Dissertations / Theses on the topic 'Olfactory system'
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1
Clark, Stephen. "Aging in the mammalian olfactory system /." View online, 2009. http://repository.eiu.edu/theses/docs/32211131566906.pdf.
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Farivar, Shabnam Sarah Laurent Gilles. "Cytoarchitecture of the locust olfactory system /." Diss., Pasadena, Calif. : California Institute of Technology, 2005. http://resolver.caltech.edu/CaltechETD:etd-04212005-143332.
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Pascarella, Giovanni. "Targeting the complexity of mouse olfactory system." Doctoral thesis, SISSA, 2008. http://hdl.handle.net/20.500.11767/4677.
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In recent years the research on the olfactory system has entered a phase of deep innovation, regardless of the animal model taken as a reference. While the advancements achieved in different fields have provided answer to old questions, the striking evidences that have emerged in this new olfactory landscape have brought new ideas, new hypothesis and new scientific problems that necessarily need to be approached with adequate tools and strategies. The work presented in this thesis has targeted three different issues among the more
intriguing ones concerning the murine olfactory system. The project described in the first section has conf
ronted with the molecular identity of the Calcium-activated chloride channel responsible for the amplification of cationic currents in olfactory sensory neurons, a key mechanism for the triggering of action potentials after binding of odour molecules with their specific receptors.
Olfactory microvillar cells constitute a cell population largely represented in the main olfactory epithelium, but their role is still poorly understood mostly because a precise genomic characterization of this cell-type has never been undertaken; the project presented in the second section has tried to reveal the genomic fingerprint of microvillar cells through a custom gene expression profiling.
The data presented in the third section of this thesis are the result of a deep genomic investigation that has targeted the entire transcriptome of the olfactory sensory epithelium exploiting a newly developed high-throughput tagging approach derived from the Cap-Analysis of Gene Expression (CAGE) technology. The potential of this workflow has allowed revealing new details about the expression of pheromone vomeronasal receptors in the main olfactory epithelium.
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Millman, Daniel Joseph. "Emergence of Reward Coding in the Olfactory System." Thesis, Harvard University, 2016. http://nrs.harvard.edu/urn-3:HUL.InstRepos:33493347.
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Identifying dangerous or rewarding elements in an animal’s surroundings is an important – if not primary – function of sensory systems. This holds particularly true for the mouse olfactory system since odors convey crucial information about predators, mates, kin and food. Thus, the olfactory system needs to effectively determine which odors are present as well as whether each odor has a positive or negative association, termed valence. Currently, we have little knowledge of how reward influences the processing of odors in the olfactory system of behaving mice. My work focuses on two high-level olfactory areas, the posterior piriform cortex (pPC) and olfactory tubercle (OT), that are situated at the intersection of sensory and reward-related brain regions. The pPC receives direct input from early olfactory areas and makes reciprocal connections to cognitive brain regions such as orbitofrontal cortex, limbic structures and the medial temporal lobe. The OT is a part of the ventral striatum which also receives input from early olfactory areas and is heavily interconnected with the reward system. To examine odor and reward coding in these areas, I developed a novel odor categorization task and recorded individual pPC and OT neurons during task performance. Mice successfully learn multiple, novel odor-response associations after only a few repetitions when the contingencies predict reward. I find that an explicit representation for reward category emerges in the OT within minutes of learning a novel odor-response association, whereas the pPC lacks an explicit representation even after more than one month of overtraining. The explicit representation is visible in the first sniff of an odor on each trial, when the motor decision is made, and is not correlated with the trial-to-trial motor decision. Together, these results suggest that decoding of stimulus information required for reward-driven sensorimotor decision making does not occur within olfactory cortex, rather decoding occurs in circuits involving olfactory striatum.Medical Sciences
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Prieto, Godino Laura Lucía. "Embryonic development of the olfactory system in Drosophila melanogaster." Thesis, University of Cambridge, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609400.
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Che, Harun Fauzan Khairi. "Mimicking the human olfactory system : a portable e-mucosa." Thesis, University of Warwick, 2009. http://wrap.warwick.ac.uk/3130/.
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The study of electronic noses has been an active area of research for over 25 years. Commercial instruments have been successfully deployed within niche application areas, for example, the food, beverage and pharmaceutical industries. However, these instruments are still inferior to their human counterparts and have not achieved mainstream success. Humans can distinguish and identify many thousands of different aromas, even at very low concentration levels, with relative ease. The human olfactory system is extremely sophisticated, which allows it to out-perform artificial instruments. Though limited, artificial instruments can provide a lower cost option to specific problems and can be an alternative to the use of organoleptic panels. Most existing commercial electronic nose (e-nose) instruments are expensive, bulky, desktop units, requiring a PC to operate. In addition, these instruments usually require a trained operator to gather and analyse the data. Motivated to improve the performance, size and cost of e-nose instruments, this research aims to extract biological principles from the mammalian olfactory system to aid the implementation of a portable e-nose instrument. This study has focused on several features of the biological system that may provide the key to its superior performance. Specifically, the large number of different olfactory receptors and the diversity of these receptors; the nasal chromatograph effect; stereo olfaction; sniff rate and odour conditioning. Based on these features, a novel, portable, cost effective instrument, called the Portable e-Mucosa (PeM), has been designed, implemented and tested. The main components of the PeM are three sensor arrays each containing 200 carbon black composite chemoresistive sensors (totalling 600 sensors with 24 different tunings) mimicking the large number of olfactory receptors and two gas chromatographic columns (coated with non-polar and polar compounds to maximise the discrimination) emulating the “nasal chromatograph” effect of the human mucus. A preconcentrator based on thermal desorption is also included as an odour collection system to further improve the instrument. The PeM provides USB and Multimedia Memory Card support for easy communication with a PC. The instrument weighs 700g and, with dimensions of 110 x 210 x 110 mm, is slightly larger than the commercial Cyranose 320 (produced by Smiths Detection). This novel instrument generates ‘spatio-temporal’ data and when coupled with an appropriate pattern recognition algorithm, has shown an enhanced ability to discriminate between odours. The instrument successfully discriminates between simple odours (ethanol, ethyl acetate and acetone) and more complex odours (lavender, ylang ylang, cinnamon and lemon grass essential oils). This system can perhaps be seen as a foundation for a new generation of e-noses.
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Hawkins, Sara Joy. "The timing of regeneration in the amphibian olfactory system." Master's thesis, Universidade de Aveiro, 2015. http://hdl.handle.net/10773/15444.
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Mestrado em Biologia Molecular e CelularComprehending the mechanisms that make lifelong neurogenesis possible has a clear interest for the better understanding of the basic principles that govern cellular and molecular interactions in the nervous system, as well as a relevant clinical interest. The limited ability of the central nervous system to generate new neurons in order to replace those that have been lost is a formidable obstacle to recovery from neuronal damage caused by injury or neurodegenerative disease. The olfactory system (OS) is an ideal system to study the process of neuronal recovery after injury, as it is known for its lifelong capacity to replenish cells lost during natural turnover, as well as its remarkable ability to regenerate after severe lesion. The olfactory epithelium (OE) shows neurogenesis throughout life. Newly differentiated olfactory receptor neurons (ORNs) are continuously reintegrated into an existing circuitry to maintain the sense of smell. The aim of this thesis is to describe the morphological and functional alterations that occur over time in the OS of larval Xenopus laevis, after transection of the olfactory nerve (ON). Results obtained using immunohistochemistry essays, as well as sensory neuron labeling and calcium imaging techniques, indicate that ORN cell death reaches its peak 48 hours after transection, and that proliferating stem cells found in the basal cell layer of the OE are quickly upregulated after lesion. Supporting cells seem to maintain both morphological and functional integrity after transection of the ON. The OE recovers its original morphological structure 1 week after transection, at which time the first axons reach the olfactory bulb (OB) and begin the process of reinnervation. Spontaneous activity of mitral/tufted cells occurs in the OB during the first weeks after transection but no odor-induced activity is observed. After 3-4 weeks glomerular responses were observed in some animals upon application of stimulus, but the response and glomerular morphology are clearly altered as compared to control. After 6-7 weeks responses seem to have fully recovered, indicating that the OS of larval X. laevis recovers morphologically and functionally 6-7 weeks after ON transection.
