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PubMed1993

Strychnine-insensitive glycine binding to cerebral cortical membranes in developing and ageing mice.

The strychnine-insensitive binding of [3H]glycine was characterized in purified cerebral cortical membranes from mice aged from 7 days to 22 months. The binding was saturable, exhibiting only one component during the whole life-span studied. The binding constant KD did not change during development and ageing, whereas the maximal binding capacity Bmax, calculated per protein content, increased up to the age of two weeks and then again in ageing animals (18- and 22-month-olds). The binding was similarly inhibited by the antagonists 7-chlorokynurenate, 3-amino-1-hydroxypyrrolidin-2-one (HA-966) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) in 7-day-, 3-month- and 12-month-old mice. The inhibition caused by glycine, L-serine and beta-alanine also remained unaltered during the whole life-span. beta-Alanine was a noncompetitive inhibitor. The alterations in the maximal binding capacities during development and ageing could be of importance in the regulation of NMDA receptors, which have been implicated in synaptic potentiation, developmental processes and various pathological conditions.

Aging↗
PubMed1988

Effect of the anti-oestrogen tamoxifen on the development of renal cortical necrosis induced by oestrone + vasopressin administration in rats.

Bilateral renal cortical necrosis was observed after vasopressin administration in rats pretreated with oestrone acetate. Histochemical (succinic dehydrogenase, trichrome, periodic acid Schiff) and electronmicroscopic methods were used to examine how the anti-oestrogen, Tamoxifen, influences the development of this renal cortical necrosis. The experiments revealed that in most rats vasopressin did not induce renal tubular necrosis if the anti-oestrogen was administered simultaneously, even during oestrogen pretreatment. The results suggest that oestrogen receptors in the kidney are involved in the induction of renal cortical necrosis by vasopressin.

Animals↗
PubMed1994

Topography of developing thalamic and cortical pathways in the visual system of the cat.

Adult patterns of connectivity could emerge during development by a process of selective elimination from an earlier, more widespread, connectivity. We have addressed this issue by examining the topography of developing projections to area 17 in the cat. At different postnatal ages, paired injections of the retrograde tracers diamidino yellow and fast blue were made in area 17. Interinjection separations were carefully controlled and the spatial distribution of the two populations of labelled neurones investigated. Projections to the striate cortex from the lateral geniculate nucleus, area 18, as well as connections intrinsic to area 17 were analysed quantitatively with a graphic method that uses a two-dimensional model of the projection. This allows two parameters of the projection to be calculated: the divergence (the spatial extent of area 17 contacted by an infinitely small region of an afferent structure) and the convergence (the extent of an afferent structure that projects to an infinitely small region of area 17). During postnatal development, the bulk of the connections making up the geniculostriate and corticocortical pathways showed no variation either in their convergence and divergence. However, the projection of area 18 to area 17 and the intrinsic area 17 connections (but not the geniculostriate projection) in the 3-15-day-old kittens were each found to contain a small subpopulation of widely scattered neurones with widespread axonal trajectories. These results, showing that many initially formed connections display a high degree of topographical order, are discussed in terms of the control mechanisms specifying axonal trajectories during development.

Aging↗
PubMed2006

A shift from diffuse to focal cortical activity with development.

Recent imaging studies have suggested that developmental changes may parallel aspects of adult learning in cortical activation becoming less diffuse and more focal over time. However, while adult learning studies examine changes within subjects, developmental findings have been based on cross-sectional samples and even comparisons across studies. Here, we used functional MRI in children to test directly for shifts in cortical activity during performance of a cognitive control task, in a combined longitudinal and cross-sectional study. Our longitudinal findings, relative to our cross-sectional ones, show attenuated activation in dorsolateral prefrontal cortical areas, paralleled by increased focal activation in ventral prefrontal regions related to task performance.

Age Factors↗
PubMed1994

Patterns of capillaries in developing cerebral and cerebellar cortices of rats.

Patterns of capillaries in cerebral and cerebellar cortices were studied in developing rats. In cerebral cortex, the ventricular zone is well vascularized throughout the developmental period. The cell dense cortical plate is poorly vascularized, with capillary branches appearing in individual layers as they emerge from the cortical plate. In cerebellar cortex, the external granular layer appears devoid of capillary branches. Capillary branching appears first in the Purkinje and granule cell layers and later in the molecular layer. These results indicate: (1) an inside-out pattern of development of capillaries in both cortices, and (2) marked differences in vascularization of the proliferative zones for cerebral and cerebellar cortical neurons.

Aging↗
PubMed1994

Regulation of D-aspartate release by glutamate and GABA receptors in cerebral cortical slices from developing and ageing mice.

