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At least 19 recordsLinked to original sources
PubMed2001

Fluorescent tracer in pilocarpine-treated rats shows widespread aberrant hippocampal neuronal connectivity.

Neuronal fibres of the hippocampal formation of normal and chronic epileptic rats were investigated by fluorescent tracing methods using the pilocarpine model of limbic epilepsy. Two months after onset of spontaneous limbic seizures, hippocampal slices were prepared and maintained in vitro for 10 h. Small crystals of fluorescent dye [fluorescein (fluoro-emerald) and tetramethylrhodamine (fluoro-ruby)] were applied to different hippocampal regions. The main findings were: (i) in control rats there was no supragranular labelling when the mossy fibre tract was stained in stratum radiatum of area CA3. However, in epileptic rats a fibre network in the inner molecular layer of the dentate gyrus was retrogradely labelled; (ii) a retrograde innervation of area CA3 by CA1 pyramidal cells was disclosed by labelling remote CA1 neurons after dye injection into the stratum radiatum of area CA3 in chronic epileptic rats; (iii) labelling of CA1 neurons apart from the injection site within area CA1 was observed in epileptic rats but not in control animals; and (iv), a subicular-hippocampal projection was present in pilocarpine-treated rats when the tracer was injected just below the stratum pyramidale of area CA1. The findings show that fibre rearrangement in distinct regions of the epileptic hippocampal formation can occur as an aftermath of pilocarpine-induced status epilepticus.

Action Potentials↗
PubMed2002

The neurotrophins NT3 and BDNF induce selective specification of neuropeptide coexpression and neuronal connectivity in arcuate and periventricular hypothalamic neurons in vitro.

Little is known on the influence of epigenetic factors in the developing hypothalamus, a region particularly involved in neuroendocrine regulation and rich in neuropeptides. The present study evaluated the effects of neurotrophins and neuronal activity on neuronal differentiation in hypothalamic cultures sampled from either arcuate or anterior periventricular regions of 17-day-old Sprague-Dawley fetuses. Expression of neuropeptides, tyrosine hydroxylase, neurotrophins and neurotrophin receptors was tested on young (6 days in vitro, DIV) and more mature (14 DIV) cultured neurons by multiple reverse transcription polymerase chain reaction on single cells. In parallel, spontaneous postsynaptic currents were recorded as an index of neuronal connectivity. Neurotrophin-3 (NT3) was expressed in a much larger population of neurons than brain-derived neurotrophic factor (BDNF) at both culture times. At 6 DIV, synaptic currents were scarce and expression of the neurotrophin receptors trkB and trkC was found in a small proportion of neurons only. These parameters increased markedly between 6 and 14 DIV, and also upon addition of neurotrophins. The most striking consequence of arcuate neuron maturation in vitro between 6 and 14 DIV was a marked phenotypic specification affecting somatostatin, neuropeptide Y and pro-opiomelanocortin, the three major neuropeptides expressed in the cultures. NT3, but not BDNF, was able to reproduce maturation-related phenotypic specification in 6 DIV arcuate cultures. Maturation-dependent phenotypic specification was less marked in periventricular cultures; in that case BDNF, not NT3 had a slight effect on phenotype specification. It is concluded that NT3 plays a selective role in phenotypic specification of neuropeptides in the arcuate region, whereas other maturation parameters (neurotrophin receptor expression and/or synaptogenesis) can be potentiated by either neurotrophin in both structures.

Animals↗
PubMed1992

Determining the neuronal connectivity of Golgi-impregnated neurons: ultrastructural assessment of functional aspects.

The combined light and electron microscopic analysis of Golgi-impregnated neural tissue is a potent tool for determining the connectivity of neural networks within the brain. In the experimental paradigms commonly applied in these studies, the Golgi-impregnated neurons are typically examined as the postsynaptic neuronal components. The structural characteristics and the pattern of distribution of their synaptic connections with other groups of identified neurons are analyzed. Due to the high power of resolution of the Golgi-electron microscopic technique, the ultrastructural analysis of Golgi-impregnated neurons can be expanded to elucidate activity-dependent structural alterations in their cytoarchitecture. These structural alterations can then be correlated under different physiological conditions with changes in the functional efficacy of the subcellular neuronal components.