O estudo dos mecanismos responsáveis pela neuro-regeneração tem um marcado interesse para a compreensão dos princípios básicos que governam as interações celulares e moleculares no sistema nervoso, bem como um interesse clínico relevante. A limitada capacidade do sistema nervoso central para dar origem a novos neurónios é um obstáculo formidável para a recuperação do sistema após lesão neuronal ou doença neurodegenerativa. O sistema olfativo é um sistema ideal para o estudo do processo de recuperação após lesão neuronal, pois é conhecido no mundo científico pela sua capacidade contínua e vitalícia para repor células perdidas durante a renovação celular natural, bem como a sua notável capacidade para regenerar após uma lesão grave. O epitélio olfativo apresenta a capacidade para dar origem a novos neurónios ao longo de toda a vida. Neurónios sensoriais olfativos diferenciados são continuamente reintegrados num circuito já existente, mantendo assim o sentido do olfato. O objetivo desta tese é descrever as alterações morfológicas e funcionais que ocorrem ao longo do tempo no sistema olfativo de Xenopus laevis em estado larvar, após o corte do nervo olfativo. Os resultados obtidos através do uso de ensaios de imunohistoquímica, bem como técnicas de marcação neuronal sensorial e de imagiologia de cálcio, indicam que a morte celular na população de neurónios sensoriais olfativos atinge o seu máximo 48 horas após a lesão, e que células estaminais encontradas na camada basal do epitélio olfativo são positivamente reguladas após lesão e proliferam rapidamente. Células de suporte parecem manter tanto a integridade morfológica como funcional após o corte do nervo olfativo. O epitélio olfativo recupera a sua estrutura morfológica inicial 1 semana após a lesão, momento em que os primeiros axónios atingem o bolbo olfativo e começam o processo de reintegração. Ocorre atividade espontânea das células mitrais/tufados do bolbo olfativo durante as primeiras semanas após a lesão, mas nenhuma atividade induzida por estímulo com odor foi observada. Depois de 3-4 semanas, atividade glomerular foi observada em alguns animais após a aplicação de estímulos, mas a resposta e morfologia glomerular foram claramente alteradas em relação ao controlo. Depois de 6-7 semanas as respostas parecem ter recuperado totalmente, indicando que o sistema olfativo de X. laevis em estado larvar recupera morfológica e funcionalmente 6-7 semanas após o corte do nervo olfativo.
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Lee, Mary Elizabeth. "Axon growth and neuron-glia interactions in the olfactory system /." Thesis, Connect to this title online; UW restricted, 1997. http://hdl.handle.net/1773/5684.
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Sinding, Charlotte, François Valadier, Viviana Al-Hassani, Gilles Feron, Anne Tromelin, Ioannis Kontaris, and Thomas Hummel. "New determinants of olfactory habituation." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2017. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-227051.
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Habituation is a filter that optimizes the processing of information by our brain in all sensory modalities. It results in an unconscious reduced responsiveness to continuous or repetitive stimulation. In olfaction, the main question is whether habituation works the same way for any odorant or whether we habituate differently to each odorant? In particular, whether chemical, physical or perceptual cues can limit or increase habituation. To test this, the odour intensity of 32 odorants differing in physicochemical characteristics was rated by 58 participants continuously during 120s. Each odorant was delivered at a constant concentration. Results showed odorants differed significantly in habituation, highlighting the multifactoriality of habituation. Additionally habituation was predicted from 15 physico-chemical and perceptual characteristics of the odorants. The analysis highlighted the importance of trigeminality which is highly correlated to intensity and pleasantness. The vapour pressure, the molecular weight, the Odor Activity Value (OAV) and the number of double bonds mostly contributed to the modulation of habituation. Moreover, length of the carbon chain, number of conformers and hydrophobicity contributed to a lesser extent to the modulation of habituation. These results highlight new principles involved in the fundamental process of habituation, notably trigeminality and the physicochemical characteristics associated.
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Lim, Jung-Eun Jane. "INVESTIGATING THE ROLE OF NEUROGLIAN IN OLFACTORY RECEPTOR AXON PATHFINDING IN THE DEVELOPING OLFACTORY SYSTEM OF DROSOPHILA MELANOGASTER." Thesis, The University of Arizona, 2009. http://hdl.handle.net/10150/192534.
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Tucker, Eric S. "Dynamic interactions between olfactory receptor axons and glial cells from the olfactory system of the moth Manduca sexta." Diss., The University of Arizona, 2002. http://hdl.handle.net/10150/280217.
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Across species, glial cells in both peripheral and central nervous systems cooperate extensively with neurons to shape multiple aspects of neural development. In vertebrate and invertebrate olfactory systems, neuron-glia interactions are thought to underlie critical developmental events, including glomerulus formation, and the growth, sorting, and targeting of olfactory receptor neuron (ORN) axons. The olfactory system of the moth Manduca sexta has many similarities to vertebrate olfactory systems, and has been used extensively to explore intercellular interactions involved in the formation of the olfactory pathway. In particular, glial reduction experiments have implicated two types of central olfactory glia, the sorting zone and neuropil-associated glia, in axon sorting and glomerulus stabilization. The developmental roles of a third glial cell type, the antennal nerve glia, remain elusive, yet their peripheral origin and association with ORN axons are similar to mammalian olfactory ensheathing cells. The present body of work uses a defined co-culture system to characterize interactions between ORN axons growing from explants of olfactory receptor epithelium and glial cells from the primary olfactory system of Manduca. We have monitored how particular types of glia, known to influence the behavior of ORN axons in vivo, directly affect the behavior and morphology of individual ORN growth cones in vitro. Time-lapse imaging of neuron-glia cultures revealed that olfactory receptor growth cones elaborate extensively and cease advancement following contact with sorting zone and neuropil-associated glial cells. In contrast, growth cones advance along the surfaces of antennal nerve glial cells without prolonged changes in morphology. Cytoskeletal staining of fixed preparations reinforced live-cell findings, as contact with sorting zone and neuropil-associated glial cells caused statistically significant changes in growth cone morphology. Finally, ORN axons induce antennal nerve glia, but not sorting zone or neuropil glia, to form multicellular arrays through proliferation and process extension. These findings have led to the formation of hypotheses concerning the nature of neuron-glia interactions in vivo.
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Sandström, Malin. "Early Information Processing in the Vertebrate Olfactory System : A Computational Study." Licentiate thesis, KTH, Numerical Analysis and Computer Science, NADA, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-4408.
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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).
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.
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Vukovic, Jana. "An in vitro and in vitro study on the role of the glycoprotein fibulin-3 in olfactory nerve growth and repair." University of Western Australia. School of Anatomy and Human Biology, 2008. http://theses.library.uwa.edu.au/adt-WU2008.0182.
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The primary olfactory pathway in adult mammals has retained a remarkable potential for self-repair. Olfactory ensheathing cells (OECs), specialized glial cells within the olfactory nerve, are thought to play an important role in the ongoing growth and replenishment of sensory connections in this system. To gain insight into novel molecules that could mediate OEC-supported growth of axons within the olfactory nerve, gene expression profiling experiments revealed very high expression of the fibulin-3 glycoprotein in OECs. To date, research on fibulin-3 has been limited and mainly focused on its involvement in Doyne honeycomb retinal dystrophy, vasculogenesis and tumor formation. As the extracellular matrix associated with OECs is thought to be an important contributor to a growth-permissive environment, the main aim of this thesis was to define a putative role for fibulin-3 during olfactory receptor neuron replacement and regeneration. This hypothesis was investigated in a series of in vitro and in vivo experiments that involved lentiviral vectors to manipulate fibulin-3 gene expression in OECs as well as the use of knock-out mice. Using genetically-modified OECs, experimental data showed that increased levels of fibulin-3 induced morphological changes in OECs and also impeded their migration. Lentiviral vector-mediated expression of fibulin-3 in OECs also had an inhibitory effect on neurite outgrowth from dorsal root ganglion explants. On the other hand, knock-down of fibulin-3 levels via siRNA technology resulted in reduced proliferation. Comparative lesioning experiments in fibulin-3 knock-out and wild-type mice allowed for further assessment of a role for fibulin-3 in olfactory nerve repair in vivo. Two experimental injury models, i.e. epithelial (Triton-X) lesioning and olfactory bulbectomy, were employed. The results obtained were in line with in vitro observations. A lack of fibulin-3 in knock-out mice resulted in a seemingly augmented regeneration of the olfactory epithelium at 10 days post-injury. However, at the latest recovery time point of 42 days post-injury, an impaired recovery of the olfactory epithelium from the experimental insults was observed. Although the precise mechanism for the latter phenomenon is not yet fully understood, our data point towards several factors which include vascular abnormalities and altered cell proliferation within the olfactory epithelium. Additionally, the precise protein distribution of another wide-spread family of extracellular matrix molecules, the laminins, was investigated in this thesis. It was of interest to investigate the spatiotemporal expression of laminin isoforms during iii olfactory nerve development and regeneration as these molecules may have distinct roles in promoting olfactory sensory neuron growth and patterning. In situ hybridization and immunohistochemical studies concluded that laminin-211 and laminin-411 were the most likely candidates to play such a role. In summary, this thesis provides new insights into the role of the extracellular matrix, fibulin-3 in particular, in regulating cell migration, division and axonal growth in the primary olfactory pathway. Such knowledge also gives a greater understanding of the molecular mechanisms by which OEC transplants may enhance axonal regeneration elsewhere in the CNS.
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Franceschini, Isabelle A. "Cellular and molecular studies on olfactory bulb ensheathing cells." Thesis, University of Glasgow, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.301803.
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Persson, Eva. "Bioactivation and transport of foreign materials in the olfactory system /." Uppsala : Dept. of Pharmacology and Toxicology, Swedish Univ. of Agricultural Sciences, 2003. http://epsilon.slu.se/v145.pdf.
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Ghaninia, Majid. "Olfaction in mosquitoes : neuroanatomy and electrophysiology of the olfactory system /." Alnarp : Dept. of Plant Protection Biology, Swedish University of Agricultural Sciences, 2007. http://epsilon.slu.se/200793.pdf.
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Isles, Anthony Roger. "Investigations of parent of origin effects in the olfactory system." Thesis, University of Cambridge, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.621562.
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Jansson, Björn. "Models for the transfer of drugs from the nasal cavity to the central nervous system /." Uppsala : Acta Universitatis Upsaliensis: Univ.-bibl. [distributör], 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3905.
