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Results for “functional network connectivity”

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PubMed2001

Feature selectivity and interneuronal cooperation in the thalamocortical system.

Action potentials are a universal currency for fast information transfer in the nervous system, yet few studies address how some spikes carry more information than others. We focused on the transformation of sensory representations in the lemniscal (high-fidelity) auditory thalamocortical network. While stimulating with a complex sound, we recorded simultaneously from functionally connected cell pairs in the ventral medial geniculate body and primary auditory cortex. Thalamic action potentials that immediately preceded or potentially caused a cortical spike were more selective than the average thalamic spike for spectrotemporal stimulus features. This net improvement of thalamic signaling indicates that for some thalamic cells, spikes are not propagated through cortex independently but interact with other inputs onto the same target cell. We then developed a method to identify the spectrotemporal nature of these interactions and found that they could be cooperative or antagonistic to the average receptive field of the thalamic cell. The degree of cooperativity with the thalamic cell determined the increase in feature selectivity for potentially causal thalamic spikes. We therefore show how some thalamic spikes carry more receptive field information than average and how other inputs cooperate to constrain the information communicated through a cortical cell.

Acoustic Stimulation↗

PubMed1984

Localization of type V collagen and type IV collagen in human cornea, lung, and skin. Immunohistochemical evidence by anti-collagen antibodies characterized by immunoelectroblotting.

Tissue distribution of Type V collagen in comparison with Type IV collagen was investigated by indirect immunofluorescence microscopy. Affinity-purified rat antibodies to Type IV and Type V collagens obtained from human placenta reacted specifically only with the corresponding type of collagen in both native and denatured conformations. In indirect immunofluorescent stainings of human skin, lung, and cornea tissues, Type IV and Type V collagens showed distinct distributions. Type IV collagen was distributed exclusively in basement membrane. However, Type V collagen had two characteristic features; a diffuse distribution in interstitium and the locations on or adjacent to basement membrane. On the basis of these findings and of biochemical characterization of the collagens, it is postulated that Type V collagen is an intermediate collagen, possibly having a function of binding or connecting of interstitial collagen fibrils with membranous collagen networks.

Adult↗

PubMed1998

[Features of the structure and parameters of the intra-alveolar septa in residents of Western Siberia].

In inhabitants of Novosibirsk and Moscow district intraalveolar septum, the basic functional element of the lung consists of interstitial connective tissue and capillar network, limited with basement membranes, on which cells of epithelial lining are placed. There are no principal differences in septal structure between individuals from both regions. The majority of morphometric parameters are statistically similar, although certain peculiarities were noted in human subjects from Siberia, the most important of which is that air-blood barrier in them is 33% thinner than those in inhabitants of Moscow district. Majority of capillaries possess the air-blood barrier from both sides. This increases diffous capacity of the lungs and blood oxygenation level.

Adult↗

PubMed2005

Revealing the large-scale network organization of growth hormone-secreting cells.

Pituitary growth hormone (GH)-secreting cells regulate growth and metabolism in animals and humans. To secrete highly ordered GH pulses (up to 1,000-fold rise in hormone levels in vivo), the pituitary GH cell population needs to mount coordinated responses to GH secretagogues, yet GH cells display an apparently heterogeneous scattered distribution in 2D histological studies. To address this paradox, we analyzed in 3D both positioning and signaling of GH cells using reconstructive, two-photon excitation microscopy to image the entire pituitary in GH-EGFP transgenic mice. Our results unveiled a homologous continuum of GH cells connected by adherens junctions that wired the whole gland and exhibited the three primary features of biological networks: robustness of architecture across lifespan, modularity correlated with pituitary GH contents and body growth, and connectivity with spatially stereotyped motifs of cell synchronization coordinating cell activity. These findings change our view of GH cells, from a collection of dispersed cells to a geometrically connected homotypic network of cells whose local morphology and connectivity can vary, to alter the timing of cellular responses to promote more coordinated pulsatile secretion. This large-scale 3D view of cell functioning provides a powerful approach to identify and understand other networks of endocrine cells that are thought to be scattered in situ. Many dispersed endocrine systems exhibit pulsatile outputs. We suggest that cell positioning and associated cell-cell connection mechanisms will be critical parameters that determine how well such systems can deliver a coordinated secretory pulse of hormone to their target tissues.

