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Response of complex networks to stimuli.

We consider the response of complex systems to stimuli and argue for the importance of both sensitivity, the possibility of large response to small stimuli, and robustness, the possibility of small response to large stimuli. Using a dynamic attractor network model for switching of patterns of behavior, we show that the scale-free topologies often found in nature enable more sensitive response to specific changes than do random networks. This property may be essential in networks where appropriate response to environmental change is critical and may, in such systems, be more important than features, such as connectivity, often used to characterize network topologies. Phenomenologically observed exponents for functional scale-free networks fall in a range corresponding to the onset of particularly high sensitivities, while still retaining robustness.

Biology↗

Brown-Séquard and cerebral localization as illustrated by his ideas on aphasia.

Brown-Séquard's concept of localization was built on the phenomena of inhibition and dynamogenesis, constituting a dynamic system in which reflex mechanisms, that played a part not only in the spinal cord but in the brain as well, were considered of particular importance. The use of this concept is considered in Brown-Séquard's discussion of the subject of cerebral localization, and especially of aphasia. The origin and development of Brown-Séquard's ideas on aphasia from 1861 onwards are discussed, as is the part he possibly played in the transfer of knowledge from Paris to London (Broca and Jackson). In the 1870's Brown-Séquard debated on cerebral localization with Charcot before the Société de Biologie. Opposing the cluster theory of localization, Brown-Séquard developed the theory of "réseau de cellules anastomosées", a kind of network theory in which scattered cells subserving the same function are connected by nerve fibers. This was to him a plausible theory, with which he was able to explain the fact that damage in several locations may produce the same effect, and, to account for observations that some functions remain unimpaired despite extensive brain-injury. Although Brown-Séquard's arguments were not always valid, because they were based on imprecise observations, his dynamic model, nowadays, seems valuable. He influenced "anti-localizers" such as Goltz, but also Jackson and probably Von Monakow and Sherrington.

Aphasia↗

Network information and connected correlations.

Entropy and information provide natural measures of correlation among elements in a network. We construct here the information theoretic analog of connected correlation functions: irreducible N-point correlation is measured by a decrease in entropy for the joint distribution of N variables relative to the maximum entropy allowed by all the observed N-1 variable distributions. We calculate the "connected information" terms for several examples and show that it also enables the decomposition of the information that is carried by a population of elements about an outside source.

Information Services↗

Jacques Benoit Lecture. Information processing in the hypothalamus: peptides and analogue computation.

Peptides in the hypothalamus are not like conventional neurotransmitters; their release is not particularly associated with synapses, and their long half-lives mean that they can diffuse to distant targets. Peptides can act on their cells of origin to facilitate the development of patterned electrical activity, they can act on their neighbours to bind the collective activity of a neural population into a coherent signalling entity, and the co-ordinated population output can transmit waves of peptide secretion that act as a patterned hormonal analogue signal within the brain. At their distant targets, peptides can re-programme neural networks, by effects on gene expression, synaptogenesis, and by functionally rewiring connections by priming activity-dependent release.

Animals↗

Network system: the integrated picture archiving and communication system with the hospital information system.

We describe the outline of Hokkaido University picture archiving and communication system (HU-PACS) and its network functions. HU-PACS processes 0.5 Gbytes of images daily through 10 acquisition devices. Functional integration of hospital information system (HIS) and PACS has been implemented. The HU-PACS can access common data base with HIS. Multi-image data-base systems provide fast throughput of image retrieval. The system is composed of 4 modules: (1) 2 image data-base systems (IDS), (2) 1 image management system (IMS), (3) image display terminals (IDT), and (4) 8 image acquisition nodes interfaced to 10 modalities and 1 film scanner. These 4 modules are connected by branch and loop type local area networks (LAN). HU-PACS has functions other than basic PACS functions. Images in optical disk library (ODL) are loaded onto magnetic disks (MD) in advance according to patient booking information, the images expected to be viewed are transferred to the local storage automatically, and the desired images can be pre-downloaded into local storage by instruction through HIS terminals.

Computer Communication Networks↗

Coding specificity in cortical microcircuits: a multiple-electrode analysis of primate prefrontal cortex.

