Resumo: O presente trabalho objetivou avaliar o desenvolvimento da planta e a produtividade de bulbos de dois híbridos de cebola quando submetidas a doses de nitrogênio e potássio em diferentes populações de plantas e a influência desses fatores na classificação do bulbo. O estudo foi conduzido no município de São José do Rio Pardo-SP. Avaliaram-se a altura da planta, número de folhas, diâmetro do pseudocaule, comprimento do pseudocaule, ciclo das plantas, massa do bulbo, massa seca da parte aérea, massa seca de bulbos, produtividade, classificação de bulbos, acúmulo e exportação de macronutrientes. O nitrogênio foi o fator que mais influenciou no crescimento da parte aérea e do bulbo das duas cultivares. O ciclo foi menor quanto maior a dose de nitrogênio aplicada e quanto maior a população de plantas. A massa do bulbo foi altamente influenciada pela população de plantas. O fator população de plantas e doses de potássio não influenciaram significativamente a produtividade, mas houve incrementos significativos na produção com a aplicação das doses de nitrogênio. / Abstract: The objective of this paper was to study the effects of nitrogen and potassium fertilizer doses on plant growth, yield and bulb quality of two onion cultivars, growing in different plants population. The experiment was carried out in São José do Rio Pardo in São Paulo State, Brazil. Parameters studied were: plant height, leaf number, pseudostem diameter and length, growing season duration, bulb and aereal part dry matter, bulb mass, yield and bulb classification, nutrient accumulation and exportation. The cicle was less in the higher nitrogen dose and higher plant density. Higher nitrogen fertilizer doses increased bulb yield. Plant population and potash doses did not influence yield, but its was bigger with nitrogen application. / Orientador: Arthur Bernardes Cecílio Filho / Coorientador: José Carlos Barbosa / Banca: Leila Trevizan Braz / Banca: Paulo César Tavares de Melo / Banca: Rumy Goto / Banca: Joaquim Adelino de Azevedo Filho / Doutor

O conhecimento da distribuição da umidade no solo para diferentes tipos de solos e diferentes vazões pode ser aplicado na otimização do dimensionamento de um sistema de irrigação, no manejo da água na zona radicular, bem como, auxiliar na aplicação eficiente de fertilizantes na rizosfera. Portanto, objetivou-se com a presente pesquisa desenvolver um modelo numérico bidimensional capaz de simular a distribuição da umidade no perfil de solo para diferentes sistemas de irrigação. Sendo que para tal, o modelo utiliza o método das diferenças finitas, mediante uma discretização da solução da equação de Richards e o método iterativo de Picard, o qual foi utilizado para garantir a conservação da massa. O modelo numérico ainda torna possível considerar a extração de água pelas plantas e a evaporação da água na superfície do solo. E para avaliar o seu desempenho foi feita uma análise de sensibilidade. O modelo matemático foi desenvolvido no Departamento de Engenharia de Biossistemas, pertencente à Escola Superior de Agricultura \"Luiz de Queiroz\" - ESALQ/USP. A linguagem de programação utilizada foi Fortran 90. A estrutura computacional foi feita de forma a permitir ao usuário a entrada de informações tais como: a) dados do perfil do solo, no que se refere às suas propriedades físico-hídricas, b) informações sobre o tipo de irrigação, tempo de simulação, tempo de aplicação de água via irrigação. O programa permite ao usuário a opção entre simular a extração de água pela as plantas ou não. Para a validação do modelo foram utilizados os dados obtidos por Rivera (2004), em um experimento conduzindo no antigo Departamento de Engenharia Rural da Escola Superior de Agricultura \"Luiz de Queiroz\". O desempenho do modelo foi avaliado com base nos parâmetros estatísticos: índice de concordância de Willmott; coeficiente de eficiência, raiz quadrada do erro médio, erro médio e o erro máximo absoluto. A análise de sensibilidade do modelo foi avaliada em função dos parâmetros: densidade de fluxo de água, condutividade hidráulica do solo saturado, alfa e n (parâmetros de ajuste da curva de retenção). Pelos resultados obtidos, o modelo apresentou um desempenho satisfatório na simulação dos