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Biomedical subjects

A van Ooyen

Publications and source records attributed to A van Ooyen.

At least 19 recordsLinked to original sources
PubMed2001

The role of calcium signaling in early axonal and dendritic morphogenesis of rat cerebral cortex neurons under non-stimulated growth conditions.

The effects of depolarizing stimuli on neurite outgrowth have been shown to depend on an influx of extracellular calcium. However, the role of calcium under non-stimulated growth conditions is less well established. Here we investigated the contribution of calcium signaling to early neuronal morphogenesis of rat cerebral cortex neurons at three levels by blocking L-type voltage sensitive calcium channels, by depleting intracellular calcium or by blocking myosin light chain kinase. Detailed quantitative morphological analysis of neurons treated for 1 day revealed that depletion of intracellular calcium strongly decreased the density of filopodia, arrested axonal outgrowth and strongly decreased dendritic branching. Preventing calcium influx through L-type voltage sensitive calcium channels and blocking of myosin light chain kinase activity selectively decreased dendritic branching. Our observations support an essential role for basal intracellular calcium levels in axonal elongation. Furthermore, under non-stimulated conditions calcium entry through L-type voltage sensitive calcium channels and myosin light chain kinase play an important role in dendritic branching.

Animals↗
PubMed2001

The need for integrating neuronal morphology databases and computational environments in exploring neuronal structure and function.

Neurons connect to each other through a myriad of dendritic and axonal arborisations. Dendritic structures provide the substrate for integration of postsynaptic potentials and control of action potential generation. Axonal structures provide the substrate for action potential dissemination and signalling to target neurons. The morphological complexity of dendritic arborisations is assumed to play a critical role in the transformation of spatio-temporal patterns of postsynaptic potentials into time-structured series of action potentials. Although these transformations lie at the basis of information processing in the brain, it is still far from understood how their details are influenced by dendritic shape. To facilitate research in this area, it is necessary that data on both the morphology and electrical properties of neurons, as well as computational tools for analysis, become available in an integrated way. This requires a combined effort from the fields of informatics and neurosciences (together called neuroinformatics) in order to create data acquisition, databasing and computational tools. Focusing on neuronal morphology, this chapter will give a brief review of the current neuroinformatics developments in both reconstruction techniques, morphological quantification, modeling of morphological complexity, modeling of function and the need for databasing neuronal morphologies. Additionally, one of the dendritic modeling approaches is described in more detail in the Appendix.

Animals↗
PubMed2001

Competition in the development of nerve connections: a review of models.

The establishment and refinement of neural circuits involve both the formation of new connections and the elimination of already existing connections. Elimination of connections occurs, for example, in the development of mononeural innervation of muscle fibres and in the formation of ocular dominance columns in the visual cortex. The process that leads to the elimination of connections is often referred to as axonal or synaptic competition. Although the notion of competition is commonly used, the process is not well understood-with respect to, for example, the type of competition, what axons and synapses are competing for, and the role of electrical activity. This article reviews the types of competition that have been distinguished and the models of competition that have been proposed. Models of both the neuromuscular system and the visual system are described. For each of these models, the assumptions on which it is based, its mathematical structure, and the extent to which it is supported by the experimental data are evaluated. Special attention is given to the different modelling approaches and the role of electrical activity in competition.

Animals↗
PubMed2000

Development of nerve connections under the control of neurotrophic factors: parallels with consumer-resource systems in population biology.

The development of connections between neurons and their target cells involves competition between axons for target-derived neurotrophic factors. Although the notion of competition is commonly used in neurobiology, the process is not well understood, and only a few formal models exist. In population biology, in contrast, the concept of competition is well developed and has been studied by means of many formal models of consumer-resource systems. Here we show that a recently formulated model of axonal competition can be rewritten as a general consumer-resource system. This allows neurobiological phenomena to be interpreted in population biological terms and, conversely, results from population biology to be applied to neurobiology. Using findings from population biology, we have studied two extensions of our axonal competition model. In the first extension, the spatial dimension of the target is explicitly taken into account. We show that distance between axons on their target mitigates competition and permits the coexistence of axons. The model can account for the fact that in many types of neurons a positive correlation exists between the size of the dendritic tree and the number of innervating axons surviving into adulthood. In the second extension, axons are allowed to respond to more than one neurotrophic factor. We show that this permits competitive exclusion among axons of one type, while at the same time there is coexistence with axons of another type innervating the same target. The model offers an explanation for the innervation pattern found on cerebellar Purkinje cells, where climbing fibres compete with each other until only a single one remains, which coexists with parallel fibre input to the same Purkinje cell.

