Modelling inter-segmental coordination of neuronal oscillators: synaptic mechanisms for uni-directional coupling during swimming in Xenopus tadpoles

Locomotion requires longitudinal co-ordination. We have examined uni-directional synaptic coupling processes between two classes of neuronal network oscillators: autonomously active intrinsic oscillators, and potential oscillators that lack sufficient excitatory drive for autonomous activity. We model such oscillator networks in the bilaterally-symmetrical, Xenopus tadpole spinal cord circuits that co-ordinate swimming. Glutamate coupling EPSPs can entrain a second oscillator of lower frequency provided their strength is sufficient. Fast (AMPA) EPSPs advance spiking on each cycle, while slow (NMDA) EPSPs increase frequency over many cycles. EPSPs can also enable rhythmicity in potential oscillators and entrain them. IPSPs operate primarily on a cycle-by-cycle basis. They can advance or delay spiking to entrain a second intrinsic oscillator with higher, equal or lower frequency. Bilaterally symmetrical coupling connections operate twice per cycle: once in each half-cycle, on each side of the receiving oscillator. Excitatory and inhibitory coupling allow entrainment in complimentary areas of parameter space.     

A feature extractor for curvilinear patterns: a design suggested by the mammalian visual system

Summary A feature extractor for a pattern recognizer which can effectively process curvilinear drawings has been synthesized and simulated on a digital computer.The design of the network was suggested by the visual system of higher animals — especially the structure of the receptive fields of cortical neurons. This feature extractor is a multilayered parallel network composed of analog threshold elements. It consists of six layers in cascade. The first layer is a two-dimensional array of photoreceptors. The second layer is a contrast-detecting layer, each element of which has an on-center-type receptive field. The third one is a line-detecting layer. An element of this layer corresponds to a simple cortical cell, and responds to lines whose orientation is proper for the element. Each element has a receptive field consisting of an elongated excitatory region flanked on either side by inhibitory regions. The fourth layer is also a line-detecting layer, but each element, which corresponds to a complex cell, is not sensitive to the exact position of the line. An element of the fifth layer, which may correspond to a hypercomplex cell, responds when the line detected in the preceeding layer is curved. In the final layer, the curvature of the line is detected regardless of the orientation of the line, that is, an element of this layer gives an output approximately proportional to the curvature of the line presented in its receptive field.     

Assortative interactions and social networks in fish

The mechanisms underpinning the structure of social networks in multiple fish populations were investigated. To our knowledge this is the first study to provide replication of social networks and therefore probably the first that allows general conclusions to be drawn. The social networks were all found to have a non-random structure and exhibited social cliquishness. A number of factors were observed to contribute to this structuring. Firstly, social network structure was influenced by body length and shoaling tendency, with individuals interacting more frequently with conspecifics of similar body length and shoaling tendency. Secondly, individuals with many social contacts were found to interact with each other more often than with other conspecifics, a phenomenon known as a positive degree correlation. Finally, repeated interactions between pairs of individuals occurred within the networks more often than expected by random interactions. The observed network structures will have ecological and evolutionary implications. For example, the occurrence of positive degree correlations suggests the possibility that pathogens and information (that are socially transmitted) could spread very fast within the populations. Furthermore, the occurrence of repeated interactions between pairs of individuals fulfils an important pre-requisite for the evolution of reciprocal altruism.     

Response analysis of vertebrate retina

In a recent work (Ouztöreli, 1980) a mathematical model for studying the neural activities in a vertebrate retina has been investigated, where the basic network contains five interconnected neurons: a receptor cell, a bipolar cell, a horizontal cell, an amacrine cell, and a retinal ganglion cell. More recently, in (Ouztöreli and O'Mara, 1980) the basic network has been extended to a larger network containing twelve neurons. In both of these works, the performances of the basic and extended models were discussed under different structural and processing conditions with constant inputs by using the results of one of our earlier work (Ouztöreli, 1979). In the present paper we investigate by simulations the responses of the basic retinal network to piecewise constant and periodic inputs. The step and frequency responses of the extended retinal network will be discussed in a forthcoming paper.This work was partially supported by the Natural Sciences and Engineering Research Council of Canada under Grant A-4345 through the University of alberta     