perfis de umidade em relação aos dados medidos em condições de experimento em solo não saturado. Em relação à análise de sensibilidade, o modelo apresentou maior sensibilidade aos parâmetros de fluxo de entrada e ao parâmetro n da equação de retenção, indicando que tais parâmetros de entrada, necessitam ser determinados com maior precisão. Houve baixa sensibilidade ao parâmetro \"alfa\" da curva de retenção. / The soil moisture distribution for different soil types under different flow regimes can be used to optimize the design of an irrigation system, water manage water in the root zone, or increase the precision of the application of fertilizers in the rhizosphere. Therefore, the objective of this research was to develop a two-dimensional numerical model capable of simulating the soil moisture distribution in soil profile for different irrigation systems. The model is a finite difference solution of the Richards equation solution, in which the Picard iteration method is used to ensure the conservation of mass. The numerical model also takes water extraction by plants and water evaporation on the soil surface into account. The mathematical model was developed in the Department of Biosystems Engineering, College of Agriculture \"Luiz de Queiroz\", ESALQ / USP. It was coded in Fortran 90, and structured to allow interactive input of a) physical and hydraulic properties soil profile, and b) type of irrigation, irrigation application time, and simulation. The simulation of water extraction by the plants is optional. And to evaluate its performance a sensitivity analysis was done. Data obtained in an experiment carried out in the older Rural Engineering Department, College of Agriculture \"Luiz de Queiroz\" by Rivera (2004), were used to validate the model. Model performance was evaluated using the Willmott index of agreement; efficiency coefficient, root mean square error, average error and the maximum absolute error. Sensitivity analyses were performed on the density of water flow, saturated hydraulic conductivity, and on alpha and n (setting parameters of the soil water retention curve). From the results obtained, the model satisfactory simulated the measured soil moisture distributions in the experimental soil moisture profiles. The model was most sensitive to variations in the parameters of the input stream and to n, a parameter in the soil water retention equation (van Genuchten model, 1980). This results is indicative that these input parameters need to be determined with greater accuracy. The model output was not very sensitive to alpha, a shape parameter in the soil water retention curve.

La représentation corticale des informations sensorielles est fondamentale dans la perception, la reconnaissance et la mémorisation des différents objets de l’environnement. Les mécanismes de codage d’un stimulus sensoriel au niveau d’une population neuronale prennent place dans le temps et l’espace, deux composantes que nous avons étudiées successivement dans ce travail de thèse. Dans le bulbe olfactif, la dynamique des activités neuronales se traduit par de larges oscillations du potentiel de champ local. Plusieurs études indiquent que ces activités oscillatoires varient en fonction de l’environnement olfactif ou de l’expérience de l’animal. Toutefois peu d’études ont comparé les réponses oscillatoires aux odeurs entre les états d’éveil et d’anesthésie. La composante spatiale du traitement olfactif dans le bulbe se manifeste par l’activation d’unités fonctionnelles, les glomérules. Visualisées par des techniques d’imagerie fonctionnelle, ces activités distribuées à la surface du bulbe olfactif forment une topographie lâche des molécules olfactive reconnues en périphérie par les neurorécepteurs olfactifs. L’existence d’une plasticité de ces cartes spatiales, un aspect crucial du codage de la représentation de l’information dans d’autres modalités sensorielles, est débattue dans le bulbe olfactif. Dans ce cadre, les travaux présentés dans cette thèse s’articulent autour de deux questions : quel est l’impact de l’état d’éveil de l’animal sur les oscillations du potentiel de champ local enregistré dans le bulbe olfactif ? Existe-t-il une plasticité des cartes glomérulaires suite à un