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PubMed2006

Network theory to understand microarray studies of complex diseases.

Complex diseases, such as allergy, diabetes and obesity depend on altered interactions between multiple genes, rather than changes in a single causal gene. DNA microarray studies of a complex disease often implicate hundreds of genes in the pathogenesis. This indicates that many different mechanisms and pathways are involved. How can we understand such complexity? How can hypotheses be formulated and tested? One approach is to organize the data in network models and to analyze these in a top-down manner. Globally, networks in nature are often characterized by a small number of highly connected nodes, while the majority of nodes have few connections. The highly connected nodes serve as hubs that affect many other nodes. Such hubs have key roles in the network. In yeast cells, for example, deletion of highly connected proteins is associated with increased lethality, compared to deletion of less connected proteins. This suggests the biological relevance of networks. Moving down in the network structure, there may be sub-networks or modules with specific functions. These modules may be further dissected to analyze individual nodes. In the context of DNA microarray studies of complex diseases, gene-interaction networks may contain modules of co-regulated or interacting genes that have distinct biological functions. Such modules may be linked to specific gene polymorphisms, transcription factors, cellular functions and disease mechanisms. Genes that are reliably active only in the context of their modules can be considered markers for the activity of the modules and may thus be promising candidates for biomarkers or therapeutic targets. This review aims to give an introduction to network theory and how it can be applied to microarray studies of complex diseases.

Humans↗
PubMed2004

A system of networks and continuing education for physical therapists in rheumatology: a feasibility study.

PURPOSE: To evaluate the feasibility of regional physical therapy networks including continuing education in rheumatology. The aim of these networks was to improve care provided by primary care physical therapists by improving specific knowledge, technical and communicative skills and the collaboration with rheumatologists. METHODS: In two regions in The Netherlands continuing education (CE) programmes, consisting of a 5-day postgraduate training course followed by bimonthly workshops and teaching practices, were organised simultaneously. Network activities included consultations, newsletters and the development of a communication guideline. Endpoint measures included the participation rate, compliance, quality of the CE programme, teaching practices, knowledge, network activities, communication, number of patients treated and patient satisfaction. RESULTS: Sixty-three physical therapists out of 193 practices (33%) participated in the project. They all completed the education programmes and were formally registered. All evaluations of the education programmes showed positive scores. Knowledge scores increased significantly directly after the training course and at 18 months. A draft guideline on communication between physical therapists and rheumatologists was developed, and 4 newsletters were distributed. A substantial proportion of physical therapists and rheumatologists reported improved communication at 18 months. The mean number of patients treated by physical therapists participating in the networks increased significantly. Patients' satisfaction scores within the networks were significantly higher than those from outside the networks at 18 months. CONCLUSIONS: Setting up a system of networks for continuing education for physical therapists regarding the treatment of patients with rheumatic diseases is feasible. Further research will focus on the effectiveness of the system and its implementation on a larger scale.

Journal Article↗
PubMed1999

Social network characteristics associated with risky behaviors among runaway and homeless youth.

Runaway and homeless youth are at high risk for substance abuse and unsafe sexual behavior. Our study describes the personal social networks of these youth and examines network characteristics associated with risky behaviors. In 1995 and 1996, we interviewed a purposive sample of youth aged 14 through 21 who were living in Washington, DC and were identified on the streets or through shelters or other service agencies (N = 327). Although we found that most youth reported current social relationships, a significant minority (26%) did not. Youth without a social network were significantly more likely to report current illicit drug use, multiple sex partners, and survival sex than youth with a network. For youth with a network, the networks were small, strong in affective and supportive qualities, comprised primarily of friends, typically included an alcohol or illicit drug user, and usually were not a source of pressure for risky behaviors. Our results indicate that networks had risk-enhancing and risk-decreasing properties in that network characteristics were associated in both positive and negative directions with risky behaviors.

Adolescent↗
PubMed1975

Radiological topography and classification of angioma-like arterial networks in cerebro-vascular collateral circulation.

The radiological appearance and localization of collateral cerebrovascular networks are described. The development and distribution of these arterial networks is due to the site of internal carotid artery stenoses. Including interposed arterial nets, the following types are classified: (1) basal arterial networks near the carotid siphon; (2) arterial networks in the region of the basal ganglia (Moyamoya syndrome); (3) ethmoid arterial networks; (4) arterial networks on the cerebral convexity representing transdural external-internal carotid anastomoses, and (5) circumscribed arterial networks interposed in the course of a major cerebral vessel. The differential diagnostic criteria and aetiological factors of these anastomotic intracranial networks are discussed.