Animals↗
PubMed1998

An in vitro technique for tracing neuronal connections in the teleost brain.

The availability of neuronal tract-tracing techniques has been fundamental to the development of the neurosciences. While most of the previously described methods are performed in vivo, in the present paper, detailed protocols are reported for tracing neuronal connections in an in vitro preparation. This technique, tested in various neural systems of the teleost brain, allows precise application of tracer substance(s) under visual control. After the isolation of the brain, the tissue is kept alive by superfusion with oxygenated artificial cerebrospinal fluid in a slice chamber. Neuronal connections are traced by the application of crystals of biocytin or dextran-tetramethylrhodamine to the region of interest. Following intracellular transport over 8-18 h, the tissue is fixed and processed histochemically for visualization of structures filled with the tracer substance. This method can readily be modified for double labelling. Step-by-step procedures are outlined for (a) the simultaneous detection of two tracer substances in the same tissue sample, (b) the combination of tract tracing with the immunohistochemical identification of various biochemical markers such as 'classical' transmitters and neuropeptides, and (c) the visualization of both traced structures and mitotically active cells labelled with the thymidine analogue 5-bromo-2'-deoxyuridine. By exhibiting a high degree of efficiency, the described in vitro tract-tracing technique represents also a significant contribution towards a reduction of living animals in neurobiological experimentation.

Animals↗
PubMed1978

Neuronal connectivity patterns in the compound eyes of Artemia salina and Daphnia magna (Crustacea: Branchiopoda).

The neuronal types and patterns in the visual system of the species Artemia salina and Daphina magna have been studied with the Golgi method and electron microscopy. The lamina contains five classes of neurons: photoreceptor axons, monopolar, centrifugal, tangential and amacrine neurons. The terminals of the receptor axons are distributed in two (A. salina) or three (D. magna) layers. The dilated terminals have an extensive and wide array of fine branches. One axon from each ommatidium bypasses the lamina and terminates in the medula in A. salina. A. salina has four types of monopolar neurons, two of which are stratified, whereas in D. magna only two types are found, one of which is bistratified. Tangential T-neurons connect the lamina with the protocerebrum. D. magna has in addition one tangential T-neuron connecting both the lamina and the medulla with the protocerebrum. In both species monopolar-type centrifugal neurons connect the medulla and the lamina, whereas that of A. salina has a wide laminar distribution. Both species also have amacrine cells in the lamina. The medulla contains, besides those shared with the lamina, transmedullary neurons (two types in A. salina), amacrine cells and neurons originating in the protocerebrum. "Cartridge"-type synaptic compartments are lacking in the investigated species, although a periodic arrangement is discernible in the distal portion of the lamina of A. salina. The receptors from three types of specialized contacts in Artemia, one of which involves a dyad. D. magna has only one-to-one synapses. Neurosecretory fibres are absent in A. salina.

Animals↗
PubMed2006

Heparan sulfate proteoglycans and the emergence of neuronal connectivity.

With the identification of the molecular determinants of neuronal connectivity, our understanding of the extracellular information that controls axon guidance and synapse formation has evolved from single factors towards the complexity that neurons face in a living organism. As we move in this direction - ready to see the forest for the trees - attention is returning to one of the most ancient regulators of cell-cell interaction: the extracellular matrix. Among many matrix components that influence neuronal connectivity, recent studies of the heparan sulfate proteoglycans suggest that these ancient molecules function as versatile extracellular scaffolds that both sculpt the landscape of extracellular cues and modulate the way that neurons perceive the world around them.

