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At least 577 records · Page 32Linked to original sources
PubMed2005

Reconstructing the regulatory network controlling commitment and sporulation in Physarum polycephalum based on hierarchical Petri Net modelling and simulation.

We reconstruct the regulatory network controlling commitment and sporulation of Physarum polycephalum from experimental results using a hierarchical Petri Net-based modelling and simulation framework. The stochastic Petri Net consistently describes the structure and simulates the dynamics of the molecular network as analysed by genetic, biochemical and physiological experiments within a single coherent model. The Petri Net then is extended to simulate time-resolved somatic complementation experiments performed by mixing the cytoplasms of mutants altered in the sporulation response, to systematically explore the network structure and to probe its dynamics. This reverse engineering approach presumably can be employed to explore other molecular or genetic signalling systems where the activity of genes or their products can be experimentally controlled in a time-resolved manner.

Animals↗
PubMed2004

PSTH-based classification of sensory stimuli using ensembles of single neurons.

The problem of understanding how ensembles of neurons code for somatosensory information has been defined as a classification problem: given the response of a population of neurons to a set of stimuli, which stimulus generated the response on a single-trial basis? Multivariate statistical techniques such as linear discriminant analysis (LDA) and artificial neural networks (ANNs), and different types of preprocessing stages, such as principal and independent component analysis, have been used to solve this classification problem, with surprisingly small performance differences. Therefore, the goal of this project was to design a new method to maximize computational efficiency rather than classification performance. We developed a peri-stimulus time histogram (PSTH)-based method, which consists of creating a set of templates based on the average neural responses to stimuli and classifying each single trial by assigning it to the stimulus with the 'closest' template in the Euclidean distance sense. The PSTH-based method is computationally more efficient than methods as simple as linear discriminant analysis, performs significantly better than discriminant analyses (linear, quadratic or Mahalanobis) when small binsizes are used (1 ms) and as well as LDA with any other binsize, is optimal among other minimum-distance classifiers and can be optimally applied on raw neural data without a previous stage of dimension reduction. We conclude that the PSTH-based method is an efficient alternative to more sophisticated methods such as LDA and ANNs to study how ensemble of neurons code for discrete sensory stimuli, especially when datasets with many variables are used and when the time resolution of the neural code is one of the factors of interest.

Action Potentials↗
PubMed2005

Investigating the neural basis of the auditory continuity illusion.

In this study, we investigated one type of auditory perceptual grouping phenomena--the auditory continuity illusion (also called temporal induction). We employed a previously developed, neurobiologically realistic, large-scale neural network model of the auditory processing pathway in the cortex, ranging from the primary auditory cortex to the prefrontal cortex, and simulated temporal induction without changing any model parameters. The model processes tonal contour stimuli, composed of combinations of upward and downward FM sweeps and tones, in a delayed match-to-sample task. The local electrical activities of the neuronal units of the model simulated accurately the experimentally observed electrophysiological data, where available, and the model's simulated BOLD-fMRI data were quantitatively matched with experimental fMRI data. In the present simulations, intact stimuli were matched with fragmented versions (i.e., with inserted silent gaps). The ability of the model to match fragmented stimuli declined as the duration of the gaps increased. However, when simulated broadband noise was inserted into these gaps, the matching response was restored, indicating that a continuous stimulus was perceived. The electrical activities of the neuronal units of the model agreed with electrophysiological data, and the behavioral activity of the model matched human behavioral data. In the model, the predominant mechanism implementing temporal induction is the divergence of the feedforward connections along the auditory processing pathway in the temporal cortex. These simulation results not only attest to the robustness of the model, but further predict the primary role of the anatomical connectivity of the auditory processing areas in mediating the continuity illusion.

Acoustic Stimulation↗
PubMed1993

Modularity and parallel processing in the oculomotor integrator.

