period = 3.78 years, SD = 0.21) and also completed self-report measures of trait positive and negative affect (at baseline). To examine the specificity of these effects, the relation between negative affect and brain development was also examined. The degree of volume reduction in the right caudate over time was predicted by PA. Independent of time, larger hippocampal volumes were associated with higher PA, and negative affect was associated with smaller left amygdala volume. The moderating effect of negative affect on the development of the left caudate varied as a function of lifetime psychiatric history. These findings suggest that early to mid-adolescence is an important period whereby neurodevelopmental processes may underlie key phenotypes conferring both risk and resilience for emotional and behavioral difficulties later in life.

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±3.1 years) 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 10-11 years 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.

High-resolution 3-T MR imaging of the temporal part of the caudate tail in children.

BACKGROUND AND PURPOSE: This study aims to investigate the high-resolution 3-T MRI appearance and morphological variation of the temporal part of the caudate tail in pediatric subjects with normal brain MR examinations. PATIENTS AND METHODS: One hundred pediatric patients were retrospectively evaluated using a high-resolution 3-T imaging protocol. Different morphological parameters including shape, size, and symmetry were evaluated. The appearance and shape of the caudate tail were classified into nodular, linear, or imperceptible. The location and relation of the caudate tail to the temporal horn and adjacent brain parenchyma were categorized. Relationships between age, gender, shape, location, side, and the cross-sectional area of the caudate tail were investigated. RESULTS: The caudate tail was imperceptible in 22 %, had a nodular shape in 66.5 %, and was flat in 11.5 %. There was asymmetry of the caudate tail between the two sides in 37 % of subjects. The caudate tail was completely embedded within the temporal lobe parenchyma in 8.3 %, completely protruding into the temporal horn in 27.5 %, or intermediate in 64.1 %. The mean cross-sectional area of the caudate tail was constant across ages despite the varied age range of the subjects. There was no difference in overall mean cross-sectional area of the caudate tail between the two sides. CONCLUSION: There is a wide variation in the appearance of the caudate tail adjacent to the temporal horn of the lateral ventricle. Identification of anatomical variation of the caudate tail may prevent potential diagnostic pitfalls, especially with respect to subependymal heterotopia.

Prenatal stress changes learning strategies in adulthood.

It is well known that stressful experiences may shape hippocampus-dependent learning and memory processes. However, although most studies focused on the impact of stress at the time of learning or memory testing, very little is known about how stress during critical periods of brain development affects learning and memory later in life. In this study, we asked whether prenatal stress exposure may influence the engagement of hippocampus-dependent spatial learning strategies and caudate nucleus-dependent response learning strategies in later life. To this end, we tested healthy participants whose mothers had experienced major negative life events during their pregnancy in a virtual navigation task that can be solved by spatial and response strategies. We found that young adults with prenatal stress used rigid response learning strategies more often than flexible spatial learning strategies compared with participants whose mothers did not experience major negative life events during pregnancy. Individual differences in acute or chronic stress do not account for these findings. Our data suggest that the engagement of hippocampal and nonhippocampal learning strategies may be influenced by stress very early in life.

Estrogen receptor alpha, G-protein coupled estrogen receptor 1, and aromatase: Developmental, sex, and region-specific differences across the rat caudate-putamen, nucleus accumbens core and shell.

Sex steroid hormones such as 17ß-estradiol (estradiol) regulate neuronal function by binding to estrogen receptors (ERs), including ERα and GPER1, and through differential production via the enzyme aromatase. ERs and aromatase are expressed across the nervous system, including in the striatal brain regions. These regions, comprising the nucleus accumbens core, shell, and caudate-putamen, are instrumental for a wide-range of functions and disorders that show sex differences in phenotype and/or incidence. Sex-specific estrogen action is an integral component for generating these sex differences. A distinctive feature of the striatal regions is that in adulthood neurons exclusively express membrane but not nuclear ERs. This long-standing finding dominates models of estrogen action in striatal regions. However, the developmental etiology of ER and aromatase cellular expression in female and male striatum is unknown. This omission in knowledge is important to address, as developmental stage influences cellular estrogenic mechanisms. Thus, ERα, GPER1, and aromatase cellular immunoreactivity was assessed in perinatal, prepubertal, and adult female and male rats. We tested the hypothesis that ERα, GPER1, and aromatase exhibits sex, region, and age-specific differences, including nuclear expression. ERα exhibits nuclear expression in all three striatal regions before adulthood and disappears in a region- and sex-specific time-course. Cellular GPER1 expression decreases during development in a region- but not sex-specific time-course, resulting in extranuclear expression by adulthood. Somatic aromatase expression presents at prepuberty and increases by adulthood in a region- but not sex-specific time-course. These data indicate that developmental period exerts critical sex-specific influences on striatal cellular estrogenic mechanisms.