Animals↗

PubMedDate not supplied

Micropatterned substrates for the growth of functional neuronal networks of defined geometry.

The in vitro assembly of neuronal networks with control over cell position and connectivity is a fascinating approach not only for topics in basic neuroscience research but also in diverse applications such as biosensors and tissue engineering. We grew rat embryonic cortical neurons on patterned substrates created by microcontact printing. Polystyrene was used as a cell repellent background, onto which a grid pattern of physiological proteins was applied. We printed laminin and a mixture of extracellular matrix proteins and additionally both systems mixed with polylysine. Attachment of cells to the pattern with high fidelity as well as the formation of chemical synapses between neighboring cells on the pattern could be observed in all four cases, but cell attachment was strongly increased on samples containing polylysine. Neurons grown on patterned substrates had a membrane capacity smaller than that of neurons on homogeneously coated controls, which we attributed to the geometrical restrictions, but did not differ either in resting membrane potential or in the quality of synapses they formed. We therefore believe that the cells attach and differentiate normally on the pattern and form functional, mature synapses following the predefined geometry.

Action Potentials↗

PubMed2006

Dimensional reduction for reward-based learning.

Reward-based learning in neural systems is challenging because a large number of parameters that affect network function must be optimized solely on the basis of a reward signal that indicates improved performance. Searching the parameter space for an optimal solution is particularly difficult if the network is large. We show that Hebbian forms of synaptic plasticity applied to synapses between a supervisor circuit and the network it is controlling can effectively reduce the dimension of the space of parameters being searched to support efficient reinforcement-based learning in large networks. The critical element is that the connections between the supervisor units and the network must be reciprocal. Once the appropriate connections have been set up by Hebbian plasticity, a reinforcement-based learning procedure leads to rapid learning in a function approximation task. Hebbian plasticity within the network being supervised ultimately allows the network to perform the task without input from the supervisor.

Animals↗

PubMed1989

Electromyography of the fin musculature of the cuttlefish Sepia officinalis.

The musculature of the fins of the cuttlefish Sepia officinalis (Mollusca, Cephalopoda) was studied with electromyography to test predictions of the functional role of the various muscle masses. Previous research had shown the fins to consist of a tightly packed, three-dimensional array of muscle with distinct zones of anaerobic glycolytic and oxidative muscle fibres. In addition, a network of crossed oblique connective tissue fibres was observed within the musculature. In a previous paper a model of the function of the muscle and connective tissue was presented. In the present paper, we present recordings of electrical activity from the various muscle bundles in the fin, in conjunction with the output from an electronic movement-monitoring device, and correlate muscle activity with both the phase and the intensity of the fin-beat cycle. The results obtained here support the hypothesis that the oxidative muscle fibres produce gentle fin movements and are consistent with the hypothesis that the network of crossed oblique connective tissue fibres provides skeletal support. The results also support predictions that the anaerobic glycolytic muscle fibres both produce vigorous fin movements and provide support for that movement. This study provides a critical test of models of the role of the tightly packed, three-dimensional array of muscle found in muscular hydrostats such as the arms and tentacles of cephalopods and tongues of mammals and lizards.

Animals↗

PubMed2004

Chemical genomics: probing protein function using small molecules.

Chemical genomics is concerned with the effects of both genetic variation and chemical perturbation on the cellular effects of small molecules. Chemical genomics relies on selecting biological networks for study, such as those represented by different cell types or disease models, in order to build the desired specificity into the experimental design. The most relevant network property for such experiments is the global connectivity of all cellular proteins comprising the functional ensemble, as illustrated by case studies of the evolution of cyclooxygenase inhibitors and heat-shock protein modulators. Recent examples of chemical genomic profiling, particularly of different cell types, highlight the power of carefully planned experimental approaches in chemical genomics. These new approaches demonstrate the use of the genome to find new targets or new modes of biological interaction.