apprentissage associatif ? Par l’enregistrement, chez les mêmes souris, des régimes oscillatoires en condition éveillée et anesthésiée (par un mélange de kétamine-xylazine ou kétamine-médétomidine), nous montrons que les profils de réponses oscillatoires évoquées par l’odeur sont similaires dans les deux conditions, et que l’activité spontanée est modulée différemment selon le régime anesthésique. Pour étudier le codage spatial nous avons en premier lieu visualisé et décrit les variations des cartes glomérulaires évoquées par les odeurs en enregistrant par imagerie optique deux types de signaux basés sur l’activité métabolique, le signal intrinsèque et l’autofluorescence des flavoprotéines. Suite au développement d’une fenêtre optique dans le bulbe olfactif en chronique, nous avons pu comparer les cartes spatiales obtenues avant et après un apprentissage olfactif. Nous avons mis en évidence un impact différentiel de deux types de conditionnement sur la représentation spatiale de l’odeur. / The cortical representation of sensory information is fundamental for perception, recognition and storage of different objects in the environment. Sensory coding by neuronal population has two components, time and space, that we studied successively in this thesis. In the olfactory bulb, the rhythmic and transient’s dynamic of the extracellular activities are represented as large oscillations of the local field potential. Several studies indicate that these oscillatory activities vary with the olfactory environment or the experience of the animal. However, very few studies have compared oscillatory profiles evoked by odors between awake and anesthetized animals. The spatial component of sensory processing in the olfactory bulb is characterized by the activation of functional units, the glomeruli, which can be visualized by functional imaging techniques. These distributed activities at the surface of the olfactory bulb form a coarse topography of the olfactory molecules that bind on peripheral olfactory neuroreceptors. However, the fact that these spatial maps are plastic, a crucial aspect of encoding the representation of information in other sensory modalities, is still debated in the olfactory bulb. In this context, the work presented in this thesis is driven by two questions: what is the impact of the level of arousal on the oscillations of local field potential recorded in the olfactory bulb? Are glomerular maps plastic after associative learning? In the same mice, we recorded oscillatory activities in awake and anesthetized conditions (using ketamine-xylazine or ketamine-medetomidine mixtures). We show that the profiles of oscillatory responses evoked by odor stimulations are similar in the two conditions, and that spontaneous activity is differentially modulated according to the anesthetic regime. To study odor spatial coding, we used optical imaging to record odor-evoked glomerular maps using two types of metabolic signals, the intrinsic signal and flavoproteins autofluorescence. We developed chronic optical window on the olfactory bulb that allowed us to compare the spatial maps obtained before and after olfactory learning. We have shown that two types of conditioning exerted a differential impact on the spatial representation of the odor.

Introdução: Existem evidências clínicas de que os movimentos do mecanismo velofaríngeo (MVF) podem ser aumentados com o uso do obturador faríngeo a ponto de o mesmo ser descartado ou até que se consiga diminuir ao máximo o gap velofaríngeo. O aumento do movimento das paredes faríngeas torna o individuo um melhor candidato para correção cirúrgica da disfunção velofaríngea (DVF). Este aumento na atividade das paredes faríngeas, no entanto, não é um achado universal com o uso do obturador, principalmente para aqueles pacientes que apresentam articulações compensatórias ou que apresentam velofaringe hipodinâmica. Objetivo: O presente estudo tem por objetivo avaliar o movimento das estruturas do MVF durante a fala, em pacientes que apresentam insuficiência velofaríngea (IVF) e que fazem uso de obturador faríngeo. A avaliação foi realizada antes (C1) e após pelo menos seis meses de uso do mesmo (C2). Material e Método: A casuística foi constituída de 25 