Developmental regulation of nerve growth factor and its receptor in the rat caudate-putamen.

In prior studies, nerve growth factor (NGF) administration induced a robust, selective increase in the neurochemical differentiation of caudate-putamen cholinergic neurons. In this study, expression of NGF and its receptor was examined to determine whether endogenous NGF might serve as a neurotrophic factor for these neurons. The temporal pattern of NGF gene expression and the levels of NGF mRNA and protein were distinct from those found in other brain regions. NGF and high-affinity NGF binding were present during cholinergic neurochemical differentiation and persisted into adult-hood. An increase in NGF binding during the third postnatal week was correlated with increasing choline acetyltransferase activity. The data are consistent with a role for endogenous NGF in the development and, possibly, the maintenance of caudate-putamen cholinergic neurons.

Neurogenesis in the caudate nucleus of the adult rabbit.

Stem cells with the potential to give rise to new neurons reside in different regions of the adult rodents CNS, but in vivo only the hippocampal dentate gyrus and the subventricular zone-olfactory bulb system are neurogenic under physiological condition. Comparative analyses have shown that vast species differences exist in the way the mammalian brain is organized and in its neurogenic capacity. Accordingly, we have demonstrated recently that, in the adult rabbit brain, striking structural plasticity persists in several cortical and subcortical areas. Here, by using markers for immature and mature neuronal and glial cell types, endogenous and exogenously administered cell-proliferation markers, intraventricular cell tracer injections coupled to confocal analysis, three-dimensional reconstructions, and in vitro tissue cultures, we demonstrate the existence of newly formed neurons in the caudate nucleus of normal, untreated, adult rabbit. Our results suggest that neurogenesis in the caudate nucleus is a phenomenon independent from that occurring in the adjacent subventricular zone, mostly attributable to the activity of clusters of proliferating cells located within the parenchyma of this nucleus. These clusters originate chains of neuroblasts that ultimately differentiate into mature neurons, which represent only a small percentage of the total neuronal precursors. These results indicate that striatum of rabbit represents a favorable environment for genesis rather than survival of newly formed neurons.

Two years changes in the development of caudate nucleus are involved in restricted repetitive behaviors in 2-5-year-old children with autism spectrum disorder.

Caudate nucleus volume is enlarged in autism spectrum disorder (ASD) and is associated with restricted and repetitive behaviors (RRBs). However, the trajectory of caudate nucleus volume in RRBs of young children remains unclear. Caudate nucleus volume was measured in 36 children with ASD and 18 matched 2-3-year-old subjects with developmentally delayed (DD) at baseline (Time 1) and at 2-year follow-up (Time 2). The differential growth rate in caudate nucleus volume was calculated. Further, the relationships between the development of caudate nucleus volume and RRBs were analyzed. Our results showed that caudate nucleus volume was significantly larger in the ASD group at both time points and the magnitude of enlargement was greater at Time 2. The rate of caudate nucleus growth during this 2-year interval was faster in children with ASD than DD. Right caudate nucleus volume growth was negatively correlated with RRBs. Findings from this study suggest developmental abnormalities of caudate nucleus volume in ASD. Longitudinal MRI studies are needed to explore the correlation between atypical growth patterns of caudate nucleus and phenotype of RRBs.

MR quantitation of volume and diffusion changes in the developing brain.

BACKGROUND AND PURPOSE: Brain volume and diffusion change during maturation. Quantitation of these changes may be helpful in understanding normal brain development. We used diffusion-weighted imaging to characterize the volumetric and diffusion changes in vivo. METHODS: We recruited 30 pediatric volunteers (aged 1 month-17 years; 14 male, 16 female). Diffusion was measured in three orthogonal directions with a b value of 1000 s/mm2. The diffusion parameters from the entire brain were calculated and fitted to a triple gaussian model. In addition, region-of-interest measurements were made in caudate, thalamus, genu and splenium of the corpus callosum, and periventricular white matter (PVWM). The brain volume was measured by counting pixels and by using the model. RESULTS: Water diffusion of the whole brain, caudate, thalamus, genu and splenium of the corpus callosum, and PVWM decreased during maturation, with the most significant change within the first 2 years. Robust negative correlations were found between age and the measured average diffusion constant (Dav) values in each of the measured locations (P <.005). Volumes of different cerebral compartments and the total intracranial volume (ICV) increased rapidly during the first 2 years of life and then had a slower growth process through adolescence. Age was correlated with the ICV and the volume of each brain compartment (P <.005). CONCLUSION: Brain diffusion decreases and brain volume increases during maturation, with the most significant changes occurring within the first 2 years of life. The brain model used in this study provides a good estimate of the increasing brain volume.