Animals↗

PubMed2006

Operational principles of neurocognitive networks.

Large-scale neural networks are thought to be an essential substrate for the implementation of cognitive function by the brain. If so, then a thorough understanding of cognition is not possible without knowledge of how the large-scale neural networks of cognition (neurocognitive networks) operate. Of necessity, such understanding requires insight into structural, functional, and dynamical aspects of network operation, the intimate interweaving of which may be responsible for the intricacies of cognition. Knowledge of anatomical structure is basic to understanding how neurocognitive networks operate. Phylogenetically and ontogenetically determined patterns of synaptic connectivity form a structural network of brain areas, allowing communication between widely distributed collections of areas. The function of neurocognitive networks depends on selective activation of anatomically linked cortical and subcortical areas in a wide variety of configurations. Large-scale functional networks provide the cooperative processing which gives expression to cognitive function. The dynamics of neurocognitive network function relates to the evolving patterns of interacting brain areas that express cognitive function in real time. This article considers the proposition that a basic similarity of the structural, functional, and dynamical features of all neurocognitive networks in the brain causes them to function according to common operational principles. The formation of neural context through the coordinated mutual constraint of multiple interacting cortical areas, is considered as a guiding principle underlying all cognitive functions. Increasing knowledge of the operational principles of neurocognitive networks is likely to promote the advancement of cognitive theories, and to seed strategies for the enhancement of cognitive abilities.

Animals↗

PubMed2002

Undersulfation of proteoglycans and proteins alter C6 glioma cells proliferation, adhesion and extracellular matrix organization.

Proteoglycans are considered to be important molecule in cell-microenvironment interactions. They are overexpressed in neoplastic cells modifying their growth and migration in hosts. In this work we verified that undersulfation of proteoglycans and other sulfated molecules, induced by sodium chlorate treatment, inhibited C6 glioma cells proliferation in a dose-dependent way. This effect was restored by the addition of exogenous heparin. We could not detect significant cell mortality in our culture condition. The treatment also impaired in a dose-dependent manner, C6 cell adhesion to extracellular matrix (ECM) proteins (collagen IV, laminin and fibronectin). In addition, sodium chlorate treatment altered C6 glioma cell morphology, from the fibroblast-like to a more rounded one. This effect was accompanied by increased synthesis of fibronectin and alterations in its extracellular network organization. However, we could not observe modifications on laminin organization and synthesis. The results suggest an important connection between sulfation degree with important tumor functions, such as proliferation and adhesion. We suggest that proteoglycans may modulate the glioma microenvironment network during tumor cell progression and invasion.

Animals↗

PubMedDate not supplied

Anterograde axonal transport, transcytosis, and recycling of neurotrophic factors: the concept of trophic currencies in neural networks.

Traditional views of neurotrophic factor biology held that trophic factors are released from target cells, retrogradely transported along their axons, and rapidly degraded upon arrival in cell bodies. Increasing evidence indicates that several trophic factors such as brain-derived neurotrophic factor (BDNF), fibroblast growth factor (FGF-2), glial cell-line derived neurotrophic factor (GDNF), insulin-like growth factor (IGF-I), and neurotrophin-3 (NT-3), can move anterogradely along axons. They can escape the degradative pathway upon internalization and are recycled for future uses. Internalized ligands can move through intermediary cells by transcytosis, presumably by endocytosis via endosomes to the Golgi system, by trafficking of the factor to dendrites or by sorting into anterograde axonal transport with subsequent release from axon terminals and uptake by second- or third-order target neurons. Such data suggest the existence of multiple "trophic currencies," which may be used over several steps in neural networks to enable nurturing relationships between connected neurons or glial cells, not unlike currency exchanges between trading partners in the world economy. Functions of multistep transfer of trophic material through neural networks may include regulation of neuronal survival, differentiation of phenotypes and dendritic morphology, synapse plasticity, as well as excitatory neurotransmission. The molecular mechanisms of sorting, trafficking, and release of trophic factors from distinct neuronal compartments are important for an understanding of neurotrophism, but they present challenging tasks owing to the low levels of the endogenous factors.