The basal release of D-[3H]aspartate, an unmetabolized analogue of glutamate, from cerebral cortical slices remained at the same level from three-day-old to 24-month-old mice, but the response to K+ stimulation (50 mM) was smaller in young than in adult or aged mice. Kainate, N-methyl-D-aspartate and quisqualate (0.1 mM) stimulated the basal release of D-aspartate in the cerebral cortex of seven-day-old mice, the effects of kainate and N-methyl-D-aspartate being reduced by their antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and dizocilpine maleate, respectively, indicating that in the immature cerebral cortex the kainate and N-methyl-D-aspartate types of the glutamate receptor are involved in the basal release. The K(+)-stimulated release was not affected by glutamate agonists in developing mice, though they markedly attenuated the evoked release in adults. The inhibitory amino acids GABA, taurine and glycine depressed the K(+)-stimulated release only in the adult cerebral cortex. The action of GABA was abolished by bicuculline, demonstrating the involvement of presynaptic GABAA receptors. The glycine effect was strychnine-insensitive, characteristic of the glycine modulatory site in the N-methyl-D-aspartate receptor. This kind of regulation by both kainate and N-methyl-D-aspartate receptors could be of physiological significance, particularly in the immature cerebral cortex.

Aging↗
PubMed1983

The embryonic development of the cortical plate in reptiles: a comparative study in Emys orbicularis and Lacerta agilis.

From the earliest stage of its ontogenesis, the mammalian cerebral cortex displays a remarkable cytoarchitectonic organization, with its neurons oriented radially within the cortical plate (CP). It is not known whether this radial organization of cortical neurons is characteristic of every cerebral cortex or whether it reflects a progressive phylogenetic acquisition. In order to study this question, the embryonic development of the cortex has been examined in reptiles, where it is the most primitive. Two species, Emys orbicularis and Lacerta agilis, representative of the two principal reptilian orders (chelonians and squamates), have been studied with histological methods. Golgi impregnation, and electron microscopy. Very similar patterns of cell proliferation, migration, maturation, and synaptogenesis have been observed. However, important species differences are present in the cellular organization of the cortical plate. Whereas in Emys the structure of the cortical plate is rudimentary, in Lacerta it appears well developed and quite reminiscent of its mammalian counterpart. Preliminary comparisons with embryological preparations of Sphenodon and Crocodilus niloticus show that the organization of the cortical plate displays significant variations among the different reptilian groups. The present results suggest that the radial organization of cortical neurons is not an all or nothing phenomenon but has been acquired independently and is thus a case of homoplasy, probably due to convergence (Northcutt, 81). Several possible implications of these findings are discussed and a working hypothesis based on the role of radial glial cells in the formation of cytoarchitectonic patterns (Rakic, '80) is presented.

Animals↗
PubMed1978

Early development of visual cortical cells in normal and dark-reared kittens: relationship between orientation selectivity and ocular dominance.

1. 535 units were recorded in the primary visual cortex in twelve normally reared and fifteen dark-reared kittens aged between 8 and 50 days. These results were pooled with a previous study of 582 units recorded from thirty-five kittens reared in similar conditions. 2. These 1117 cells were classified into four functional classes of neurones: (a) visually unresponsive cells, (b) non-specific cells which were sensitive to spots or slits of light moving in any direction, (c) immature cells which were preferentially activated by a rectilinear stimulus but unselective regarding its precise orientation and (d) specific cells that appeared to be as selective for orientation as the simple or complex cells in the adult cat. 3. The results confirm that cells having the same orientation-specific response properties as adult cortical visual neurones are present in the earliest stages of post-natal development, independently of visual experience. However, to maintain and develop these specific cells after the third week of post-natal life, visual experience is necessary. 4. The ocular dominance of visual cells is not constant from the earliest stages of development. A significant increase in binocularly driven neurones occurs with age. 5. Before 3 weeks of age, whatever the rearing conditions, there are more specific cells coding horizontal and vertical orientations than those coding oblique orientations. These 'horizontal and vertical detectors' are preferentially driven by the contralateral eye. 5. After 4 weeks of age, specific neurones are found at all orientations in normally reared kittens. At this stage of development the ocular dominance is independent of orientation preference, of the functional class of neurones considered and of the rearing conditions. The proportion of binocularly driven cells is slightly below adult standard. 7. A hypothesis of differential plasticity is proposed: contralateral, monocular 'horizontal and vertical detectors' are supposed to be stable; they would remain so until they become binocular. Binocular cells, for which competition between two inputs occurs, are the labile units which can be despecified or specified under the control of visual experience.

