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Synchronous development of motor cortical output to different muscles in the kitten.

Previous observations indicate that the output linkages from motor cortex (area 4) to triceps brachii motoneurons develop relatively late in the postnatal kitten. Responses in multiple, simultaneously-recorded EMG's from facial, forelimb and proximal hindlimb musculature to intracortical microstimulation appear over gestational days 107-111 (about 41 days postnatally). Thus, output from the motor cortex to alpha motoneurons develops in a synchronous, rather than a sequential manner across the area 4 homunculi.

Aging↗

Paired-pulse and frequency potentiation of cortical responses in developing rats.

The postnatal development of paired-pulse and frequency potentiations of the first positive and negative components (P1N1) of the cortical interhemispheric response (IHR) was studied in urethane anesthetized rats aged from 7 to 90 days. The paired-pulse potentiation appeared in the rat sensorimotor cortex starting from the age of 15 days. The magnitude of potentiation increased with age. The interpulse interval inducing maximum potentiation shortened from 125 ms in 15-day-old rats to 70 ms in adult rats. Similar results concerning the paired-pulse responses were found for visual cortex but the maturation was somewhat delayed--potentiation first appeared at postnatal day (PND) 18. The frequency potentiation reached adult properties in the sensorimotor cortex by PND 25. There is no time coincidence in the development of the two potentiation phenomena studied, paired pulse potentiation appeared earlier than frequency potentiation.

Animals↗

Effect of a glutamate receptor antagonist (GYKI 52466) on 4-aminopyridine-induced seizure activity developed in rat cortical slices.

In the present experiments we have tested the effect of the noncompetitive AMPA antagonist GYKI 52466 (20-80 microM) on spontaneous epileptic discharges developed as the consequence of 4-aminopyridine application in neocortex slices of adult rats. Parallel to the changes of spontaneous activity, the field potentials, evoked by electrical stimulation of the corpus callosum, were also analyzed. Glass microcapillary extracellular recording electrode was positioned in the third layer of the somatosensory cortex slice, while the stimulating electrode was placed at the border of the white and gray matter. 4-aminopyridine and GYKI 52466 were bath-applied. The application of 40 microM GYKI 52466 caused about 40% decrease in the frequency and the amplitude of spontaneous seizures as well as the duration of each discharges developed in 4-amino-pyridine. Pre-incubation with the AMPA antagonist effectively inhibited both the development of seizure activity and the maintenance of the discharges. GYKI 52466 also decreased the duration and amplitude of field responses evoked by stimulation of the corpus callosum. This inhibitory effect was dose-dependent. Our data in the in vitro cortex slice epilepsy model suggest that the non-competitive AMPA antagonist GYKI 52466 is a potent anticonvulsant and neuroprotective compound because it reduced the fully developed epileptic discharges or prevented their development.

4-Aminopyridine↗

Short-term synaptic plasticity in the rat geniculo-cortical pathway during development in vivo.

The critical period for visual system development in rats normally peaks at postnatal three weeks and ends at postnatal five weeks. However, the change of short-term synaptic plasticity during this period has rarely been investigated. In the present study, we compared the short-term plasticity of visual cortical responses to lateral geniculate nucleus stimulation in rats at different development stages (P20, P30 and adult) in vivo. The results show that paired-pulse depression (PPD) and frequency-dependent depression of evoked field potentials (FP) are present in P20 rats and increase in magnitude with development. The time course of this maturation of synaptic depression parallels that of the visual critical period. The weak synaptic depression observed in juvenile rats may be important in enhancing excitatory neurotransmission at a time when synapses are immature; this could endow immature synapses with wide integrative capabilities. In contrast, suppressive temporal interactions could provide an important substrate for neuronal processing of visual information in the mature cortex.

Animals↗

Oligoclonal peripheral T-cell lymphocytosis as a result of aberrant T-cell development in a cortical thymoma.

