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PubMed2000

Generic modeling of chemotactic based self-wiring of neural networks.

The proper functioning of the nervous system depends critically on the intricate network of synaptic connections that are generated during the system development. During the network formation, the growth cones migrate through the embryonic environment to their targets using chemical communication. A major obstacle in the elucidation of fundamental principles underlying this self-wiring is the complexity of the system being analyzed. Hence much effort is devoted to in vitro experiments of simpler (two-dimensional) 2D model systems. In these experiments neurons are placed on Poly-L-Lysine (PLL) surfaces, so it is easier to monitor their self-wiring. We developed a model to reproduce the salient features of the 2D systems, inspired by the study of the growth of bacterial colonies and the aggregation of amoebae. We represent the neurons (each composed of cell's soma, neurites and growth cones) by active elements that capture the generic features of the real neurons. The model also incorporates stationary units representing the cells' soma and communicating walkers representing the growth cones. The stationary units send neurites one at a time, and respond to chemical signaling. The walkers migrate in response to chemotaxis substances emitted by the soma and communicate with each other and with the soma by means of chemotactic "feedback". The interplay between the chemo-repulsive and chemo-attractive responses is determined by the dynamics of the walker's internal energy which is controlled by the soma. These features enable the neurons to perform the complex task of self-wiring. We present numerical experiments of the model to demonstrate its ability to form fine structures in simple networks of few neurons. Our results raise two fundamental issues: (1) one needs to develop characterization methods (beyond number of connections per neuron) to distinguish the various possible networks; (2) what are the relations between the network organization and its computational properties and efficiency?

Animals↗

PubMed2001

Effects of olanzapine on cerebellar functional connectivity in schizophrenia measured by fMRI during a simple motor task.

BACKGROUND: According to current theories, schizophrenia results from altered connectivity in brain circuits for fundamental cognitive operations. Consequently, the poorly understood mechanisms of neuroleptic treatment may be explainable by altered functional interactions within such networks. The 'cognitive dysmetria' model hypothesizes that one key structure in these circuits is the cerebellum. To investigate the effects of olanzapine on cerebellar functional connectivity (CFC), a seed-voxel correlation analysis (SVCA) was used in a functional magnetic resonance imaging (fMRI) study of a simple finger-tapping task. METHODS: fMRI scans were obtained from six schizophrenic patients under both drug-free and olanzapine-treated conditions and from a matched control group of six healthy subjects at corresponding time points. SVCAs were performed for anatomically and functionally standardized seed voxels in the anterior cerebellum. SVCA results were then processed by three different randomization analyses. RESULTS: The analyses revealed that olanzapine caused widespread changes of CFC, including prominent changes in prefrontal cortex and mediodorsal thalamus. Significant changes in motor structures were found after subtractions within both groups and may thus indicate repetition effects rather than drug effects. Olanzapine 'normalized' the patients' CFC patterns for the right, but not for the left cerebellum. CONCLUSION: Even for a simple motor task, olanzapine affects functional interactions between the cerebellum and many non-motor brain regions, including elements of the 'cognitive dysmetria' circuit. Altogether, our findings suggest that olanzapine has a stronger differential effect on neural activity in prefrontal cortex and thalamus than in motor structures.

Adult↗

PubMed1999

Orientation topography of layer 4 lateral networks revealed by optical imaging in cat visual cortex (area 18).

