Slow oscillations in neural networks with facilitating synapses

The synchronous oscillatory activity characterizing many neurons in a network is often considered to be a mechanism for representing, binding, conveying, and organizing information. A number of models have been proposed to explain high-frequency oscillations, but the mechanisms that underlie slow oscillations are still unclear. Here, we show by means of analytical solutions and simulations that facilitating excitatory (E _f) synapses onto interneurons in a neural network play a fundamental role, not only in shaping the frequency of slow oscillations, but also in determining the form of the up and down states observed in electrophysiological measurements. Short time constants and strong E _f synapse-connectivity were found to induce rapid alternations between up and down states, whereas long time constants and weak E _f synapse connectivity prolonged the time between up states and increased the up state duration. These results suggest a novel role for facilitating excitatory synapses onto interneurons in controlling the form and frequency of slow oscillations in neuronal circuits.     

Persistent activity in neural networks with dynamic synapses

Persistent activity states (attractors), observed in several neocortical areas after the removal of a sensory stimulus, are believed to be the neuronal basis of working memory. One of the possible mechanisms that can underlie persistent activity is recurrent excitation mediated by intracortical synaptic connections. A recent experimental study revealed that connections between pyramidal cells in prefrontal cortex exhibit various degrees of synaptic depression and facilitation. Here we analyze the effect of synaptic dynamics on the emergence and persistence of attractor states in interconnected neural networks. We show that different combinations of synaptic depression and facilitation result in qualitatively different network dynamics with respect to the emergence of the attractor states. This analysis raises the possibility that the framework of attractor neural networks can be extended to represent time-dependent stimuli.     

Adaptive thresholds for neural networks with synaptic noise

The inclusion of a macroscopic adaptive threshold is studied for the retrieval dynamics of both layered feedforward and fully connected neural network models with synaptic noise. These two types of architectures require a different method to be solved numerically. In both cases it is shown that, if the threshold is chosen appropriately as a function of the cross-talk noise and of the activity of the stored patterns, adapting itself automatically in the course of the recall process, an autonomous functioning of the network is guaranteed. This self-control mechanism considerably improves the quality of retrieval, in particular the storage capacity, the basins of attraction and the mutual information content.     

Homeostatic synaptic plasticity: from single synapses to neural circuits

Homeostatic synaptic plasticity remains an enigmatic form of synaptic plasticity. Increasing interest on the topic has fuelled a surge of recent studies that have identified key molecular players and the signaling pathways involved. However, the new findings also highlight our lack of knowledge concerning some of the basic properties of homeostatic synaptic plasticity. In this review we address how homeostatic mechanisms balance synaptic strengths between the presynaptic and the postsynaptic terminals and across synapses that share the same postsynaptic neuron.     

Artificial neural networks modeling gene-environment interaction

ABSTRACT: BACKGROUND: Gene-environment interactions play an important role in the etiological pathway of complex diseases. An appropriate statistical method for handling a wide variety of complex situations involving interactions between variables is still lacking, especially when continuous variables are involved. The aim of this paper is to explore the ability of neural networks to model different structures of gene-environment interactions. A simulation study is set up to compare neural networks with standard logistic regression models. Eight different structures of gene-environment interactions are investigated. These structures are characterized by penetrance functions that are based on sigmoid functions or on combinations of linear and non-linear effects of a continuous environmental factor and a genetic factor with main effect or with a masking effect only. RESULTS: In our simulation study, neural networks are more successful in modeling gene-environment interactions than logistic regression models. This outperfomance is especially pronounced when modeling sigmoid penetrance functions, when distinguishing between linear and nonlinear components, and when modeling masking effects of the genetic factor. CONCLUSION: Our study shows that neural networks are a promising approach for analyzing gene-environment interactions. Especially, if no prior knowledge of the correct nature of the relationship between co-variables and response variable is present, neural networks provide a valuable alternative to regression methods that are limited to the analysis of linearly separable data.     