The neural signals that hold eye position originate in a brainstem structure called the neural integrator, so-called because it is thought to compute these position signals using a process equivalent to mathematical integration. Most previous experiments have assumed that the neural integrator reacts to damage like a single mathematical integrator: the eye is expected to drift towards a unique resting point at a simple exponential rate dependent on current eye position. Physiologically, this would require a neural network with uniformly distributed internal connections. However, Cannon et al. (1983) proposed a more robust modular internal configuration, with dense local connections and sparse remote connections, computationally equivalent to a parallel array of independent sub-integrators. Damage to some sub-integrators would not affect function in the others, so that part of the position signal would remain intact, and a more complex pattern of drift would result. We evaluated this parallel integrator hypothesis by recording three-dimensional eye positions in the light and dark from five alert monkeys with partial neural integrator failure. Our previous study showed that injection of the inhibitory gamma aminobutyric acid agonist muscimol into the mesencephalic interstitial nucleus of Cajal (INC) causes almost complete failure of the integrators for vertical and torsional eye position after approximately 30 min. This study examines the more modest initial effects. Several aspects of the initial vertical drift could not be accounted for by the single integrator scheme. First, the eye did not initially drift towards a single resting position; rapid but brief drift was observed towards multiple resting positions. With time after the muscimol injection, this range of stable eye positions progressively narrowed until it eventually approximated a single point. Second, the drift had multiple time constants. Third, multiple regression analysis revealed a significant correlation between drift rate and magnitude of the previous saccade, in addition to a correlation between drift rate and position. This saccade dependence enabled animals to stabilize gaze by making a series of saccades to the same target, each with less post-saccadic drift than its predecessor. These observations were predicted and explained by a model in which each of several parallel integrators generated a fraction of the eye-position command.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Hypothalamic-pituitary-adrenal axis and immune system.

Complex and bidirectional relationships operate between the hypothalamic-pituitary-adrenal (HPA) axis and the immune system (IS) and either in vivo or in vitro evidence supports a physiological role of the HPA axis-IS network. A part of the well-known pharmacological effects of glucocorticoid hormones (GC) as immunodepressive agents, the direct effects of many HPA axis hormones on IS functions are actually documented also in physiologic conditions. Conversely, numerous IS soluble mediators are reported to affect the HPA axis functions at various steps of HPA axis regulation, in both physiologic and pathologic conditions. Stress and aging may represent two paradigmatic conditions to show the relevance of the bidirectional network between HPA axis and IS, as in both HPA activation and IS impairment are frequently coexistent. Finally, in the context of the wide spectrum of HIV-related HPA axis abnormalities, a case of a Cushing's syndrome associated to an acquired immunodeficiency syndrome (AIDS-related complex) in a 24-year-old homosexual drug abuser is reported.

AIDS-Related Complex↗
PubMed2005

Genome-scale reconstruction of the metabolic network in Staphylococcus aureus N315: an initial draft to the two-dimensional annotation.

BACKGROUND: Several strains of bacteria have sequenced and annotated genomes, which have been used in conjunction with biochemical and physiological data to reconstruct genome-scale metabolic networks. Such reconstruction amounts to a two-dimensional annotation of the genome. These networks have been analyzed with a constraint-based formalism and a variety of biologically meaningful results have emerged. Staphylococcus aureus is a pathogenic bacterium that has evolved resistance to many antibiotics, representing a significant health care concern. We present the first manually curated elementally and charge balanced genome-scale reconstruction and model of S. aureus' metabolic networks and compute some of its properties. RESULTS: We reconstructed a genome-scale metabolic network of S. aureus strain N315. This reconstruction, termed iSB619, consists of 619 genes that catalyze 640 metabolic reactions. For 91% of the reactions, open reading frames are explicitly linked to proteins and to the reaction. All but three of the metabolic reactions are both charge and elementally balanced. The reaction list is the most complete to date for this pathogen. When the capabilities of the reconstructed network were analyzed in the context of maximal growth, we formed hypotheses regarding growth requirements, the efficiency of growth on different carbon sources, and potential drug targets. These hypotheses can be tested experimentally and the data gathered can be used to improve subsequent versions of the reconstruction. CONCLUSION: iSB619 represents comprehensive biochemically and genetically structured information about the metabolism of S. aureus to date. The reconstructed metabolic network can be used to predict cellular phenotypes and thus advance our understanding of a troublesome pathogen.

Bacterial Proteins↗
PubMed2006

Remodeling of neuronal networks by stress.