Synchronization and Oscillatory Dynamics in Heterogeneous, Mutually Inhibited Neurons

We study some mechanisms responsible for synchronous oscillations and loss of synchrony at physiologically relevant frequencies (10–200 Hz) in a network of heterogeneous inhibitory neurons. We focus on the factors that determine the level of synchrony and frequency of the network response, as well as the effects of mild heterogeneity on network dynamics. With mild heterogeneity, synchrony is never perfect and is relatively fragile. In addition, the effects of inhibition are more complex in mildly heterogeneous networks than in homogeneous ones. In the former, synchrony is broken in two distinct ways, depending on the ratio of the synaptic decay time to the period of repetitive action potentials (_s/T), where T can be determined either from the network or from a single, self-inhibiting neuron. With _s/T > 2, corresponding to large applied current, small synaptic strength or large synaptic decay time, the effects of inhibition are largely tonic and heterogeneous neurons spike relatively independently. With _s/T < 1, synchrony breaks when faster cells begin to suppress their less excitable neighbors; cells that fire remain nearly synchronous. We show numerically that the behavior of mildly heterogeneous networks can be related to the behavior of single, self-inhibiting cells, which can be studied analytically.     

Molecular biologists, biochemists, and messenger RNA: The birth of a scientific network

Conclusion This paper investigated the part played by collaborative practices in chaneling the work of prominent biochemists into the development of molecular biology. The RNA collaborative network that emerged in the 1960s in France encompassed a continuum of activities that linked laboratories to policy-making centers. New institutional frameworks such as the DGRST committees were instrumental in establishing new patterns of funding, and in offering arenas for multidisciplinary debates and boundary assessment. It should be stressed however, that although this collaborative network was based on centralized initiatives aimed at developing molecular biology as a new biological specialty, it operated above all as a nexus of practices. The main argument of this paper is that the central allocation of funds and resources, exemplified by the DGRST operation, actually enhanced the creation of a self-conscious community of biochemists turned molecular biologists by virtue of an increased circulation of tools, skills, and results that took place within the RNA network and a few analogous systems of exchange.Having hands on things viewed as identical for all practical purposes was a potent factor in changing the experimental systems and their meanings. Limited but shared means of doing helped to reduce uncertainties, change representations, and turn contingent decisions into meaningful choices. The collaborative enterprises then resulted in personal contacts and the transfer of skills and materials, which gradually incorporated the biochemical tools into systems producing facts relevant to molecular biology as defined by its early practitioners. In that sense, networking was a regulatory process that stabilized new research objects and acculturated French biochemists.The mere existence of such a collaborative network also changed the scale of the disciplining process. Collaborations may have been started for contingent motives, but multiple exchanges resulted in the emergence of a new collective, and amplified small displacements. Collaborations, however, worked both ways, and the RNA network may be viewed as an efficient trading-post. An unexpected outcome of the development of a conversion zone is the fact that, by the late 1960s, the former biochemists dominated the new world of molecular biology — both in terms of research habits, since interests in structural studies dominated the field, and in terms of institutional initiatives such as the creation of laboratories and institutes for molecular biology.As an example of the cognitive displacements achieved by the network, I have focused here on the stabilization of messenger RNA as a new biological entity. This process illustrates the role of boundary objects and other mediating innovations in the development of disciplinary structures. Students of science trained in the symbolic interactionism tradition have proposed that boundary objects enhance the multiple interactions between heterogeneous social worlds: they are robust enough to enhance unity, but plastic enough to be manipulated in different social and cultural contexts.⁸¹ Within the emerging network, messenger RNA was a weakly structured genetic information carrier in common use, but it could, at the same time, be a strongly structured macromolecular structure adapted to practical and local uses. Consequently, messenger RNA favored the association of groups of heterogeneous scientists with backgrounds and interests in medical biochemistry, genetics, physical chemistry, organic chemistry, and so forth. This contrast between general and local uses was also instrumental in integrating the manipulation of things and the negotiation of aims. In contrast to transfer RNAs, which in the French context remained objects for chemical (and mainly structural) studies, messenger RNA became a key component of the new culture of genetic information. Messenger RNA was a loose theoretical entity described as a genetic information carrier in the policy-making documents, while operational but tacit and more conflicting definitions prevailed at the bench. In other words, messenger RNA was not only a classical boundary object but also a flag object, which tightened the collaborative network by mediating between the DGRST offices and the laboratories.     