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Dahlin, Maria. "Nasal administration of compounds active in the central nervous system : Exploring the olfactory system." Doctoral thesis, Uppsala University, Department of Pharmacy, 2000. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-545.
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The nasal administration of drugs offers advantages over administration by intravenous injection. Drugs can be rapidly absorbed through the nasal mucosa, resulting in a rapid onset of action, and also avoiding degradation in the gastrointestinal tract and first-pass metabolism in the liver. The olfactory receptor cells, which are in direct contact with both the environment and the central nervous system (CNS), are potential routes for drugs into the CNS. The olfactory pathway thus circumvents the blood brain barrier (BBB) which prevents many systemically administered drugs from entering the brain.
The studies used compounds active in the CNS and the experiments were performed in rodents. The nasal bioavailability of (S)-UH-301, NXX-066 and [3H]-dopamine was investigated in a rat model; uptake into the cerebrospinal fluid (CSF) was compared after nasal and intravenous administration. The concentrations of S-UH-301 and NXX-066 in plasma and CSF were measured with high performance liquid chromatography. The possible transfer of dopamine and neurotensin along the olfactory pathway after nasal administration to mice was studied using brain tissue sampling and autoradiography. The radioactivity content in blood, CSF and dissected brain tissue samples after administration of [3H]-dopamine and [3H]-neurotensin was assessed using liquid scintillation, and thin layer chromatography (TLC) was used to investigate the metabolic fate of [3H]-dopamine.
The results of this thesis suggest that nasal administration of CNS-active compounds with low oral bioavailability is an interesting and workable alternative to intravenous injection. The small lipophilic compounds (S)-UH-301 and NXX-066 were rapidly and completely absorbed after nasal administration, although hard evidence of direct transfer from the nose remains elusive. Radioactivity measurements in the olfactory bulb following nasal administration of
[3H]-dopamine and [3H]-neurotensin indicate that transfer occurred. The TLC results showed the presence of unchanged dopamine in the olfactory bulb but it is less clear from initial results with neurotensin, which radioactive products of this molecule reached the olfactory bulb, and further studies are required.
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Sandström, Malin. "Computational Modelling of Early Olfactory Processing." Doctoral thesis, KTH, Beräkningsbiologi, CB, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-12090.
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Chemical sensing is believed to be the oldest sensory ability. The chemical senses, olfaction and gustation, developed to detect and analyze information in the form of air- or waterborne chemicals, to find food and mates, and to avoid danger. The organization of the olfactory system 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 seems to have 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 within several fields, both experimental and theoretical, and it has often been used asa model system. And 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 several approaches to biologically realistic computational models of parts of the olfactory system, with an emphasis on the earlier stages of the vertebrate olfactory system – olfactory receptor neurons (ORNs) and the olfactory bulb (OB). I have investigated the behaviour of the enzyme CaMKII, which is known to be critical for olfactory adaptation (suppression of constant odour stimuli) in the ORN, using a biochemical model. By constructing several OB models of different size, I have shown that the size of the OB network has an impact on its ability to process noisy information. Taking into account the reported variability of geometrical, electrical and receptor-dependent neuronal characteristics, I have been able to model the frequency response of a population of ORNs. I have used this model to find the key properties that govern most of the ORN population’s response, and investigated some of the possible implications of these key properties in subsequent studies of the ORN population and the OB – what we call the fuzzy concentration coding hypothesis.Detektion av kemiska ämnen anses allmänt vara den äldsta sensoriska förmågan. De kemiska sinnena, lukt och smak, utvecklades för att upptäcka och analysera kemisk information i form av luft- eller vattenburna ämnen, för att hitta mat och partners, och för att undvika fara. Luktsystemet är organiserat efter samma principer hos nästan alla djurarter, insekter såväl som däggdjur. Troligen beror likheterna på parallell evolution – samma organisation verkar ha uppstått mer än en gång. Därför antas det ofta att luktsystemet är nära optimalt anpassat för sina arbetsuppgifter.Paradoxalt nog är luktsystemets arbetsprinciper ännu inte väl kända, 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 är grunden för vår nuvarande förståelse av luktsystemet. Luktsystemet har länge varit ett fokus för vetenskapligt intresse inom flera fält, experimentella såväl som teoretiska, och har ofta använts som ett modellsystem. Och ända sedan fältet beräkningsneurobiologi grundades har luktsystemet undersökts genom datormodellering. I denna avhandling presenterar jag flera ansatser till biologiskt realistiskaberäkningsmodeller av luktsystemet, med tonvikt på de tidigare delarna av ryggradsdjurens luktsystem – luktreceptorceller och luktbulben. Jag har undersökt beteendet hos enzymet CaMKII, som anses vara kritiskt viktigt för adaptation (undertryckning av ständigt närvarande luktstimuli) i luktsystemet, i en biokemisk modell. Genom att konstruera flera olika stora modeller av luktbulben har jag visat att storleken på luktbulbens cellnätverk påverkar dess förmåga att behandla brusig information. Genom att ta hänsyn till nervcellernas rapporterade variationer i geometriska, elektriska och receptor-beroende karaktärsdrag har jag lyckats modellera svarsfrekvenserna från en population av luktreceptorceller. Jag har använt denna modell för att hitta de nyckelprinciper som styr huvuddelen av luktreceptorneuron-populationens svar, ochundersökt några av de tänkbara konsekvenserna av dessa nyckelprinciper i efterföljande studier av luktreceptorneuron-populationen och luktbulben – det vi kallar ”fuzzy concentration coding”-hypotesen.
QC20100723
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Raman, Baranidharan. "Sensor-based machine olfaction with neuromorphic models of the olfactory system." Diss., Texas A&M University, 2005. http://hdl.handle.net/1969.1/4984.
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Electronic noses combine an array of cross-selective gas sensors with a pattern recognition engine to identify odors. Pattern recognition of multivariate gas sensor response is usually performed using existing statistical and chemometric techniques. An alternative solution involves developing novel algorithms inspired by information processing in the biological olfactory system. The objective of this dissertation is to develop a neuromorphic architecture for pattern recognition for a chemosensor array inspired by key signal processing mechanisms in the olfactory system. Our approach can be summarized as follows. First, a high-dimensional odor signal is generated from a chemical sensor array. Three approaches have been proposed to generate this combinatorial and high dimensional odor signal: temperature-modulation of a metal-oxide chemoresistor, a large population of optical microbead sensors, and infrared spectroscopy. The resulting high-dimensional odor signals are subject to dimensionality reduction using a self-organizing model of chemotopic convergence. This convergence transforms the initial combinatorial high-dimensional code into an organized spatial pattern (i.e., an odor image), which decouples odor identity from intensity. Two lateral inhibitory circuits subsequently process the highly overlapping odor images obtained after convergence. The first shunting lateral inhibition circuits perform gain control enabling identification of the odorant across a wide range of concentration. This shunting lateral inhibition is followed by an additive lateral inhibition circuit with center-surround connections. These circuits improve contrast between odor images leading to more sparse and orthogonal patterns than the one available at the input. The sharpened odor image is stored in a neurodynamic model of a cortex. Finally, anti-Hebbian/ Hebbian inhibitory feedback from the cortical circuits to the contrast enhancement circuits performs mixture segmentation and weaker odor/background suppression, respectively. We validate the models using experimental datasets and show our results are consistent with recent neurobiological findings.
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Sandström, Malin. "Early information processing in the vertebrate olfactory system : a computational study /." Stockholm : Numerisk analys och datalogi, Kungliga Tekniska högskolan, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-4408.
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Tallkvist, Jonas. "Nickel permeation pathways in the small intestine and the olfactory system /." Uppsala : Swedish Univ. of Agricultural Sciences (Sveriges lantbruksuniv.), 1997. http://epsilon.slu.se/avh/1997/91-576-5422-0.gif.
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Auffarth, Benjamin. "Machine Learning Techniques with Specific Application to the Early Olfactory System." Doctoral thesis, KTH, Beräkningsbiologi, CB, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-90474.