Animals↗
PubMedDate not supplied

[Reflection of the plastic properties of very simple neuronal assemblies in the statistical characteristics of the spike activity of their elements. Monosynaptically connected neurons].

Changes of cross-correlation histograms (CCH) of impulse trains and of mean interspike intervals (ISI) of monosynaptically connected neurones under changes of interneuronal connection efficiency, neuronal excitability and action on these neurones of independent irregular afferent synaptic inflows, were studied by methods of mathematical and biomathematical modelling of synaptic neuronal interaction (computer-controlled experiment on mollusc neurones). It was shown that statistical of increase of efficiency of monosynaptic excitatory or inhibitory interneuronal connection (amplitude enhancement of corresponding postsynaptic potential) is an increase of the main peak or trough of normalized CCH of impulse trains accompanied by a decrease of mean ISIs of both neurones.

Animals↗
PubMed2006

Small-world connectivity, motif composition, and complexity of fractal neuronal connections.

Connection patterns of the cerebral cortex consist of pathways linking neuronal populations across multiple levels of scale, from whole brain regions to local minicolumns. This nested interconnectivity suggests the hypothesis that cortical connections are arranged in fractal or self-similar patterns. We describe a simple procedure to generate fractal connection patterns that aim at capturing the potential self-similarity and hierarchical ordering of neuronal connections. We examine these connection patterns by calculating a broad range of structural measures, including small-world attributes and motif composition, as well as some global measures of functional connectivity, including complexity. As we vary fractal patterns by changing a critical control parameter, we find strongly correlated changes in several structural and functional measures, suggesting that they emerge together and are mutually linked. Measures obtained from some modeled fractal patterns closely resemble those of real neuroanatomical data sets, supporting the original hypothesis.

Animals↗
PubMed1994

Reduction of functional neuronal connectivity in long-term treated hypertension.

BACKGROUND AND PURPOSE: Anatomic imaging of patients with chronic well-treated hypertension has demonstrated dilatation of the lateral cerebral ventricles and left brain atrophy, whereas positron emission tomography has shown only subtle reductions in regional cerebral metabolic rates for glucose in some subcortical nuclei. To further explore the implications of the imaging changes, an analytic technique designed to determine functional neuronal connectivity between regions of interest (ROIs) was applied to the data on regional cerebral metabolic rates for glucose to determine if and where in the brain reduction of functional neuronal connectivity occurred. METHODS: Glucose metabolism was measured by positron emission tomography in 17 older men (age, 68 +/- 8 years) with well-controlled, noncomplicated hypertension of at least 10 years' duration and in 25 age- and sex-matched healthy control subjects. A significant correlation difference analysis was performed to determine which ROI pairs had reduced correlation coefficients (reduced functional neuronal connectivity). The vascular pattern of the reduction was determined after allocating the ROIs to their appropriate vascular territories. RESULTS: Compared with the control subjects, hypertensive patients had reduced correlation coefficients in cortical territories of the internal carotid arteries but not of the vertebrobasilar arteries. The border zone supplied by the middle and anterior cerebral arteries was most affected. CONCLUSIONS: The border zone between the anterior and middle cerebral arteries is vulnerable to ischemia from carotid pathology, systemic hypotension, or both. We hypothesize that although these hypertensive patients were "well controlled" and had normal neuropsychological tests, they may have experienced ischemia severe enough to cause border zone reduction of functional neuronal connectivity as a result of carotid pathology, antihypertensive medications, hypotensive episodes with a right-shifted autoregulation curve, or other factors in isolation or combination.

Aged↗
PubMed2001

Interfacing a silicon chip to pairs of snail neurons connected by electrical synapses.