Temporal Sequence Compression by an Integrate-and-Fire Model of Hippocampal Area CA3

Cells in the rat hippocampus fire as a function of the animal's location in space. Thus, a rat moving through the world produces a statistically reproducible sequence of place cell firings. With this perspective, spatial navigation can be viewed as a sequence learning problem for the hippocampus. That is, learning entails associating the relationships among a sequence of places that are represented by a sequence of place cell firing. Recent experiments by McNaughton and colleagues suggest the hippocampus can recall a sequence of place cell firings at a faster rate than it was experienced. This speedup, which occurs during slow-wave sleep, is called temporal compression. Here, we show that a simplified model of hippocampal area CA3, based on integrate-and-fire cells and unsupervised Hebbian learning, reproduces this temporal compression. The amount of compression is proportional to the activity level during recall and to the relative timespan of associativity during learning. Compression seems to arise from an alteration of network dynamics between learning and recall. During learning, the dynamics are paced by external input and slowed by a low overall level of activity. During recall, however, external input is absent, and the dynamics are controlled by intrinsic network properties. Raising the activity level by lowering inhibition increases the rate at which the network can transition between previously learned states and thereby produces temporal compression. The tendency for speeding up future activations, however, is limited by the temporal range of associations that were present during learning.     

Integrated information in discrete dynamical systems: motivation and theoretical framework

This paper introduces a time- and state-dependent measure of integrated information, , which captures the repertoire of causal states available to a system as a whole. Specifically, quantifies how much information is generated (uncertainty is reduced) when a system enters a particular state through causal interactions among its elements, above and beyond the information generated independently by its parts. Such mathematical characterization is motivated by the observation that integrated information captures two key phenomenological properties of consciousness: (i) there is a large repertoire of conscious experiences so that, when one particular experience occurs, it generates a large amount of information by ruling out all the others; and (ii) this information is integrated, in that each experience appears as a whole that cannot be decomposed into independent parts. This paper extends previous work on stationary systems and applies integrated information to discrete networks as a function of their dynamics and causal architecture. An analysis of basic examples indicates the following: (i) varies depending on the state entered by a network, being higher if active and inactive elements are balanced and lower if the network is inactive or hyperactive. (ii) varies for systems with identical or similar surface dynamics depending on the underlying causal architecture, being low for systems that merely copy or replay activity states. (iii) varies as a function of network architecture. High values can be obtained by architectures that conjoin functional specialization with functional integration. Strictly modular and homogeneous systems cannot generate high because the former lack integration, whereas the latter lack information. Feedforward and lattice architectures are capable of generating high but are inefficient. (iv) In Hopfield networks, is low for attractor states and neutral states, but increases if the networks are optimized to achieve tension between local and global interactions. These basic examples appear to match well against neurobiological evidence concerning the neural substrates of consciousness. More generally, appears to be a useful metric to characterize the capacity of any physical system to integrate information.     

Performance of a neural-network-based determination of amino acid class and secondary structure from 1H-15N NMR data

A neural network which can determine both amino acid class andsecondary structure using NMR data from ¹⁵N-labeled proteinsis described. We have included nitrogen chemical shifts,³J_HN_H coupling constants, -protonchemical shifts, and side-chain proton chemical shifts as input to athree-layer feed-forward network. The network was trained with 456 spinsystems from several proteins containing various types of secondarystructure, and tested on human ubiquitin, which has no sequence homologywith any of the proteins in the training set. A very limited set of data,representative of those from a TOCSY-HSQC and HNHA experiment, was used.Nevertheless, in 60% of the spin systems the correct amino acid classwas among the top two choices given by the network, while in 96% ofthe spin systems the secondary structure was correctly identified. Theperformance of this network clearly shows the potential of the neuralnetwork algorithm in the automation of NMR spectral analysis.     

