Cette thèse vise à étudier certains modèles biologiques dans le réseau neuronal et dans la chimiotaxie avec la méthode d’analyse spectrale. Afin de traiter les principaux problèmes, tels que l’existence et l’unicité des solutions et des états stationnaires ainsi que les comportements asymptotiques, le modèle linéaire ou linéarisé associé est considéré par l’aspect du spectre et des semi-groupes dans les espaces appropriés, puis la stabilité de modèle non linéaire suit. Plus précisément, nous commençons par une équation de courses-et-chutes linéaire dans la dimension d≥1 pour établir l’existence d’un état stationnaire unique, positif et normalisé et la stabilité exponentielle asymptotique dans l’espace L¹ pondéré basé sur la théorie de Kerin-Rutman avec quelques estimations du moment de la théorie cinétique. Ensuite, nous considérons le modèle du temps écoulé sous les hypothèses générales sur le taux de tir et nous prouvons l’unicité de l’état stationnaire et sa stabilité exponentielle non linéaire en cas sans ou avec délai au régime de connectivité faible de la théorie de l’analyse spectrale pour les semi-groupes. Enfin, nous étudions le modèle sous une hypothèse de régularité plus faible sur le taux de tir et l’existence de la solution ainsi que la même stabilité exponentielle sont généralement établies n’importe la prise en compte du délai ou non, au régime de connectivité faible ou forte. / This thesis is aimed to study some biological models in neuronal network and chemotaxis with the spectral analysis method. In order to deal with the main concerning problems, such as the existence and uniqueness of the solutions and steady states as well as the asymptotic behaviors, the associated linear or linearized model is considered from the aspect of spectrum and semigroups in appropriate spaces then the nonlinear stability follows. More precisely, we start with a linear runs-and-tumbles equation in dimension d≥1 to establish the existence of a unique positive and normalized steady state and the exponential asymptotic stability in weighted L¹ space based on the Krein-Rutman theory together with some moment estimates from kinetic theory. Then, we consider time elapsed model under general assumptions on the firing rate and prove the uniqueness of the steady state and its nonlinear exponential stability in case without or with delay in the weak connectivity regime from the spectral analysis theory for semigroups. Finally, we study the model under weaker regularity assumption on the firing rate and the existence of the solution as well as the same exponential stability are established generally no matter taking delay into account or not and no matter in weak or strong connectivity regime.

Indiana University-Purdue University Indianapolis (IUPUI) / The sympathetic nervous system strongly modulates the contractile and electrical function of the heart. The anatomical underpinnings that enable a spatially and temporally coordinated dissemination of sympathetic signals within the cardiac tissue are only incompletely characterized. In this work we took the first step of unraveling the in situ 3D microarchitecture of the cardiac sympathetic nervous system. Using a combination of two-photon excitation fluorescence microscopy and computer-assisted image analyses, we reconstructed the sympathetic network in a portion of the left ventricular epicardium from adult transgenic mice expressing a fluorescent reporter protein in all peripheral sympathetic neurons. The reconstruction revealed several organizational principles of the local sympathetic tree that synergize to enable a coordinated and efficient signal transfer to the target tissue. First, synaptic boutons are aligned with high density along much of axon-cell contacts. Second, axon segments are oriented parallel to the main, i.e., longitudinal, axes of their apposed cardiomyocytes, optimizing the frequency of transmitter release sites per axon/per cardiomyocyte. Third, the local network was partitioned into branched and/or looped sub-trees which extended both radially and tangentially through the image volume. Fourth, sub-trees arrange to not much overlap, giving rise to multiple annexed innervation domains of variable complexity and configuration. The sympathetic network in the epicardial border zone of a chronic myocardial infarction was observed to undergo substantive remodeling, which included almost complete loss of fibers at depths >10 µm from the surface, spatially heterogeneous gain of axons, irregularly shaped synaptic boutons, and formation of axonal plexuses composed of nested loops of variable length. In conclusion, we provide, to the best of our knowledge, the first in situ 3D reconstruction of the local cardiac sympathetic network in normal and injured mammalian myocardium. Mapping the sympathetic network connectivity will aid in elucidating its role in sympathetic signal transmisson and processing.