Brain Neoplasms↗
PubMed2002

Neuronal activity regulates correlated network properties of spontaneous calcium transients in astrocytes in situ.

Spontaneous neuronal activity is essential to neural development. Until recently, neurons were believed to be the only excitable cells to display spontaneous activity. However, cultured astrocytes and, more recently, astrocytes in situ are now known to exhibit spontaneous Ca2+ transients. Here we used Ca2+ imaging of astrocytes from transgenic mice for the simultaneous monitoring of [Ca2+]i changes in large numbers of astrocytes. We found that spontaneous activity is a common property of most brain astrocytes that is lost in response to a lesion. These spontaneous [Ca2+]i oscillations require extracellular and intracellular Ca2+. Moreover, network analysis revealed that most astrocytes formed correlated networks of dozens of these cells, which were synchronous with both astrocytes and neurons. We found that decreasing spontaneous [Ca2+]i transients in neurons by TTX does not alter the number of active astrocytes, although it impairs their synchronous network activity. Conversely, bicuculline-induced epileptic patterns of [Ca2+]i transients in neurons cause an increase in the number of active astrocytes and in their network synchrony. Furthermore, activation of non-NMDA and NMDA ionotropic glutamate receptors is required to correlate astrocytic networks. These results show that spontaneous activity in astrocytes and neurons is patterned into correlated neuronal/astrocytic networks in which neuronal activity regulates the network properties of astrocytes. This network activity may be essential for neural development and synaptic plasticity.

Animals↗
PubMed2004

Design of reverse osmosis (RO) water treatment networks subject to fouling.

Identifying the optimal design for an RO membrane network is not straightforward when significant fouling occurs. The most robust optimal network design will feature the minimal capital and operating costs over the anticipated lifetime of the plant, and is therefore strongly dependent on the fouling behaviour and associated mitigation. This study considers the case where the likely fouling behaviour is known and investigates how to incorporate this knowledge into the design and operation of a network. The optimisation task is complicated by the highly non-linear nature of the problem owing to membrane behaviour, fouling behaviour, network interactions and operating parameter constraints (pressures and flows). In this work, fouling is modelled as an exponential decay in membrane permeability. Three optimisation approaches are used to evaluate candidate networks: (i) laborious comparison of pre-selected individual network designs; (ii) deterministic gradient search methods, and (iii) a simulated-annealing-based hybrid stochastic-deterministic method. All of the approaches consider various configurations of a two-stage network with a maximum of three membrane units in each stage, represented in a superstructure model. The results from the approaches are compared and the most effective method for network design is discussed.

Biofilms↗
PubMed2004

American society of health-system pharmacists' pain management network.

The American Society of Health-System Pharmacists' (ASHP) Pain Management Network is one of several informal networking groups of pharmacist practitioners who specialize in a clinical practice area. Pharmacy practitioners are showing an increased interest in the management of pain because of expanding clinical roles, the Joint Commission on Accreditation of Health Care Organizations' development of pain management standards, and involvement with performance improvement and quality initiatives. The Pain Management Network is one of the American Society of Health-system Pharmacists (ASHP) Section of Clinical Specialists and Scientists specialty practice networks. The Network serves as an informal venue for practitioners interested in pain management to gather and share information. Pain Management Network Assemblies are held at each ASHP national meeting. Practitioners communicate between meetings via the Section's e-mail list server. Pharmacists who participate in the Pain Management Network have a variety of roles in both acute and chronic pain management. Their roles may be consultative in nature or they may be involved in the actual medication management as part of a collaborative drug therapy management agreement with a physician. Pharmacists are involved with acute pain, cancer-related pain, and chronic nonmalignant pain management. Current issues involve education of pharmacy students and practicing pharmacists as well as the use of meperidine as an analgesic agent. Compounding of non-sterile drugs for intraspinal use is another current issue. Access to evidence-based pain management resources may be difficult to locate and access but is essential to good pain management. The ASHP Pain Management Network has proven to be a valuable way for participants to gather and exchange new information and share in their clinical practice experiences.

Community Pharmacy Services↗
PubMed2004

Statistical and integrative approach for constructing biological network maps.