Cytoplasmic protein network in HeLa cells

Summary Monolayer HeLa culture nuclei isolated in situ with nonionic detergents remained attached to the glass as a nuclear monolayer. Searching for nuclear fixing structures a fine continous protein network was revealed around the isolated nuclei with fluorescence microscope after acridine orange staining.     

Paraquat induces irreversible actin cytoskeleton disruption in cultured human lung cells

The herbicide paraquat (PQ) induces the selective necrosis of type I and type II alveolar pneumocytes. We investigated the effect of PQ on human lung A549 cells to determine the possible role of cytoskeleton in lung cytotoxicity. At 80 mol/L PQ, a concentration that did not affect cell viability, the organization of actin cytoskeleton network depended on incubation time with the herbicide. Microfilaments appeared less numerous in 30% of the cells treated for 1 h. After 24 h, all the treated cells displayed only short filaments in the periphery. The effect of PQ on actin cytoskeleton was irreversible. Moreover, no modification of microtubule network was observed in PQ-treated cells. Next, we studied the effect of PQ on Chang Liver, an epithelial cell line from human liver. These cells appeared less sensitive to the herbicide than A549, and no cytoskeletal alteration was observed. To verify whether actin filament modifications in A549 cells were related to intracellular alterations of ATP concentrations, nucleotide levels during incubation with PQ were determined. The intracellular levels of ATP were not different in control and treated cells. Our results indicate that PQ induces specifically an irreversible actin filament disorganization on A549 cells and that the observed effect is independent of intracellular concentration of ATP.Abbreviations BSA bovine serum albumin - IC₅₀ concentration that produces 50% inhibitiition - PBS phosphate-buffered saline - PQ paraquat, 1,1-dimethyl-4,4-bipyridinium dichloride - SE standard error of the mean     

‘Small’-proteoglycan: collagen interactions: Keratan sulphate proteoglycan associates with rabbit corneal collagen fibrils at the ‘a’ and ‘c’ bands

l. Proteoglycans (PGs) in rabbit corneal stroma and mouse sclera have been stained for electron microscopy with Cupromeronic blue in a critical electrolyte concentration (CEC) mode, with and without prior digestion of the tissue by keratanase or chondroitinase ABC to remove the keratan sulphate (KS) or chondroitin-dermatan sulphates (CS or DS) respectively.2. Two classes of PGs, located orthogonally to the corneal collagen fibrils at either the step (band a or c) or gap zone (band d or e) are shown to be KS-PGs or DS-PGs respectively. Four separate and specific PG binding sites on Type I collagen fibrils have thus been identified.3. Rabbit corneal KS and DS PGs each contain two kinds of PG (Gregory JD, Coster L & Damle SP (1982) J. Biol. Chem.257, 6965–6970). We propose that each small protein-rich PG is associated with a specific binding site on the collagen fibril.     

Class II genes of miniature swine

Class II genes of miniature swine have been characterized by restriction fragment length polymorphism (RFLP) analysis and by analysis of a series of clones isolated from a lymphocyte genomic library. For RFLP analysis, DNA samples from three independent major histocompatibility complex homozygous lines and three intra-MHC recombinant lines were digested with a variety of restriction enzymes and analyzed in Southern blots using human cDNA probes for DP, DQ, DR, and DZ alpha genes, and DP, DQ, DR, and DO beta genes. One, or at most two, unique fragments were detected by hybridization with each of the human probes tested. In contrast, multiple bands (five to six for most enzymes examined) were detected by each of the human probes tested, the majority of which were found to cross-react with at least three of these probes under conditions of moderate stringency. Genomic DNA from the SLA ^c haplotype was cloned into an EMBL-3 bacteriophage vector, and the corresponding genomic library was screened with each of these human cDNA probes. The class II genes thereby isolated from this library showed characteristics consistent with those anticipated from the RFLP analysis. Thus, unique genes were obtained which showed no evidence of cross-hybridization, while genes showed extensive cross-hybridization and were frequently detected in the library by more than one human gene probe. These data are consistent with early evolutionary divergence of a genes, prior to mammalian speciation, and with continuing evolution of genes, with possible shared usage of these genes by different a loci. The data also imply that genes can readily be assigned to loci homologous to their human counterparts, but that genes will require further mapping and/or sequence analysis to confirm assignments.     