Neurons with directional specificities are active in the prefrontal cortex (PFC) during tasks that require spatial working memory. Although the coordination of neuronal activity in PFC is thought to be maintained by a network of recurrent connections, direct physiological evidence regarding such networks is sparse. To gain insight into the functional organization of the working memory system in vivo, we recorded simultaneously from multiple neurons spaced 0.2-1 mm apart in monkeys performing an oculomotor delayed response task. We used cross-correlation analysis and characterized the effective connectivity between neurons in relation to their spatial and temporal response properties. The majority of narrow (<5 msec) cross-correlation peaks indicated common input and were most often observed between pairs of neurons within 0.3 mm of each other. Neurons recorded at these distances represented the full range of spatial locations, suggesting that the entire visual hemifield is represented in modules of corresponding dimensions. Nearby neurons could be activated in any epoch of the behavioral task (stimulus presentation, delay, response). The incidence and strength of cross-correlation, however, was highest among cells sharing similar spatial tuning and similar temporal profiles of activation across task epochs. The dependence of correlated discharge on the functional properties of neurons was observed both when we analyzed firing from the task period as well as from baseline fixation. Our results suggest that the coding specificity of individual neurons extends to the local circuits of which they are part.

Action Potentials↗

[Characteristics of neural connections and capillary networks in field 17 of the cerebral cortex in rabbits and cats].

Some structural-functional relations in the analyzer's optic nucleus and adjacent associative fields were investigated comparing it with the cortical limbic area in the rabbit and cat. New approaches for the structural brain cortex analysis were applied: method of retrograde elective detection of cortical and subcortical neurons (with the body and dendritic processes) after surgical lesion of their axons in the cortical focus of destruction, field 17. This method demonstrated the presence, in the fields surrounding the cortical optic nucleus, of associative neurons mediating the modal signals into the nucleus of the optical analyzer, as well as some constructive details of the optical analyzer at the subcortical level. Comparing angioarchitectonics of the capillary network, indirect data were obtained on structural-functional specialization of the nucleus of the optical analyzer, that explains the meaning of mediating into it the optical signals which come to other cortical areas (from the zone of scattered elements).

Animals↗

Advancing the boundaries of high-connectivity network simulation with distributed computing.

The availability of efficient and reliable simulation tools is one of the mission-critical technologies in the fast-moving field of computational neuroscience. Research indicates that higher brain functions emerge from large and complex cortical networks and their interactions. The large number of elements (neurons) combined with the high connectivity (synapses) of the biological network and the specific type of interactions impose severe constraints on the explorable system size that previously have been hard to overcome. Here we present a collection of new techniques combined to a coherent simulation tool removing the fundamental obstacle in the computational study of biological neural networks: the enormous number of synaptic contacts per neuron. Distributing an individual simulation over multiple computers enables the investigation of networks orders of magnitude larger than previously possible. The software scales excellently on a wide range of tested hardware, so it can be used in an interactive and iterative fashion for the development of ideas, and results can be produced quickly even for very large networks. In contrast to earlier approaches, a wide class of neuron models and synaptic dynamics can be represented.

Action Potentials↗

Liver tissue engineering within alginate scaffolds: effects of cell-seeding density on hepatocyte viability, morphology, and function.

Tissue engineering with three-dimensional biomaterials represents a promising approach for developing hepatic tissue to replace the function of a failing liver. Herein, we address cell seeding and distribution within porous alginate scaffolds, which represent a new type of porous biomaterial for tissue engineering. The hydrophilic nature of the alginate scaffold as well as its pore structure and interconnectivity enabled the efficient seeding of hepatocytes into the scaffolds, that is, 70-90% of the initial cells depending on the seeding method. Utilization of centrifugal force during seeding enhanced cell distribution in the porous scaffolds, consequently enabling the seeding of concentrated cell suspensions (>1 x 10(7) cells/mL). Cell density in scaffolds affected hepatocyte viability as judged by MTT assay. At a cell density of 0.28 x 10(6) cells/cm3 scaffold, the number of viable hepatocytes decreased to 33% of its initial value within 7 days, whereas at the denser cultures, 5.7 x 10(6) cells/cm3 scaffold and higher, the cells maintained higher viability while forming a network of connecting spheroids. In the high-density cellular constructs, hepatocellular functions such as albumin and urea secretion, and detoxification (cytochrome P-450 and phase II conjugating enzyme activities), remained high during the 7-day culture. Collectively, the results of the present study highlight the importance of cell density on the hepatocellular functions of three-dimensional hepatocyte constructs as well as the advantages of alginate matrices as scaffoldings.

7-Alkoxycoumarin O-Dealkylase↗

Comparative analysis of the Saccharomyces cerevisiae and Caenorhabditis elegans protein interaction networks.