A 42-year-old man presented with a locally invasive cortical thymoma. Before chemotherapy was commenced 36 months after presentation, an unusual peripheral lymphocytosis of 19 x 10(9)/l had slowly developed over time. After the first course of chemotherapy, the lymphocytosis showed a sharp decline to normal absolute cell numbers and subsequently remained at normal levels. Currently, the patient is in stable partial remission and doing well. Immunophenotypic analysis showed a mature T-cell phenotype with 78% TcR-a beta and 16% TcR-gamma delta in the absence of an immature component. Pretreatment Southern blot analysis of peripheral blood mononuclear cells showed an oligoclonal pattern with 13-20 rearranged fragments of different intensity for the TcR beta-gene. TcR gamma also showed a pattern compatible with an oligoclonal proliferation. After treatment, after normalization of absolute blood counts, the distribution of T-cell subsets still showed a slightly aberrant pattern. Immunophenotypic analysis of a blood sample taken 6 months later, also at normal absolute cell counts, showed an increase of thymocytes as well as of mature T cells with a polyclonal pattern on Southern blot analysis. These findings may be interpreted as the result of aberrant positive and negative selection and development of thymocytes in the microenvironment of neoplastic thymic epithelial cells and clonal selection through continuous peripheral stimulation. Moreover, this case stresses the importance of integrated interpretation of clinical, morphological, immunophenotypical, and molecular data to gain insight in unusual clinical problems.

Adult↗

The relevance of visual perception to cortical evolution and development.

The quality of brightness--perhaps the simplest visual attribute we perceive--appears to be determined probabilistically. In this empirical conception of the perception of light, the stimulus-induced activity of visual cortical neurons does not encode the retinal image or the properties of the stimulus per se, but associations (percepts) determined by the relative probabilities of the possible sources of the stimulus. If this theory is correct, the rationale for the prolonged postnatal construction of visual circuitry--and the evolution of this visual scheme--is to strengthen and/or create by activity-dependent feedback the empirically determined association on which vision depends.

Animals↗

Cortical photons in early development of frog eggs: comparative study of photon emission between nuclear division and cytoplasmic fission.

In the study of cell division in the early development of frog eggs, cortical photon emission was investigated by converting small light emission from living cells into digital pulses of potentials and recording the integrals of these pulses (analog method), counting the number of pulses (photon-counting method), and counting the number of integrated pulses (improved photon-counting method). By the analog and improved photon-counting methods, changes in photon emission due to cell division could be clearly detected. The emitted light increased about 5.10(-19)W at the start of a cleavage furrow. Rapid changes in chemical reactions causing photon emission were compared during nuclear division and cytoplasmic phases. This emission occurred mainly in cytoplasmic fission, the rate being greater than in nuclear division by a factor of about 2.9. Chemical reaction rates were shown to differ according to bulk emission, thus indicating the mechanisms for the reactions to also differ.

Animals↗

The role of leptin in the development of the cortical neuron in mouse embryos.

Leptin is an obese gene product that decreases appetite and raises energy expenditure in adults. We previously reported that leptin was detected in the sera of mouse embryos and leptin receptors were expressed in the mouse embryonic cerebrum, suggesting that leptin plays a role in cerebral development. In this study, we injected leptin into the lateral ventricle of the cerebrum in leptin-deficient ob/ob mouse embryos to investigate the function of leptin in cerebral development. When leptin was injected on embryonic day (E) 14, the ratio of the number of cells in the cortical plate (CP) to that in the intermediate zone (IZ) was higher in leptin-injected than in vehicle-injected ob/ob embryos on E16, although there was no significant difference in the number of cells in the ventricular zone (VZ), IZ, or CP between these groups. The number of postmitotic BrdU-positive CP cells was larger in leptin-injected than in vehicle-injected ob/ob embryos on E16 and E17 when BrdU labeling and leptin injection were performed on E14. By in situ hybridization, NPY mRNA expression in CP neurons on E18 was weaker in leptin-injected than in vehicle-injected ob/ob embryos when leptin was injected on E16. These results suggest that leptin promotes the migration of neuronal lineage cells to CP and that the leptin-NPY axis in neurons works in the cerebral cortex on E16.

Age Factors↗

The cortical reaction and development of activation competence in mammalian oocytes.