Associations between beta-tubulin and mitochondria in adult isolated heart myocytes as shown by immunofluorescence and immunoelectron microscopy

Summary We have investigated the associations between -tubulin and mitochondria in freshly isolated cardiac myocytes from the rat. Beta-tubulin was identified by using monoclonal antibodies for immunofluorescence and high resolution immunogold electron microscopy. In addition, conventional transmission and scanning electron microscopic studies were performed. After chemical stabilization in a formaldehyde solution, the myocytes were shock-frozen at –150°C, cryosectioned at –70°C and subsequently processed for immunohistochemical and immunocytochemical microscopy. A characteristic of the rod shaped myocytes is the presence of a dense network of microtubules in the cytoplasm displaying a pattern of strong anti--tubulin reaction. The complexity of this network however varies considerably among the myocytes reflecting microtubule dynamic instability. Further, our findings demonstrate that the -tubulin label in rod cells is confined to the perinuclear and interfibrillar spaces and, therefore, is largely colocalized with the cytoplasmic organelles. In myocytes undergoing severe contracture the distribution of -tubulin is entirely restricted to the outer mitochondrial-containing domain. This implies that, in a cell model with marked segregation of the contractile filaments and organelles, mitochondria are codistributed with microtubules in the total absence of desmin intermediate filaments. Moreover, our immunogold preparations demonstrate anti--tubulin labelling in the outer mitochondrial membrane as well as of fibres in close apposition to this membrane. These results indicate the presence of a specific -tubulin binding to the outer mitochondrial membrane that probably also involves microtubule based translocators and/or MAPs.     

Neural state estimation and prediction in amino acid fermentation

Summary On-line control of amino acid fermentations is complicated by uncertainties typical of biological processes and by difficulties in real-time monitoring of key process variables. Lysine is an essential amino acid in human nutrition, and also widely used in animal feed formulations. The paper discusses the construction and application of feed-forward, back-propagation neural networks as software sensors in state estimation, and multi-step ahead prediction of produced lysine and consumed sugar. Neural networks were programmed in MS Visual C++ for Windows for implementation in a PC, with a userfriendly interface for convenience and ease of operation. It is demonstrated that a well trained neural network of optimal architecture can be succesfsully used in control of amino acid production     

Developmental biochemistry of cottonseed embryogenesis and germination. XIX. Sequences and genomic organization of the α globulin (vicilin) genes of cottonseed

The globulin storage protein genes of cotton are found to exist as gene tandems that contain a gene from each of the 2 globulin subfamilies separated by a spacer region of about 2700 or 3400 base pairs. Three different tandems have been identified by restriction endonuclease mapping of genomic DNA. A cDNA that is different from the genes of the tandems in map sites and/or in nucleotide sequence indicates that a fourth tandem probably exists in the cotton genome. Since the species of cotton used here (Gossypium hirsutum) is an amphidiploid, it is likely that two of the tandems are contributed from each genome.Considerable divergence in nucleotide sequence (18%) and in derived amino acid sequence (28%) is found when the 2 genes of a sequenced tandem are compared. The sequence of the cDNA closely resembles one of the genes in the tandem showing only a 4% divergence in nucleotides and a 4.2% divergence in amino acids. Thus the 2 genes of each tandem represent a relatively ancient gene duplication that has given rise to the two globulin subfamilies of cotton. Only one subfamily has a glycosylation site and the glycosylation of its derived proteins gives rise to the 2 molecular weight sets of globulins seen on gel electrophoresis.Other basic features of these genes and their derived proteins are presented.     