Quantitative morphology of medium-sized caudate spiny neurons in aged cats.

These studies were designed to assess some of the morphological alterations that occur in medium-sized spiny neurons of the caudate nucleus in aged cats. Computer assistance was used to quantify in three dimensions the extent of the dendritic trees of 164 neurons from 11 cats (5 1-3 years and 6 over 10 years of age) stained by the rapid Golgi technique. In all animals beyond 10 years of age there was a decrease in the density of spines on distal dendritic segments. This decrease was moderate (16%) in 13 year old cats and reached about 50% in 15 and 18 year old animals. In addition, there was an increase in the frequency of occurrence of spines with enlarged heads in all aged cats. In cats over 13 years there was a marked loss of portions of distal dendritic segments. All measures of dendrite length displayed statistically significant decreases of 30-40% in cats 15 and 18 years of age. There were no significant age-related alterations in numbers of dendrites, number of branches per dendrite or soma diameter. These morphological results indicate that there is a sequence of age-related changes that occurs in caudate medium-sized spiny neurons and provides a basis from which to assess functional alterations.

Catecholamines inhibit lipid peroxidation in young, aged, and Alzheimer's disease brain.

Some catecholamines and indolamines inhibit lipid peroxidation. Recent studies indicate that catecholaminergic inhibition of lipid peroxidation may be receptor mediated in vivo and in cell cultures. Because oxidative stress is one of the hypothesized pathogenic mechanisms for neurodegenerative diseases, including Alzheimer's disease (AD), we hypothesized that catecholaminergic and indolaminergic inhibition of lipid peroxidation would be altered in AD as compared to age-matched non-AD. To test this hypothesis we studied the effect of a variety of neurotransmitters and their antagonists on ascorbate-stimulated lipid peroxidation in membrane fragment preparations derived from postmortem human brain. In this in vitro system, the inhibition of lipid peroxidation by dopamine and serotonin did not appear to be receptor mediated. Further, our findings indicate that there is no apparent effect of age or AD on the inhibition of lipid peroxidation by catecholaminergic and indolaminergic agents.

Ultrastructural localization of delta-opioid receptors in the rat caudate-putamen nucleus during postnatal development: relation to synaptogenesis.

During development, delta-opioid receptors (DORs) in the rat caudate-putamen nucleus (CPN) appear later than mu-opioid receptors (MORs), whose developmental pattern specifically relates to synaptogenesis. We used electron microscopic immunocytochemistry to determine whether there are also age-related changes in subcellular localization of DORs in the rat CPN. Sections from postnatal day (P) 0-P30 and adult dorsomedial CPN were immunogold-silver labeled to examine the plasmalemmal and cytoplasmic distribution of these receptors. In addition, immunoperoxidase labeling was used to determine the numerical density of synapses relative to DOR-labeled profiles. Immunolabeling for DOR was undetectable at P0, light at P5, and dense from P10 onward. The labeling during P5-P10 was mainly localized in somatodendritic profiles but also was readily seen in axon terminals, most of which formed asymmetric synapses with dendrites. From P15, a few immunogold particles were seen in contact with postsynaptic densities in spines, and the proportion of these particles significantly increased in P30 and adult CPN. Other particles were localized in the cytoplasm of dendrites and terminals without significant age-related changes. Stereological analysis showed that compared with labeled dendritic shafts and spines, labeled axon terminals have a closer correlation with synapse formation. These results are in marked contrast with MORs, which show an age-related increase in association with dendritic plasma membrane and a good correlation in the developmental pattern of MOR-labeled spines with synapse formation (Wang et al. [2003] Neuroscience 118:695-708). Together, our results suggest receptor-type specific roles for endogenous opioids acting at both pre- and postsynaptic sides in the developing CPN.

Glycoconjugate boundaries during early postnatal development of the neostriatal mosaic.