Dynamics of recurrent neural networks with delayed unreliable synapses: metastable clustering

The influence of unreliable synapses on the dynamic properties of a neural network is investigated for a homogeneous integrate-and-fire network with delayed inhibitory synapses. Numerical and analytical calculations show that the network relaxes to a state with dynamic clusters of identical size which permanently exchange neurons. We present analytical results for the number of clusters and their distribution of firing times which are determined by the synaptic properties. The number of possible configurations increases exponentially with network size. In addition to states with a maximal number of clusters, metastable ones with a smaller number of clusters survive for an exponentially large time scale. An externally excited cluster survives for some time, too, thus clusters may encode information.     

Artificial neural networks and their use in quantitative pathology

A brief general introduction to artificial neural networks is presented, examining in detail the structure and operation of a prototype net developed for the solution of a simple pattern recognition problem in quantitative pathology. The process by which a neural network learns through example and gradually embodies its knowledge as a distributed representation is discussed, using this example. The application of neurocomputer technology to problems in quantitative pathology is explored, using real-world and illustrative examples. Included are examples of the use of artificial neural networks for pattern recognition, database analysis and machine vision. In the context of these examples, characteristics of neural nets, such as their ability to tolerate ambiguous, noisy and spurious data and spontaneously generalize from known examples to handle unfamiliar cases, are examined. Finally, the strengths and deficiencies of a connectionist approach are compared to those of traditional symbolic expert system methodology. It is concluded that artificial neural networks, used in conjunction with other nonalgorithmic artificial intelligence techniques and traditional algorithmic processing, may provide useful software engineering tools for the development of systems in quantitative pathology.     

Artificial neural networks for solution scattering data analysis

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Artificial neural networks for species identification by taxonomists

This paper is a study of the value of applying artificial neural networks (ANNs), specifically a multilayer perceptron (MLP), to identification of higher plants using morphological characters collected by conventional means. A practical methodology is thus demonstrated to enable botanical or zoological taxonomists to use ANNs as advisory tools for identification purposes. A comparison is made between the ability of the neural network and that of traditional methods for plant identification by means of a case study in the flowering plant genus Lithops N.E. Brown (Aizoaceae). In particular, a comparison is made with taxonomic keys generated by means of the DELTA system. The ANN is found to perform better than the DELTA key generator, for conditions where the available data is limited, and species relatively difficult to distinguish.     

Artificial neural networks for decision-making in urologic oncology

Artificial neural networks (ANNs) are computational methodologies that perform multifactorial analyses, inspired by networks of biological neurons. Like neural networks, ANNs contain layers of simple points (nodes) of data that interract through carefully weighted connection lines. ANNs are "trained" and balanced by having been previously fed data, which the ANN uses as the means for adjusting its interconnections. Studies have shown that novel and highly accurate ANNs significantly enhance the ability to detect prostate cancer early (high sensitivity) while avoiding a greater number of unnecessary tissue samplings (high specificity). The use of ANNs in prostate cancer is ideal because of 1) multiple predicting factors that influence outcome; 2) the desire to offer individual consulting based on various tests; 3) the fact that prior logistic regression analysis results have had serious limitations in application; and 4) the need for an up-to-date tool that can apply easily to everyone. An ANN should be seen as an important tool that is complementary to the physician's personal knowledge and judgment in making decisions.     

Interaction of isolated synaptic vesicles with synaptic contacts in the rat brain

The effects of Mg-ATP, EGTA, EDTA and dicyclohexylcarbodiimide on the changes in the intensity of light scattering were studied in rat brain synaptic vesicles (SV) suspended in saccharose-buffer medium. Specific interactions between SV and isolated synaptic junctional complex were observed in the presence of Mg-ATP and calmodulin. An in vitro model of exocytosis is discussed.     