Stress can be a threat to the physiological and psychological integrity of an individual and may result in psychic and behavioral changes. The stress response is mediated through in-concert activity of many brain areas and there is experimental evidence that stress induces structural changes in neuronal networks, in particular in the hippocampus, the prefrontal cortex and the amygdala. Within the hippocampal formation, stress exposure results in remodeling of dendrites of the CA3 pyramidal neurons and in reduced numbers of synapses on these neurons. Furthermore, stress inhibits adult neurogenesis in the dentate gyrus and appears to modulate the GABAergic system. In the prefrontal cortex, repeated exposure to stress causes dendritic retraction and loss of spines in pyramidal neurons whereas in the amygdala stress can elicit dendritic hypertrophy. These microscopically detectable changes in neuronal structures indicate the reorganization of neuronal networks. Moreover, molecular studies show that stress modulates expression of genes involved in neuronal differentiation and/or structural remodeling. Since a wealth of data documents the adverse effects of stress on emotions and cognition these alterations are commonly interpreted as the deleterious effect of chronic stress on the central nervous system. However, it is also possible that at least part of these changes reflect adaptive responses, as the network system rearranges its connections in order to cope with the changing requirements from the internal or external environment.

Cell Differentiation↗
PubMed2003

Is there a psychoneuroimmunological pathway between alexithymia and immunity? Immune and physiological correlates of alexithymia.

The term "alexithymia" was coined by Sifneos. It is characterised by a lack of words to express emotion (a: absence of; lexi: words; thymia: emotions, affects). Its characteristics were suggested to occur more frequently in individuals with so-called "psychosomatic disorders", but this is still a matter of controversy. Here we review the psychosomatic network of alexithymia, i.e. the immune and physiological correlates of alexithymia. Some studies suggest that inaccuracy in recognising emotional states, or the way of coping with negative emotions, may influence immune function. Alexithymia is associated with higher tonic baseline levels of sympathetic activity and lower sympathetic reactivity during acute stress. Few studies have reported a diminished immune-mediated cellular response in alexithymics with oversecretion of glucocorticoids. We hypothesise that alexithymic subjects may suffer from unnoticed chronic stress with physiological and endocrine and immune consequences. Alexithymia may skew the Th-1/Th-2 balance toward Th-2 dominant immunity and lower cell-mediated (Th-1) immune response and may increase an individual's risk for stress-related disorder.

Affective Symptoms↗
PubMed1996

Unilateral LTP triggers bilateral increases in hippocampal neurotrophin and trk receptor mRNA expression in behaving rats: evidence for interhemispheric communication.

Induction of long-term potentiation (LTP) in the dentate gyrus of awake rats triggered a rapid (2 hour) elevation in tyrosine kinase receptor (trkB and trkC) gene expression and a delayed (6-24 hour) increase in brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) gene expression. Depending on the mRNA species, LTP induction led to highly selective unilateral or bilateral increases in gene expression. Specifically, trkB and NT-3 mRNA elevations were restricted to granule cells in the ipsilateral dentate gyrus, whereas bilateral increases in trkC, BDNF, and nerve growth factor (NGF) mRNA levels occurred in granule cells and hippocampal pyramidal cells. Both unilateral and bilateral changes in gene expression were N-methyl-D-aspartate (NMDA) receptor-dependent and LTP-specific. Bilateral electrophysiological recordings demonstrated that LTP was unilaterally induced; this was corroborated by a dramatic unilateral increase in the expression of the immediate early gene zif/268, a marker for LTP, restricted to the ipsilateral granule cells. The results indicate that LTP triggers an interhemispheric communication manifested as selective, bilateral increases in gene expression at multiple sites in the hippocampal network. Furthermore, our findings suggest that physiological plastic changes in the adult brain may involve coordinated, time-dependent regulation of multiple neurotrophin and trk receptor genes.

Animals↗
PubMed1979

A hypothetical explanation of saccadic oscillations.

Eye movements in a patient with saccadic oscillations (ocular flutter) were recorded and analyzed. Findings were related to recent microelectrode studies in the monkey pontine reticular formation which have identified three types of premotor neurons related to saccadic eye movements: burst, tonic, and pause cells. We incorporated these cell types into a hypothetical circuit that generates saccades by rapidly driving the eye to a designated orbital position rather than preprogramming a distance for movement. Physiological measurements suggest that this neural network is unstable and that the burst neurons must be tonically inhibited to prevent saccadic oscillations during periods of fixation. Pause cells, which discharge tonically except during saccades, when they pause, appear to inhibit burst cells and prevent such saccadic oscillations. Analysis of our patient's behavior indicates that many types of saccadic oscillations can be explained and classified by assuming an abnormality of pause cell control over saccadic burst neurons.

Adult↗
PubMed2001

Target-dependent modulation of neurotransmitter release in cultured Helix neurons involves adhesion molecules.