The dispositions of galactosyl-containing glycoconjugates were studied during postnatal development of the caudate putamen in mice. The binding of the lectin peanut agglutinin, which has an affinity for galactosyl B-1,3 N-acetylgalactosamine residues, was compared to acetylcholinesterase staining and tyrosine hydroxylase immunoreactivity in the immature and adult neostriatum. The binding of peanut agglutinin conjugated to horseradish peroxidase, in sections that were processed for peroxidase histochemistry, was extremely pronounced in the neostriatum through the first postnatal week and constituted ringlike or polygonally shaped structures, which, overall, produced a variegated mosaic. These structures consist of outer rims of dense lectin-associated reaction product surrounding lightly labeled centers. Lectin delineations of the neostriatal mosaic are no longer visible in the second postnatal week. When adjacent sections were processed for lectin binding or acetylcholinesterase histochemistry, the dense lectin binding sites represented borders of acetylcholinesterase-rich and -poor zones. The distribution of dense patches of tyrosine hydroxylase immunoreactive fibers and terminals also coincides with the acetylcholinesterase-rich zones during the same times, and thus the glycoconjugate-delineated boundaries can also be directly compared with the distribution of nigrostriatal dopaminergic projections. The findings presented here represent the first demonstration of a probe that recognizes apparent borders of neostriatal compartments during a limited period of development. They are consistent with previous observations made on transient glycoconjugate "hidden boundaries" during development of other central nervous system structures, including the somatosensory cortical barrel field, and thalamic and brainstem nuclei (Cooper and Steindler, '86a,b; Steindler and Cooper, in press). In those studies, glia were shown to be the major source of glycoconjugate-associated patterns, and thus, glia and glycoconjugates that they synthesize during pattern formation events may be involved in the formation and stabilization of neurochemically distinct components of the neostriatal mosaic.

Postnatal development of caudate input neurons in the cat.

Lectin-bound horseradish peroxidase (WG-HRP) was pressure-injected into the caudate nucleus (Cd) of neonatal (less than 24 hours of age) and adult cats in order to assess the postnatal development of monosynaptic Cd input neurons. Tissue was processed for peroxidase activity with a benzidine dihydrochloride chromagen. The injection of WG-HRP produced relatively similar labelled zones of marker uptake in the caudate nuclei of both neonates and adults. Similar axonal projections were also labelled in both age groups. While many characteristics of retrogradely labelled CD input neurons were apparently constant throughout postnatal life, each of these features had a particular developmental modification. (1) Regardless of age, neuronal somata that projected to the CD were located in the neocortex, thalamus, substantia nigra, mesencephalic raphe nuclei, and globus pallidus. In each of these brain sites, labelled CD input neurons appeared to migrate postnatally. (2) The Cd afferent axons originated from the same neuronal lines in neonates and adults--small-to-medium-sized cortical neurons and medium-sized-to-large fusiform cells in all other brain sites. In each of the brain sites, labelled neurons displayed marked postnatal somatic growth. (3) In both age groups, there was a characteristic intrasomatic reaction product density in the labelled neurons located in each brain site (substantia nigra greater than thalamus = raphe = globus pallidus greater than cortex). In each of these brain sites, the intrasomatic reaction product density was less in neonates than in adults.

The developing caudate nucleus in the euthyroid and hypothyroid rat.

The basal ganglia are presently implicated in learning, and thyroid deficiency induced neonatally is known to affect mentation. The effects of such a deficiency on the developing causate nucleus might be used to provide insight into structure and function of the normal subcortical brain, as well as possible influences of these extrapyramidal structures on mental retardation. Propylthiouracil was added to the diet of lactating rat dams and observations of the developing caudate nuclei of normal hypothyroid rats were made at 8, 14, 20, 30 and 42 days by using various tissue stains and Golgi-Cox preparations. Seven different types of neurons were distinguished in the caudate nucleus. Differences in the size of cell somata and the varying morphology of axons and dendrites were criteria used to make distinctions. Normally, the nucleus acquires cytoarchitectural complexity during the first three postnatal weeks. Within this period, neuron incidence increases in the caudate neuropil with age while the germinal matrix density decreases. Neuron accumulation reaches a plateau after the third week and cell migration is essentially complete at the end of the first postnatal month as shown by computer analysis of Nissl stained cell counts. Branching of cellular processes, attainment of receptor spines and complexity of the fiber network also appeared during this period. Retardation of structural development with thyroid hormone deficiency was shown by decreased numbers of neurons, inhibition of dendritic arborization, decreased numbers of dendritic spines and a reduced complexity of axonal plexuses. Thyroid deficiency delays cell migration during the first three weeks when compared to age-matched normal controls. The lack of thyroid hormone does not appear to influence the size of neuron somata, and the extent of related dendritic fields, nor does hypothyroidism affect a specific cell type population. Generalized disturbances of caudate nuclear morphological maturation are caused by the deficiency. An apparent compensatory process, including a spurt of neural growth and differentiation, takes place in the period between days 14 and 30 in the deficient animals and a seemingly "normal" caudate cytoarchitecture is seen after the third postnatal week. Quantitative data, however, show that this rapid "catch up" process is inadequate. The developmental imperfection of the caudate nucleus which persists might be a part of the underlying substrate for the mental retardation, disturbed motor performance and perceptual handicaps which are found in the human patient.