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This thesis deals with machine learning techniques for the extraction of structure and the analysis of the vertebrate olfactory pathway based on related methods. Some of its main contributions are summarized below. We have performed a systematic investigation for classification in biomedical images with the goal of recognizing a material in these images by its texture. This investigation included (i) different measures for evaluating the importance of image descriptors (features), (ii) methods to select a feature set based on these evaluations, and (iii) classification algorithms. Image features were evaluated according to their estimated relevance for the classification task and their redundancy with other features. For this purpose, we proposed a framework for relevance and redundancy measures and, within this framework, we proposed two new measures. These were the value difference metric and the fit criterion. Both measures performed well in comparison with other previously used ones for evaluating features. We also proposed a Hopfield network as a method for feature selection, which in experiments gave one of the best results relative to other previously used approaches. We proposed a genetic algorithm for clustering and tested it on several realworld datasets. This genetic algorithm was novel in several ways, including (i) the use of intra-cluster distance as additional optimization criterion, (ii) an annealing procedure, and (iii) adaptation of mutation rates. As opposed to many conventional clustering algorithms, our optimization framework allowed us to use different cluster validation measures including those which do not rely on cluster centroids. We demonstrated the use of the clustering algorithm experimentally with several cluster validity measures as optimization criteria. We compared the performance of our clustering algorithm to that of the often-used fuzzy c-means algorithm on several standard machine learning datasets from the University of California/Urvine (UCI) and obtained good results. The organization of representations in the brain has been observed at several stages of processing to spatially decompose input from the environment into features that are somehow relevant from a behavioral or perceptual standpoint. For the perception of smells, the analysis of such an organization, however, is not as straightforward because of the missing metric. Some studies report spatial clusters for several combinations of physico-chemical properties in the olfactory bulb at the level of the glomeruli. We performed a systematic study of representations based on a dataset of activity-related images comprising more than 350 odorants and covering the whole spatial array of the first synaptic level in the olfactory system. We found clustered representations for several physico-chemical properties. We compared the relevance of these properties to activations and estimated the size of the coding zones. The results confirmed and extended previous studies on olfactory coding for physico-chemical properties. Particularly of interest was the spatial progression by carbon chain that we found. We discussed our estimates of relevance and coding size in the context of processing strategies. We think that the results obtained in this study could guide the search into olfactory coding primitives and the understanding of the stimulus space. In a second study on representations in the olfactory bulb, we grouped odorants together by perceptual categories, such as floral and fruity. By the application of the same statistical methods as in the previous study, we found clustered zones for these categories. Furthermore, we found that distances between spatial representations were related to perceptual differences in humans as reported in the literature. This was possibly the first time that such an analysis had been done. Apart from pointing towards a spatial decomposition by perceptual dimensions, results indicate that distance relationships between representations could be perceptually meaningful. In a third study, we modeled axon convergence from olfactory receptor neurons to the olfactory bulb. Sensory neurons were stimulated by a set of biologically-relevant odors, which were described by a set of physico-chemical properties that covaried with the neural and glomerular population activity in the olfactory bulb. Convergence was mediated by the covariance between olfactory neurons. In our model, we could replicate the formation of glomeruli and concentration coding as reported in the literature, and further, we found that the spatial relationships between representational zones resulting from our model correlated with reported perceptual differences between odor categories. This shows that natural statistics, including similarity of physico-chemical structure of odorants, can give rise to an ordered arrangement of representations at the olfactory bulb level where the distances between representations are perceptually relevant.QC 20120224
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Dubuque, Suzanne Hope. "Tyrosine kinase activity in the developing olfactory system of Manduca sexta." Diss., The University of Arizona, 1998. http://hdl.handle.net/10150/282786.
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To begin to determine the role tyrosine kinases play in the development of the antennal lobe in Manduca sexta, phosphotyrosine levels were examined immunocytochemically during critical periods of development. Tyrosine phosphorylation was found to be highest in the region of the antennal lobe known to contain the growing tips of antennal-lobe neurons and forming synapses. To explore the relationship between synapses and tyrosine kinase activity a marker for synapses was developed for light level microscopy. Manduca synaptotagmin was cloned and sequenced and a polyclonal antibody (SYNT76) was produced against the amino terminal of the predicted peptide sequence. SYNT76 labeled known synaptic neuropils in the brain of Manduca and recognized a single 61 kd protein on immunoblots. Immunocytochemical double labeling of antennal lobes for synaptotagmin and phosphotyrosine showed that although the patterns were very similar there was surprisingly little direct signal overlap. The similarity of immunolabeling suggests that tyrosine kinases may affect synapses in the developing antennal lobe but the lack of dramatic signal overlap shows that this association does not occur at the active zone. A trk-like protein was identified immunocytochemically, using an antibody against mammalian neurotrophin receptors, in the same regions of the developing lobe that contained high levels of phosphotyrosine. Trk-like proteins and phosphotyrosine were also found in the growing processes of cultured antennal lobe neurons. To examine the role of trk-like kinases in process outgrowth of antennal-lobe neurons, a tyrosine kinase inhibitor specific for trk-like kinases (Tyrphostin AG879) was applied to cultured neurons and was found to inhibit process outgrowth from antennal-lobe neurons significantly when compared to cells grown under control conditions. To determine the identity of the antennal-lobe trk-like proteins outside of their kinase domains the process of cloning trk-like messenger RNA was begun with reverse transcriptase polymerase chain reactions (RT-PCR). Northern blot analysis using RT-PCR fragments with significant sequence similarity to mammalian trk receptors identified a single 4.5 kb trk-like transcript in the brain and specifically in the antennal lobe during development. These data suggest that a trk-like kinase may mediate a developmental signal that causes antennal-lobe neurons to grow processes.
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Yarid, Colin R., Rudy T. Chapman, and Diego J. Rodriguez-Gil. "Maturation and synapse formation of olfactory sensory neurons after injury." Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/asrf/2019/schedule/94.
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The olfactory system is a great model to ask questions related to neuronal regeneration, axon guidance and synapse formation. Processing of smell begins in the olfactory epithelium where sensory neurons are present and the olfactory bulb is the first stop in processing odor information in the central nervous system. While the olfactory bulb has neurons that regenerate as well, we are interested in the regeneration that occurs in the olfactory epithelium after being injured because it possesses a source of neural stem cells – something unique to the rest of the body. Earlier studies have proven that the introduction of methimazole will effectively damage the olfactory sensory neurons while keeping the neural stem cells intact. By using a fate mapping technique involving Cre-ERT2 mice, we are able to track the regeneration of these sensory neurons after a methimazole induced injury. Using immunohistochemistry in combination with ImageJ software analysis, we are able to pinpoint the colocalization of markers of new olfactory sensory neurons (green fluorescent protein (GFP)) with markers of neuron maturation (olfactory marker protein (OMP)) and synapse formation (tyrosine hydroxylase (TH) and synaptophysin). Analysis of maturation was done in the olfactory epithelium by studying the colocalization of the protein OMP and GFP. Data shows that after regeneration, neurons coexpress both markers 11 days after lesion. In the olfactory bulb, we characterized the recovery of synaptic markers TH and synaptophysin after axons reached the olfactory bulb, where olfactory sensory neuron axons make synaptic contacts with dendrites of projection neurons. Overall, these data are the first one to establish a timeline for axonal regeneration and synapse formation after injury in the olfactory system.
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Kaplan, Bernhard. "Modeling prediction and pattern recognition in the early visual and olfactory systems." Doctoral thesis, KTH, Beräkningsbiologi, CB, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-166127.
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Our senses are our mind's window to the outside world and determine how we perceive our environment.Sensory systems are complex multi-level systems that have to solve a multitude of tasks that allow us to understand our surroundings.However, questions on various levels and scales remain to be answered ranging from low-level neural responses to behavioral functions on the highest level.Modeling can connect different scales and contribute towards tackling these questions by giving insights into perceptual processes and interactions between processing stages.In this thesis, numerical simulations of spiking neural networks are used to deal with two essential functions that sensory systems have to solve: pattern recognition and prediction.The focus of this thesis lies on the question as to how neural network connectivity can be used in order to achieve these crucial functions.The guiding ideas of the models presented here are grounded in the probabilistic interpretation of neural signals, Hebbian learning principles and connectionist ideas.The main results are divided into four parts.The first part deals with the problem of pattern recognition in a multi-layer network inspired by the early mammalian olfactory system with biophysically detailed neural components.Learning based on Hebbian-Bayesian principles is used to organize the connectivity between and within areas and is demonstrated in behaviorally relevant tasks.Besides recognition of artificial odor patterns, phenomena like concentration invariance, noise robustness, pattern completion and pattern rivalry are investigated.It is demonstrated that learned recurrent cortical connections play a crucial role in achieving pattern recognition and completion.The second part is concerned with the prediction of moving stimuli in the visual system.The problem of motion-extrapolation is studied using different recurrent connectivity patterns.The main result shows that connectivity patterns taking the tuning properties of cells into account can be advantageous for solving the motion-extrapolation problem.The third part focuses on the predictive or anticipatory response to an approaching stimulus.Inspired by experimental observations, particle filtering and spiking neural network frameworks are used to address the question as to how stimulus information is transported within a motion sensitive network.In particular, the question if speed information is required to build up a trajectory dependent anticipatory response is studied by comparing different network connectivities.Our results suggest that in order to achieve a dependency of the anticipatory response to the trajectory length, a connectivity that uses both position and speed information seems necessary.The fourth part combines the self-organization ideas from the first part with motion perception as studied in the second and third parts.There, the learning principles used in the olfactory system model are applied to the problem of motion anticipation in visual perception.Similarly to the third part, different connectivities are studied with respect to their contribution to anticipate an approaching stimulus.The contribution of this thesis lies in the development and simulation of large-scale computational models of spiking neural networks solving prediction and pattern recognition tasks in biophysically plausible frameworks.QC 20150504
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Cameron, Nicholas John. "Developing Olfactory Ensheathing Cells for ex vivo Delivery of GDNF." Thesis, Griffith University, 2010. http://hdl.handle.net/10072/365205.