The secretory capabilities of the serotonergic neuron C1 of cerebral ganglion of Helix pomatia were markedly reduced when it was cultured in contact with the wrong target neuron, C3. When the neuron B2, one of its physiological targets, was micromanipulated within the network made of intermingled neurites originating from the axonal stumps of both C1 and C3 neurons, C1 increased the amount of the evoked transmitter release, which, after 30 min, reached the level observed when cocultured with the appropriate target. The removal of the appropriate target brought C1 back to the low release condition. By imaging C1 neurites with a fluorescent dye, morphological changes involving a local increase in the number of varicosities could be observed as early as 30 min after contact with the appropriate target. Monoclonal antibody 4E8 against apCAM, a family of Aplysia adhesion molecules, recognizes apCAM-like molecules of the Helix central nervous system on immunocytochemistry and Western blot analysis. The contact with the appropriate target previously incubated in a 4E8 solution, which did not interfere with its capacity to respond to serotonin, failed to increase the transmitter release of C1 cocultured in the presence of the wrong target, C3. These results suggest that the apCAM-like antigens bound to the target membrane participate in the molecular processes responsible for the assembly of the "release machinery" present in the functional presynaptic structure.

Animals↗
PubMed2003

Model of the human vasculature for studying the influence of contrast injection speed on cerebral perfusion MRI.

Simulations of dynamic susceptibility contrast (DSC) MRI are frequently performed by assuming a certain shape for the input function and the microvascular response function. However, to investigate the influence of parameters that will affect the shape of the input function, a more complex model of the human vasculature is required. In this study, a model of the human vasculature is proposed that consists of a network of vascular operators based on physiological data typical of a 35-year-old male subject. The simulated contrast passage curves were found to be within the range of observed contrast passage curves in a population of patients without vascular disease. The model was used to predict the effect of different injection speeds of the contrast agent on the accuracy of the perfusion experiment. It was found that injection speeds of <3 ml/s lead to an underestimation of the observed cerebral blood flow (CBF). Additionally, it was determined that decreasing the temporal resolution of the acquisition results in an underestimation of the CBF values, and an increase of the standard deviation (SD) of CBF measurements.

Adult↗
PubMed2001

Human articular chondrocytes express functional leptin receptors.

The effects of leptin hormone are mediated by interactions with several physiological regulatory systems and the cytokine network, and by targeting cells directly. The leptin receptor is a member of the class I cytokine receptor family, and its signal transduction resembles that induced by many cytokines. We demonstrated that serially cultured human articular chondrocytes possess the leptin receptor (Ob-R), and that this receptor was present on chondrocytes in native human cartilage. In cultured chondrocytes we detected mRNA for the functional isoform of leptin receptor (Ob-Rb or Ob-R(L)), and it was revealed that ligand binding resulted in phosphorylation of signal transducers and activators of transcription, namely STAT1 and STAT5. Chondrocytes stimulated with leptin exhibited an increased proliferation and an enhanced synthesis of extracellular matrix (proteoglycans and collagen). These results indicate that leptin affects cartilage generation directly, which is a novel role for leptin in skeletal growth and development.

Blotting, Western↗
PubMed1999

Physical activity monitoring based on accelerometry: validation and comparison with video observation.

The objective of this feasibility study is to evaluate the use of the 'Physilog' device, an ambulatory physical-activity recorder based on acceleration measurement, for the monitoring of daily physical activities. Accelerations measured at the level of the chest and the thigh are recorded by Physilog over a period of 1 h in five normal subjects. A specially designed studio-like room allowing the performance of most usual activities of everyday life is used. A video film synchronised with the Physilog is obtained for each subject to check the accuracy of the data derived from Physilog. Based on the analysis on the average and the deviation of the acceleration signal, an algorithm is developed to classify the activities in four categories, i.e. lying, sitting, standing and locomotion. Compared with the video observations, the results from the algorithm show an overall misclassification of 10.7%, which is mainly due to confusion between dynamic activities and the standing posture. In contrast, the misclassification between postures is negligible. It is concluded that Physilog can be used in the clinical setting for the reliable measurement and long-term recording of most usual physical activities.

Activities of Daily Living↗
PubMed2005

Threading neural feedforward into a mechanical spring: how biology exploits physics in limb control.

A solution is proposed of the hitherto unsolved problem as to how neural feedforward through inverse modelling and negative feedback realised by a mechanical spring can be combined to achieve a highly effective control of limb movement. The revised spring approach that we suggest does not require forward modelling and produces simulated data which are as close as possible to experimental human data. Control models based on peripheral sensing with forward modelling, which are favoured in the current literature, fail to create such data. Our approach suggests that current views on motor control and learning should be revisited.