Animals↗
PubMed2000

Lateral cell movement driven by dendritic interactions is sufficient to form retinal mosaics.

The formation of retinal mosaics is thought to involve lateral movement of retinal cells from their clonal column of origin. The forces underlying this lateral cell movement are currently unknown. We have used a model of neurite outgrowth combined with cell movement to investigate the hypothesis that lateral cell movement is guided by dendritic interactions. We have assumed that cells repel each other in proportion to the degree of dendritic overlap between neighbouring cells. Our results first show that small cell movements are sufficient to transform random cell distributions into regular mosaics, and that all cells within the population move. When dendritic fields are allowed to grow, the model produces regular mosaics across all cell densities tested. We also find that the model can produce constant coverage of visual space over varying cell densities. However, if dendritic field sizes are fixed, mosaic regularity is proportional to the cell density and dendritic field size. Our model suggests that dendritic mechanisms may therefore provide sufficient information for rearrangement of cells into regular mosaics. We conclude by mentioning possible future experiments that might suggest whether dendritic interactions are adaptive or fixed during mosaic formation.

Adaptation, Physiological↗
PubMed1999

Models of axon guidance and bundling during development.

Diffusible chemoattractants and chemorepellants, together with contact attraction and repulsion, have been implicated in the establishment of connections between neurons and their targets. Here we study how such diffusible and contact signals can be involved in the whole sequence of events from bundling of axons, guidance of axon bundles towards their targets, to debundling and the final innervation of individual targets. By means of computer simulations, we investigate the strengths and weaknesses of a number of particular mechanisms that have been proposed for these processes.

Animals↗
PubMed1999

Competition for neurotrophic factor in the development of nerve connections.

The development of nerve connections is thought to involve competition among axons for survival promoting factors, or neurotrophins, which are released by the cells that are innervated by the axons. Although the notion of competition is widely used within neurobiology, there is little understanding of the nature of the competitive process and the underlying mechanisms. We present a new theoretical model to analyse competition in the development of nerve connections. According to the model, the precise manner in which neurotrophins regulate the growth of axons, in particular the growth of the amount of neurotrophin receptor, determines what patterns of target innervation can develop. The regulation of neurotrophin receptors is also involved in the degeneration and regeneration of connections. Competition in our model can be influenced by factors dependent on and independent of neuronal electrical activity. Our results point to the need to measure directly the specific form of the regulation by neurotrophins of their receptors.

Animals↗
PubMed1999

Poly- and mononeuronal innervation in a model for the development of neuromuscular connections.

In the normal development of connections between motor neurons and muscle fibres, an initial stage of polyneuronal innervation is followed by withdrawal of connections until each muscle fibre is innervated by a single axon. However, polyneuronal innervation has been found to persist after prolonged nerve conduction block, in spite of the resumption of normal neuromuscular activity. Here we analyse in detail a model proposed for the withdrawal of nerve connections in developing muscle, based on competition between nerve terminals. The model combines competition for a pre-synaptic resource with competition for a post-synaptic resource. Using bifurcation and phase space analysis, we show that polyneuronal innervation, as well as mononeuronal innervation, can be stable. The model accounts for the development of mononeuronal innervation and for persistent polyneuronal innervation after prolonged nerve conduction block, which appears as a consequence of the general competitive interactions operating during normal development.

Animals↗
PubMed1997

Effects of inhibition on neural network development through activity-dependent neurite outgrowth.

Empirical studies have demonstrated that electrical activity of the neuron can directly affect the outgrowth of its neurites. In this paper, the implications of activity-dependent neurite outgrowth are studied in a simple two-cell model, containing one excitatory and one inhibitory cell. We show that activity-dependent outgrowth in combination with the presence of inhibition can account for biostability. The attractors, which can be both point and limit cycle attractors, may be associated with "normal" and "pathological" end states of network development. A slight modification of the model makes it applicable also to a range of other activity-dependent processes in neurons, such as changes in the number of efficacy of receptors. The main results of the previous model are also found in the modified model.