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Olfactory ensheathing cells have well described neurotrophic properties and can promote repair of damaged nerves in the central nervous system. Genetically engineering these cells to deliver therapeutic proteins could ‘supercharge’ their existing abilities to repair damaged nerves and prevent neurodegeneration in disease. The present study used retroviral vectors to engineer human olfactory ensheathing cells to co-express the potent neurotrophin GDNF and reporter genes under a tetracycline-inducible promoter. The goal here was to provide proof of concept for using olfactory ensheathing cells (OECs) for controlled ex vivo delivery of GDNF in preclinical studies. Until now, OECs from the olfactory mucosa have not been examined or developed for this purpose. Here a systematic evaluation of OECs revealed their suitability for developing ex vivo gene therapies. Olfactory ensheathing cells from rats and humans were successfully purified from the olfactory mucosa by p75NTR immunopanning and did not express secreted GDNF protein prior to genetic modification. The immunopanning method did not purify putative neural precursors or stem cells from the human source tissue. Lentiviral vectors incorporating bi-cistronic gene expression cassettes directed drug-inducible co-expression of GDNF and reporter gene in transduced OECs. Here for the first time the foot and mouth disease virus 2A cleavage factor was used to co-express GDNF and reporter genes in human OECs. Biological activity of GDNF and reporter genes (EGFP and β-Galactosidase) was not affected by 2A cleavage in transduced OECs. Owing to robust reporter gene expression in these cells, highly purified cultures of drug-inducible and constitutive expressing OECs were isolated by fluorescence activated cell sorting. In the inducible cell lines, more than 20-fold induction of gene expression was seen after treatment with minocycline however, unsatisfactory baseline expression or ‘leakage’ was observed in the absence of minocycline. Cells constitutively co-expressing GDNF and EGFP were then transplanted into the intact rat striatum. After 9 days, transplanted OECs expressed transgenes, but the majority of grafted cells died. Overcoming the poor cell survival and leakage of expression in inducible cells must precede transplanting these cells in animal models of disease. In conclusion, a robust method for co-expressing therapeutic genes in OECs for preclinical ex vivo gene therapy studies was developed using 2A cleavage and lentiviral vectors. The results present a strong case for using OECs as vehicles to deliver therapeutic genes but also highlight shortcomings of drug-inducible gene expression systems.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Biomolecular and Physical Sciences
Science, Environment, Engineering and Technology
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Amaya, Daniel Alejandro. "Integration of the Peripheral and Central Nervous System During Development of the Murine Olfactory Nerve." Thesis, Griffith University, 2016. http://hdl.handle.net/10072/367158.
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The need to develop therapies for neurodegenerative diseases and spinal cord injuries has led researchers to study the primary olfactory system, as it continuously renews itself throughout life, and completely regenerates after injury.
A pool of cells that line the basal surface of the olfactory epithelium gives rise to new olfactory neurons both during normal olfactory nervous system turnover and to a greater extent following injury. The unique, growth promoting olfactory system environment is crucial for this neurogenesis and regeneration. Significantly glial scarring (as is typically seen in neurodegeneration and neural damage elsewhere in the nervous system) is largely absent following injury to the olfactory tract. Thus replicating the favourable condition in the olfactory nervous system would be invaluable for developing these successful therapies. If we can mimic the cellular and molecular mechanisms responsible for maintenance andregeneration of the olfactory neurons, we can promote regeneration and facilitate the reestablishment of connectivity in damaged neural tracts. To model neural regeneratio n strategies in the olfactory nervous system we need to understand the normal olfactory system biology.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Natural Sciences
Science, Environment, Engineering and Technology
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Hoare, Derek J. "Olfactory coding in a simple neural system : integrative processes and behavioural outputs." Thesis, University of Manchester, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.493945.
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The peripheral olfactory system of the Drosophila larva consists of a pair of dorsal organs each comprising 21 olfactory sensory neurons (OSNs). Each OSN expresses one or two classes of olfactory receptor (OR) in addition to the ubiquitously expressed protein OR83b. The neuronal wiring from OSNs to higher brain centres in Drosophila larvae mirrors the organization seen in higher organisms but is reduced numerically to a simple 1:1:1 connectivity. Presented here is the first in situ electrophysiological data for individual larval OSNs.
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Spice, Rachel Helen. "The molecular basis of thiol odorant sensitivity in the mammalian olfactory system." Thesis, University of Liverpool, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.406662.
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This thesis is an investigation into the potential mechanisms that could explain the olfactory sensitivity to thiol compounds ~ought to be conserved across mammalian species. Proteomics techniques were employed as unbiased tools to search for highly conserved proteins in olfactory cilia theoretically capable of strong interactions with thiol odorants. Comparisons of the protein profiles and directed protein labelling studies of olfactory cilia from three mammalian species - the house mouse (Mus musculus), the rat (Rattus norvegicus) and the sheep (Ovis aries) - and respiratory cilia preparations from the rat enabled the identification of cytoskeletal proteins and olfactory receptors as potential targets for sulphydryl-mediated thiol odorant interactions. It is therefore predicted that olfactory detection of thiol odorants utilises a traditional olfactory receptor conserved across mammalian. species, the observed thiol sensitivity potentially a byproduct of a strong interaction between odorant and receptor. This study also represents the first broad ranging study of the protein complement of mammalian olfactory cilia derived from the three model species. The characterisation of olfactory and respiratory cilia proteomes from multiple mammalian species has highlighted a novel family of putative pheromone binding proteins uniquely associated with mouse olfactory cilia preparations. It has also provided further evidence for the ongoing investigations of the functions of odorant-binding proteins and annexins.
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Broome, Bede Michael Konishi Masakazu. "Population coding and reconstruction of complex stimuli in the locust olfactory system /." Diss., Pasadena, Calif. : Caltech, 2006. http://resolver.caltech.edu/CaltechETD:etd-03142006-171138.
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Cassenaer, Stijn Laurent Gilles Konishi Masakazu. "Spike-timing dependent plasticity and synchronous oscillations in an invertebrate olfactory system /." Diss., Pasadena, Calif. : California Institute of Technology, 2008. http://resolver.caltech.edu/CaltechETD:etd-12202007-160330.
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Weiss, Lukas [Verfasser]. "Information processing in the olfactory system of different amphibian species / Lukas Weiss." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2020. http://d-nb.info/1218780711/34.
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Swiergiel, Jennifer Joan. "Expression of Pax-6 in the developing olfactory system of Xenopus laevis." Diss., The University of Arizona, 1995. http://hdl.handle.net/10150/187103.
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The expression of the transcription factor Pax-6 in the developing olfactory system of the African clawed frog Xenopus laevis was examined using the Xenopus Pax-6 homolog. Pax-6 cDNA clones were isolated from a Xenopus cDNA library with a zebrafish Pax-6 probe. Using a Xenopus Pax-6 sequence that spans the paired box and a majority of the paired-type homeobox, I performed whole mount in situ hybridization analysis on unfertilized eggs and on animals ranging from stages 1 through 66 (i.e., through metamorphosis). Pax-6 is expressed in Xenopus beginning at the late gastrula stage and continuing through metamorphosis. Expression is detected in the olfactory system, the developing eye and regions of the forebrain, hindbrain and spinal cord. The expression pattern of Pax-6 is consistent with a role for Pax-6 in influencing developmental signaling between the olfactory placode and the developing olfactory bulb. Pax-6 is detected in the frog olfactory system from the earliest indication of the olfactory system, the olfactory placode, at stage 23. Light expression of Pax-6 remains in the developing nose as the olfactory axons contact and synapse on the developing olfactory bulb, and throughout formation of the layers of the olfactory bulb. The olfactory bulb primordium expresses Pax-6 from its earliest detection and throughout its development. Therefore, it appears that Pax-6 may play a role in the development and maturation of the olfactory system, as well as the eye and several regions within the central nervous system of Xenopus. Six additional cDNA clones were sequenced and compared at the nucleotide level and predicted amino acid level. Comparisons between Xenopus Pax-6 and other known Pax-6 sequences reveal a striking degree of sequence similarity. The Xenopus Pax-6 sequence encodes two DNA binding regions: the paired domain and the paired-type homeodomain. Greater than 90% sequence identity exists among the paired domains, and there is 100% identity among the paired-type homeodomains. Unlike other Pax-6 sequences reported, some Xenopus Pax-6 cDNAs differ in their predicted carboxy termini. One type of Xenopus Pax-6 cDNA sequence encodes a predicted carboxy terminus nearly identical to Pax-6 sequences reported in other animals. The second type of Xenopus Pax-6 cDNA sequence encodes a predicted protein with an altered carboxy terminal end due to the absence of 151 bp in the 3$\sp\prime$ end and a consequent downstream change in the reading frame. Based on PCR analysis of RNA from animals at different stages, these two sequences each are expressed in a unique and developmentally significant manner.
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PENNAZZA, GIORGIO. "SAMPLING AND SENSING STRATEGIES FOR NOVEL APPLICATIONS WITH AN ARTIFICIAL OLFACTORY SYSTEM." Doctoral thesis, Università degli Studi di Roma "Tor Vergata", 2005. http://hdl.handle.net/2108/177.
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L’utilizzo dei cinque sensi, di cui ognuno di noi è normalmente dotato, ci
permette quotidianamente di percepire ed interpretare il mondo che ci circonda,
molto spesso senza aver coscienza di farne uso, ma semplicemente sfruttando i
risultati che ne otteniamo per l’interazione con l’ambiente circostante.
L’olfatto è probabilmente uno dei sensi del quale l’essere umano, nella sua
evoluzione, ha perso maggiormente la capacità di sfruttare al massimo le
potenzialità. Tuttavia l’odore rappresenta una importante sorgente di
informazioni, grazie alla capacità di sintesi di una serie di parametri e di
interazioni che noi non siamo in grado di raccogliere, interpretare ed elaborare
contemporaneamente.