Future hybrid neuron-semiconductor chips will consist of complex neural networks that are directly interfaced to electronic integrated circuits. They will help us to understand the dynamics of neuronal networks and may lead to novel computational facilities. Here we report on an elementary step towards such neurochips. We designed and fabricated a silicon chip for multiple two-way interfacing, and cultured on it pairs of neurons from the pedal ganglia of the snail Lymnaea stagnalis. These neurons were joined to each other by an electrical synapse, and to the chip by a capacitive stimulator and a recording transistor. We obtained a set of neuroelectronic units with sequential and parallel signal transmission through the neuron-silicon interface and the synapse, with a bidirectionally interfaced neuron-pair and with a signal path from the chip through a synaptically connected neuron pair back to the chip. The prospects for assembling more involved hybrid networks on the basis of these neuroelectronic units are considered.

Animals↗
PubMed2004

[Molecular mechanisms of neuronal connective tissue genesis during the course of cerebral cortex development].

The cerebral cortex constitutes one of the most complex structures in our brain. In correlation with its elaborate functions, it is characterized by the great complexity of its neuronal connections, but the mechanisms responsible for the generation of these connections remain poorly known. We have recently initiated the characterization of a new multigenic family of axon guidance factors, the ephrin/Eph gene family, during the development of neuronal connections in the mouse cortex. Combining expression studies, in vitro guidance essays, and in vivo analysis of mutant mice, enabled us to demonstrate the critical role of ephrin/Eph genes in the development of cortical networks. Mutant mice for ephrin/Eph genes display a topographic distortion of their cortical somatosensory map, as well as ectopic projections from the motor thalamus to the somatosensory cortex. The identification of factors like ephrins, capable to (re)specify the pattern of neuronal connections, has implications for our understanding of pathological brain development (epilepsy, abnormal movements, psychiatric diseases), and in the perspective of the rational design of cell therapies of neurodegenerative diseases.

Animals↗
PubMed2005

[Changes of the structure of neuronal connections in visual cortex of cats with experimentally induced bilateral strabismus].

The spatial distribution of neuronal connections in cortical area 17 in cats with bilateral convergent strabismus, surgically induced on postnatal days 10-14, was investigated. Single cortical columns of areas 17 and 18 were microiontophoretically injected with horseradish peroxidase and retrogradely labeled cells in both hemispheres were detected. The intrahemispheric connections in area 17 along the mediolateral direction (the projection of visual field horizontal meridian) were found to be either dilated or reduced. For most columns, the interhemispheric connections in this direction were increased, which may provide for more reliable unification of two visual hemifields. Moreover, the extension of intra- and interhemispheric connections in rostrocaudal direction (along the visual field vertical meridian projection) was detected in some cortical columns. Thus bilateral strabismus induced during the developmental critical period, modifies the structure of both of intra- and inter-hemispheric spatial neuronal connections of individual cortical columns in areas 17 and 18.

Animals↗
PubMed1999

Activity influences on neuronal connectivity within the auditory pathway.

HYPOTHESIS: Sensorineural hearing loss may be associated with altered patterns of neuronal connections within the central auditory pathway. STUDY DESIGN: The cat auditory system was used to address the relative importance of impulse traffic within the auditory nerve in maintaining central nervous system connections. METHODS: Acute, unilateral deafness was induced by tetrodotoxin intoxication of cochlear hair cells. Analysis focused on the structural patterns of contact between auditory nerve endings called end bulbs of Held and their target neurons. Specifically, end bulb morphology and target cell size within the cochlear nucleus were examined. Highly specialized synaptic contacts at this junction provide a powerful site for study. RESULTS: The principal finding was that abolished activity in the auditory nerve caused nerve endings to assume a different shape, typified by more branching and smaller terminal swellings. The new shape is one typically associated with only a subpopulation of fibers in normal-hearing cats--those exhibiting a high-threshold, low-spontaneous activity profile. This result implies that abolished activity alters patterns of nerve fiber contact with second-order neurons. Tetrodotoxin produced differential effects on subpopulations of target neurons within the brainstem and is interpretable on the basis of "weighing" synaptic inputs. Second-order neurons that receive large axosomatic inputs from their parent fiber were significantly smaller than neurons that receive small, axodendritic terminals. Thus, attenuated auditory activity may produce differential effects across the auditory pathway, thereby disrupting the normal balance of inputs into synaptic stations. CONCLUSIONS: Impulse traffic is a critical factor in the interaction between the ear and central auditory stations and appears necessary for the maintenance of key synapses. As hearing disorders with impaired comprehension may be modeled by studies of auditory deafferentation, these observations extend the possibility that changes in central neuronal connections underlie reduced capabilities for processing restored auditory input.