Animals↗
PubMed1996

Complex periodic behaviour in a neural network model with activity-dependent neurite outgrowth.

Empirical studies have demonstrated that electrical activity of the neuron can directly affect neurite outgrowth. High levels of activity cause neurites to retract, whereas low levels allow further outgrowth. Previously we studied networks in which all the cells reacted in the same way on electrical activity. Since experiments have shown that neurons may in fact react differentially, we study in this paper networks in which the range of activity where outgrowth takes place varies among cells. We show that this can lead to complex periodic behaviour in electrical activity and connectivity of individual cells. The precise behaviour depends on the spatial distribution of the cells and the distribution of the outgrowth properties over the cells. Any other cellular property that adapts slowly to electrical activity such that neuronal activity is attempted to be maintained at a given level, can lead to similar results.

Animals↗
PubMed1996

Growth cone dynamics and activity-dependent processes in neuronal network development.

Many structural and functional properties of neuronal networks find their origin in the dynamic behavior of growth cones during development. The variation in dendritic morphologies can be traced back to random branching of growth cones. Segment length characteristics arise under random branching and steady growth cone propagation. Delayed outgrowth, as a result of competition between growth cones after splitting, is hypothesized to explain different lengths of paired terminal segments in Purkinje cells. The implications of activity-dependent neurite outgrowth were studied using an outgrowth function based on the theory of Kater et al. (1988, 1990). This theory embodies a homeostatic principle, according to which a neuron adapts its neuritic field so as to maintain a certain level bioelectric activity. It is shown that such homeostasis has many implications for neuromorphogenesis and network formation, as it may underlie phenomena such as overshoot during development, size differences among cells, differentiation between excitatory and inhibitory cells and compensatory sprouting. Finally, function-dependent regulation of development involves physiological as well as morphological variables. For instance, activity dependent regulation of ionic conductances such as to stabilize functional activity can result in a differentiation of certain neurons into, respectively, bursting and regular firing sub-types (Abbot et al., 1993; LeMasson et al., 1993). Similarly, the GABAergic phenotype comes fully to expression in hindbrain (cerebellar) and forebrain (neocortical) networks only if the level of ongoing excitatory activity during development is sufficiently high, whereas chronically intensified activity leads to a compensatory hypertrophy of inhibitory mechanisms (for review, see Corner 1994). Many of these results could only have been obtained by the use of mathematical models which allow rigorous analysis of the consequences of basic assumptions in the dynamics of neurite outgrowth. All in all, the findings further emphasize the role of spontaneous bioelectric activity during early development in neuronal network formation, the importance of which was first established in cultures of developing neural tissue.

Animals↗
PubMed1993

Pattern recognition in the neocognitron is improved by neuronal adaptation.

We demonstrate that equipping the neurons of Fukushima's neocognitron with the phenomenon that a neuron decreases its activity when repeatedly stimulated (adaptation) markedly improves the pattern discriminatory power of the network. By means of adaptation, circuits for extracting discriminating features develop preferentially. In the original neocognitron, in contrast, features shared by different patterns are preferentially learned, as connections required for extracting them are more frequently reinforced.

Adaptation, Physiological↗
PubMed1993

Endemic acinetobacter in intensive care units: epidemiology and clinical impact.

AIMS: To assess whether Acinetobacter isolates obtained over 20 months in a tertiary care hospital were epidemiologically related; to establish the clinical importance of the organisms; and to identify the isolates according to the recent taxonomy. METHODS: Fifty eight Acinetobacter isolates from 49 patients collected during 1984 and 1985 were investigated. Most isolates were from respiratory tract specimens from intensive care patients. The organisms were typed by cell envelope protein electrophoresis and by a quantitative carbon source growth assay; patients' charts were reviewed to differentiate between colonisation and infection; representative isolates were identified to species level by DNA-DNA hybridisation. RESULTS: Twelve protein profiles were distinguished in the isolates. Forty two isolates were of the same protein profile (profile I); other profiles were observed in a few or single isolates. Cluster analysis of carbon source growth divided profile I isolates into two groups--one of isolates from 1984 and one from 1985. They were identified as A baumannii and associated with infections in eight patients. Four other infections were caused by acinetobacters with other protein profiles (three of A baumannii; one of the unnamed DNA group 3). CONCLUSIONS: Apart from sporadic strains, two strains of the same protein profile, but distinguishable by carbon source growth, were successively endemic. Cluster analysis was a valuable tool in the interpretation of typing and epidemiological data. The 12 (28%) infections of Acinetobacter in 43 patients in intensive care suggest that the presence of these organisms in wards of severely ill patients should be a cause of concern.