A goal of systems biology is to build a concrete biochemical network map, which provides an important instruction to trace the pathways of interest or to understand the mechanism of a biological system. In the postgenomic era, not only the concrete biochemical maps, but also postgenomic maps (mRNA coexpression and protein-protein interaction networks) have been extensively produced. In the biochemical map, the individual reactions are reliable, but the number of the reactions is limited, because molecular biology requires extensive experiments to verify them. By contrast, postgenomic data provide much information regarding interactions, but are coarse-grained. To expand the biochemical network, an intuitional approach, which superposes postgenomic data on the map one by one, has been carried out, but it is not effective when a large amount of the coarse-grained data is handled. In order to effectively integrate such postgenomic interactions into a biochemical map, a statistical approach would be suitable rather than intuition. In this article, we proposed a novel statistical approach that integrates postgenomic interaction networks into the biochemical network, predicting novel pathways. A statistical correlation for such different types of networks identifies functional modules; subsequently the superposition of the different networks on the functional modules predicts inter-modular relations, which are the key pathways to construct a large-scale biochemical network.

Computer Simulation↗
PubMed2005

Age-related changes in the structure of myocardial collagen network of auricle of the right atrium in healthy persons and ischemic heart disease patients.

The objective of the study was to examine and evaluate morphometrically age-related changes in the structure of myocardium collagen network of auricle of the right atrium in control group persons, who were not diagnosed with cardiac pathology leading to heart lesion or overload, and in ischemic heart disease patients. Material of 56 persons of both genders aged 20-94 years was used for study purposes. Biopsy material of 17 healthy persons (control group, average age 60.53+/-9.89 years) and autopsy material of 39 ischemic heart disease patients (average age 63.83+/-15.67 years) taken from the basis of auricle of the right atrium (specimen size--2 mm x 2 mm) were examined. Morphometric analysis of collagen network was performed using histologic and video morphometric methods. After this investigation we evaluated quantitative parameters of the bundles of collagen net--namely area, number, perimeter. The percentile occupied area of bundles in control group was 17.6+/-2.5%; ischemic heart disease patients group--26.8+/-2.9%; number of bundles was 4179+/-1073 and 2523+/-867; perimeter--24163+/-3308 mm and 23426+/-409 mm, respectively. After investigation of age-related changes of collagen network in control group and ischemic heart disease patients' group, which did not statistically significantly differed by age, we determined that collagen network area in auricle of the right atrium increased with age in both groups, however, spatial distribution of collagen network was different. Collagen network area enlarged with lengthening of its fibers along cardiomyocytes in control group. In ischemic heart disease group, it enlarged both in parallel to cardiomyocytes and by separate collagen fibers merging into bigger bundles. Fibrillar collagen network area and its total perimeter of healthy persons increased with age, and number of fibers did not change. Consequently, collagen fiber area of one location increased with age; its shape, judging by in parallel increasing total perimeter, became branchier, i.e. proliferated in endomysium in parallel with cardiomyocytes. In ischemic heart disease group fibrillar collagen network percentage area increased with age, however, total perimeter and number of separate fibers in visual field decreased. Consequently, in ischemic heart disease group separate collagen fibers merged, their locations enlarged, taking an integral structure, which allowed assuming development of interstitial fibrosis.

Adult↗
PubMed2005

A practical guide to social networks.

Saying that networks are important is stating the obvious. But harnessing the power of these seemingly invisible groups to achieve organizational goals is an elusive undertaking. Most efforts to promote collaboration are haphazard and built on the implicit philosophy that more connectivity is better. In truth, networks create relational demands that sap people's time and energy and can bog down entire organizations. It's crucial for executives to learn how to promote connectivity only where it benefits an organization or individual and to decrease unnecessary connections. In this article, the authors introduce three types of social networks, each of which delivers unique value. The customized response network excels at framing the ambiguous problems involved in innovation. Strategy consulting firms and new-product development groups rely on this format. By contrast, surgical teams and law firms rely mostly on the modular response network, which works best when components of the problem are known but the sequence of those components in the solution is unknown. And the routine response network is best suited for organizations like call centers, where the problems and solutions are fairly predictable but collaboration is still needed. Executives shouldn't simply hope that collaboration will spontaneously occur in the right places atthe right times in their organization. They need to develop a strategic, nuanced view of collaboration, and they must take steps to ensure that their companies support the types of social networks that best fit their goals. Drawing on examples from Novartis, the FAA, and Sallie Mae, the authors offer managers the tools they need to determine which network will deliver the best results for their organizations and which strategic investments will nurture the right degree of connectivity.