The functional specificity of corticocortical connections with respect to the topography of orientation selectivity was studied by optical imaging of intrinsic signals and bulk injections of fluorescent latex beads (green and red) and biocytin into layer 4. The distributions of retrogradely labelled cells and anterogradely labelled axon terminals were histologically reconstructed from all cortical laminae, and the resulting anatomical maps compared with the optically imaged functional maps. Layer 4 injections produced extensive horizontal labelling up to 2-3 mm from the injection centres albeit without the clear patchy pattern described after layer 2/3 injections (Gilbert & Wiesel 1989, J. Neurosci., 9, 2432-2442; Kisvárday et al. 1997, Cerebral Cortex, 7, 605-618). The functional (orientation) distribution of the labelled projections was analysed according to laminar location and lateral spread. With regard to the former, no major difference in the orientation topography between supragranular- (upper tier), granular- (middle tier) and infragranular (lower tier) layers was seen. Laterally, proximal and distal projections were distinguished and further dissected into three orientation categories, iso- (+/- 30 degrees ), oblique- (+/- 30-60 degrees ) and cross-orientations (+/- 60-90 degrees ) with respect to the orientation preference at the injection sites. The majority of distal connections (retrograde and anterograde) was equally distributed across orientations (35.4% iso-, 33.7% oblique-, and 30.9% cross-orientations) that are equivalent with a preponderance to dissimilar orientations (oblique- and cross-orientations, 64.6%). In one case, distal excitatory and inhibitory connections could be morphologically distinguished. For both categories, a marked bias to dissimilar orientations was found (excitatory, 63.7%; inhibitory, 86.6%). Taken together, these results suggest that the long-range layer 4 circuitry has a different functional role from that of the iso-orientation biased (52.9%, Kisvárday et al. 1997, Cerebral Cortex, 7, 605-618) layer 2/3 circuitry, and is perhaps involved in feature difference-based mechanisms, e.g. figure ground segregation.

Animals↗

PubMed2001

Immediate reorganization of the rat somatosensory thalamus after partial ligation of sciatic nerve.

Nerve injury can result in neuropathic pain, which persists after the injury and may occur after healing is completed. The long-term central reorganization associated with neuropathic pain has been previously studied in animal models. The immediate effects of nerve injury on central representation, however, are poorly understood. We examined the population response properties of closely neighboring neurons located in the hindlimb representation area of the somatosensory thalamus. Changes in the neuronal population properties were characterized before, during, and after (up to 6 hours) partial ligation of the sciatic nerve in the rat. Changes in these properties were observed within minutes after nerve injury. There were changes in neuronal class and receptive field size, emergence of new receptive fields, receptive fields observed before ligation disappeared temporarily after ligation, and changes in number of spikes evoked by the same stimulus. The rates of these changes in central representation were essentially zero before ligation, maximal within minutes after ligation, and decreased to a steady sustained rate of change within 1 to 2 hours. The incidence of functional connectivity, as measured by cross-correlations, remained unchanged. However, the strength of functional connectivity increased after ligation. The results show immediate reorganization of lateral thalamic networks with peripheral nerve damage. When the population response is considered as the underlying code, this reorganization does not reflect the behavioral manifestations of hyperalgesia and allodynia, even though some of the individual neuronal responses do reflect properties consistent with the hyperalgesia and allodynia reported within the same time frame after nerve injury in the rat.

Journal Article↗

PubMed2006

Measuring asymmetric temporal interdependencies in simulated and biological networks.

We use a newly developed metric to characterize asymmetric temporal interdependencies in networks of coupled dynamical elements. We studied the formation of temporal ordering in a system of coupled Rossler oscillators for different connectivity ratios and network topologies and also applied the metric to investigate the functional structure of a biological network (cerebral ganglia of Helix snail). In the former example we show how the local ordering evolves to the global one as a function of structural parameters of the network, while in the latter we show spontaneous emergence of functional interdependence between two groups of electrodes.

Action Potentials↗

PubMed1996

Hebb's concept of cell assemblies and the psychophysiology of word processing.

Hebb's brain-theoretical approach suggests that tightly connected networks of neurons, Hebbian cell assemblies, are the building blocks of cognitive functions. These assemblies are not necessarily restricted to a small cortical locus but may be dispersed over distant cortical areas. Assemblies with different topographies can be postulated for different kinds of words, such as meaningful content versus grammatical function words or words eliciting motor versus visual associations. Evidence from evoked potentials and gamma-band electrocortical responses elicited by lexical material supports a cell assembly model of language and other higher cognitive functions.

Brain↗

PubMed2002

Reciprocal intraglomerular excitation and intra- and interglomerular lateral inhibition between mouse olfactory bulb mitral cells.