pacientes, com fissura de palato e/ou de lábio e palato (8 mulheres e 17 homens), com idades variando entre 20 e 47 anos (média= 36 anos). Todos os pacientes apresentavam IVF após a cirurgia de palato e utilizavam obturador faríngeo havia pelo menos 6 meses. Para a avaliação do MVF com e sem o obturador faríngeo, todos pacientes haviam sido submetidos à avaliação nasoendoscópica durante fala. As 50 video-gravações dos exames de nasoendoscopia (25 na condição C1 e 25 na condição C2) foram editadas em um DVD e avaliadas por três fonoaudiólogas experientes, designadas juízas, quanto aos seguintes aspectos: movimento do véu palatino, movimento das paredes laterais da faringe, tamanho e tipo do gap velofaríngeo e anel de Passavant. Para a avaliação foi utilizado o protocolo proposto por Golding-Kushner et al (1990), especialmente adaptado para este estudo. Resultados: Neste estudo o grau de concordância intra-juízas foi de 82% para a juíza A, e 62% para as juízas B e C, para todos os aspectos do MVF avaliados. Já o grau de concordância inter-juízas variou de 49 a 88%, com média de 69%. Apesar de não terem sido encontradas diferenças estatisticamente significantes entre as condições C1 e C2, observamos que 17 (68%) dos 25 pacientes avaliados apresentaram diferenças na atividade muscular em pelo menos um dos 11 aspectos estudados. Conclusão: Os achados deste estudo demonstraram mudanças na atividade velofaríngea sugerindo que o uso do obturador faríngeo no tratamento da DVF pode ser útil tanto no processo de diagnóstico (para identificação do potencial de mudança no funcionamento velofaríngeo e na fala) quanto durante o tratamento da IVF (otimizando os resultados cirúrgicos). / Introduction: There are clinical evidence that movements of velopharyngeal mechanism can be increased with the use of speech bulbs to the point of elimination of the bulbo or until the maximum reduction of the velopharyngeal gap is achieved. An increase in the movements of pharyngeal wall turns the individual to a better candidate for surgical correction of velopharyngeal dysfunction (VPD). An increase in the activity of pharyngeal walls, however, is not an universal finding for all individual with speech bulbs, particularly for those Who use compensatory articulation or that present hypodynamic velopharynx.Objective: The present study has the objective of evaluate movement of the velopharyngeal structures during speech in patients with velopharyngeal insufficiency using speech bulbs. The evaluation was done before (C1) and at least 6 months after use of the bulb (C2).Material and Methods: The sample included 25 patients with cleft palate and/or cleft lip and palate (8 males and 17 females), with ages varying between 20 and 47 years (mean=36 years). All patients presented with velopharyngeal insufficiency and were using speech bulbs for at least 6 months. For the evaluation of the velopharyngeal mechanism with and without the speech bulb, all patients were submitted to nasoendoscopic evaluation during production of speech. All 50 video-recordings (25 in the C1 condition and 25 in the C2 condition) were edited into a DVD and evaluated by three experienced speech-language pathologists who judged the samples regarding the following aspects: movement of velum, movement of pharyngeal walls, type and size of velopharyngeal gap and Passavants Pad. For this study was used the protocol proposed by Golding-Kushner et al (1990), specially adapted for this evaluation.Results: In this study intra-judge agreement of 82% was found for judge A, and 62% for judges B and C, when all aspects rated were considered. Inter-judge agreement varied between 49% and 88% with a mean of 69%. Even though a significant difference was not found between the pré and pot speech bulb conditions, 17 (68%) subjects presented with differences in velopharyngeal activity in at least on of the 11 aspects studied. Conclusion: The findings of this study demonstrated changes in the velopharyngeal activity suggesting that the use of speech bulbs during treatment of VPD can help the diagnostic process (in the identification of the potential for changes of velopharyngeal functioning and of speech) and also can help in the treatment (by optimizing surgical results).