Commerce↗
PubMed1992

Growth restraint and differentiation by LPS/TNF-alpha/IFN-gamma reorganization of the microtubule network in human leukemia cell lines.

The microtubule (MT) network of the cytoskeleton has been implicated as a mediator of cellular signal transduction; disorganization of this network may allow for mitogenesis. In previous work, loss of MT network organization in human MOLT4 and HUT78 T-cell leukemias was demonstrated in contrast to an organized "spoke-wheel-like arrangement" in normal human T-lymphocytes. In this study, loss of MT network organization was shown in several representative acute myeloid leukemia (AML) cell lines: KG1 myeloblastic, HL60 promyelocytic, and U937 myelomonocytic cells. Re-organization of the MT network was observed in HL60 and U937 AML cells treated with combined lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). This re-organization paralleled earlier work which showed this combination was effective in inducing monocytic pathway differentiation and growth restraint in HL60 cells, and growth restraint in U937 cells. In contrast, KG1 cells exhibited growth restraint, but did not re-organize with LPS/TNF-alpha/IFN-gamma treatment. These results are consistent with a role for the MT network in mitogenesis. Loss of MT network organization appeared to parallel the neoplastic phenotype in three AML cell lines, whereas MT network re-organization accompanied recovery of growth control in 2 of 3 AML cell lines.

Interferon-gamma↗
PubMed2003

Efficient reconstruction of phylogenetic networks with constrained recombination.

A phylogenetic network is a generalization of a phylogenetic tree, allowing structural properties that are not tree-like. With the growth of genomic data, much of which does not fit ideal tree models, there is greater need to understand the algorithmics and combinatorics of phylogenetic networks [10, 11]. However, to date, very little has been published on this, with the notable exception of the paper by Wang et al.[12]. Other related papers include [4, 5, 7] We consider the problem introduced in [12], of determining whether the sequences can be derived on a phylogenetic network where the recombination cycles are node disjoint. In this paper, we call such a phylogenetic network a "galled-tree". By more deeply analysing the combinatorial constraints on cycle-disjoint phylogenetic networks, we obtain an efficient algorithm that is guaranteed to be both a necessary and sufficient test for the existence of a galled-tree for the data. If there is a galled-tree, the algorithm constructs one and obtains an implicit representation of all the galled trees for the data, and can create these in linear time for each one. We also note two additional results related to galled trees: first, any set of sequences that can be derived on a galled tree can be derived on a true tree (without recombination cycles), where at most one back mutation is allowed per site; second, the site compatibility problem (which is NP-hard in general) can be solved in linear time for any set of sequences that can be derived on a galled tree. The combinatorial constraints we develop apply (for the most part) to node-disjoint cycles in any phylogenetic network (not just galled-trees), and can be used for example to prove that a given site cannot be on a node-disjoint cycle in any phylogenetic network. Perhaps more important than the specific results about galled-trees, we introduce an approach that can be used to study recombination in phylogenetic networks that go beyond galled-trees.

Computer Simulation↗
PubMed2006

Computational strategy for discovering druggable gene networks from genome-wide RNA expression profiles.

We propose a computational strategy for discovering gene networks affected by a chemical compound. Two kinds of DNA microarray data are assumed to be used: One dataset is short time-course data that measure responses of genes following an experimental treatment. The other dataset is obtained by several hundred single gene knock-downs. These two datasets provide three kinds of information; (i) A gene network is estimated from time-course data by the dynamic Bayesian network model, (ii) Relationships between the knocked-down genes and their regulatees are estimated directly from knock-down microarrays and (iii) A gene network can be estimated by gene knock-down data alone using the Bayesian network model. We propose a method that combines these three kinds of information to provide an accurate gene network that most strongly relates to the mode-of-action of the chemical compound in cells. This information plays an essential role in pharmacogenomics. We illustrate this method with an actual example where human endothelial cell gene networks were generated from a novel time course of gene expression following treatment with the drug fenofibrate, and from 270 novel gene knock-downs. Finally, we succeeded in inferring the gene network related to PPAR-alpha, which is a known target of fenofibrate.

Bayes Theorem↗
PubMed2007

sispread: A software to simulate infectious diseases spreading on contact networks.