Action Potentials↗
PubMed1996

The hierarchical development of monkey visual cortical regions as revealed by the maturation of parvalbumin-immunoreactive neurons.

The prefrontal cortex is known to be involved in behavioral paradigms requiring decisions based on short-term working memory, and visually related areas of prefrontal cortex represent the final point in a proposed hierarchical sequence of visual signal processing that begins in primary visual cortex. This study asks if the development of at least certain aspects of the circuitry of each region involved in this hierarchy proceeds in a sequential fashion from primary to higher-order areas. The timing and patterns of expression of immunoreactivity for the calcium-binding protein parvalbumin were examined in areas V1, V2, TE, 7a, and 46 in two series of macaque monkeys ranging in age from embryonic day 132 to adult. The number and laminar distribution of parvalbumin-labeled neurons reached adult levels first in area V1 (primary visual cortex), followed by the adjacent visual association area V2, and then by the higher-order regions of the inferior temporal (TE), posterior parietal (7a) and prefrontal (46) cortices. The appearance of parvalbumin immunoreactivity in the axons of the two major classes of local circuit neurons that express this protein, basket and chandelier cells, followed a similar regional pattern. Furthermore, striking differences were present between these two neuronal populations in the laminar pattern and time course of parvalbumin labeling of their axons. These findings demonstrate that at least some aspects of the intrinsic circuitry of the neocortex mature in accordance with a functional hierarchy of cortical regions. In addition, they illustrate the complexity of cortical development in terms of the different timing of expression of even a single protein in different compartments within single neurons, in different cell types, in different laminae within a region, and across different cortical regions.

Animals↗
PubMed1990

Early development of SI cortical barrel subfield representation of forelimb in normal and deafferented neonatal rat as delineated by peroxidase conjugated lectin, peanut agglutinin (PNA).

Development of the barrel field representation of the forelimb in the primary somatosensory cortex (SI) was studied in normal and deafferented neonatal rat pups by means of the peroxidase conjugated lectin peanut agglutinin (PNA), which most likely binds to radial glial cells within barrel boundaries. 1. Alterations in lectin binding were seen in animals sacrificed on postnatal day 8 (PND-8) if deafferentation took place on PND-1 (day of birth) through PND-6. 2. Deafferentation on PND-5 or on PND-6 had the least effect on lectin binding. In these animals, lectin binding was reduced, although the prospective representation was intact. 3. Deafferentation on PND-2, 3, and 4 had the greatest effect on lectin binding. In these animals, lectin binding was reduced and the prospective cortical representation was disrupted. 4. Deafferentation on PND-1 resulted in reduced lectin binding, however the prospective cortical representation was only slightly impaired compared to that in animals deafferented on PND-2, 3, and 4. 5. These results suggest that SI barrel field boundaries are important to plasticity and that a sensitive period for predevelopment of the forelimb barrels consists of postnatal days 1 through 6. Furthermore, the formation of normal SI barrel field boundaries requires an ongoing interaction between incoming afferents and radial glial cells.

Afferent Pathways↗
PubMed2002

Interaction of excitatory amino acid agonists with cortical afterdischarges in developing rats.

PURPOSE: To determine the role of excitatory amino acids (EAAs) in genesis of two types of epileptic afterdischarges. METHODS: Cortical stimulation and recording electrodes were implanted in 12-, 18-, and 25-day-old rats. Epileptic afterdischarges were induced by rhythmic stimulation of sensorimotor cortex. The stimulation was repeated 6 times with 20-min intervals. Ten minutes after the first afterdischarge, N-methyl-d-aspartate, homocysteine, or kainic acid was injected. The doses were chosen individually for different age groups to be subconvulsive. Type and duration of afterdischarges as well as type and severity of motor correlates were evaluated. RESULTS: N-methyl-d-aspartate prolonged afterdischarges only in 12-day-old rats, whereas two other drugs did it in all age groups. Motor correlates of afterdischarges were changed to flexion seizures in 12-day-old rats after N-methyl-d-aspartate and homocysteine; in 25-day-old rats homocysteine led to generalized tonic-clonic seizures (i.e., both patterns seen after substantially higher doses of these drugs in nonstimulated rats). Seizures lasted tens of minutes. Kainic acid did not change the motor pattern in any age group, but nonconvulsive EEG seizures were recorded in the interstimulation periods mainly in 18- and 25-day-old rats. Increased transition into the limbic type of afterdischarges appeared only after homocysteine in 18- and 25-day-old rats. CONCLUSIONS: A mutual potentiation of epileptic phenomena was induced by two agents. The actions of N-methyl-d-aspartate and kainic acid differ in all age groups; the effects of homocysteine were identical with those of N-methyl-d-aspartate in 12-day-old rats but not later. Only homocysteine augmented transition into the limbic type of afterdischarges.