Indiana University-Purdue University Indianapolis (IUPUI) / Aromatase inhibitors (AIs) are the current standard of care for the treatment of hormone receptor positive breast cancer in postmenopausal women. Nearly one-half of patients receiving AI therapy develop musculoskeletal toxicity that is characterized by joint and/or muscle pain and approximately one-fourth of patients discontinue their therapy as a result of musculoskeletal pain. Since there are no effective strategies for prevention or treatment, insight into the mechanisms of AI-induced pain is critical to improve treatment. However, there are few studies of AI effects in animal models of nociception. To determine whether AIs produce hypersensitivity in animal models of pain, I examined the effects of AI administration on mechanical, thermal, and chemical sensitivity in rats. The results demonstrate that (1) repeated injection of 5 mg/kg letrozole in male rats produces mechanical, but not thermal, hypersensitivity that extinguishes when drug dosing is stopped; (2) administering a single dose of 1 or 5 mg/kg letrozole in ovariectomized (OVX) rats also induces mechanical hypersensitivity, without altering thermal sensitivity and (3) a single dose of 5 mg/kg letrozole or daily dosing of letrozole or exemestane in male rats augments flinching behavior induced by intraplantar ATP injection. To determine whether the effects of AIs on nociceptive behaviors are mediated by activation or sensitization of peptidergic sensory neurons, I determined whether letrozole exposure alters release of calcitonin gene-related peptide (CGRP) from isolated rat sensory neurons and from sensory nerve endings in rat spinal cord slices. No changes in basal, capsaicin-evoked or high extracellular potassium-evoked CGRP release were observed in sensory neuronal cultures acutely or chronically exposed to letrozole. Furthermore, letrozole exposure did not alter the ability of ATP to augment CGRP release from sensory neurons in culture. Finally, chronic letrozole treatment did not augment neuropeptide release from spinal cord slices. Taken together, these results do not support altered release of this neuropeptide into the spinal cord as mediator of letrozole-induced mechanical hypersensitivity and suggest the involvement of other mechanisms. Results from this dissertation provide a new experimental model for AI-induced hypersensitivity that could be beneficial in delineating mechanisms mediating pain during AI therapy.

Indiana University-Purdue University Indianapolis (IUPUI) / Chronic inflammatory disorders are characterized by an increase in excitability of small diameter sensory neurons located in dorsal root ganglia (DRGs). This sensitization of neurons is a mechanism for chronic inflammatory pain and available therapies have poor efficacy and severe adverse effects when used chronically. Prostaglandin E₂ (PGE₂) is an inflammatory mediator that plays an important role in sensitization by activating G-protein coupled receptors (GPCRs) known as E-series prostaglandin receptors (EPs) coupled to the protein kinase A (PKA) pathway. EPs are known to downregulate upon prolonged exposure to PGE₂ or in chronic inflammation, however, sensitization persists and the mechanism for this is unknown. I hypothesized that persistence of PGE₂-induced hypersensitivity is associated with a switch in signaling caused by prolonged exposure to PGE₂ or the neurotrophin nerve growth factor (NGF), also a crucial inflammatory mediator. DRG cultures grown in the presence or absence of either PGE₂ or NGF were used to study whether re-exposure to the eicosanoid is able to cause sensitization and activate PKA. When cultures were grown in the presence of NGF, PGE₂-induced sensitization was not attenuated by inhibitors of PKA. Activation of PKA by PGE₂ was similar in DRG cultures grown in the presence or absence of NGF when phosphatase inhibitors were added to the lysis and assay buffers, but significantly less in cultures grown in the presence of NGF when phosphatase inhibitors were not added. In DRG cultures exposed to PGE₂ for 12 hours-5 days, sensitization after re-exposure to PGE₂ is maintained and resistant to PKA inhibition. Prolonged exposure to the eicosanoid caused complete loss of PKA activation after PGE₂ re-exposure. This desensitization was homologous, time dependent, reversible, and insurmountable by a higher concentration of PGE₂. Desensitization was attenuated by reduction of expression of G-protein receptor kinase 2 and was not mediated by PKA or protein kinase C. The presented work provides evidence for persistence of sensitization by PGE₂ as well as switch from the signaling pathway mediating this sensitization after long-term exposure to NFG or PGE₂.

No description available.