<p>This thesis deals with the highly potent olfactory mucosa toxicant 2,6-dichlorophenyl methylsulphone (2,6-diClPh-MeSO₂) and its non-toxic 2,5-chlorinated isomer (2,5-diClPh-MeSO₂). In mice, both substances bind firmly in the olfactory mucosa and the olfactory bulb, which are important components of the sensory system. The 2,6-isomer induces olfactory mucosal necrosis with permanent loss of olfactory neuroepithelium and olfactory nerves. A major objective was to clarify the cause of this isomer-specific toxicity, and to identify which physicochemical characteristics determine the olfactory toxicity. The neurobehavioural toxicity of these substances was also examined.</p><p>The results revealed a rapid CYP-catalysed covalent binding of 2,6-diClPh-MeSO₂ in the rat olfactory mucosa, whereas the 2,5-dichlorinated isomer was not covalently bound. </p><p>Acute and chronic olfactory mucosal pathology were investigated and compared in rats and mice. Twenty-four hours after dosing to rats, 2,6-diClPh-MeSO₂ induced Bowman’s glands necrosis and sloughing of the olfactory epithelium similar to that previously reported in mice. At 3 weeks, however, there were dramatic differences in histological lesions. In mice, large parts of olfactory epithelium were replaced by respiratory-like epithelium. Large, bilateral, fibrous, cartilage and bone containing polyps occluding the lumen were confirmed. In rats, only minor patches of olfactory epithelium were replaced by a metaplastic atypical respiratory-like epithelium. 2,5-diClPh-MeSO₂ was non-toxic in rats as well as in mice.</p><p>In mice, 2,6-diClPh-MeSO₂ induced a dose-dependent and long-lasting ( ≥12 weeks) hyperactivity as well as long-lasting maze learning deficits. At 2 weeks hyperactivity and maze learning deficits were observed also in rats. Unexpectedly, 2,5-diClPh-MeSO₂ induced hyperactivity that lasted for two weeks. No effect on maze learning was observed with this isomer. No major differences between male and female rats or mice were found.</p><p>In conclusion, the results show that a CYP-catalysed formation and covalent binding of a reactive 2,6-diClPh-MeSO₂-metabolite in the Bowman’s glands precede the high olfactory mucosal toxicity in rodents. As determined by QSAR-modelling, a 2,6-dichlorinated benzene derivative with a large, polar, and strong electron withdrawing substituent in the primary position has the potential of being an olfactory mucosal toxicant. The observed 2,6-diClPh-MeSO₂-induced increase in motor activity, and maze learning deficits, were not correlated to the olfactory mucosal lesions. I propose that 2,6-diClPh-MeSO₂ causes a direct effect in the brain leading to neurobehaviuoral deficits. </p>

This thesis deals with the highly potent olfactory mucosa toxicant 2,6-dichlorophenyl methylsulphone (2,6-diClPh-MeSO2) and its non-toxic 2,5-chlorinated isomer (2,5-diClPh-MeSO2). In mice, both substances bind firmly in the olfactory mucosa and the olfactory bulb, which are important components of the sensory system. The 2,6-isomer induces olfactory mucosal necrosis with permanent loss of olfactory neuroepithelium and olfactory nerves. A major objective was to clarify the cause of this isomer-specific toxicity, and to identify which physicochemical characteristics determine the olfactory toxicity. The neurobehavioural toxicity of these substances was also examined. The results revealed a rapid CYP-catalysed covalent binding of 2,6-diClPh-MeSO2 in the rat olfactory mucosa, whereas the 2,5-dichlorinated isomer was not covalently bound. Acute and chronic olfactory mucosal pathology were investigated and compared in rats and mice. Twenty-four hours after dosing to rats, 2,6-diClPh-MeSO2 induced Bowman’s glands necrosis and sloughing of the olfactory epithelium similar to that previously reported in mice. At 3 weeks, however, there were dramatic differences in histological lesions. In mice, large parts of olfactory epithelium were replaced by respiratory-like epithelium. Large, bilateral, fibrous, cartilage and bone containing polyps occluding the lumen were confirmed. In rats, only minor patches of olfactory epithelium were replaced by a metaplastic atypical respiratory-like epithelium. 2,5-diClPh-MeSO2 was non-toxic in rats as well as in mice. In mice, 2,6-diClPh-MeSO2 induced a dose-dependent and long-lasting ( ≥12 weeks) hyperactivity as well as long-lasting maze learning deficits. At 2 weeks hyperactivity and maze learning deficits were observed also in rats. Unexpectedly, 2,5-diClPh-MeSO2 induced hyperactivity that lasted for two weeks. No effect on maze learning was observed with this isomer. No major differences between male and female rats or mice were found. In conclusion, the results show that a CYP-catalysed formation and covalent binding of a reactive 2,6-diClPh-MeSO2-metabolite in the Bowman’s glands precede the high olfactory mucosal toxicity in rodents. As determined by QSAR-modelling, a 2,6-dichlorinated benzene derivative with a large, polar, and strong electron withdrawing substituent in the primary position has the potential of being an olfactory mucosal toxicant. The observed 2,6-diClPh-MeSO2-induced increase in motor activity, and maze learning deficits, were not correlated to the olfactory mucosal lesions. I propose that 2,6-diClPh-MeSO2 causes a direct effect in the brain leading to neurobehaviuoral deficits.