OBJECTIVES: We present a simulation software which allows studying the dynamics of a hypothetic infectious disease within a network of connected people. The software is aimed to facilitate the discrimination of stochastic factors governing the evolution of an infection in a network. In order to do this it provides simple tools to create networks of individuals and to set the epidemiological parameters of the outbreaks. METHODS: Three popular models of infectious disease can be used (SI, SIS, SIR). The simulated networks are either the algorithm-based included ones (scale free, small-world, and random homogeneous networks), or provided by third party software. RESULTS: It allows the simulation of a single or many outbreaks over a network, or outbreaks over multiple networks (with identical properties). Standard outputs are the evolution of the prevalence of the disease, on a single outbreak basis or by averaging many outbreaks. The user can also obtain customized outputs which address in detail different possible epidemiological questions about the spread of an infectious agent in a community. CONCLUSIONS: The presented software introduces sources of stochasticity present in real epidemics by simulating outbreaks on contact networks of individuals. This approach may help to understand the paths followed by outbreaks in a given community and to design new strategies for preventing and controlling them.

Algorithms↗
PubMed1989

[Changes of the periodontal vascular network, periodontal fiber and alveolar bone incident to tooth extrusion].

During the application of orthodontic force to a tooth, the surrounding tissues undergo changes of bone resorption and apposition, thereby resulting in tooth movement. The purpose of this study was to investigate the interrelationship between alveolar bone changes and the periodontal vascular network caused by extrusive orthodontic force using a scanning electron microscopy. Extrusive orthodontic force was applied to the mandibular 2nd and 3rd premolars of adult dogs. At the completion of the loading process, the inferior alveolar arteries were injected with a low viscosity MMA resin (Mercox). The following results were obtained. 1) At 3 days post-extrusion, various types of vascular network showing a loop pattern were seen along the direction of the tooth movement. 2) At 7 days post-extrusion, various types of vascular network with a hairpin loop pattern along the direction of the tooth movement were observed. Histologically, the fibers of periodontal ligament were stretched in the direction of the extrusion, Vascular hairpin loop formations were observed within the fibers of periodontal ligament. Bone apposition was not observed on the surface of alveolar bone. 3) At 14 days post-extrusion, a much more extensive and developed hairpin loop pattern occurred. Furthermore, new bone apposition was seen on the alveolar bone beneath under the hairpin loops. The periodontal ligament space was retained in the same width, even after bony apposition. 4) At 21 days post-extrusion, the tooth side microvascular network showed abundant low hairpin loops which anastomosed each other, and new spinous bony apposition was observed right below the periodontal vascular network. 5) At 30 days post-extrusion, the periodontal vascular network showed a almost normal appearance, with the rearrangement of vascular network. The surface of the spinous bony apposition became flat. The appositional bone had a lower degree of calcification than the alveolar bone in control group. 6) At 60 days post-extrusion, the periodontal vascular network completed the rearrangement of vasculature.

Alveolar Bone Loss↗
PubMed1989

Incorporation of exogenous circular DNA into large catenated networks in isolated nuclei. Evidence for involvement of the nuclear scaffold.

Circular plasmid DNA was efficiently converted into huge catenated intranuclear networks by incubation with isolated nuclei in the presence of ATP. The network production is abolished by omission of ATP, strongly inhibited by etoposide (VP-16), but only slightly inhibited by antibody to topoisomerase I, indicating that the major enzyme responsible for catenation is DNA topoisomerase II. Under optimal conditions, a single nucleus incorporates about 4.2 x 10(4) DNA rings into its networks. Under the light microscope, networks retrieved from nuclei appear like spheres of various sizes. Sedimentation analysis showed that most of the networks are composed of thousands of catenated rings, which was confirmed by electron microscopy. Data from experiments that caused partial disruption of the networks were submitted to analysis based on probable models of catenane structure. The results suggest that the predominant pattern is a linear alignment of catenated rings. Similar networks are formed when the nuclear scaffold is incubated with circular DNA in the presence of nuclear extract containing topoisomerase II. Titration experiments showed that the scaffold binds a stoichiometric amount of the substrate and that a critical level of DNA is required for network formation. The results are consistent with the idea that DNA-binding sites are fixed on the scaffold and mediate catenation of bound DNA circles by holding them in close proximity to each other. We propose that catenation by the nuclear scaffold also occurs in intact nuclei, suggesting additional roles for the scaffold in vivo.

Adenosine Triphosphate↗
PubMed1989

The vegetative network in the thoracolumbar spinal cord of the guinea pig: a comparison of the distribution of AChE-enzyme activity and choline acetyltransferase-like immunoreactivity.