Работа содержит исследования трех моделей живых систем с дискретным временем. В первой главе рассматривается одномерная модель нейронной активности, задаваемая кусочно-гладким отображением. Показывается, что в случае одномерного отображения наличие случайного возмущения приводит к появлению всплесков (спайкингу). Исследуются два механизма генерации спайков, вызванных добавлением случайного возмущения в один из параметров. Иллюстрируется, что сосуществование двух аттракторов является не единственной причиной возникновения спайкинга. Для прогнозирования уровня интенсивности шума, необходимого для генерации спайков, применяется метод доверительных областей, который основан на функции стохастической чувствительности. Также находятся основные характеристики межспайковых интервалов в зависимости от интенсивности шума. Вторая глава работы посвящена применению метода функции стохастической чувствительности к аттракторам кусочно-гладкого одномерного отображения, описывающего динамику численности популяции. Первым этапом исследования является параметрический анализ возможных режимов детерминированной модели: определение зон существования устойчивых равновесий и хаотических аттракторов. Для определения параметрических границ хаотического аттрактора применяется теория критических точек. В случае, когда на систему оказывает влияние случайное воздействие, на основе техники функции стохастической чувствительности дается описание разброса случайных состояний вокруг равновесия и хаотического аттрактора. Проводится сравнительный анализ влияния параметрического и аддитивного шума на аттракторы системы. С помощью техники доверительных интервалов изучаются вероятностные механизмы вымирания популяции под действием шума. Анализируются изменения параметрических границ существования популяции под действием случайного возмущения. В третьей главе проводится анализ возможных динамических режимов детерминированной и стохастической модели Лотки-Вольтерры. В зависимости от двух параметров системы строится карта режимов. Изучаются параметрические зоны существования устойчивых равновесий, циклов, замкнутых инвариантных кривых, а также хаотических аттракторов. Описываются бифуркации удвоения периода, Неймарка--Саккера и кризиса. Демонстрируется сложная форма бассейнов притяжения. Помимо детерминированной системы подробно изучается стохастическая, описывающая влияние внешнего случайного воздействия. В случае хаоса дан алгоритм нахождения критических линий, описывающих границу хаотического аттрактора. Опираясь на найденную чувствительность аттракторов, строятся доверительные полосы и эллипсы, позволяющие описать разброс случайных состояний вокруг детерминированного аттрактора. / The work contains study of three models of biological systems with discrete time. In the first chapter a one-dimensional model of neural activity defined by a piecewise-smooth map is considered. It is shown that in the case of a one-dimensional model, the presence of a random disturbance leads to a spike generation. Two mechanisms of spike generation caused by the presence of a random disturbance in one of the parameters are investigated. It is illustrated that the coexistence of two attractors is not the only reason of spiking. To predict the level of noise intensity needed to generate spikes, the confidence-domain method is used, which is based on the stochastic sensitivity function. The main characteristics of interspike intervals depending on the intensity of the noise are also described. The second chapter is devoted to the application of the method of the stochastic sensitivity function to attractors of a piecewise-smooth one-dimensional map, which describes the population dynamics. The first stage of the study is a parametric analysis of the possible regimes of the deterministic model: determining the zones of existence of stable equilibria and chaotic attractors. The theory of critical points is used to determine the parametric boundaries of a chaotic attractor. In the case where the system is affected by a random noise, based on the stochastic sensitivity function, a description of the spread of random states around equilibrium and a chaotic attractor is given. A comparative analysis of the influence of parametric and additive noise on the attractors is carried out. Using the technique of confidence intervals, the probabilistic mechanisms of extinction of a population under the influence of noise are studied. Changes in the parametric boundaries of the existence of population under the influence of random disturbance are analyzed. In the third chapter the possible dynamic modes of the Lotka-Volterra model in determi\-nistic and stochastic cases are analyzed. Depending on the two parameters of the system, bifurcation diagram is constructed. Parametric zones of the existence of stable equilibria, cycles, closed invariant curves, and also chaotic attractors are studied. The bifurcations of the period doubling, Neimark--Sacker and the crisis are described. The complex shape of the basins of attraction is demonstrated. In addition to the deterministic system, the stochastic system is studied in detail, which describes the influence of external random disturbance. In the case of chaos, an algorithm for finding critical lines describing the boundary of a chaotic attractor is given. Based on the stochastic sensitivity function, confidence bands and ellipses are constructed to describe the spread of random states around a deterministic attractor.