L’oggetto di questa tesi è il naso elettronico realizzato presso i laboratori del
Gruppo Sensori e Microsistemi dell’Università degli Studi di Roma ‘Tor Vergata’.
L’obiettivo del lavoro è quello di individuare le problematiche fondamentali
relative all’utilizzo di questa tecnologia e, tramite lo studio delle possibili
soluzioni, raggiungere un generale perfezionamento dell’intero sistema.
Sono svariati i campi nei quali le grandi potenzialità di un sistema olfattivo
artificiale possono trovare utile applicazione. La caratteristica multidisciplinare di
un così differenziato ventaglio di applicazioni, richiede la progettazione di una
serie di sistemi di campionamento specifici per ogni scopo.
Sebbene il cuore dell’intero sistema consista nei suoi principi di
funzionamento e nel tipo di materiale sensibile utilizzato, il campionamento
riveste una importanza fondamentale all’interno della catena di misura, perché
attraverso la sua ottimizzazione si rende possibile un efficace utilizzo dello
strumento nella pratica dei problemi reali relativi ai diversi campi. Proprio per
questa ragione, il modo migliore di operare è quello di progettare dei protocolli
sperimentali ‘ad hoc’ specifici per ogni applicazione.
In questa tesi sono considerate tre differenti sperimentazioni: applicazioni
in campo medico ed ambientale, e campionamento dell’odore in condizioni
statiche. In particolare viene presentata l’esperienza di sei anni di sperimentazioni
relative allo studio del tumore al polmone tramite l’analisi dell’espirato per mezzo
del naso elettronico.Everyday, everyone of us uses the five senses, very often without consciousness at all of using them, but simply exploiting the results. The results consist in an interpretation of the real world around us. Olfaction is probably one of the senses humans have lost potentiality to exploit during evolution, but odour is a very important source of data, because of the power of synthesis of a lot of interactions and parameters we are not able to collect, read and elaborate at the same time. An existing technology, the Electronic Nose of the Sensors and Microsystems Group of the University of Rome ‘Tor Vergata’, is the objective of this Thesis. The aim is to ask fundamental questions about it, and by studying the possible solutions, reach the whole system improvement. The great potentialities of artificial olfactory systems can be exploited in many fields. This multidisciplinary range of applications asks for designing of dedicated sampling systems depending on the different scope. Although the working principle and the sensitive material are the basis on which these devices are developed, the sampling, within the measure chain, is a fundamental step to optimize the whole system performances. According to these considerations the best way for designing “ad hoc“ experimental set is to specialize a specific sampling procedure for each application. In this thesis three different studies are considered: medical and environmental applications, and odour sampling in static conditions. In particular, the experience of the six years of experiments dedicated to lung cancer study by mean of e-nose breath analysis is illustrated.
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Borowski, Peter. "Stochastic dynamics in olfactory signal transduction and development." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2006. http://nbn-resolving.de/urn:nbn:de:swb:14-1159519135136-22697.
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The purpose of the senses of animals (and humans) is to translate information available in the external environment into internal information that can be processed by the brain. In the case of the olfactory sense -- the sense of smell -- this is information about the type and concentration of odourants. In the last 15 years major progress has been made in the experimental understanding of the first two stages of the olfactory sense: the signal transduction inside the cilia of the olfactory receptor neurons and the first 'relay station' in the brain, the olfactory bulb, as well as the connection between these two. Theoretical studies that classify the experimentally achieved knowledge or help in testing different biological hypotheses are only starting to be developed. The present work aims to contribute to the theoretical understanding of the first two stages of the olfactory sense. The first processing of the olfactory information, the olfactory signal transduction, is accomplished by a complex chemical network in the sensory cells with the task of coding the available information reliably over a wide range of stimulus strength. In the present work, methods from nonlinear dynamics combined with network theory (namely stoichiometric network analysis) are used to identify a specific negative feedback mechanism that accounts for a number of recently measured experimental results, e.g. oscillations in calcium concentration or the adaptation of the cell towards strong stimuli. This feedback is an experimentally well-established inhibition of cationic channels by the calcium-loaded form of the protein calmodulin. The results of the set of coupled nonlinear deterministic differential equations describing these dynamics agree quantitatively with experimental data. A bifurcation analysis of the system considered shows the robustness of the oscillatory solution against changes in parameters used. It also gives predictions that could serve as an experimental test of the proposed mechanism. Further abstraction and simplification of this specific signal transduction unit leads to a stochastic two-level system with negative feedback, that can not only be found in signalling systems but also in other branches of cell biology, e.g. regulated enzyme activity or in transcription dynamics. Whereas the description outlined above is fully deterministic, here the model system is intrinsically noisy. The influence of the feedback on the intrinsic noise as well as on the signalling properties of the module are analysed in detail by computing mean values, correlation and response functions of the two dynamical system variables using different analytical approaches. Common to all of them is that the intrinsic noise of the system is calculated from its dynamics rather than being introduced by hand. A master equation is used to get generally valid expressions for the mean values. Correlation and response functions for weak feedback are calculated within a path-integral description, and an easier self-consistent method with restricted validity is developed for future extensions of the module such as, e.g., the inclusion of diffusion. The results of the analytical methods are compared to each other and to the results of extended numerical simulations. The considered quantities allow for statements regarding the quality of the signal transduction properties of this module and the positive and negative effects of feedback on it. Going one step up in the information processing in the olfactory sense, another system is found that shows interesting dynamics during development and is influenced by stochastic effects: the formation of the neural map on the surface of the olfactory bulb -- stage two in the olfactory system. The dynamics of this very complex biological pattern formation process is studied mostly numerically focusing on three different aspects of axonal growth. Possible chemical guidance cues and the reaction of axonal growth cones to them are described using different levels of detail. There is strong experimental evidence for interactions among growing axons which is implemented in different ways into models. Finally, axon turnover is considered and used in the most promising simulation approach, where many axons grow as interacting directed random walkers. For each of these aspects, qualitative features of respective experiments are reproducedDie Sinne der Tiere (und Menschen) dienen dazu, Informationen über die Aussenwelt in neuronale, ' interne' Information zu 'übersetzen'. Im Falle des Geruchssinns sind dies Informationen über die Art und Konzentration von Geruchsstoffen. In den letzten 15 Jahren wurden grosse Fortschritte im experimentellen Verständnis der ersten beiden Stufen des Geruchssinns gemacht, sowohl was die Signaltransduktion in den Zilien der Geruchszellen betrifft, als auch bezüglich der ersten 'Schaltstelle' im Gehirn, dem olfaktorischen Bulbus (sowie in der Verbindung dieser beiden Stufen). Die Entwicklung theoretischer Studien, die die experimentell gewonnenen Daten klassifizieren können, befindet sich dagegen erst am Anfang. Ziel der vorliegenden Arbeit ist es, zum theoretischen Verständnis dieser ersten beiden Stufen beizutragen. Die erste Verarbeitung der olfaktorischen Information, die olfaktorische Signaltransduktion, wird durch ein komplexes chemisches Netzwerk in den Sinneszellen bewerkstelligt. In dieser Dissertation werden Methoden der nichtlinearen Dynamik, kombiniert mit Netzwerktheorie (stöchiometrische Netzwerkanalyse) benutzt, um einen negativen Rückkopplungsmechanismus zu identifizieren, der einige in neuerer Zeit gewonnene experimentelle Ergebnisse erklären kann, u.a. Oszillationen der Kalziumkonzentration oder die Anpassung der Zelle an starke Reize. Bei dieser Rückkopplung handelt es sich um eine experimentell gut bestätigte Hemmung eines Kationenkanals durch den Kalziumkomplex des Proteins Calmodulin. Das Ergebnis der vier gekoppelten nichtlinearen deterministischen Differenzialgleichungen, die das dynamische Verhalten des Systems beschreiben, stimmt quantitativ mit experimentellen Daten überein. Eine Bifurkationsanalyse zeigt die Robustheit der oszillierenden Lösung gegenüber Veränderungen der verwendeten Parameter und macht Vorhersagen möglich, die als experimentelle Tests des vorgeschlagenen Mechanismus dienen können. Eine weitere Abstrahierung der oben beschriebenen Signaltransduktionseinheit führt zu einem stochastischen Zweiniveausystem mit negativer Rückkopplung, das nicht nur in Signalsystemen gefunden werden kann, sondern auch in anderen Bereichen der Zellbiologie. Im Gegensatz zu der oben beschriebenen, komplett deterministischen Beschreibung zeigt das hier betrachtete Modellsystem intrinsisches Rauschen. Der Einfluss der Rückkopplung auf das Rauschen sowie auf die Signalübertragungseigenschaften des Moduls werden detailliert analysiert, indem mit Hilfe verschiedener analytischer Methoden Mittelwerte, Korrelations- und Antwortfunktionen des Systems ausgerechnet werden. Diese Methoden habe alle gemein, dass das intrinsische Rauschen des Systems aus der Dynamik selbst berechnet wird und nicht ' von Hand' eingefügt wird. Um allgemeingültige Ausdrücke für die Mittelwerte zu bekommen, wird eine Mastergleichung aufgestellt und gelöst. Die Korrelations- und Antwortfunktionen werden für schwache Rückkopplung mit Hilfe einer Pfadintegralmethode ausgerechnet, und eine einfachere, selbstkonsistente Methode begrenzter Gültigkeit wird für mögliche Erweiterungen des Systems, z.B. die Berücksichtigung von Diffusion, entwickelt. Die Ergebnisse der verschiedenen analytischen Methoden werden miteinander und mit den Ergebnissen ausführlicher numerischer Simulationen verglichen. Die betrachteten Grössen ermöglichen Aussagen über die Qualität der Signaltransduktion dieses Moduls sowie über die positiven und negativen Effekte der Rückkopplung auf diese. Ein weiteres Beispiel für interessante und von stochastischen Effekten beeinflusste Dynamik findet man einen Schritt weiter in der olfaktorischen Signalverarbeitung: Die während der Entwicklung stattfindende Ausbildung der neuronalen Karte auf der Oberfläche des olfaktorischen Bulbus, der zweiten Stufe des olfaktorischen Systems. Die Dynamik dieser sehr komplexen biologischen Musterbildung wird mittels numerischer Simulationen untersucht, wobei der Schwerpunkt auf drei verschiedene Aspekte axonalen Wachstums gesetzt wird. Die Reaktion axonaler Wachstumskegel auf mögliche chemische Signalstoffe wird verschieden detailliert beschrieben. Es gibt deutliche experimentelle Hinweise auf Wechselwirkung zwischen Axonen, was in den Modellen auf verschiedene Arten implementiert wird. Schliesslich wird die Erneuerung der Axone betrachtet und im vielversprechendsten Modell, in dem viele Axone als wechselwirkende gerichtete random walkers simuliert werden, berücksichtigt und analysiert. Für jeden dieser drei Aspekte können entsprechende experimentelle Ergebnisse qualitativ reproduziert werden
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Strauch, Christina [Verfasser], Denise [Akademischer Betreuer] Manahan-Vaughan, and Christian [Akademischer Betreuer] Bellebaum. "Exploration of olfactory information processing within different components and associated structures of the olfactory system / Christina Strauch. Gutachter: Denise Manahan-Vaughan ; Christian Bellebaum." Bochum : Ruhr-Universität Bochum, 2016. http://d-nb.info/1099703875/34.