<p>Altered dietary availability of the vital nutrient choline during early development leads to persistent changes in brain and behavior throughout adulthood. Prenatal choline supplementation during embryonic days (ED) 12-17 of the rodent gestation period enhances memory capacity and precision and hippocampal plasticity in adulthood, and protects against spatial learning and memory deficits shortly after excitotoxic seizures, whereas prenatal choline deficiency can compromise hippocampal memory and plasticity in adulthood. Recent evidence from our laboratory has determined that lifelong proliferation of newborn neurons in the adult hippocampus, a feature of adult hippocampal plasticity that has been implicated in some aspects of learning and memory, is modulated by early choline availability. Prenatal choline's effects on adult neurogenesis may be one mechanism for diet-induced cognitive changes throughout life and in response to injury, although little is known about the mechanisms underlying how prenatal choline alters adult neurogenesis or the neural mechanisms underlying prenatal choline supplementation's protection against cognitive deficits after seizures. To address these issues, the present set of experiments investigated how prenatal choline availability modulates specific properties of neurogenesis in the adult brain (in the intact brain and in response to injury), as well as hippocampal markers known to change in response to excitotoxin-induced seizures, and sought to relate changes in neurogenesis and in neuropathological markers following injury to changes in performance on spatial learning and memory tasks. Subjects in each experiment were adult offspring from rat dams that received either a control diet or diet supplemented with choline chloride or deficient of choline on ED 12-17. To measure neurogenesis, rats were given injections of the mitotic marker bromodeoxyurdine to label dividing cells in the hippocampus. Prenatal choline supplementation enhanced several properties of basal adult hippocampal neurogenesis (cell division and survival, neural stem/progenitor cell phenotype and proliferative capacity, trophic support), and this increase was associated with improvements in spatial working memory retention in a delayed-matching-to-place water maze task. In contrast, prenatal choline deficiency had little effect on basal adult hippocampal neurogenesis, and no effect on spatial memory performance. Prenatal choline supplementation also enhanced olfactory bulb neurogenesis without altering cell proliferation in the subventricular zone, while prenatal choline deficiency had no effect on either measure, showing for the first time that prenatal choline's effects on adult neurogenesis is similarly expressed in another distinct neurogenic region of the adult brain. Altered prenatal choline availability also modulated the hippocampal response to kainic acid-induced seizures where supplementation attenuated while deficiency had no effect on the injury-induced proliferative response of the dentate gyrus shortly after injury. Prenatal choline supplementation also attenuated other markers of hippocampal neuropathology shortly after seizures and promoted the long-term hippocampal recovery from seizures months after injury, including rescuing declines in adult hippocampal neurogenesis and in spatial memory performance in a standard water maze task. Taken together, these findings demonstrate a robust neuroprotective effect of prenatal choline supplementation that may be driven by enhanced adult hippocampal plasticity and trophic support prior to injury, and shed light on the mechanisms underlying how prenatal choline availability alters adult hippocampal neurogenesis, which may contribute to changes in memory capacity and precision both throughout life and following neural assault.</p> / Dissertation

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<p>The olfactory system is believed to be the oldest sensory system. It developed to detect and analyse chemical information in the form of odours, and its organisation follows the same principles in almost all living animals - insects as well as mammals. Likely, the similarities are due to parallel evolution - the same type of organisation has arisen more than once. Therefore, the olfactory system is often assumed to be close to optimally designed for its tasks. Paradoxically, the workings of the olfactory system are not yet well known, although several milestone discoveries have been made during the last decades. The most well-known is probably the disovery of the olfactory receptor gene family, announced in 1991 by Linda Buck and Richard Axel. For this and subsequent work, they were awarded a Nobel Prize Award in 2004. This achievement has been of immense value for both experimentalists and theorists, and forms the basis of the current understanding of olfaction. The olfactory system has long been a focus for scientific interest, both experimental and