Cette thèse étudie l'origine de l'activité spontanée dans l'utérus. Cet organe n'a aucune activité jusqu'à la délivrance, où les contractions rapides et efficaces sont générés. Le but de ce travail est de fournir un aperçu de l'origine des oscillations spontanées et de la transition de l'activité asynchrone à synchronisé dans l'utérus gravide. Un aspect intéressant de l'utérus est l'absence de pacemaker. L'organe est composé de cellules musculaires, qui sont excitables, et conjonctives, dont le comportement est purement passif, aucune de ces cellules, pris isolément, oscillent spontanément. Nous développons une hypothèse basée sur l'augmentation grande du couplage électrique entre les cellules observée pendant la grossesse. L'étude est basée sur deux modèles des cellules excitables, couplé à l'autre sur un réseau régulier, et un nombre variable de cellules passives, en accord avec la structure connue de l'utérus. Les deux paramètres du modèle, le couplage entre les cellules excitables, et entre les cellules excitables et passive, croissent pendant la grossesse. En utilisant les deux modèles, nous démontrons que les oscillations peuvent apparaître spontanément lorsque l'on augmente les coefficients de couplage, conduisant finalement à des oscillations cohérentes sur l'ensemble du tissu. Nous étudions la transition vers un régime cohérent, à la fois numériquement et semi-analytique, en utilisant le modèle simple des cellules excitables. Enfin, nous montrons que le modèle réaliste reproduit irréguliers modes de la propagation d'action potentiels ainsi que le comportement de bursting, observé dans les expériences in vitro. / This thesis investigates the origin of spontaneous activity in the uterus. This organ does not show any activity until shortly before delivery, where fast and efficient contractions are generated. The aim of this work is to provide insight into the origin of spontaneous oscillations and into the transition from asynchronous to synchronized activity in the pregnant uterus. One intriguing aspect in the uterus is the absence of any pacemaker cell. The organ is composed of muscular cells, which are excitable, and connective cells, whose behavior is purely passive; None of these cells, taken in isolation, spontaneously oscillates. We develop an hypothesis based on the observed strong increase in the electrical coupling between cells in the last days of pregnancy. The study is based on a mathematical model of excitable cells, coupled to each other on a regular lattice, and to a fluctuating number of passive cells, consistent with the known structure of the uterus. The two parameters of the model, the coupling between excitable cells, and between excitable and passive cells, grow during pregnancy.Using both a model based on measured electrophysiological properties, and a generic model of excitable cell, we demonstrate that spontaneous oscillations can appear when increasing the coupling coefficients, ultimately leading to coherent oscillations over the entire tissue. We study the transition towards a coherent regime, both numerically and semi-analytically, using the simple model of excitable cells. Last, we demonstrate that, the realistic model reproduces irregular action potential propagation patterns as well as the bursting behavior, observed in the in-vitro experiments.

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Submitted by Renata Lopes (renatasil82@gmail.com) on 2018-07-26T12:29:23Z No. of bitstreams: 1 pedroandrearroyosilva.pdf: 4154699 bytes, checksum: 1875b7d54dd015591fcdd55db287ee37 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2018-09-03T16:20:02Z (GMT) No. of bitstreams: 1 pedroandrearroyosilva.pdf: 4154699 bytes, checksum: 1875b7d54dd015591fcdd55db287ee37 (MD5) / Made available in DSpace on 2018-09-03T16:20:02Z (GMT). No. of bitstreams: 1 pedroandrearroyosilva.pdf: 4154699 bytes, checksum: 1875b7d54dd015591fcdd55db287ee37 (MD5) Previous issue date: 2018-04-23 / A formação de padrões espaço-temporais são observados em processos químicos e bio-lógicos. Apesar dos sistemas bioquímicos serem altamente heterogêneos, aproximações homogenizadas contínuas formadas por equações diferenciais parciais são utilizadas fre-quentemente. Estas aproximações são usualmente justificadas pela diferença de escalas entre as heterogeneidades e o tamanho da característica espacial dos padrões. Em certas condições do meio, por exemplo, quando há um acoplamento fraco entre as células car-díacas, os modelos homogenizados discretos são mais adequados. Entretanto, os modelos discretos são menos manejáveis, por exemplo, na geração de malha para 2D e 3D, se comparado com os modelos contínuos. Aqui estudamos um modelo matemático homoge-nizado contínuo que se aproxima do modelo homogenizado. Este modelo é dado a partir de equações diferencias parciais com um parâmetro que depende da discretização da ma-lha. Dessa maneira nos referimos a este por um modelo matemático com parâmetros que dependem da discretização. Validamos nossa aproximação em um meio excitável genérico que simula três fenômenos em 1D: a propagação do potencial de ação transmembrânico no tecido cardíaco, a propagação do potencial de ação em filamentos de axônios cobertos por bainhas de mielina e a propagação do ativador e inibidor em microemulsões químicas. Para o caso 2D desenvolvemos uma versão da nossa aproximação que reproduz ondas espirais em um meio com acoplamento fraco. / The spatio-temporal patterns formations are observed in chemical and biological pro-cesses. Although biochemical systems are highly heterogeneous, homogenized continuum approaches formed by partial differential equations have been employed frequently. These approaches are usually justified by the difference scales between the characteristic spatial size of the patterns. Under some conditions of the medium, for instance, under weak coupling between cardiac cells, discrete models are more adequate. On the other hand discrete models may be less manageable, for instance, in terms of mesh generation, com-pared to the continuum models. Here we study a mathematical model to approach the discreteness which permits the computer implementation on non-uniform meshes. The model is cast as a partial differential equation but with a parameter that depends on the discretization mesh. Therefore we refer to it as a mathematical model with parameters dependent of discretization. We validate the approach in a generic excitable media that simulates three different phenomena in 1D: the propagation of action potential in car-diac tissue, the propation of the action potentialin filaments of axons wrapped by myelin sheaths, and the propagation of the activator/inhibitor in chemical microemulsions. For the 2D case we develop a version to this approach in microemulsions where it was possible to reproduce spiral waves with weak coupling of the medium.

Cellular automata (CA) are fully discrete dynamical systems. Space is represented by a regular lattice while time proceeds in finite steps. Each cell of the lattice is assigned a state, chosen from a finite set of "values". The states of the cells are updated synchronously according to a local interaction rule, whereby each cell obeys the same rule. Formal definitions of deterministic, probabilistic and lattice-gas CA are presented. With the so-called mean-field approximation any CA model can be transformed into a deterministic model with continuous state space. CA rules, which characterise movement, single-component growth and many-component interactions are designed and explored. It is demonstrated that lattice-gas CA offer a suitable tool for modelling such processes and for analysing them by means of the corresponding mean-field approximation. In particular two types of many-component interactions in lattice-gas CA models are introduced and studied. The first CA captures in abstract form the essential ideas of activator-inhibitor interactions of biological systems. Despite of the automaton´s simplicity, self-organised formation of stationary spatial patterns emerging from a randomly perturbed uniform state is observed (Turing pattern). In the second CA, rules are designed to mimick the dynamics of excitable systems. Spatial patterns produced by this automaton are the self-organised formation of spiral waves and target patterns. Properties of both pattern formation processes can be well captured by a linear stability analysis of the corresponding nonlinear mean-field (Boltzmann) equations.