Animals↗
PubMed2002

Synaptic precedence during synapse formation between reciprocally connected neurons involves transmitter-receptor interactions and AA metabolites.

The cellular mechanisms that determine specificity of synaptic connections between mutually connected neurons in the nervous system have not yet been fully examined in vertebrate and invertebrate species. Here we report on a novel form of synaptic interaction during early stages of synapse formation between reciprocally connected Lymnaea neurons. Specifically, using soma-soma synapses between an identified dopaminergic neuron (also known as the giant dopamine cell), right pedal dorsal 1 (RPeD1), and a FMRFamidergic neuron, visceral dorsal 4 (VD4), we demonstrate that although reciprocal inhibitory synapses re-form between the somata after 24-36 h of pairing, VD4 is, however, the first cell to establish synaptic contacts with RPeD1 (within 12-18 h). We show that VD4 "captures" RPeD1 first as a postsynaptic cell by suppressing its transmitter secretory machinery during early stages of cell-cell pairing. The VD4-induced suppression of transmitter release from RPeD1 was transient, and it required transcription and de novo protein synthesis dependent step in VD4 but not in RPeD1. The VD4-induced effects on RPeD1 were mimicked by a FMRFamide-like peptide. Perturbation of FMRFamide-activated metabolites of the arachidonic acid pathway in RPeD1 not only prevented FMRFamide-induced suppression of transmitter release from the giant dopamine cell but also shifted the synaptic balance in favor of RPeD1, thus making it the first cell to begin synaptic transmission with VD4 within 12-18 h. A single RPeD1 that had developed dopamine secretory capabilities overnight and was subsequently paired with VD4 for 12-18 h was, however, immune to VD4-induced suppression of transmitter release. Under these experimental conditions, both cells developed mutual inhibitory synapses concurrently. Taken together, our data provide evidence for novel synaptic interaction between reciprocally connected neurons and underscore the importance of transmitter-receptor interplay in regulating the timing of synapse formation in the nervous system.

Animals↗
PubMedDate not supplied

Stress and the adaptive self-organization of neuronal connectivity during early childhood.

A conceptual framework is proposed for a better understanding of the biological role of the stress-response and the relationship between stress and brain development. According to this concept environmental stimuli (in children mainly psychosocial challenges and demands) exert profound effects on neuronal connectivity through repeated or long-lasting changes in the release of especially such transmitters and hormones which contribute, as trophic, organizing signals, to the stabilization or destabilization of neuronal networks in the developing brain. The increased release of noradrenaline associated with the repeated short-lasting activation of the central stress-responsive systems in the course of the stress-reaction-process to psychosocial challenges which are felt to be controllable acts as a trigger for the stabilization and facilitation of those synaptic and neuronal pathways which are activated in the course of the cognitive, behavioral and emotional response to such stressors. The long-lasting activation of the central stress-responsive systems elicited by uncontrollable psychosocial conflicts in conjunction with the activation of glucocorticoid receptors by the sustained elevation of circulating glucocorticoid levels favors the destabilization of already established synaptic connections and neuronal pathways in associative cortical and limbic brain structures. The facilitation and stabilization of neuronal pathways triggered by the experience of controllable stress is thus opposed, attenuated or even reversed in the course of lon-lasting uncontrollable stress. This destabilization of previously established synaptic connections and neuronal pathways in cortical and limbic brain structures is a prerequisite for the acquisition of novel patterns of appraisal and coping and for the reorganization of the neuronal connectivity in the developing brain. Alternating experiences of repeated controllable stress and of long-lasting uncontrollable stress are therefore needed for the "self-adjustment" of neuronal connectivity and information processing the developing brain to changing environmental (psychosocial) demands during childhood. The brain structures and neuronal circuits involved in the regulation of behavioral responding become thus repeatedly reoptimized and refitted, not the changing conditions of life per se but rather to those conditions which are still able to activate the central stress responsive systems of an individual at a certain developmental stage.