Animals↗

PubMed2004

Exploring structure-function relationships in neocortical networks by means of neuromodelling techniques.

Determining the neuronal architecture underlying certain visual functions is of fundamental importance for understanding how sensory processing is implemented in the brain. The wealth of anatomical, physiological and biophysical data that is being currently acquired on the neocortex could be used to constrain its functional architecture. However, given the intrinsic complexity and diversity of the data, it is difficult to provide a comprehensive framework to use these data in order to characterize structure-function relationships. Here, we discuss the use of biophysically plausible models of dynamics of neuronal networks, constructed to reflect the known properties of neocortical connectivity and modularity, as a tool to bring together anatomy and physiology. We illustrate the utility and rationale of the neuro-dynamics modelling approach by considering recent studies on the relationship between functional structure of the visual cortex and its response timing, and on the cellular and network origin of neuronal oscillations in the gamma frequency range. We also critically discuss how an interaction between theory and experiments could help this approach to become directly relevant for clinical applications.

Animals↗

PubMed2006

Artificial neural network properties associated with wiring patterns in the visual projections of vertebrates and arthropods.

We model the functioning of different wiring schemes in visual projections using artificial neural networks and so speculate on selective factors underlying taxonomic variation in neural architecture. We model the high connective overlap of vertebrates (where networks have a dense mesh of connections) and the less overlapping, more modular architecture of arthropods. We also consider natural variation in these basic wiring schemes. Generally, arthropod networks are as efficient or more efficient in functioning compared to vertebrate networks. They do not show the confusion effect (decreasing targeting accuracy with increasing input group size), and they train as well or better. Arthropod networks are, however, generally poorer at reconstructing novel inputs. The ability of vertebrate networks to effectively process novel stimuli could promote behavioral sophistication and drive the evolution of vertebrate wiring schemes. Vertebrate networks with less connective overlap have, surprisingly, similar or superior properties compared to those with high connective overlap. Thus, the partial connective overlap seen in real vertebrate visual projections may be an optimal, evolved solution. Arthropod networks with and without whole-cell neural connections within neural layers have similar properties. This indicates that neural connections mediated by offshoots of single cells (dendrites) may be fundamental to generating the confusion effect.

Animals↗

PubMed2004

Deformability-based flow cytometry.

BACKGROUND: Elasticity of cells is determined by their cytoskeleton. Changes in cellular function are reflected in the amount of cytoskeletal proteins and their associated networks. Drastic examples are diseases such as cancer, in which the altered cytoskeleton is even diagnostic. This connection between cellular function and cytoskeletal mechanical properties suggests using the deformability of cells as a novel inherent cell marker. METHODS: The optical stretcher is a new laser tool capable of measuring cellular deformability. A unique feature of this deformation technique is its potential for high throughput, with the incorporation of a microfluidic delivery of cells. RESULTS: Rudimentary implementation of the microfluidic optical stretcher has been used to measure optical deformability of several normal and cancerous cell types. A drastic difference has been seen between the response of red blood cells and polymorphonuclear cells for a given optically induced stress. MCF-10, MCF-7, and modMCF-7 cells were also measured, showing that while cancer cells stretched significantly more (five times) than normal cells, optical deformability could even be used to distinguish metastatic cancer cells from nonmetastatic cancer cells. This trimodal distribution was apparent after measuring a mere 83 cells, which shows optical deformability to be a highly regulated cell marker. CONCLUSIONS: Preliminary work suggests a deformability-based cell sorter similar to current fluorescence-based flow cytometry without the need for specific labeling. This could be used for the diagnosis of all diseases, and the investigation of all cellular processes, that affect the cytoskeleton.