How patterns of odour-evoked glomerular activity are transformed into patterns of mitral cell action potentials (APs) in the olfactory bulb is determined by the functional connectivity of the cell populations in the bulb. We have used paired whole-cell voltage recordings from olfactory bulb slices to compare the functional connectivity of mitral cells to the known anatomy of the mitral cell network. Both inhibitory and excitatory coupling were observed between pairs of mitral cells. Inhibitory coupling was seen as an increased frequency of small, asynchronous GABAergic IPSPs following APs in the presynaptic cell. Excitatory coupling was short in latency, beginning about 1.3 ms after the presynaptic AP and was mediated by both NMDA and AMPA receptors. Mitral cell pairs were coupled by excitation if and only if their apical dendrites terminated in the same glomerulus. The excitatory coupling between mitral cells resembles conventional fast synaptic transmission in its time course, amplitude and latency, despite the absence of evidence for anatomically defined synapses between mitral cells.

Action Potentials↗

PubMedDate not supplied

[Development and application of an expert system for analysis of the functional continuum of regulatory peptides].

An expert computer system was developed to analyze the effects of regulatory peptides (RPs) and some other biologically active compounds. The database includes information on their structures and physiological and inductive effects taking in account the method of administration, doses, and types of organisms. The developed method of vector representation of RP effects and the software modules provide for the estimation of the role of single RPs and their combinations in the regulatory system of organism. The expert system was used for solving the following tasks: (1) an analysis of the structural and functional organization of the RP continuum and a search for effective RP combinations regulating the levels of anxiety, depression, cognitive processes, etc; (2) design of a network of complicated cross inductive connections of major members of RP families; and (3) an analysis of the peculiar features of functioning of numerous internal reward factors. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2006, vol. 32, no. 3; see also http://www.maik.ru.

Animals↗

PubMed2003

Myofascial force transmission between a single muscle head and adjacent tissues: length effects of head III of rat EDL.

Force transmission from muscle fibers via the connective tissue network (i.e., myofascial force transmission) is an important determinant of muscle function. This study investigates the role of myofascial pathways for force transmission from multitendoned extensor digitorum longus (EDL) muscle within an intact anterior crural compartment. Effects of length changes exclusively of head III of rat EDL muscle (EDL III) on myofascial force transmission were assessed. EDL III was lengthened at the distal tendon. For different lengths of EDL III, isometric forces were measured at the distal tendon of EDL III, as well as at the proximal tendon of whole EDL and at the distal tendons of tibialis anterior and extensor hallucis longus (TA+EHL) muscles. Lengthening of EDL III caused high changes in force exerted at the distal tendon of EDL III (from 0 to 1.03 +/- 0.07 N). In contrast, only minor changes were found in force exerted at the proximal EDL tendon (from 2.37 +/- 0.09 to 2.53 +/- 0.10 N). Increasing the length of EDL III decreased TA+EHL force significantly (by 7%, i.e., from 5.62 +/- 0.27 to 5.22 +/- 0.32 N). These results show that force is transmitted between EDL III and adjacent tissues via myofascial pathways. Optimal force exerted at the distal tendon of EDL III (1.03 +/- 0.07 N) was more than twice the force expected on the basis of the physiological cross-sectional area of EDL III muscle fibers (0.42 N). Therefore, a substantial fraction of this force must originate from sources other than EDL III. It is concluded that myofascial pathways play an important role in force transmission from multitendoned muscles.

Animals↗

PubMed2004

Connectivity and dynamics of neural information processing.

In this article, we systematically review the current literature on neural connectivity and dynamics, or equivalently, structure and function. In particular, we discuss how changes in the connectivity of a neural network affect the spatiotemporal network dynamics qualitatively. The three major criteria of comparison are, first, the local dynamics at the network nodes which includes fixed point dynamics, oscillatory and chaotic dynamics; second, the presence of time delays via propagation along connecting pathways; and third, the properties of the connectivity matrix such as its statistics, symmetry, and translational invariance. Since the connection topology changes when anatomical scales are traversed, so will the corresponding network dynamics change. As a consequence different types of networks are encountered on different levels of neural organization.

Animals↗

PubMed2006

An in vitro study of horizontal connections in the intermediate layer of the superior colliculus.