Histochemically the acetylcholinesterase (AChE) enzyme activity and immunocytochemically the choline acetyltransferase-like immunoreactivity (ChAT-LI) were located in the components of the vegetative network of the thoracolumbar spinal cord of the guinea pig. Both reaction products showed an identical distribution among the preganglionic sympathetic cells and the processes of the vegetative network, namely: cells of the nucleus intermediolateralis pars principalis (ILp), the nucleus intermediolateralis pars funicularis (ILf), the nucleus intercalatus spinalis (IC) and the nucleus intercalatus paraependymalis (ICpe; terminology according to Petras and Cummings 1972). In longitudinal horizontal sections through the intermediate zone of the thoracolumbar spinal cord both AChE-positive- and ChAT-like immunoreactive nerve fibers were organized into two longitudinal lateral fascicles (FLL), two longitudinal medial fascicles (FLM) as well as oblique and transverse bundles that interconnect repeatedly the autonomic cell groups of this zone along the spinal cord and contribute to the ladder-like shape of the vegetative network. The ChAT-like immunostaining of the vegetative network showed that the dendrites of the ILp cells are oriented mainly in a rostrocaudal, but also in a mediolateral direction. Similar orientation of the dendrites was observed for the ICpe cell groups of the thoracolumbar intermediate zone. Thus it is evident that ILp cell bodies and dendrites are involved in the formation of the FLL, whereas the ICpe cells and their dendrites--of the FLM. The IC cells send their dendrites towards both the ILp and ICpe cells and build up together with dendrites of the ILp and ICpe cells the transverse and oblique interconnecting bundles. The vegetative network is strongly developed within the intermediate zone of T1-T4 (mostly T3) and T7-T8 segments of the spinal cord. In these segments a greater variety of interconnections between the preganglionic sympathetic cell groups which are constituents of the network are also revealed. In the remaining segments the vegetative network is more poor developed. In the first two lumbar segments the distance between the interconnecting bundles in the rostrocaudal direction diminishes to 100 microns in contrast to 300-500 microns within the upper segments. The results obtained reveal that the cholinergic preganglionic sympathetic nuclei of the intermediate zone of the thoracolumbar spinal cord together with their dendrites represent the basis (frame) of the ladder-like vegetative network to which join in addition different peptidergic fibers of supraspinal, peripheral and propriospinal origin.

Acetylcholinesterase↗
PubMed1994

Muscarinic modulation of a pattern-generating network: control of neuronal properties.

The aim of this article is to investigate the cellular mechanisms underlying cholinergic modulation of the pyloric network in the stomatogastric ganglion (STG) of the Cape lobster Jasus Ialandii. Bath application of the muscarinic agonists muscarine, oxotremorine, and pilocarpine on the STG activates a rhythmic pattern from a quiescent pyloric network. The mechanisms of this modulation were investigated on individual pyloric neurons isolated both from synaptic interactions within the network (by photoinactivation of most of the presynaptic neurons and pharmacological blockade of the remaining synapses) and from central inputs (by a sucrose block of the input nerve). All three muscarinic agonists activated bursting and plateau properties of all the neurons comprising the pyloric network. The activation was dose dependent, and was blocked by the muscarinic antagonists atropine, pirenzepine, and scopolamine. The oscillatory behavior triggered by the muscarinic stimulation was specific to each type of pyloric neuron. The isolated neuron AB had the shortest oscillation period and depolarizing phase. The constrictor neurons (LP, PY, IC) were the slowest oscillators, and only oscillated upon hyperpolarizing current injection. Under muscarinic modulation, the individual bursting activities of the isolated pyloric neurons were of the same type as their activities when isolated from the network but modulated by central inputs (Bal et al., 1988). The VD neuron is an exception since it was a rapid oscillator in the latter situation and became a slow oscillator when modulated by a single muscarinic agonist. To determine the relative importance of the muscarinic-dependent bursting properties of the individual pyloric neurons in the operation of the intact network, a progressive reconstruction of the synaptic circuitry was attempted. We found that under certain conditions of muscarinic modulation a new composite pacemaker could be created, composed of the electrically coupled VD, AB, and PD neurons. This can result in the generation of new pyloric patterns that were very sensitive to the membrane potential of individual network neurons. The data also confirmed that, in a rhythmic "pattern-generating network," the pacemaker role may not be definitely attributed to a given neuron but instead could be assigned to other neurons by modulation of their respective oscillatory capabilities.

Animals↗