Aging↗
PubMedDate not supplied

Development of corticospinal tract fibers and their plasticity. II. Neonatal unilateral cortical damage and subsequent development of the corticospinal tract in mice.

In this study, the right cerebral cortices of mice on postnatal day 0 (P0) were cryocoagulated with dry ice. Subsequent development of the corticospinal tract (CST) was studied morphologically and quantitatively, and was compared with that in age-matched controls. When the pyramidal tract was traced anterogradely by injecting HRP into the sensorimotor area of the left cerebral cortex of adult operated mice, the right CST originating from the healthy left hemisphere showed remarkable hypertrophy. The number of axons in the CST at the C4-C6 level became maximum on P14 in the control mice and rapidly decreased thereafter. In the operated mice, the axonal number in the right CST also was maximal on P14 and then rapidly decreased. However, the decrease in axonal number after P21 was less in the operated mice than in the controls. Moreover, the number of axons showed a slight increase after P56. These results indicate that the physiological elimination of the parent axons and their collaterals is much lower in the operated mice than in the controls, and that the increase in axon collaterals from parent axons in the hypertrophic right CST persists a long time in the operated mice.

Animals↗
PubMed1994

Binocular interactions in striate cortical neurons of cats reared with discordant visual inputs.

The postnatal development of cortical binocularity is known to be adversely affected by early abnormal visual experience. However, little information exists on how the signals from the two eyes are combined in individual cortical neurons of animals reared with early discordant binocular visual experience. Since this is a fundamental issue in understanding visual cortical development, we used extracellular single-unit recording methods to study binocular integration in striate cortical neurons of strabismic cats. Specifically, we measured the sensitivity of individual cells to the relative interocular spatial phase of dichoptically presented drifting sinusoidal gratings (i.e., to binocular retinal image disparity). Clear alterations in ocular dominance were observed in all strabismic subjects. Nevertheless, the majority of cortical neurons exhibited some form of binocular interactions when both eyes were stimulated together. The most prominent aspect of cortical physiology in the strabismic animals was the relatively high prevalence of suppressive binocular interactions. Suppression was most frequently found in kittens reared with 2 weeks of early optical dissociation and among adult cats that received 2 weeks of early optical dissociation and a prolonged recovery period. However, substantial excitatory binocular interactions were also maintained in these animals. With an extended period of interocular misalignment (3 or 8 months), all forms of binocular interactions, excitatory and suppressive, were drastically reduced and a greater number of neurons were truly monocular. Although the reduction in the strength of binocular interactions occurred in all units irrespective of their monocular spatial properties, the effect was more pronounced among those units tuned to higher spatial frequencies and this spatial-frequency-dependent effect was larger in the subjects receiving longer periods of binocular dissociation. The results suggest that the "breakdown" of cortical binocular properties in strabismic subjects is not an all-or-none process, and that suppressive binocular interactions may be closely associated with the abnormal binocular interactions exhibited by strabismic humans. Furthermore, our findings are consistent with the notion that cortical disparity-detecting mechanisms are spatial-frequency dependent and, thus, can be selectively altered depending on an animal's early visual experience.

Animals↗
PubMed1981

Prenatal formation of cortical input and development of cytoarchitectonic compartments in the neostriatum of the rhesus monkey.

The timing, hemispheric laterality, and mode of termination of input from the prefrontal association cortex to the neostriatum were studied in fetal and neonatal rhesus monkeys using autoradiography for tracing connections. In addition, the cytological maturation of the neostriatum was examined in Nissl-stained sections from the same and other monkeys of selected prenatal and postnatal ages. A small contingent of corticostriatal axons reaches both the caudate nucleus and the putamen by the 69th embryonic day (E69) of the 165-day gestation period in this species and steadily expands over the next 3 fetal months. Throughout this period, ipsilateral perfrontostriatal connections predominate, and only a small and variable amount of label is detectable over the contralateral neostriatum. A major feature of the developing corticostriatal projection is a transfiguration in the distribution of its terminals: from E69 to E95, cortical terminals are distributed uniformly among neostriatal neurons; beginning around E105, areas of higher and lower grain density begin to emerge until finally, by E133, 250- to 500-micrometers-wide circular and elliptically shaped label-free cores perforate a field of densely labeled cortical terminals as in the neostriatum of the adult monkey (Goldman, P. S., and W. J. H. Nauta (1977) J. Comp. Neurol. 171: 369-386). The cytoarchitectonic composition of the neostriatum also changes during gestation: from E69 through E95, the small postmitotic neurons of the immature neostriatum are packed densely and, for the most part, are distributed homogeneously; by E105, they become segregated into cellular islands consisting of densely packed neurons that are encapsulated by fiber-rich annuli and embedded in a matrix of less densely arrayed neurons. The shape and size of the islands in Nissl-stained sections correspond to label-free cores in autoradiograms of fetuses with cortical injections, while the surrounding annuli and adjacent matrix cells correspond to areas of dense accumulation of label. Thus, the formation of the corticostriatal projection in primates involves a transformation in the distribution of ingrowing terminals synchronized with changes in cellular organization of the neostriatum.