Acinetobacter↗
PubMed1992

The emergence of long-lasting transients of activity in simple neural networks.

The question was investigated whether long-lasting transients of activity, observed to occur in the intact cerebral cortex (EEG slow (delta) waves and 'K' complexes) as well as in isolated tissues cultured in vitro, can also emerge in a model network of excitatory and inhibitory cells. We show that such transients can indeed occur even if the cells do not have built-in slow kinetics. For certain parameter settings, the network is in a bistable state in which periods of increased activity (long-lasting transients) alternate with minimal activity. Transients are triggered by spontaneously firing cells ('noise'), which, rather than via a build-up of recurrent synaptic inhibition, also initiate their termination. During a transient, the network continually makes transitions from one equilibrium to another as a result of spontaneous firing until it is switched back to the quiescent state, i.e., after a variable period of time of noise-induced transitions the transient is terminated. If the network is small, activity can terminate even without inhibition. In large networks, inhibition keeps the network sensitive to spontaneously firing cells by holding it in the neighbourhood of a critical point between active and quiescent state.

Action Potentials↗
PubMed1990

Iterative character weighting based on mutation frequency: a new method for constructing phyletic trees.

In this paper we present an iterative character weighting method for the construction of phyletic trees. An initial tree is used to calculate the character weights, which are the number of mutations normalized so that the possible range is corrected for. The weights obtained are used to adjust the tree; this process is iterated until a stable tree is found. Using data generated according to a model tree, we show that the trees constructed by the iterative character weighting method converge to the true underlying tree. Using biological data, the trees become closer to the systematic classification of the species concerned, and patterns conflicting with the phylogenetic pattern can be singled out. The method involves a combination of minimal length methods and similarity methods, whereby the strict parsimony criterion is relaxed.

Animals↗
PubMed1990

The Wnt-1 (int-1) oncogene promoter and its mechanism of activation by insertion of proviral DNA of the mouse mammary tumor virus.

Wnt-1 (int-1) is a cellular oncogene often activated by insertion of proviral DNA of the mouse mammary tumor virus. We have mapped the 5' end and the promoter area of the Wnt-1 gene by nuclease protection and primer extension assays. In differentiating P19 embryonal carcinoma cells, in which Wnt-1 is naturally expressed, two start sites of transcription were found, one preceded by two TATA boxes and one preceded by several GC boxes. In P19 cells, a 1-kilobase upstream sequence of Wnt-1 was able to confer differentiation-specific expression on a heterologous gene. We have investigated how Wnt-1 transcription was affected by mouse mammary tumor virus proviral integrations in various configurations near the promoters of the gene. One provirus has been inserted in the 5' nontranslated part of Wnt-1, in the same transcriptional orientation, and has functionally replaced the Wnt-1 promoters. Wnt-1 transcription in this tumor starts in the right long terminal repeat of the provirus, with considerable readthrough transcription from the left long terminal repeat. Another provirus has been inserted in the orientation opposite that of Wnt-1 into a GC box, disrupting the first Wnt-1 transcription start site but not the downstream start site. Most insertions have not structurally altered the Wnt-1 transcripts and have enhanced the activity of the normal two promoters.

Animals↗
PubMed1986

Construction of a retroviral cDNA version of the int-1 mammary oncogene and its expression in vitro.

The int-1 mammary oncogene is activated by proviruses of the Mouse Mammary Tumor Virus in many different mammary tumors. We have inserted a genomic fragment containing the protein-encoding domain of the gene into the retroviral shuttle vector pZIPneoSV(X)1. After one round of virus replication we recovered recombinant proviral DNA containing a correctly spliced copy of int-1. In vitro transcription of this cDNA version of int-1 using SP6 polymerase and translation in a reticulocyte lysate yielded a protein of approximately 37,000 daltons. High expression of int-1 in NIH-3T3 cells infected with recombinant virus did not lead to morphological transformation.

Animals↗