ErbB2 gehört zu den Klasse I Rezeptor-Tyrosinkinasen und funktioniert als Ko-rezeptor bei der Vermittlung des Neuregulin-Signals. Während der Embryonal-entwicklung wird ErbB2 im Herzen, in den Neuralleistenzellen, im Muskel und in den Epithelien exprimiert (Kokai et al. 1987). Embryonen mit einer Null-Mutation im ErbB2 Gen sterben am Tag 10,5 der Embryonalentwicklung. Die Mutation bewirkt eine morphogenetische Fehlbildung des Herzens, die durch das Fehlen von ventrikulären Trabekeln gekennzeichnet ist (Lee et al. 1995). Weiterhin zeigen diese Embryonen Defekte in den Kranialganglien und in der primären sympathischen Ganglien-Kette, die von Neuralleistenzellen gebildet werden (Lee et al. 1995; Erickson et al. 1997; Britsch et al. 1998). Die herzspezifische Expression von ErbB2 cDNA ermöglicht ErbB2-/- Tieren, sich bis zur Geburt zu entwickeln. Dies erlaubte mir, spätere Funktionen des Rezeptors zu untersuchen. In den geretteten ErbB2-/- Embryonen erfolgte die Bildung der ventrikulären Trabekel, der fingerähnlichen Ausstülpungen des Myokards, zwischen dem 9. und 10. Tag in der Embryonalentwicklung. In den späteren Phasen der intrauterinen Entwicklung war das Herz der geretteten Tiere normal ausgebildet. In den ErbB2-/-R Embryonen fehlten Schwann'sche Zellen entlang der peripheren Nerven. Die Abwesenheit von Schwann'schen Zellen führte zum massiven Absterben von sensorischen und motorischen Neuronen des Rückenmarkes. Dabei zeigten sensorische Neuronen eine frühe Abhängigkeit von neurotrophen Faktoren, die von Schwann'schen Zellen produziert werden, während Motoneuronen diese Faktoren in einer späteren Phase benötigen. Zusätzlich ist bekannt, daß sensorische Neuronen und Motoneuronen neurotrophe Fakten benötigen, die von den Zielorganen, z.B. den Muskeln, produziert werden. Motoneuronen im thorakalen Rückenmark sind nur minimal betroffen, während die Degeneration von Moto-neuronen in den zervikalen und lumbalen Segmenten stark ausgeprägt ist. Verschiedene Motoneuron-Typen unterscheiden sich also in ihrer Abhängigkeit von neurotrophen Signalen. Weiterhin sind die peripheren Nerven der ErbB2-/-R Tiere defaszikuliert und ungeordnet. Der N. phrenicus, der das Diaphragma innerviert, retrahiert und ist am Tag 17 der Entwicklung vollständig degeneriert. Deshalb können die mutanten Tiere bei der Geburt nicht atmen und sterben infolgedessen. Überraschenderweise erfolgt in den geretteten ErbB2-/-R Embryonen die post-synaptische Expression und Aggregation der Acetylcholin-Rezeptoren. Die Phäno-typen der ErbB2-/-R und ErbB3-/- mutanten Tieren sind sehr ähnlich. Dies zeigt, daß ErbB2 eine essentielle Korezeptor-Funktion für ErbB3 in der Vermittlung der Neuregulin-Signale übernimmt. / ErbB2 belongs to class I of receptor tyrosine kinases and functions as a co-receptor by the transduction of the neuregulin signal. During embryonic development the ErbB2 gene is expressed in the heart, neural crest, in muscle and epithelial cells (Kokai et al. 1987). Embryos with null mutation of the ErbB2 gene die at midgestation. The mutation causes a morphogenetic defect that results in the absence of trabecules (Lee et al. 1995). In addition the mutant embryos show defects in cranial ganglia and in the primary sympathetic ganglia chain (Lee et al. 1995; Erickson et al. 1997; Britsch et al. 1998). The heart specific expression of ErbB2 cDNA allowed the mutant animals to survive till birth. This enabels me to study the late function of the receptor. In rescued ErbB2-/- embryos the ventricular trabecules, which are finger-like extensions of the myocardium, form properly between E9 and E10 of embryonic development. At late stages of intrauteral development the hearts of the rescued animals showed an overall normal growth. ErbB2-/- embryos lack Schwann cells along peripheral nerves. The absence of Schwann cells leads to enormous degeneration of sensory and motoneurons. Whereas sensory neurons show an early dependency on neurotrophic factors produced by Schwann cells, motoneurons revealed requirement of these factors during the late phase of their development. Moreover it is known that sensory and motoneurons require neurotrophic factors which are produced by their target tissues such as muscle. Motoneurons at the thoracic level of the spinal cord are minimaly affected, whereas the degeneration of motoneurons at cervical and lumbar segments of the spinal cord are pronounced. This indicates that different motoneuron types differ in their dependency on neurotrophic signals. Furthermore axons of peripheral nerves in ErbB2-/-R (rescued) animals show defasciculation and desorganization. Nervous phrenicus, that innervates the diaphragm muscle retracts and degenerates entirely at E17 of embryonic development. As a result newborn animals can not breath and die shortly after birth. Surprisingly, the expression and aggregation of AchRs (Acetylcholine Receptors) take place in rescued ErbB2-/-R embryos. The overall phenotype of ErbB2-/-R embryos is very similar to that of ErbB3-/- embryos. This substantiates the essential function of ErbB2 as the functional co-receptor for ErbB3 to transmit the neuregulin signal.