Artificial neural networks and the study of evolution of prey coloration

In this paper, I investigate the use of artificial neural networks in the study of prey coloration. I briefly review the anti-predator functions of prey coloration and describe both in general terms and with help of two studies as specific examples the use of neural network models in the research on prey coloration. The first example investigates the effect of visual complexity of background on evolution of camouflage. The second example deals with the evolutionary choice of defence strategy, crypsis or aposematism. I conclude that visual information processing by predators is central in evolution of prey coloration. Therefore, the capability to process patterns as well as to imitate aspects of predator's information processing and responses to visual information makes neural networks a well-suited modelling approach for the study of prey coloration. In addition, their suitability for evolutionary simulations is an advantage when complex or dynamic interactions are modelled. Since not all behaviours of neural network models are necessarily biologically relevant, it is important to validate a neural network model with empirical data. Bringing together knowledge about neural networks with knowledge about topics of prey coloration would provide a potential way to deepen our understanding of the specific appearances of prey coloration.     

Learning in spiking neural networks by reinforcement of stochastic synaptic transmission

It is well-known that chemical synaptic transmission is an unreliable process, but the function of such unreliability remains unclear. Here I consider the hypothesis that the randomness of synaptic transmission is harnessed by the brain for learning, in analogy to the way that genetic mutation is utilized by Darwinian evolution. This is possible if synapses are "hedonistic," responding to a global reward signal by increasing their probabilities of vesicle release or failure, depending on which action immediately preceded reward. Hedonistic synapses learn by computing a stochastic approximation to the gradient of the average reward. They are compatible with synaptic dynamics such as short-term facilitation and depression and with the intricacies of dendritic integration and action potential generation. A network of hedonistic synapses can be trained to perform a desired computation by administering reward appropriately, as illustrated here through numerical simulations of integrate-and-fire model neurons.     

Artificial neural networks trained to detect viral and phage structural proteins

Phages play critical roles in the survival and pathogenicity of their hosts, via lysogenic conversion factors, and in nutrient redistribution, via cell lysis. Analyses of phage- and viral-encoded genes in environmental samples provide insights into the physiological impact of viruses on microbial communities and human health. However, phage ORFs are extremely diverse of which over 70% of them are dissimilar to any genes with annotated functions in GenBank. Better identification of viruses would also aid in better detection and diagnosis of disease, in vaccine development, and generally in better understanding the physiological potential of any environment. In contrast to enzymes, viral structural protein function can be much more challenging to detect from sequence data because of low sequence conservation, few known conserved catalytic sites or sequence domains, and relatively limited experimental data. We have designed a method of predicting phage structural protein sequences that uses Artificial Neural Networks (ANNs). First, we trained ANNs to classify viral structural proteins using amino acid frequency; these correctly classify a large fraction of test cases with a high degree of specificity and sensitivity. Subsequently, we added estimates of protein isoelectric points as a feature to ANNs that classify specialized families of proteins, namely major capsid and tail proteins. As expected, these more specialized ANNs are more accurate than the structural ANNs. To experimentally validate the ANN predictions, several ORFs with no significant similarities to known sequences that are ANN-predicted structural proteins were examined by transmission electron microscopy. Some of these self-assembled into structures strongly resembling virion structures. Thus, our ANNs are new tools for identifying phage and potential prophage structural proteins that are difficult or impossible to detect by other bioinformatic analysis. The networks will be valuable when sequence is available but in vitro propagation of the phage may not be practical or possible.     

Artificial neural networks and three-dimensional digital morphology: a pilot study

In this pilot study, we used an unsupervised learning algorithm for self-organization and pattern matching to create feature maps that can be applied to morphological problems. We designed a network to analyze 83 first and/or second upper and lower molar sets representing 13 anthropoid primate species, based on three-dimensional measures obtained from laser-digitized, virtual specimens. As shown in a comparison with a principal-component analysis of the virtual specimens, the artificial neural network approach provided more biologically meaningful information than the conventional multivariate analysis approach. The methodology discovered partitions and hierarchical clusters consistent with anthropoid systematics, from the species (or subspecies) level to the highest categories, by sorting and allocating upper and lower molar teeth. As one might expect, measures of upper molars were richer in phenetic information than those of lower molars, even among the anatomically diverse platyrrhines. We also show that reducing taxonomic noise (i.e. biological variation) by limiting the analysis to a monophyletic subset improves discrimination.     