Adult↗
PubMed2006

A model of cerebrocerebello-spinomuscular interaction in the sagittal control of human walking.

A computationally developed model of human upright balance control (Jo and Massaquoi on Biol cybern 91:188-202, 2004) has been enhanced to describe biped walking in the sagittal plane. The model incorporates (a) non-linear muscle mechanics having activation level -dependent impedance, (b) scheduled cerebrocerebellar interaction for control of center of mass position and trunk pitch angle, (c) rectangular pulse-like feedforward commands from a brainstem/ spinal pattern generator, and (d) segmental reflex modulation of muscular synergies to refine inter-joint coordination. The model can stand when muscles around the ankle are coactivated. When trigger signals activate, the model transitions from standing still to walking at 1.5 m/s. Simulated natural walking displays none of seven pathological gait features. The model can simulate different walking speeds by tuning the amplitude and frequency in spinal pattern generator. The walking is stable against forward and backward pushes of up to 70 and 75 N, respectively, and with sudden changes in trunk mass of up to 18%. The sensitivity of the model to changes in neural parameters and the predicted behavioral results of simulated neural system lesions are examined. The deficit gait simulations may be useful to support the functional and anatomical correspondences of the model. The model demonstrates that basic human-like walking can be achieved by a hierarchical structure of stabilized-long loop feedback and synergy-mediated feedforward controls. In particular, internal models of body dynamics are not required.

Cerebellum↗
PubMed1997

Neural control of interlimb oscillations. I. Human bimanual coordination.

How do humans and other animals accomplish coordinated movements? How are novel combinations of limb joints rapidly assembled into new behavioral units that move together in in-phase or anti-phase movement patterns during complex movement tasks? A neural central pattern generator (CPG) model simulates data from human bimanual coordination tasks. As in the data, anti-phase oscillations at low frequencies switch to in-phase oscillations at high frequencies, in-phase oscillations occur at both low and high frequencies, phase fluctuations occur at the anti-phase in-phase transition, a "seagull effect" of larger errors occurs at intermediate phases, and oscillations slip toward in-phase and anti-phase when driven at intermediate phases. These oscillations and bifurcations are emergent properties of the CPG model in response to volitional inputs. The CPG model is a version of the Ellias-Grossberg oscillator. Its neurons obey Hodgkin-Huxley type equations whose excitatory signals operate on a faster time scale than their inhibitory signals in a recurrent on-center off-surround anatomy. When an equal command or GO signal activates both model channels, the model CPG can generate both in-phase and anti-phase oscillations at different GO amplitudes. Phase transitions from either in-phase to anti-phase oscillations, or from anti-phase to in-phase oscillations, can occur in different parameter ranges, as the GO signal increases.

Extremities↗
PubMed1997

Neural control of interlimb oscillations. II. Biped and quadruped gaits and bifurcations.

Behavioral data concerning animal and human gaits and gait transitions are simulated as emergent properties of a central pattern generator (CPG) model. The CPG model is a version of the Ellias-Grossberg oscillator. Its neurons obey Hodgkin-Huxley type equations whose excitatory signals operate on a faster time scale than their inhibitory signals in a recurrent on-center off-surround anatomy. A descending command or GO signal activates the gaits and triggers gait transitions as its amplitude increases. A single model CPG can generate both in-phase and anti-phase oscillations at different GO amplitudes. Phase transitions from either in-phase to anti-phase oscillations or from anti-phase to in-phase oscillations can occur in different parameter ranges, as the GO signal increases. Quadruped vertebrate gaits, including the amble, the walk, all three pairwise gaits (trot, pace, and gallop), and the pronk are simulated using this property. Rapid gait transitions are simulated in the order--walk, trot, pace, and gallop--that occurs in the cat, along with the observed increase in oscillation frequency. Precise control of quadruped gait switching uses GO-dependent modulation of inhibitory interactions, which generates a different functional anatomy at different arousal levels. The primary human gaits (the walk and the run) and elephant gaits (the amble and the walk) are simulated, without modulation, by oscillations with the same phase relationships but different waveform shapes at different GO signal levels, much as the duty cycles of the feet are longer in the walk than in the run. Relevant neural data from spinal cord, globus pallidus, and motor cortex, among other structures, are discussed.

Animals↗