Postnatal maturation of subcortical projections from the prefrontal cortex in the rhesus monkey.

Orbital and dorsolateral prefrontal lesions were performed on a series of rhesus monkeys at 2, 6, or 24 months of age. The consequent degeneration in the efferent pathways from these cortical regions to the caudate nucleus, the dorsomedial nucleus of the thalamus and adjacent structures was studied at 5- and 15-day survival times by a modification of the Nauta-Gygax method for tracing degenerating fibers. Following dorsolateral lesions, considerable numbers of black-impregnated degenerating fibers were found in the parvocellular division of the dorsomedial nucleus and in the fiber bundles of the internal capsule and the subcallosal fasciculus at all ages.

Early postnatal development of the monkey neostriatum: a Golgi and ultrastructural study.

Paired specimens of the neostriatum were taken from monkeys at zero (newborn), one, two, four, eight, and 16 weeks of age, and prepared for Golgi impregnations and electron microscopy. Light microscopy shows that in the first postnatal week, the structure contains the five neuronal types and four categories of afferent axons described in the adult, as well as some cells too undifferentiated to classify. Most neurons exhibit immature dendritic features, including local enlargements, terminal growth cones with filopodia, and filiform processes. In spiny type I cells, various levels of maturity may coexist in regions of a single dendrite, in different dendrites of the same neuron, and among individual cells. Spine density increases progressively with age, but the relative distribution of spine types remains about the same. Spiny type II neurons show some decline in spine density, and generally mature sooner than spiny type I cells. The long axons of spiny neurons have varicosities which disappear at about eight weeks. In younger animals (newborn and one week), the dendrites of aspiny neurons (types I, II, and III) may have a "spiny" appearance, exhibiting many spine-like and filiform processes. Concurrently, the short axons vary in degree of arborization from very immature to well developed. Electron microscopy corroborates the developmental features recognized in the Golgi material: dendritic and axonal growth cones, filopodia and varicosities, as well as various stages of maturation in somata and dendrites. Degenerating elements, mostly of an axonal nature, are seen up to eight weeks. The synapses which reach maturity at birth are of the asymmetric axospinous type, in which the axonal profile contains small round vesicles, and of the symmetric axodendritic class, with the presynaptic elements having pleomorphic vesicles. Some synapses are slower to mature and appear at one to eight postnatal weeks. These include those made by profiles with pleomorphic vesicles, forming either symmetric contacts with somata and axon initial segments, or asymmetric contacts with spines. The same applies to the asymmetric axodendritic synapses made by elements containing small round vesicles. Finally, profiles containing large round or flat vesicles are the latest to participate in mature synapses formation. Findings indicate that a considerable degree of qualitative and quantitative change takes place in the monkey neostriatal neuropil during early postnatal development, especially in the first eight-week period.

An autoradiographic study of the subcortical projections of the rabbit striate cortex in the adult and during postnatal development.

The subcortical projections of the rabbit striate cortex were studied by autoradiography. Small injections of 3H-leucine were placed into the striate cortex of 15 rabbit pups aged between one day and one month and six adult rabbits (strain Chbb:Ch). Terminal fields of projection occurred only ipsilateral to the injection, and these were found in the caudate nucleus (CN), the claustrum (Cla), the thalamic reticular nucleus (TRN), the dorsal (LGNd) and the ventral (LGNv) lateral geniculate nuclei, the pulvinar (Pul), the ventrolateral (Vl) the posterior (Po) thalamic nuclei, the anterior (APN) and posterior (PPN) pretectal nuclei, the nucleus of the optic tract (NOT), the superior colliculus (SC) and the basal pontine nuclei (PN). Cla was innervated via the superficial corticocortical and CN via the corticocaudate pathways. The remaining projections were innervated via the subcortical pathway which comprised three bundles: The deep bundle (to TRN, LGNd, Pul and Po), the superficial bundle (to LGNv, APN, PPN, NOT, and SC), and the peduncular bundle (to PN). The projection to SC showed remarkable changes of its terminal pattern during the first and second postnatal weeks. These changes were characterized by a strong reduction of the horizontal extension of the terminal labelling and an increasing concentration on the stratum griseum superficiale. Similar changes were not observed in the other projections.