Adaptation, Physiological↗
PubMed1997

Patterning neuronal connections by chemorepulsion: the semaphorins.

Axonal growth cones navigate long distances along specific pathways to establish complex patterns of neuronal connections. A growing number of signals have been identified that participate in these steering decisions. This review will concentrate on a large and growing family of chemorepellents, the semaphorins. This family contains both secreted and membrane-bound proteins expressed in many neuronal and non-neuronal tissues of invertebrates and vertebrates. Ongoing studies have given us a better understanding of how their highly conserved signalling system is involved in patterning neuronal connections.

Animals↗
PubMed2000

Neuronal connections in the medial geniculate body of the guinea-pig.

The spontaneous and evoked activities of individual pairs of single units were recorded simultaneously with the same microelectrode in the medial geniculate body (MGB) of ketamine-xylazine-anaesthetised guinea-pigs. Cross-correlograms (CCGs) of spike train pairs were computed and divided on the basis of correlation peak shape into four classes [a unilateral narrow (UN) peak, a centrally positioned wide (CW) peak, a complex peak and no significant peak] interpreted in terms of the functional connection between neighbouring neurones. The shift predictor procedure was applied with the aim of removing the effect of the stimulus on the final CCG shape. The occurrence of correlation peak types and the distribution of correlation coefficients were found to be similar for the spontaneous activity during silent periods following acoustical stimulation and for the long-lasting recording of spontaneous activity. CCGs in 38% of pairs computed during silent interstimulus intervals contained a UN peak, suggesting a monosynaptic excitatory connection. Almost 20% of all pairs expressed a CCG shape typical for a common input, i.e. a CW peak. In 5% of cases multiple, so-called complex peaks, were found. About 20% of the CCGs contained no significant correlation peak in the interstimulus period, which is typical for a very weak or absent functional connection between recorded neurones. No inhibitory interaction (groove in the CCGs) between recorded pairs was observed. The distribution of correlation peak shapes was similar when calculated during acoustical stimulation and during silent interstimulus intervals. CCGs computed during presentation of four acoustical stimuli (pure tone bursts, noise bursts, natural call whistle and artificially inverted whistle) showed most frequently a UN peak (28-37%) followed by CCGs with no significant peak (18-28%) and with a UN/CW peak (14-23%). On average, the occurrence of UN peaks tended to be less frequent during stimulus presentation than in silent conditions, but the difference was not statistically significant. The most frequent occurrence of clear UN peaks was found in the medial part of the MGB (from 52-64% of pairs depending on the type of acoustical stimulus), while the least was observed in the ventral part of the MGB (12-22%). In contrast, CW peaks were most frequently expressed in pairs located in the ventral part of the MGB (18-33%), while neuronal pairs in the medial part revealed a very low occurrence of CW peaks (0-7%). The occurrence of independently firing neurones was lowest in the medial part of the MGB (8-20% of pairs) in comparison with the ventral (31-39%) and dorsal (12-41%) parts. In 20% of pairs acoustical stimulation produced a change in the type of correlation peak present during spontaneous activity. Most frequently, a CW peak (shared input) changed to a flat CCG, which represents independently firing neurones. In some pairs higher connection strengths (as expressed by the value of the correlation coefficient) were found for silent interstimulus intervals than for acoustical stimulation. This suggests that in the MGB the stimulus may desynchronise the spontaneous activity of simultaneously firing units in neuronal pairs.

Acoustic Stimulation↗