theoretical. Ever since the field of computational neuroscience was founded, the functions of the olfactory system have been investigated through computational modelling. In this thesis, I present the basis of a biologically realistic model of the olfactory system. Our goal is to be able to represent the whole olfactory system. We are not there yet, but we have some of the necessary building blocks; a model of the input from the olfactory receptor neuron population and a model of the olfactory bulb. Taking into account the reported variability of geometrical, electrical and receptor-dependent neuronal characteristics, we have been able to model the frequency response of a population of olfactory receptor neurons. By constructing several olfactory bulb models of different size, we have shown that the size of the bulb network has an impact on its ability to process noisy information. We have also, through biochemical modelling, investigated the behaviour of the enzyme CaMKII which is known to be critical for early olfactory adaptation (suppression of constant odour stimuli).</p> / <p>Luktsystemet anses allmänt vara det äldsta sensoriska systemet. Det utvecklades för att upptäcka och analysera kemisk information i form av lukter, och det är organiserat efter samma principer hos nästan alla djurarter: insekter så väl som däggdjur. Troligen beror likheterna på parallell evolution -- samma organisation har uppstått mer än en gång. Därför antas det ofta att luktsystemet är nära optimalt anpassat för sina arbetsuppgifter. Paradoxalt nog är luktsystemets arbetssätt ännu inte väl känt, även om flera banbrytande framsteg gjorts de senaste decennierna. Det mest välkända är nog upptäckten av genfamiljen av luktreceptorer, som tillkännagavs 1991 av Linda Buck och Rikard Axel. För detta och efterföljande arbete belönades de med Nobelpriset år 2004. Upptäckten har varit mycket värdefull för både experimentalister och teoretiker, och formar grunden för vår nuvarande förståelse av luktsystemet. Luktsystemet har länge varit ett fokus för vetenskapligt intresse, både experimentellt och teoretiskt. Ända sedan fältet beräkningsbiologi grundades har luktsystemet undersökts genom datormodellering. I denna avhandling presenterar jag grunden för en biologiskt realistisk modell av luktsystemet. Vårt mål är att kunna representera hela luktsystemet. Så långt har vi ännu inte nått, men vi har några av de nödvändiga byggstenarna: en modell av signalerna från populationen av luktreceptorceller, och en modell av luktbulben. Genom att ta hänsyn till nervcellernas rapporterade variationer i geometriska, elektriska och receptor-beroende karaktärsdrag har vi lyckats modellera svarsfrekvenserna från en population av luktreceptorceller. Genom att konstruera flera olika stora modeller av luktbulben har vi visat att storleken på luktbulbens cellnätverk påverkar dess förmåga att behandla brusig information. Vi har också, genom biokemisk modellering, undersökt beteendet hos enzymet CaMKII, som är kritiskt viktigt för adaptering (undertryckning av ständigt närvarande luktstimuli) i luktsystemet.</p>

The distribution of cell types and synapses is well characterized in the rodent olfactory bulb (OB), and from that plausible models of odor processing have been constructed. Individual olfactory sensory neurons (OSNs) express only 1 of ~1000 odorant receptors (ORs) and send their axons to specific synaptic targets in the OB glomerular neuropil. Each glomerulus is innervated exclusively by OSN axons expressing the same OR. The distribution of these glomeruli is conserved across animals, as is the numerical relationship between number of expressed ORs and number of glomeruli in the OB. Our objective is to extend such results to the level of the human OB to determine how its cellular and synaptic organization, and more specifically how the number and distribution of its glomeruli, compare to what has been elucidated in mice. As there are ~2,000 glomeruli for ~1,000 ORs in mice, we predicted ~700 glomeruli in humans based on the ~350 intact OR genes identified in the human through genomic studies. Using immunohistochemistry, the organization of cells and synapses in human OBs was evaluated and quantified. While the laminar structure of the OB is broadly conserved between species, in the human OB the laminar organization as well as additional structural features suggest a less rigorously organized OB than in rodents, perhaps suggesting that odor processing in the human OB may be less efficient than in mice. Of particular note, the total number of glomeruli in the human OB differs significantly from predicted and demonstrates a high degree of variability amongst specimens, thus far ranging from approximately 3000 - 9000/OB. These results indicate that the principles of OR-homotypic axon convergence developed from mouse studies may not be readily applicable to the human, and that central processing of odor signals in the human may differ from those characterized in the mouse.