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Banger, Kulwinder Kaur. "Glutathione S-transferases of the rat nasal cavity." Thesis, Liverpool John Moores University, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.261475.
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Lai, Sen-Lin. "Neural Diversity in the Drosophila Olfactory Circuitry: A Dissertation." eScholarship@UMMS, 2007. https://escholarship.umassmed.edu/gsbs_diss/340.
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Different neurons and glial cells in the Drosophila olfactory circuitry have distinct functions in olfaction. The mechanisms to generate most of diverse neurons and glial cells in the olfactory circuitry remain unclear due to the incomprehensive study of cell lineages. To facilitate the analyses of cell lineages and neural diversity, two independent binary transcription systems were introduced into Drosophila to drive two different transgenes in different cells. A technique called ‘dual-expression-control MARCM’ (mosaic analysis with a repressible cell marker) was created by incorporating a GAL80-suppresible transcription factor LexA::GAD (GAL4 activation domain) into the MARCM. This technique allows the induction of UAS- and lexAop- transgenes in different patterns among the GAL80-minus cells. Dual-expression-control MARCM with a ubiquitous driver tubP-LexA::GAD and various subtype-specific GAL4s which express in antennal lobe neurons (ALNs) allowed us to characterize diverse ALNs and their lineage relationships. Genetic studies showed that ALN cell fates are determined by spatial identities rooted in their precursor cells and temporal identities based on their birth timings within the lineage, and then finalized through cell-cell interactions mediated by Notch signaling. Glial cell lineage analyses by MARCM and dual-expression-control MARCM show that diverse post-embryonic born glial cells are lineage specified and independent of neuronal lineage. Specified glial lineages expand their glial population by symmetrical division and do not further diversify glial cells. Construction of a GAL4-insensitive transcription factor LexA::VP16 (VP16 acidic activation domain) allows the independent induction of lexAop transgenes in the entire mushroom body (MB) and labeling of individual MB neurons by MARCM in the same organism. A computer algorithm is developed to perform morphometric analysis to assist the study of MB neuron diversity.
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Tonsor, Michael M. "Interaction of apoE with estrogen in the olfactory system during nerve maintenance and recovery /." View online, 2009. http://repository.eiu.edu/theses/docs/32211131566909.pdf.
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Clark, Jessica. "Effects of Sensory Ablation on the Young and Aged Ventriculo-Olfactory Neurogenic System." Thesis, Griffith University, 2013. http://hdl.handle.net/10072/366315.
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Adult neurogenesis is a dynamic field of study, with potential for generating therapies for neurodegenerative disorders. The demonstration of adult brain neurogenesis strengthens the rationale for regenerative therapies for neurodegenerative disorders. The ‘ventriculo-olfactory neurogenic system’ (VONS) is used in the study neurogenesis, migration and differentiation of neural stem cells. Importantly, subventricular zone (SVZ) neuroblasts recapitulate a population of dopaminergic neurons within the olfactory bulb (OB), possibly the only population of dopaminergic interneurons, generated throughout adult life. This study aims to simulate a patho physiological model for olfactory epithelial cell turnover to demonstrate a link between the olfactory epithelium (OE) and cell proliferation in the SVZ.
In order to examine the relationship between the OE and the SVZ, an ablation protocol was generated. Using a double dose of methimazole, the OE was completely ablated leading to denervation of the olfactory bulb. This denervation resulted in an increase of astrocyte and microglial activity on day 11 which remained elevated up to day 21. This was accompanied by a significant decrease of tyrosine hydroxylase immunoreactivity in type I periglomerular cells on day 17. While there was a decrease in the type II periglomerular cells on day 17, this was shown to be not significant.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Biomolecular and Physical Sciences
Science, Environment, Engineering and Technology
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Kuijten, M. M. P. "Characterisation of the olfactory system for cell-based therapies to treat neurodegenerative disease." Thesis, University College London (University of London), 2016. http://discovery.ucl.ac.uk/1511817/.
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The olfactory mucosa (OM) is an area of life-long constant regeneration and constitutes a potential cell source for cell-based treatments for neuronal injury, including olfactory ensheathing cells (OECs). Inconsistency in knowledge regarding cell isolation, characteristics and culture methods may influence the efficacy of OEC-based therapies. The aim of the work was to characterise the olfactory mucosa and the bulb to develop a method for isolation of a relatively pure population of OECs as well as to determine a suitable source of OECs. For that purpose immunohistochemical and gene analysis was performed to characterise the OM of postnatal day 16 (young) rat to identify the different cell types in the tissue. The results suggested that ecto-mesenchymal stem cells are present at the junction between the olfactory epithelium and lamina propria (LP) and that in addition, a neural crest (derived) stem cell (NCSC) population was also present at the border of the LP, near the cartilage, and that both cell populations share marker expression with OECs. Furthermore, OM cells were cultured and OECs were isolated using differential adhesion. From these studies it was inferred that this method may result in NCSC contamination in the enriched OEC culture and that a distinctive combination of markers is required to select the OECs. A similar method was used to select for NCSCs using short and long (‘all cells’) trypsination durations. The results suggested the presence of EMSCs in the short trypsination population, whereas the NCSCs were suggested to be present in the ‘all cells’ population. Although differential adhesion may select for certain stem cell populations, the method would not suffice to obtain pure populations. As alternative strategy to select for OECs, EMSCs and NCSCs an attempt at FACS-based cell sorting was made based on the combination of p75, SSEA-1 and ErbB4 expression. Unfortunately, due to low cell viability it was not possible to obtain purified populations. In addition, a comparison was made between the OM of young and adult rat and between the olfactory mucosa and the bulb to determine the most suitable tissue source of OECs. Based on immunohistochemical, gene, Western blotting and flow cytometry analysis, the NCSC population was also suggested to be present in the OM of adult rats and in the olfactory bulb. To obtain insight into neurotrophic ability of the olfactory mucosa, gene expression of six neurotrophic factors in OM tissue and isolated cell populations were studied. From the results it was inferred that BDNF, CNTF, GDNF, NGF, NT3 and NT-4/5 were expressed in both OM tissue and cultured OM cells from young and adult rats, although not to the same extent. These results may suggest that the cells release neurotrophic factors and may be used in neuroprotection strategies to treat neuronal injury. When comparing gene expression of the six factors in cultured OM cell populations to BMSCs, the results may indicate that their neurotrophic potential is not higher compared to BMSCs. The knowledge obtained from the characterisation of the olfactory system may be of use to develop new or improve existing treatment strategies for neuronal injury.
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Eckstein, Eugenia [Verfasser], and Frank [Akademischer Betreuer] Zufall. "Trpm4 and Trpm5 in the murine olfactory system / Eugenia Eckstein ; Betreuer: Frank Zufall." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2019. http://d-nb.info/1203128940/34.
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Rawal, Shilpa [Verfasser], and Karl-Friedrich [Akademischer Betreuer] Fischbach. "The role of IRM Protein Kirre in the olfactory system of Drosophila melanogaster." Freiburg : Universität, 2015. http://d-nb.info/1125903732/34.
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Williams, Sarah. "The cellular and molecular changes occurring in the degenerating and regenerating olfactory system." Thesis, University of Glasgow, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.272844.
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Nemeth, Daniel C. "Evolution of the Coeloconic Sensilla in the Peripheral Olfactory System of Drosophila Mojavensis." University of Cincinnati / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1504798790782263.