Breast Neoplasms↗

PubMed2004

Nicotine effects on brain function and functional connectivity in schizophrenia.

BACKGROUND: Nicotine in tobacco smoke can improve functioning in multiple cognitive domains. High rates of smoking among schizophrenic patients may reflect an effort to remediate cognitive dysfunction. Our primary aim was to determine whether nicotine improves cognitive function by facilitating activation of brain regions mediating task performance or by facilitating functional connectivity. METHODS: Thirteen smokers with schizophrenia and 13 smokers with no mental illness were withdrawn from tobacco and underwent functional magnetic resonance imaging (fMRI) scanning twice, once after placement of a placebo patch and once after placement of a nicotine patch. During scanning, subjects performed an n-back task with two levels of working memory load and of selective attention load. RESULTS: During the most difficult (dichotic 2-back) task condition, nicotine improved performance of schizophrenic subjects and worsened performance of control subjects. Nicotine also enhanced activation of a network of regions, including anterior cingulate cortex and bilateral thalamus, and modulated thalamocortical functional connectivity to a greater degree in schizophrenic than in control subjects during dichotic 2-back task performance. CONCLUSIONS: In tasks that tax working memory and selective attention, nicotine may improve performance in schizophrenia patients by enhancing activation of and functional connectivity between brain regions that mediate task performance.

Adult↗

PubMed2006

Differential control of active and silent phases in relaxation models of neuronal rhythms.

Rhythmic bursting activity, found in many biological systems, serves a variety of important functions. Such activity is composed of episodes, or bursts (the active phase, AP) that are separated by quiescent periods (the silent phase, SP). Here, we use mean field, firing rate models of excitatory neural network activity to study how AP and SP durations depend on two critical network parameters that control network connectivity and cellular excitability. In these models, the AP and SP correspond to the network's underlying bistability on a fast time scale due to rapid recurrent excitatory connectivity. Activity switches between the AP and SP because of two types of slow negative feedback: synaptic depression-which has a divisive effect on the network input/output function, or cellular adaptation-a subtractive effect on the input/output function. We show that if a model incorporates the divisive process (regardless of the presence of the subtractive process), then increasing cellular excitability will speed up the activity, mostly by decreasing the silent phase. Reciprocally, if the subtractive process is present, increasing the excitatory connectivity will slow down the activity, mostly by lengthening the active phase. We also show that the model incorporating both slow processes is less sensitive to parameter variations than the models with only one process. Finally, we note that these network models are formally analogous to a type of cellular pacemaker and thus similar results apply to these cellular pacemakers.

Action Potentials↗

PubMed1997

Physiological background of enuresis type I. A preliminary report.

The physiological background of enuresis Type I, which is due to a mild arousal dysfunction, has been investigated in two studies, one in rats and one in children with Type I enuresis. The results of these investigations suggest that in this type of enuresis, the fundamental arousal function following bladder distension, due to an arousal centre like the locus coeruleus and its network, is normal. In contrast, the process of multiplying the transient connection from light sleep to complete awakening, which probably relies upon functions of the thalamus and the further upper centrums, was thought to be abnormal.

Animals↗

PubMed2006

Plasticity and specificity of cortical processing networks.

The cerebral cortex is subdivided into discrete functional areas that are defined by specific properties, including the presence of different cell types, molecular expression patterns, microcircuitry and long-range connectivity. These properties enable different areas of cortex to carry out distinct functions. Emerging data argue that the particular structure and identity of cortical areas derives not only from specific inputs but also from unique processing networks. The aim of this review is to summarize current information on the interplay of intrinsic molecular cues with activity patterns that are driven by sensory experience and shape cortical networks as they develop, emphasizing synaptic connections in networks that process vision. This review is part of the TINS special issue on The Neural Substrates of Cognition.

Animals↗