Die elektrische Signalverarbeitung in Nervenzellen basiert auf deren erregbarer Zellmembran. Üblicherweise wird angenommen, dass die in der Membran eingebetteten leitfähigen Ionenkanäle nicht auf direkte Art gekoppelt sind und dass die Kapazität des von der Membran gebildeten Kondensators konstant ist. Allerdings scheinen diese Annahmen nicht für alle Nervenzellen zu gelten. Im Gegenteil, verschiedene Ionenkanäle “kooperieren” und auch die Vorstellung von einer konstanten spezifischen Membrankapazität wurde kürzlich in Frage gestellt. Die Auswirkungen dieser Abweichungen auf die elektrischen Eigenschaften von Nervenzellen ist das Thema der folgenden kumulativen Dissertationsschrift. Im ersten Projekt wird gezeigt, auf welche Weise stark kooperative spannungsabhängige Ionenkanäle eine Form von zellulärem Kurzzeitspeicher für elektrische Aktivität bilden könnten. Solche kooperativen Kanäle treten in der Membran häufig in kleinen räumlich getrennte Clustern auf. Basierend auf einem mathematischen Modell wird nachgewiesen, dass solche Kanalcluster als eine bistabile Leitfähigkeit agieren. Die dadurch entstehende große Speicherkapazität eines Ensembles dieser Kanalcluster könnte von Nervenzellen für stufenloses persistentes Feuern genutzt werden -- ein Feuerverhalten von Nutzen für das Kurzzeichgedächtnis. Im zweiten Projekt wird ein neues Dynamic Clamp Protokoll entwickelt, der Capacitance Clamp, das erlaubt, Änderungen der Membrankapazität in biologischen Nervenzellen zu emulieren. Eine solche experimentelle Möglichkeit, um systematisch die Rolle der Kapazität zu untersuchen, gab es bisher nicht. Nach einer Reihe von Tests in Simulationen und Experimenten wurde die Technik mit Körnerzellen des *Gyrus dentatus* genutzt, um den Einfluss von Kapazität auf deren Feuerverhalten zu studieren. Die Kombination beider Projekte zeigt die Relevanz dieser oft vernachlässigten Facetten von neuronalen Membranen für die Signalverarbeitung in Nervenzellen. / Electrical signaling in neurons is shaped by their specialized excitable cell membranes. Commonly, it is assumed that the ion channels embedded in the membrane gate independently and that the electrical capacitance of neurons is constant. However, not all excitable membranes appear to adhere to these assumptions. On the contrary, ion channels are observed to gate cooperatively in several circumstances and also the notion of one fixed value for the specific membrane capacitance (per unit area) across neuronal membranes has been challenged recently. How these deviations from the original form of conductance-based neuron models affect their electrical properties has not been extensively explored and is the focus of this cumulative thesis. In the first project, strongly cooperative voltage-gated ion channels are proposed to provide a membrane potential-based mechanism for cellular short-term memory. Based on a mathematical model of cooperative gating, it is shown that coupled channels assembled into small clusters act as an ensemble of bistable conductances. The correspondingly large memory capacity of such an ensemble yields an alternative explanation for graded forms of cell-autonomous persistent firing – an observed firing mode implicated in working memory. In the second project, a novel dynamic clamp protocol -- the capacitance clamp -- is developed to artificially modify capacitance in biological neurons. Experimental means to systematically investigate capacitance, a basic parameter shared by all excitable cells, had previously been missing. The technique, thoroughly tested in simulations and experiments, is used to monitor how capacitance affects temporal integration and energetic costs of spiking in dentate gyrus granule cells. Combined, the projects identify computationally relevant consequences of these often neglected facets of neuronal membranes and extend the modeling and experimental techniques to further study them.