Some models propose that the spatial and temporal distributions of premotor activity in the intermediate layer of the superior colliculus are shaped by neuronal ensembles that give rise to local excitatory and distant inhibitory connections. One function proposed for these connections is to mediate a "winner-take-all" network; the short-range excitatory connections build up the activity of neighboring cells that command orienting movements in one direction, whereas the wide-ranging inhibitory projections attenuate the activity of remote cells that command incompatible movements. We used in vitro photostimulation and whole-cell patch-clamp recording to test these models by measuring the spatial extent of synaptic interactions within the rat intermediate layer. Uncaging glutamate over whole-cell patch-clamped cells in the intermediate layer elicited long-lasting inward currents, resulting from direct activation of glutamate receptors expressed by the cells, and brief synaptic currents evoked by activation of presynaptic neurons. The synaptic responses comprised clusters of excitatory and inhibitory currents. The size of these responses depended on the location of the stimulus with respect to the clamped cell. Large responses were commonly evoked by stimuli within 200 microm of the soma in the intermediate layer; smaller responses could occasionally be evoked from sites as distant as 500 microm. Responses evoked by stimulation beyond this distance were rare. Although the results demonstrated powerful local excitatory and inhibitory connections, they did not support the pattern of short-range excitation and widespread inhibition predicted by the winner-take-all hypothesis.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed2006

The anatomical relationships between the serotonergic afferents and the neurons containing calcium-binding proteins in the rat claustrum.

Claustrum is a telencephalic structure integrating information of various modalities. Proper functioning of this structure depends on the presence of a network of intrinsic connections. This includes GABA-ergic neuronal populations that also contain calcium-binding proteins (CaBPs). The goal of this study was to analyze qualitative and quantitative the 5-HT-containing fibers in the rat claustrum and to assess the relationships between these fibers and the populations of claustral neurons expressing CaBPs. We used the methods of immunocytochemistry and morphometry. The serotonergic fibers in the claustrum are heterogeneous, both with respect to their morphology and spatial distribution. Thin varicose fibers are more numerous and are homogeneously distributed within the claustrum. Remaining fibers were thicker and possessed larger varicosities. They were present mainly in the ventral part of the claustrum. Although the serotonergic fibers are found in the vicinity of claustral cells containing CaBPs, direct contacts between these fibers and cells are rare. Other mechanisms, including volume transmission, may possibly mediate serotonergic influences.

Afferent Pathways↗

PubMed2000

Respiratory rhythm generation in neonatal and adult mammals: the hybrid pacemaker-network model.

We review a new unified model of respiratory rhythm generation - the hybrid pacemaker-network model. This model represents a comprehensive synthesis of cellular and network mechanisms that can theoretically account for rhythm generation in different functional states, from the most reduced states in the neonatal nervous system in vitro to the intact adult system in vivo. The model incorporates a critical neuronal kernel consisting of a network of excitatory neurons with state-dependent, oscillatory bursting or pacemaker properties. This kernel, located in the pre-Bötzinger complex of the ventrolateral medulla, provides a rudimentary pacemaker network mechanism for generating an inspiratory rhythm, revealed predominately in functionally reduced states in vitro. In vivo the kernel is embedded in a larger network that interacts with the kernel via inhibitory synaptic connections that provide the dynamic control required for the evolution of the complete pattern of inspiratory and expiratory network activity. The resulting hybrid of cellular pacemaker and network properties functionally endows the system with multiple mechanisms of rhythm generation. New biophysically realistic mathematical models of the hybrid pacemaker-network have been developed that illustrate these concepts and provide a computational framework for investigating interactions of cellular and network processes that must be analyzed to understand rhythm generation.

Animals↗

PubMed2006

An effective structure learning method for constructing gene networks.

MOTIVATION: Bayesian network methods have shown promise in gene regulatory network reconstruction because of their capability of capturing causal relationships between genes and handling data with noises found in biological experiments. The problem of learning network structures, however, is NP hard. Consequently, heuristic methods such as hill climbing are used for structure learning. For networks of a moderate size, hill climbing methods are not computationally efficient. Furthermore, relatively low accuracy of the learned structures may be observed. The purpose of this article is to present a novel structure learning method for gene network discovery. RESULTS: In this paper, we present a novel structure learning method to reconstruct the underlying gene networks from the observational gene expression data. Unlike hill climbing approaches, the proposed method first constructs an undirected network based on mutual information between two nodes and then splits the structure into substructures. The directional orientations for the edges that connect two nodes are then obtained by optimizing a scoring function for each substructure. Our method is evaluated using two benchmark network datasets with known structures. The results show that the proposed method can identify networks that are close to the optimal structures. It outperforms hill climbing methods in terms of both computation time and predicted structure accuracy. We also apply the method to gene expression data measured during the yeast cycle and show the effectiveness of the proposed method for network reconstruction.