Prediction of helix-helix contacts and interacting helices in polytopic membrane proteins using neural networks

Despite rapidly increasing numbers of available 3D structures, membrane proteins still account for less than 1% of all structures in the Protein Data Bank. Recent high-resolution structures indicate a clearly broader structural diversity of membrane proteins than initially anticipated, motivating the development of reliable structure prediction methods specifically tailored for this class of molecules. One important prediction target capturing all major aspects of a protein's 3D structure is its contact map. Our analysis shows that computational methods trained to predict residue contacts in globular proteins perform poorly when applied to membrane proteins. We have recently published a method to identify interacting alpha-helices in membrane proteins based on the analysis of coevolving residues in predicted transmembrane regions. Here, we present a substantially improved algorithm for the same problem, which uses a newly developed neural network approach to predict helix-helix contacts. In addition to the input features commonly used for contact prediction of soluble proteins, such as windowed residue profiles and residue distance in the sequence, our network also incorporates features that apply to membrane proteins only, such as residue position within the transmembrane segment and its orientation toward the lipophilic environment. The obtained neural network can predict contacts between residues in transmembrane segments with nearly 26% accuracy. It is therefore the first published contact predictor developed specifically for membrane proteins performing with equal accuracy to state-of-the-art contact predictors available for soluble proteins. The predicted helix-helix contacts were employed in a second step to identify interacting helices. For our dataset consisting of 62 membrane proteins of solved structure, we gained an accuracy of 78.1%. Because the reliable prediction of helix interaction patterns is an important step in the classification and prediction of membrane protein folds, our method will be a helpful tool in compiling a structural census of membrane proteins.     

Artificial neural networks for qualitative and quantitative analysis of target proteins with polymerized liposome vesicles

We investigate the feasibility of using the luminescence response of polymerized liposomes incorporating ethylenediaminetetraacetate europium(III) (EDTA-Eu(3+)) for monitoring protein concentrations in aqueous media. Quantitative analysis is based on the linear relationship between the luminescence enhancement of the lanthanide ion and protein concentration. Analytical figures of merit are presented for carbonic anhydrase, human serum albumin, gamma-globulins, and thermolysin. Qualitative analysis is based on the luminescence lifetime of the liposome sensor. This parameter, which follows well-behaved single exponential decays and provides characteristic values for each of the four studied proteins, demonstrates the selective potential for protein identification. Then partial least squares-1 and artificial neural networks are compared toward the quantitative and qualitative analysis of human serum albumin and carbonic anhydrase in binary mixtures without previous separation at the concentration levels found in aqueous humor.     

Artificial neural networks and decision tree model analysis of liver cancer proteomes

Hepatocellular carcinoma (HCC) is a heterogeneous cancer and usually diagnosed at late advanced tumor stages of high lethality. The present study attempted to obtain a proteome-wide analysis of HCC in comparison with adjacent non-tumor liver tissues, in order to facilitate biomarkers' discovery and to investigate the mechanisms of HCC development. A cohort of 66 Chinese patients with HCC was included for proteomic profiling study by two-dimensional gel electrophoresis (2-DE) analysis. Artificial neural network (ANN) and decision tree (CART) data-mining methods were employed to analyze the profiling data and to delineate significant patterns and trends for discriminating HCC from non-malignant liver tissues. Protein markers were identified by tandem MS/MS. A total of 132 proteome datasets were generated by 2-DE expression profiling analysis, and each with 230 consolidated protein expression intensities. Both the data-mining algorithms successfully distinguished the HCC phenotype from other non-malignant liver samples. The detection sensitivity and specificity of ANN were 96.97% and 87.88%, while those of CART were 81.82% and 78.79%, respectively. The three biological classifiers in the CART model were identified as cytochrome b5, heat shock 70 kDa protein 8 isoform 2, and cathepsin B. The 2-DE-based proteomic profiling approach combined with the ANN or CART algorithm yielded satisfactory performance on identifying HCC and revealed potential candidate cancer biomarkers.