Blocks to polyspermic fertilization are necessary to prevent the incorporation of two sperm nuclei into a zygote's genome, which would result in abnormal development. Many mammalian eggs utilize both an extracellular zona pellucida block to polyspermy and a plasma membrane block. Although little is known about the plasma membrane block in mammals, fertilization results in zona glycoprotein modifications caused by enzymes released by the egg and its cortical granules (CG). This article reviews other recent investigations demonstrating that the oocyte's ability to cause CG release and the block to polyspermy develops near the time of ovulation. The development of normal "activation competence' is likely to involve preovulatory changes in the oocyte's ability to signal the release of intracellular calcium as well as to respond to this calcium increase, resulting in CG exocytosis. Because normal activation competence appears to have a brief temporal window after oocyte meiotic maturation is resumed and since the oocytes are collected at various stages in assisted reproductive procedures, these studies are relevant to optimizing clinical success.

Animals↗

Acetylcholine release from rat cortical slices during postnatal development and aging.

Acetylcholine release from cortical slices superfused with choline-enriched Krebs solution containing physostigmine was investigated at birth, at 7, 20 and 30 days, and at 3 and 24 months of age, in order to assess age influence on the functional efficiency of the cortical cholinergic network. The slices were electrically stimulated at frequencies from 1 to 10 Hz for 5 min periods, preceded and followed by rest periods. The superfusate was collected every 5 min and acetylcholine content quantified by bioassay. In the newborn and 7 day-old pups acetylcholine release was approximately 50% lower than that of the 3 month-old rats at all frequencies tested. The highest release was elicited in the 30 day-old rats. Beginning with this age the evoked ACh release underwent a decline which in the 24 month-old rats brought it back to the same level as in the newborn ones. The blockade of the muscarinic autoreceptors by atropine 1.5 X 10(-8) M caused an increase in acetylcholine release at 20 day, 3 and 24 months of age but not in the newborn and 7 day-old pups. Adenosine 3 X 10(-5) M decreased acetylcholine output in newborn and adult but had no effect in the senescent rats.

Acetylcholine↗

Thalamic ablations and neocortical development: alterations of cortical cytoarchitecture and cell number.

The diversity of neocortical cytoarchitecture could arise from genetic prespecification of cell types and numbers in the ventricular zone, by interaction of cells with their immediate environment, efferent targets, or afferent inputs. Here, we examine the role of the thalamus as efferent target or afferent source in the early control of cell number and type in the developing neocortex. Electrolytic lesions of the thalamus were made in hamsters at birth prior to the thalamic innervation of layer IV. By postnatal day 7, when migration to the cortex is complete, there were no differences in cell number between the cortical plate contralateral and ipsilateral to the thalamic lesion, showing that the absence of thalamic input does not influence the last phases of neocortical cell generation or migration. However, the incidence of pyknotic cells was elevated in the upper half of the cortical plate at this time. By adulthood, the number of cells per unit column of cortex was reduced, due to the apparent absence of small, nonpyramidal cells of layer IV, as determined from Nissl-stained material. Therefore, some of the cytoarchitectonic variability of the neocortex could arise epigenetically by the interaction of neocortical cells with their afferent connections.

Animals↗

Development of the cortical dysplasia of type II lissencephaly.

A detailed neuropathological study of five immature brains with type II lissencephaly is reported. The cases described include two pairs of siblings. One infant survived for 2 months after birth, the others died at 18, 20, 20 and 32 weeks of gestation. This series of cases demonstrates the sequence in which the malformation develops from mid-gestation to post-natal life and shows that type II lissencephaly is not an intracortical malformation but is the result of massive glial and neuronal ectopia in the leptomeninges. This results from a failure of arrest of neuronal migration due to defects in the integrity of the pial/glial barrier.

Brain↗

Morphometric analysis of the development of the cortical layers and extension of the forceps major of the corpus callosum in the mouse.

The reduction of the forceps major of the corpus callosum was estimated quantitatively in relation to the lesions to the neocortex in animals to which methylazoxymethanol-acetate (MAM) had been administered on the 13 th, 15 th or 17 th day of embryonic development. The specimens which received a prenatal injection of MAM the 13 th or 15 the day of gestation show noticeable reductions in both the extension of the occipital neocortex and the forceps major of the corpus callosum. Parallelly in MAM 13 there is a significant reduction in cell density both in the deeper layers and the more superficial ones, whereas in MAM 15 only the supragranular layers seem to be altered. Such a quantitative analysis shows a close correlation among the decreases in the area of the forceps major of the corpus callosum, in the area of the occipital neocortex and in cell density of the infragranular and supragranular layers.