BACKGROUND: Protein interaction networks aim to summarize the complex interplay of proteins in an organism. Early studies suggested that the position of a protein in the network determines its evolutionary rate but there has been considerable disagreement as to what extent other factors, such as protein abundance, modify this reported dependence. RESULTS: We compare the genomes of Saccharomyces cerevisiae and Caenorhabditis elegans with those of closely related species to elucidate the recent evolutionary history of their respective protein interaction networks. Interaction and expression data are studied in the light of a detailed phylogenetic analysis. The underlying network structure is incorporated explicitly into the statistical analysis. The increased phylogenetic resolution, paired with high-quality interaction data, allows us to resolve the way in which protein interaction network structure and abundance of proteins affect the evolutionary rate. We find that expression levels are better predictors of the evolutionary rate than a protein's connectivity. Detailed analysis of the two organisms also shows that the evolutionary rates of interacting proteins are not sufficiently similar to be mutually predictive. CONCLUSION: It appears that meaningful inferences about the evolution of protein interaction networks require comparative analysis of reasonably closely related species. The signature of protein evolution is shaped by a protein's abundance in the organism and its function and the biological process it is involved in. Its position in the interaction networks and its connectivity may modulate this but they appear to have only minor influence on a protein's evolutionary rate.

Animals↗

Correlated random networks.

We develop a statistical theory of networks. A network is a set of vertices and links given by its adjacency matrix c, and the relevant statistical ensembles are defined in terms of a partition function Z= summation operator exp([-betaH(c)]. The simplest cases are uncorrelated random networks such as the well-known Erdös-Rényi graphs. Here we study more general interactions H(c) which lead to correlations, for example, between the connectivities of adjacent vertices. In particular, such correlations occur in optimized networks described by partition functions in the limit beta--> infinity. They are argued to be a crucial signature of evolutionary design in biological networks.

Brain↗

Calcium signaling in terminal Schwann cells associated with lanceolate sensory endings in rat vibrissae.

Transient elevations of the intracellular Ca2+ concentration ([Ca2+]i) in glia mediate various cell activities to regulate neuronal functions. The present study focuses on spatiotemporal dynamics of Ca2+ signaling in terminal Schwann cells, glial elements of the lanceolate sensory endings innervating the rat vibrissa. Arrays of lanceolate endings were enzymatically isolated from the vibrissal follicle, and subjected to [Ca2+]i image recording by time-lapse confocal microscopy. Each terminal Schwann cell displayed a round cell body, and extended long cytoplasmic stalks, which branched into two to five lamellae resting on different axon endings. Each axon ending, on the other hand, was covered on both flattened sides of the lancet by two Schwann lamellae of different cell origin. Thus the peripheral glia constituted an extensive network connecting the sensory endings. Image analyses of [Ca2+]i characterized the Schwann lamellae as functional compartments that can independently generate Ca2+ signals: these cell portions primarily responded to local mechanical stimuli with a [Ca2+]i spike, and individually initiated [Ca2+]i oscillations during bath application of the sensory modulator adenosine 5'-triphosphate (ATP). The stimulus-induced signals sometimes propagated along the glial network to activate neighboring lamellae after a delay of 2-4 sec. These findings suggest that the terminal Schwann cells contribute both to individual regulation and total coordination of the arrayed sensory endings.

Adenosine Triphosphate↗

A network of orthogonal ribosome x mRNA pairs.

Synthetic biology promises the ability to program cells with new functions. Simple oscillators, switches, logic functions, cell-cell communication and pattern-forming circuits have been created by the connection of a small set of natural transcription factors and their binding sites in different ways to produce different networks of molecular interactions. However, the controlled synthesis of more complex synthetic networks and functions will require an expanded set of functional molecules with known molecular specificities. Here, we tailored the molecular specificity of duplicated Escherichia coli ribosome x mRNA pairs with respect to the wild-type ribosome and mRNAs to produce multiple orthogonal ribosome x orthogonal mRNA pairs that can process information in parallel with, but independent of, their wild-type progenitors. In these pairs, the ribosome exclusively translates the orthogonal mRNA, and the orthogonal mRNA is not a substrate for cellular ribosomes. We predicted and measured the network of interactions between orthogonal ribosomes and orthogonal mRNAs, and showed that they can be used to post-transcriptionally program the cell with Boolean logic.

Binding Sites↗

Self-avoiding walks and connective constants in small-world networks.

Long-distance characteristics of small-world networks have been studied by means of self-avoiding walks (SAW's). We consider networks generated by rewiring links in one- and two-dimensional regular lattices. The number of SAW's u(n) was obtained from numerical simulations as a function of the number of steps n on the considered networks. The so-called connective constant, mu=lim(n-->infinity)u(n)/u(n-1), which characterizes the long-distance behavior of the walks, increases continuously with disorder strength (or rewiring probability p). For small p, one has a linear relation mu=mu(0)+ap, mu(0) and a being constants dependent on the underlying lattice. Close to p=1 one finds the behavior expected for random graphs. An analytical approach is given to account for the results derived from numerical simulations. Both methods yield results agreeing with each other for small p, and differ for p close to 1, because of the different connectivity distributions resulting in both cases.