Adrenal Cortex Hormones↗
PubMed1996

Glutamate receptor blockade at cortical synapses disrupts development of thalamocortical and columnar organization in somatosensory cortex.

The segregation of thalamocortical inputs into eye-specific stripes in the developing cat or monkey visual cortex is prevented by manipulations that perturb or abolish neural activity in the visual pathway. Such findings show that proper development of the functional organization of visual cortex is dependent on normal patterns of neural activity. The generalisation of this conclusion to other sensory cortices has been questioned by findings that the segregation of thalamocortical afferents into a somatotopic barrel pattern in developing rodent primary somatosensory cortex (S1) is not prevented by activity blockade. We show that a temporary block of N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors in rat S1 during the critical period for barrel development disrupts the topographic refinement of thalamocortical connectivity and columnar organization. These effects are evident well after the blockade is ineffective and thus may be permanent. Our findings show that neural activity and specifically the activation of postsynaptic cortical neurons has a prominent role in establishing the primary sensory map in S1, as well as the topographic organization of higher order synaptic connections.

2-Amino-5-phosphonovalerate↗
PubMed1995

Dizocilpine binding to cerebral cortical membranes from developing and ageing mice.

The binding of [3H]dizocilpine (MK-801) to the N-methyl-D-aspartate (NMDA)-gated ion channel was characterized in cerebral cortical membranes during the major portion of the mouse life-span (from 7-day- to 22-month-olds). The binding was saturable, consisting of only one component at all ages studied. The maximal binding capacity Bmax was very substantial in 14-day-old mice when compared to adults (3-month-olds), decreasing thereafter during ageing. The binding constant KD remained unchanged during development and increased only slightly in aged mice. Glutamate and glycine potentiated dizocilpine binding concentration-dependently. Their efficacy varied markedly with age. Both glutamate and glycine had considerably less effect on the immature cerebral cortex and in the oldest group of mice (22-month-old) than in young adults. The marked increase in dizocilpine binding sites at the age of 2 weeks coincides with the previously reported transient increase in NMDA binding sites in the cerebral cortex. The weak potentiation of dizocilpine binding by glutamate and glycine in the immature brain could be a factor which protects neurons during this period from excitotoxicity and increased susceptibility to seizures induced by acidic amino acids. The decrease in the number of dizocilpine binding sites during ageing could result partly from the loss of cortical neurons.

Age Factors↗
PubMedDate not supplied

Minicolumnar organization within somatosensory cortical segregates: I. Development of afferent connections.

This series of two articles develops a hypothesis on the modular organization of somatosensory cortex. The hypothesis is built around two functional entities: the segregate, a discrete somatosensory cortical macrocolumn approximately 0.5 mm in diameter, and the minicolumn, a smaller column approximately 0.05 mm in diameter, 40-80 of which make up a segregate. The hypothesis proposes that during perinatal development, minicolumns, acting via their short-range inhibitory and longer-range excitatory lateral connections, play an important role in the selection of thalamic connections to neighboring minicolumns. More specifically, the thalamic connections to each minicolumn are shaped by the interaction of that minicolumn primarily with those neighbors that belong to the same segregate. The outcome of this within-segregate self-organizational process is that (1) the minicolumns in a segregate acquire a complex but orderly pattern of afferent connections; (2) this connectional pattern, along with lateral inhibition, gives the minicolumns diverse receptive fields, arranged in a shuffled but orderly manner; and, most importantly, (3) the minicolumns and the segregate as a whole acquire a variety of stimulus feature-extracting properties. A computer-based model of a segregate is developed to show that under conditions found in the developing cerebral cortex, the thalamocortical connections within a segregate readily form complex patterns as proposed by the hypothesis. Furthermore, the connectional patterns developed by the model segregate, its receptive field organization, and its feature-extracting properties (the latter are described in the following article) reproduce many experimentally observed features of real cortical networks.

Animals↗