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Login, Hande. "Activity-regulated retinoic acid signaling in olfactory sensory neurons." Doctoral thesis, Umeå universitet, Institutionen för molekylärbiologi (Medicinska fakulteten), 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-89022.
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The aim of the studies included in the thesis is to better understand the interplay between neuronal activity-dependent gene regulation and the bioactive vitamin A metabolite all-trans-retinoic acid (RA) during postnatal development, refinement and maintenance of precise neuronal connectivity using the olfactory sensory neuron (OSN) in the olfactory epithelium (OE) of genetically modified mice as a model. We show that: Inhibition of RA receptor (RAR)-mediated transcription in OSNs reduces expression of the olfactory cyclic nucleotide-gated (CNG) ion channel, which is required for odorant receptor (OR)-mediated stimulus transduction. This, results in increased OSN death and errors in precise connectivity. The increased cell death may be a consequence of reduced intrinsic excitability and/or reduced influx of Ca2+ ions while the errors in connectivity may be due to altered OR-dependent expression of axonal guidance proteins, such as Kirrel-2 and Neuropilin-1. Expression of the RA catabolic enzyme Cyp26B1 in OSNs is positively regulated by RAR-mediated transcription as well as sensory stimulation in a CNG channel-dependent manner. This shows that neuronal activity and local vitamin A metabolism are parts of novel regulatory feedback loop controlling precise connectivity and neuronal survival. The feedback loop may be a form of homeostatic plasticity in response to global changes in neuronal activity. BACE1, an enzyme is implicated in Alzheimer´s disease, and Cyp26B1 are inversely regulated by CNG channel-dependent sensory stimulation. Cyp26B1 expression is switched on at birth, forms a topographic expression gradient in OE and inhibits BACE1 expression into an inverse counter gradient. Taken together these results reveal a novel neuronal activity-dependent mechanism by which sensory stimuli can shape spatial gene expression via altered RA bioavailability. Increased Cyp26B1 expression stimulates turnover of OSNs during adult neurogenesis by a non-cell-autonomous mechanism. The gradient of Cyp26B1 expression correlates with spatially-regulated diversification of OSNs into subpopulations that express different subsets of OR genes. Cyp26B1 expression influences spatial OR diversification of OSNs by two different mechanisms. In the ventrolateral OE, Cyp26B1 inhibits OR expression by blocking OSN differentiation at a stage that may be associated with the cell intrinsic mechanism regulating OR gene choice. In the dorsomedial OE the expression frequency of some ORs is unaltered while other increases, presumably as a consequence of neuronal activity-dependent competition. A probable function of graded and activity-dependent Cyp26B1 expression is to form a topographic partitioning of the olfactory sensory map into functional domains, which gradually differ from each other with regard to experience-driven plasticity and neurogenic potential along the dorsomedial-ventrolateral axis of OE.
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Dannecker, Luiz Eduardo Cabral Von. "Ric-8B, um provável GEF para Galpha-olf, promove expressão funcional de receptores olfatórios." Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-18092006-132143/.
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Os odores são detectados por uma grande família de receptores olfatórios (ORs) que são expressos nos neurônios olfatórios localizados no nariz. Os ORs ativados por um determinado odor acoplam-se à proteína Galfaolf que irá promover a ativação da adenilil ciclase III, resultando na produção de AMPc. O aumento da concentração de AMPc irá ativar canais iônicos dependentes de AMPc, tendo como consequência a despolarização do neurônio olfatório. A informação desencadeada pela ativação de determinados ORs é então transmitida para regiões específicas do cérebro promovendo a percepção do odor. A determinação da especificidade dos ORs para diferentes odores irá contribuir para o entendimento de como os odores são discriminados pelo sistema olfatório, entretanto, poucos ORs tiveram seus ligantes definidos devido a dificuldade de expressão funcional de ORs em sistema heterólogo. Em nosso trabalho, utilizamos o sistema de duplo-híbrido em levedura a fim de determinar potenciais novos reguladores para Galfaolf. Deste experimento, identificamos que Ric-8B (Ric, abreviatura de Resistant to Inhibitors of Cholinesterase), um provável GEF (GTP Exchange Factor), é capaz de interagir com Gaolf. Assim como Gaolf, Ric-8B é predominantemente expresso nos neurônios olfatórios maduros e em regiões específicas do cérebro. A restrita co-localização de Gaolf e Ric-8B fortemente indica que Ric-8B é uma proteína que participa da via de transdução de sinal de Galfaolf. Através de nossos ensaios, utilizando células HEK-293, foi possível mostrar que Ric-8B é capaz de potencializar a atividade de Galfaolf, tendo como consequência o aumento da produção de AMPc em sistema heterólogo. Por fim, nós mostramos que Ric-8B é capaz de promover a expressão funcional de ORs em sistema heterólogo. Nossos resultados demonstram que a expressão de Ric-8B é capaz de aumentar o acúmulo de Galfaolf na periferia de células HEK-293T, indicando que Ric-8B promove a expressão funcional de ORs provavelmente através da melhora da eficiência do acoplamento dos ORs com Galfaolf. Nossos resultados demonstram que o uso de Ric-8B em um sistema em larga escala irá permitir a expressão funcional de diversos ORs, permitindo a identificação de seus respectivos ligantes. Tal análise irá contribuir para o melhor entendimento do mecanismo de percepção dos odores.Odorants are detected by a large family of odorant receptors (ORs) expressed in the olfactory neurons in the nose. The activated receptors couple to an olfactory-specific G-protein (Galphaolf), which activates adenylyl cyclase III to produce cAMP. Increased cAMP levels activate cyclic nucleotide-gated channels, causing cell membrane depolarization. The information provided by the odorant receptors is transmitted to specific regions of the brain leading to odorant perception. The determination of the odorant specificities of the different ORs will contribute to the understanding of how odorants are discriminated by the olfactory system. However, only a few ORs have been linked to odorants they recognized to date because ORs are not efficiently expressed in heterologous cells since they are poorly expressed on the cell surface. Here we used yeast two-hybrid to search for potential regulators for Galphaolf. We found that Ric-8B (for Resistant to Inhibitors of Cholinesterase), a putative GTP exchange factor, is able to interact with Gaolf. Like Gaolf, Ric-8B is predominantly expressed in the mature olfactory sensory neurons and also in a few regions in the brain. The highly restricted and colocalized expression patterns of Ric-8B and Galphaolf strongly indicate that Ric-8B is a functional partner for Galphaolf. We show that Ric-8B is able to potentiate Galphaolf-dependent cAMP accumulation in human embryonic kidney 293 cells and therefore may be an important component for odorant signal transduction. Finally, we show that Ric-8B promotes efficient heterologous expression of ORs. Our results show that Ric-8B enhances accumulation of Galphaolf at the cell cortex, indicating that it promotes functional OR expression probably by improving the efficiency of OR coupling to Galphaolf. Our results demonstrate that the employment of Ric-8B in a high-throughput system will allow the functional screening of the OR family members and thereby provide further insight into the mechanisms of odor perception.
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Veleva, Desi. "The Role of Vitamin D on Cell Proliferation in the Olfactory System and the Brain." Thesis, Griffith University, 2010. http://hdl.handle.net/10072/365417.
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The clear evidence that vitamin D (referring to the hormonally active form 1,25-dixydroxyvitamin D3 all through this thesis) is involved in brain development and the widespread distribution of the VDR in neurogenic regions of the brain, propose that vitamin D may be an important regulator of neural stem and progenitor cell proliferation. The inhibitory effect of vitamin D on cell proliferation is well characterised in a wide variety of tissues. Nevertheless, little is known about the effect of vitamin D on neural stem/progenitor cell proliferation. The olfactory tissue is a well-established model for molecular factors and genes that regulate neurogenesis. The ability of the olfactory epithelium to be grown as primary cultures, to give rise to a mixture of neuronal precursors and developing neurons, and the finding that it contains multipotent stem cells (Murrel et al, 1996, 2005; Féron et al, 1998; Newman et al, 2000; McCurdy et al, 2005), make this tissue a good model for investigating the effects of vitamin D on olfactory neurogenesis. The overall aim of this thesis was to explore the effect of vitamin D on stem and progenitor cell proliferation in the olfactory system and the brain. This was achieved by using two different animal models. One model explored the effect on neurosphere formation in animals deprived of vitamin D during development (developmental vitamin D (DVD) deficiency). The other model used genetically modified animals that had a dysfunctional VDR (VDR knockout animals) to investigate the effect of vitamin D inactivation on stem and progenitor cell proliferation in the olfactory system and the brain.
Here it was found that DVD deficiency increased the number of neurospheres formed in cultures from the adult olfactory mucosa. Exogenous vitamin D added to the culture medium had no effect on olfactory neurosphere formation in the DVD cultures but it reduced the neurosphere diameter in the controls. Vitamin D reduced olfactory neurosphere number in the VDR KO animals but had no effect on their size. This thesis also shows that the lack of a functional VDR reduced cell proliferation in the adult mouse brain and olfactory system in vivo. These results demonstrate that vitamin D can regulate stem and progenitor cell proliferation in the olfactory system and the brain and provide a foundation for further investigations into the molecular basis underlying the physiological abnormalities associated with vitamin D deficiency and disruption of vitamin D signalling through VDR inactivation.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Biomolecular and Physical Sciences
Science, Environment, Engineering and Technology
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