Animals↗

Effect of protein malnutrition on development of mouse cortical barrels.

Undernutrition has been shown to have a profound effect on the central nervous system of maturing experimental animals, not only on gross brain weight and chemical constitution but also on cell structure and function. The present study was undertaken to determine the effect of protein malnutrition on the cortical barrels of mouse. Animals were conceived in and suckled by mothers maintained on an 8% casein diet or on a stock diet. After weaning, mouselings were maintained on their respective diets ad libitum. Four experiments were performed on these mouselings: (1) study of the development of the barrels by the Nissl method; (2) study of the effect of vibrissal damage at different postnatal ages; (3) study of the size of the barrel area and the number of neurons at different postnatal ages; and (4) study of the selectivity of the Golgi-Cox method. The findings from comparison of malnourished mice with mice on a normal diet were :(1) a two-day delay in the development of the barrels; (2) a two-day lengthening of the period of vulnerability of barrel field neurons to neonatal vibrissal damage; (3) the barrel field area and the relative number of neurons were reduced, with the percentage of reduction decreasing with age; and (4) there was no significant difference in the average percentage of Golgi-stained neurons at different ages. These results suggest that poor nutrition has a profound effect on the development and final form of a well-defined neocortical region. The data presented here provide a useful base line against which various therapeutic regimens to reverse the effects of malnutrition on brain structure may be tested. They also suggest that inducing malnutrition may be an important way in which to manipulate the development of the nervous system in order to study the mechanisms responsible for its final form and function.

Age Factors↗

Partial cortical deafferentation promotes development of paroxysmal activity.

This study tested the hypothesis that early functional alterations in neuronal synchrony in the partially deafferented cortex may lead to spontaneously occurring electrographic seizures. In vivo experiments with partial deafferentation of cat suprasylvian gyrus after extensive undercut of the white matter were conducted using multi-site EEG, extracellular unit and intracellular recordings. The amplitudes of EEG waves were much higher in the areas surrounding deafferented cortical fields as compared with control and with undercut cortex. In 40% of animals with undercut cortex, paroxysmal activity occurred 2-3 h after the undercut and was initiated in the relatively intact cortex, adjacent to the more disconnected one. The seizures that followed the undercut consisted of spike-wave/polyspike-wave complexes and fast runs, resembling the electrographic patterns of some clinical epileptic syndromes. An increased local synchrony in the relatively intact cortex evolved into paroxysmal activity that ultimately spread to the deafferented cortex. The electrographic seizures were found only in animals that showed a propagation of the slow sleep-like oscillation in control conditions. The increase of long-range synchrony within a given seizure was associated with seizure termination. These results indicate that alterations in neuronal synchrony following neuronal trauma can be a critical factor triggering electrographic seizures.

Animals↗

The COMT val158met polymorphism is associated with early pubertal development, height and cortical bone mass in girls.

Estrogens are involved in accretion of bone mass during puberty. Catechol-O-Methyltransferase (COMT) is involved in the degradation of estrogens. In this cross-sectional study we investigated associations between the COMT val158met polymorphism, which results in a 60-75% difference in enzyme activity between the val (high activity = H) and the met (low activity = L) variant, and skeletal phenotypes in 246 healthy pre/early pubertal girls. Girls with COMT(LL) were 5.4 cm taller than COMT(HH) girls. Dual x-ray absorptiometry showed higher values of bone mineral content (BMC), and larger areas of total body, femur and spine in COMT(LL). Cortical BMC, measured by peripheral quantitative computerized tomography in the tibia, was 9.8% higher in COMT(LL) compared with COMT(HH). This was due to a larger cortical cross sectional area while the cortical volumetric bone mineral density was not associated with COMT genotype. COMT(LL) girls had higher serum levels of free estradiol and insulin like growth factor. Regression models indicated that COMT genotype exerted effects on skeletal growth mainly via a regulation of free estradiol, resulting in an affected pubertal development (Tanner staging). We propose that the COMT(LL) genotype results in higher free estradiol levels and earlier pubertal development, leading to an increased skeletal growth in pre/early pubertal girls. Possible consequences for the adult skeleton however can be determined only after cessation of growth.

Absorptiometry, Photon↗