Journal Article↗

[The functional organization of the spatial structures of the neuronal receptive fields in field 21 of the cat cerebral cortex].

In result study of structural organization of neural receptive fields (RFs) and their different zones on the prestriate cortex level was shown that neural RFs in this area have hypercomplex structure and consist of some spatial different excitatory zones. Orientation and velocity selectivity and spatial-frequency characteristics of the excitatory zones of the same RF may differ between zones. The number of zones in RFs correlate with RF sizes: the more RF size the more zones number in them (r = 0.05, P < 0.02). About 66% of zones in RFs have approximately identical sizes (12-16 deg) and sizes those zones an dependence as from their number in RFs (r = 0.03, P > 0.05) as from the eccentricity (r = 0.3, P > 0.05). Zones in RF were distributed so that distance their centres was between 56-65 degrees (an average across all 60 degrees). If two or three zones were tested simultaneously the neuron changed own frequency and orientation tuning. Consequently the functional organization of neural RFs of prestriate cortex depend upon number simultaneously tested zones in spatial information processing. Was shown that important properties of prestriate cortex neurons is their ability to integrate and complex processing of spatial information across wide area of the visual field; in the prestriate cortex thus violate of straight retinotopical representation principle of visual field, characteristics of all investigated areas of visual system. The results represented in this review allow suppose that the structural and functional unit of cortex which make integration of spatial information from different compose this information is prestriate cortex neurons and not is no striate cortex modules. Consequently combined of neurons which make images description from different parts of visual field out of dependence of cortical area in turn integrate in neuron networks. Is known that neurons of any level have characteristics different of (from) characteristics of other levels visual system. The interaction of different elements of visual system form ultrastructure of RFs and their different zones in prestriate cortex, and ensure function of networks. So just on prestriate cortex neurons level appear whole system of surrounding world universe system of connections from different cortical areas which is morphological and functional base in process of spatial information integration RFs which have the central and peripheral representation.

Animals↗

Social cues shift functional connectivity in the hypothalamus.

We determined how social stimuli that vary in behavioral relevance differentially activate functional networks in the frog hypothalamus. As measured by egr-1 mRNA levels, activity in three hypothalamic nuclei varied with acoustic stimulus, and these responses were correlated with egr-1 responses in different auditory regions regardless of stimulus. The correlations among hypothalamic nuclei, however, varied as a function of the behavioral relevance of the stimuli. Thus relevant social cues shift the functional connectivity within the hypothalamus, consistent with principles that underlie the simultaneous processing of sensory information in cognitive tasks.

Acoustic Stimulation↗

Neural net pruning based on functional behavior of neurons.

This paper proposes a new pruning method based on merging neurons with similar functional behavior which is defined by the internal representations of each neuron for the entire training set. Classification of neurons by their functional behavior with respect to the input vectors provides a powerful tool for pruning neurons and connections, thus reducing the network complexity and increasing its generalization capability. The most remarkable property of this pruning scheme is its ability to preserve net functionality by transferring the role of every removed neuron to the most fitted neuron of the surviving ones, using a unique merging and compensation procedure. The implementation of the proposed method is demonstrated using a detailed numerical example and its performance is examined by a statistical measure calculated by repeating the training procedure several times. The influence of parameter selection on pruning performance and generalization ability is discussed and demonstrated by examining statistical results.

Animals↗

Suppression of synaptic transmission may allow combination of associative feedback and self-organizing feedforward connections in the neocortex.

Selective suppression of synaptic transmission during learning is proposed as a physiological mechanism for combining associative memory function at feedback synapses with self-organization of feedforward synapses in neocortical structures. A computational model demonstrates how selective suppression of feedback transmission allows this combination of synaptic function. During learning, sensory stimuli and the desired response are simultaneously presented as input to the network. Feedforward connections form self-organized representations of input, while suppressed feedback connections learn the transpose of the feedforward connectivity. During recall, suppression of transmission is removed, input activates the self-organized representation, and activity settles into a learned solution to the problem. This computational model can be used for learning of problems which are not linearly separable, including the negative patterning task (the XOR problem). Experiments in brain slice preparations of the rat somatosensory cortex tested whether the combination of self-organization and associative memory function could be provided by cholinergic suppression selective for feedback versus feedforward synapses. The cholinergic agonist carbachol selectively suppressed synaptic potentials elicited by stimulation of layer I (which contains a high percentage of feedback synapses), while having no effect on synaptic potentials elicited by stimulation of layer IV (with a high percentage of afferent and feedforward synapses).

Animals↗