Algorithms↗

PubMed1997

[Lymph flow and the development of the lymph nodes in human fetuses].

Since its anlage lymph node forms as a functional anastomosis between lymph and blood vessels. They make a complex with intimate anatomotopographic interrelations and their branches--an interconnected system, within which intervascular connective tissue transforms into lymphoid one. Interstitial canals networks may play a role of connecting "bridges" during lymphatic sinuses and blood microvessels unification with lymphoid tissue into a specific functional complex of counterflow system (arteries/veins--lymphatic vessels). On this basis histo- and morphogenesis of lymph node as a part of lymphatic bed occur. Lymph node uneven growth due to their depositing and resorptive function development allows to explain peculiarities of central lymph flow in human embryos.

Abdomen↗

PubMed2000

On imputing function to structure from the behavioural effects of brain lesions.

What is the link, if any, between the patterns of connections in the brain and the behavioural effects of localized brain lesions? We explored this question in four related ways. First, we investigated the distribution of activity decrements that followed simulated damage to elements of the thalamocortical network, using integrative mechanisms that have recently been used to successfully relate connection data to information on the spread of activation, and to account simultaneously for a variety of lesion effects. Second, we examined the consequences of the patterns of decrement seen in the simulation for each type of inference that has been employed to impute function to structure on the basis of the effects of brain lesions. Every variety of conventional inference, including double dissociation, readily misattributed function to structure. Third, we tried to derive a more reliable framework of inference for imputing function to structure, by clarifying concepts of function, and exploring a more formal framework, in which knowledge of connectivity is necessary but insufficient, based on concepts capable of mathematical specification. Fourth, we applied this framework to inferences about function relating to a simple network that reproduces intact, lesioned and paradoxically restored orientating behaviour. Lesion effects could be used to recover detailed and reliable information on which structures contributed to particular functions in this simple network. Finally, we explored how the effects of brain lesions and this formal approach could be used in conjunction with information from multiple neuroscience methodologies to develop a practical and reliable approach to inferring the functional roles of brain structures.

Behavior↗

PubMed1995

A network model of developmental gene hierarchy.

A network model of development governing the whole temporal and spatial hierarchy of early embryogenesis and pattern formation in Drosophila is introduced. The network is related to a neural network model, with its units being developmental genes mostly connected by the genes' DNA-binding products. The developmental network's agreement with predictions regarding architecture and function of the neural network provides adequate grounds for an analogy between the two. The model is tested through computer simulations--predictions compare favorably with experimental observations. The model not only incorporates a program of control at gene level, but also makes a direct connection with current molecular studies throughout the whole hierarchy of the early embryogenesis of Drosophila.

Animals↗

PubMed2005

Modulation of effective connectivity by cognitive demand in phonological verbal fluency.

Verbal fluency is a classic neuropsychological measure of language production. Phonological verbal fluency involves the generation of words beginning with a specified letter, and its functional neuroanatomy is comprised of a distributed network of regions which is modulated by cognitive load. In order to investigate the functional relationship of these regions, the effective connectivity was analyzed with covariance structural equation modeling under conditions of varying cognitive load. Significant path coefficients were evident between the anterior cingulate, left middle frontal gyrus, and precuneus. The left middle frontal gyrus showed a facilitory projection to the precuneus which had a suppressive influence on anterior cingulate activation. With increasing cognitive demand, the left middle frontal projection to the precuneus became suppressive, and the path coefficient from the precuneus to the anterior cingulate showed a marked diminution in strength. The path analysis suggests that the lead-in process for letter verbal fluency may primarily involve an orthographic visual strategy. The marked changes in path coefficients with the increased cognitive load may reflect the greater demands placed on executive function. The significant changes in path coefficient values with increased cognitive demand indicate the importance of accounting for task difficulty not only in the interpretation of brain activation maps but also for effective connectivity measurements.

Adult↗