Die vorliegende Arbeit beschäftigt sich mit Mechanismen, die in Einzelzellmodellen zu einer frequenzabhängigen Informationsübertragung führen können. Um dies zu untersuchen, werden Methoden aus der theoretischen Physik (Statistische Physik) und der Informationstheorie angewandt. Die Informationsfilterung in mehreren stochastischen Neuronmodellen, in denen unterschiedliche Mechanismen zur Informationsfilterung führen können, werden numerisch und, falls möglich, analytisch untersucht. Die Bandbreite der betrachteten Modelle erstreckt sich von reduzierten strombasierten ’Integrate-and-Fire’ (IF) Modellen bis zu biophysikalisch realistischeren leitfähigkeitsbasierten Modellen. Anhand numerischer Untersuchungen wird aufgezeigt, dass viele Varianten der IF-Neuronenmodelle vorzugsweise Information über langsame Anteile eines zeitabhängigen Eingangssignals übertragen. Der einfachste Vertreter der oben genannten Klasse der IF-Neuronmodelle wird dahingehend erweitert, dass ein Konzept von neuronalem ’Gedächtnis’, vermittelst positiver Korrelationen zwischen benachbarten Intervallen aufeinander- folgender Spikes, integriert wird. Dieses Model erlaubt eine analytische störungstheoretische Untersuchung der Auswirkungen positiver Korrelationen auf die Informationsfilterung. Um zu untersuchen, wie sich sogenannte ’unterschwelligen Resonanzen’ auf die Signalübertragung auswirken, werden Neuronenmodelle mit verschiedenen Nichtlinearitäten anhand numerischer Computersimulationen analysiert. Abschließend wird die Signalübertragung in einem neuronalen Kaskadensystem, bestehend aus linearen und nichtlinearen Elementen, betrachtet. Neuronale Nichtlinearitäten bewirken eine gegenläufige Abhängigkeit (engl. "trade-off") zwischen qualitativer, d.h. frequenzselektiver, und quantitativer Informations-übertragung, welche in allen von mir untersuchten Modellen diskutiert wird. Diese Arbeit hebt die Gewichtigkeit von Nichtlinearitäten in der neuronalen Informationsfilterung hervor. / Neurons transmit information about time-dependent input signals via highly non-linear responses, so-called action potentials or spikes. This type of information transmission can be frequency-dependent and allows for preferences for certain stimulus components. A single neuron can transmit either slow components (low pass filter), fast components (high pass filter), or intermediate components (band pass filter) of a time-dependent input signal. Using methods developed in theoretical physics (statistical physics) within the framework of information theory, in this thesis, cell-intrinsic mechanisms are being investigated that can lead to frequency selectivity on the level of information transmission. Various stochastic single neuron models are examined numerically and, if tractable analytically. Ranging from simple spiking models to complex conductance-based models with and without nonlinearities, these models include integrator as well as resonator dynamics. First, spectral information filtering characteristics of different types of stochastic current-based integrator neuron models are being studied. Subsequently, the simple deterministic PIF model is being extended with a stochastic spiking rule, leading to positive correlations between successive interspike intervals (ISIs). Thereafter, models are being examined which show subthreshold resonances (so-called resonator models) and their effects on the spectral information filtering characteristics are being investigated. Finally, the spectral information filtering properties of stochastic linearnonlinear cascade neuron models are being researched by employing different static nonlinearities (SNLs). The trade-off between frequency-dependent signal transmission and the total amount of transmitted information will be demonstrated in all models and constitutes a direct consequence of the nonlinear formulation of the models.

This master thesis deals with design and implementation of betting agent. It covers issues such as theoretical background of an online betting, probability and statistics. In its first part it is focused on data mining and explains the principle of knowledge mining form data warehouses and certain methods suitable for different types of tasks. Second, it is concerned with neural networks and algorithm of back-propagation. All the findings are demonstrated on and supported by graphs and histograms of data analysis, made via SAS Enterprise Miner program. In conclusion, the thesis summarizes all the results and offers specific methods of extension of the agent.