Variation of amino acid concentrations in the medium of HU β-IFN and HU IL-2 producing cell lines

There are different requirements for the nutrient medium of various mammalian cell lines. We have determined the behaviour of the amino acid concentrations in the medium of two growing cell lines used for producing human interleukin 2 and human interferon constitutively. The experiments are based on a fermentation process with a bubble free cell culture aeration system with porous moving membranes, which allows production of high cell densities without foaming. We found interesting alterations in which the actual amino acid ratios are able to trigger consumption and production of a particular component depending on the supply of other possible replacements. Such data indicate the complicated biochemical network of synthesis, conversion and transport phenomena. Finally, we demonstrated the influence of product synthesis upon the amino acid requirements using as an example transformed hu IL-2- and hu -IFN-producing mouse L-cells.Abbreviations CTLL Cytotoxic T Cell Line - DME Dulbeccos Modified Eagle - FCS Foetal Calf Serum - Hepes N(2-Hydroxyethyl)piperazine-N'-2-ethanesulfonic acid - hu -IFN human -Interferon - hu IL-2 human Interleukin 2 - THF Tetrahydrofuran     

Examining serological diversity of “cowpea” rhizobia by the ELISA technique

To appraise the usefulness of the enzyme-linked immunosorbent assay (ELISA) technique for examining the serological diversity of slow-growing rhizobia, twelve diverse strains from three countries were examined with four antisera. Eleven of the strains were from the cowpea miscellany, and the twelfth was a Rhizobium japonicum strain. Some cowpea strains showed no antigenic relatedness with each other while others were closely related, and some showed a greater affinity with the R. japonicum strain than with other cowpea strains. All of the strains showed antigenic homology to an isolate from a wild Arachis sp., while two strains isolated from adjacent plants of the same cultivar had little homology. These patterns ofrelatedness and diversity clearly demonstrated the utility of the ELISA method, and so it was used to examine 53 strains isolated from cowpeas grown at three West African locations, Maradi (Niger), Ibadan and Onne (Nigeria). Broad ranges of serological diversity were found in the rhizobia at each location, moreover each population had its own general characteristics. Maradi strains were highly reactive with the five antisera used, Onne strains less so, and Ibadan strains even less so. ELISA reactivity correlated with colony morphology but not with nodulation potential.     

Alpha-Frequency Rhythms Desynchronize over Long Cortical Distances: A Modeling Study

Neocortical networks of excitatory and inhibitory neurons can display alpha()-frequency rhythms when an animal is in a resting or unfocused state. Unlike some - and -frequency rhythms, experimental observations in cats have shown that these -frequency rhythms need not synchronize over long cortical distances. Here, we develop a network model of synaptically coupled excitatory and inhibitory cells to study this asynchrony. The cells of the local circuit are modeled on the neurons found in layer V of the neocortex where -frequency rhythms are thought to originate. Cortical distance is represented by a pair of local circuits coupled with a delay in synaptic propagation. Mathematical analysis of this model reveals that the h and T currents present in layer V pyramidal (excitatory) cells not only produce and regulate the -frequency rhythm but also lead to the occurrence of spatial asynchrony. In particular, these inward currents cause excitation and inhibition to have nonintuitive effects in the network, with excitation delaying and inhibition advancing the firing time of cells; these reversed effects create the asynchrony. Moreover, increased excitatory to excitatory connections can lead to further desynchronization. However, the local rhythms have the property that, in the absence of excitatory to excitatory connections, if the participating cells are brought close to synchrony (for example, by common input), they will remain close to synchrony for a substantial time.     

Surface morphology of taste buds in catfish barbels

Summary External taste buds abound on barbels of the adult catfish Corydoras arcuatus. When examined by scanning electron microscopy, they are visualized as a series of punctate, conical elevations projecting from the general surface epithelium. All taste buds were found to be of one type. Both their external and internal surface features could be clearly elucidated on intact barbels and in barbels fractured transversely at various positions along their length. An extensive nerve terminal network penetrates the base of each taste bud. Two populations of elongated cells bearing prominent microvilli project through the central pore at the tip of each bud. One set of microvilli is thicker, longer and more club-shaped than its counterpart. While both are randomly distributed within each central pore, the small, short microvilli appear to outnumber the larger ones. A third population of cells, devoid of any apical microvilli, was also seen in some of the taste buds examined internally. These cells do not project to the external surface and are interpreted as basal cells described in previous light and transmission electron microscope studies of taste buds in other vertebrate species. The functional significance of some of these morphological findings is discussed.Supported by grants from the Medical Research Council of Canada and the Muscular Dystrophy Association of CanadaThe excellent technical assistance of Mr. F.T. McConnell is gratefully acknowledged