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PLETTO, Daniela Rita. "CHARACTERIZATION OF MOLECULAR ISOFORMS AND ROLE OF THE SURVIVAL MOTOR NEURON (SMN) IN MOTOR NEURONS DISEASES." Doctoral thesis, Università degli Studi di Palermo, 2014. http://hdl.handle.net/10447/91238.
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La sclerosi Laterale Amiotrofica (SLA) e l'Atrofia Muscolare Spinale (SMA) sono malattie neurodegenerative caratterizzate dalla perdita progressiva dei motoneuroni.
La SMA è generalmente causata da delezione in omozigosi o mutazione del gene SMN, che codifica per una proteina ubiquitaria e multifunzionale, altamente espressa nel midollo spinale.
La SLA è una malattia che può essere familiare o sporadica.Il 20% dei casi familiari è causato da una mutazione dominante nel gene SOD1. Inoltre ci sono altri geni coinvolti in questa malattia, tra cui FUS e TDP43. Lo scopo principale della tesi è quello di studiare il gene, le isoforme, la localizzazione subcellulare ed i partners molecolari di SMN. Inoltre, poiché sia FUS che TDP43 possiedono domini ricchi in glicina e questi sono necessari per l’interazione con SMN, sono state valutate le possibili interazioni, in modo da capire se le mutazioni dei rispettivi geni possano avere una ricaduta sulle loro interazioni e quindi sulla loro funzione.
Dagli studi di RFLP-PCR, eseguiti su DNA estratto da campioni di sangue intero di pazienti SLA e di controlli neurologici, si evince che non c’è delezione a carico dell’esone 7 del gene SMN. Invece lo studio della proteina, attraverso Western blotting, ha rivelato la presenza di diverse isoforme, sia a livello nucleare che citoplasmatico di leucociti, di cellule HeLa e di cellule di neuroblastoma (SH-SY5Y). Anche le proteine TDP43 e FUS presentano diverse isoforme negli stessi campioni. Inoltre, studi di co-immunoprecipitazione SMN/FUS, fatti su cellule SH-SY5Y, hanno permesso di capire che le due proteine interagiscono a livello nucleare e nello specifico SMN interagisce con una specifica isoforma di FUS.
Poi, attraverso immunofluorescenza, è stata valutata la localizzazione delle proteine studiate in cellule Hela, SH-SY5Y ed in fibroblasti umani; la distribuzione delle proteine rimane sempre la stessa nei 3 tipi cellulari : FUS in nucleoplasma, TDP43 in nucleoplasma e citoplasma, SMN in nucleoplasma, citoplasma e GEMS. Inoltre la localizzazione di FUS e di SMN e la loro interazione non cambia durante il differenziamento delle cellule di neuroblastoma in cellule neuroni-simili attraverso trattamento con acido retinoico e pretrattamento con polilisina/poliornitina. Invece la distribuzione di FUS cambia in fibroblasti umani provenienti da biopsia cutanea di un soggetto asintomatico con mutazione P525L nel gene FUS. In tali cellule la proteina FUS localizza sia nel nucleo che nel citoplasma ma anche in alcuni granuli citoplasmatici. Il fatto che FUS traslochi nel citoplasma in caso di mutazione era già stato visto in precedenza in pazienti affetti da SLA, noi qui dimostriamo per la prima volta che avviene lo stesso fenomeno in un caso pre-clinico.The Amyotrophic Lateral Sclerosis (ALS) and the Spinal Muscular Atrophy (SMA) are neurodegenerative disorders characterized by progressive loss of motor neurons. The SMA is generally caused by homozygous deletion or mutation of the SMN gene, which encodes for a protein that is ubiquitous and multifunctional and it is highly expressed in the spinal cord. The ALS is a familial or a sporadic disease. The 20% of the cases of the familial ALS is caused by a dominant mutation in the SOD1 gene. In addition FUS and TARDBP are two other genes involved in this disease. The purpose of my thesis is to study the gene, the isoforms, the subcellular localization and the molecular partners of SMN protein. We studied the SMN gene by RFLP-PCR and we discovered that there is not deletion in exon 7 and in exon 8 of this gene. Therefore, SMN is not implicated in the pathogenesis of ALS at genetic level, for this reason we analyzed the SMN protein. We chose also two other proteins, FUS and TDP-43 because they have the prerequisites for interacting with SMN protein; in fact they have a rich in glycine domains and this is fundamental for the interaction with the SMN protein. Our studies revealed that the proteins analyzed have different isoforms. In addition we found that SMN and TDP-43 proteins are both in the nucleus and in the cytoplasm, conversely the FUS protein is only in the nucleus. We subsequently evaluated the interaction of the SMN with the FUS protein by co-immunoprecipitation. It showed that only a specific isoform of FUS interacts with the SMN protein and this interaction occurs only in the nucleus. Then we understood that the localization of the FUS and the SMN proteins and their interaction does not change during differentiation of neuroblastoma cells (SH-SY5Y) into neuronal-like adult cells by retinoic acid treatment and pretreatment with poly-lysine/poly-ornithine. Conversely, the localization of the FUS protein changes in human fibroblasts, taken from skin biopsy of an asymptomatic subject with P525L FUS mutation. In these cells the FUS protein is found both in the nucleus and in the cytoplasm. The translocation of mutated FUS from the nucleus to the cytoplasm has already been discovered by other authors in patients with amyotrophic lateral sclerosis. Here we show, for the first time, that the same phenomenon is present in a subject with FUS mutation but asymptomatic.
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Christou, Yiota Apostolou. "Generation of motor neurons from embryonic stem cells : application in studies of the motor neuron disease mechanism." Thesis, University of Sheffield, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.505426.
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Embryonic stem cells are pluripotent cells with the potential to differentiate into any cell type in the presence of appropriate stimulatory factors and environmental cues. Their broad developmental potential has led to the proposal that in the future, the use of human embryonic stem cells or their differentiated progeny may be beneficial in regenerative medicine. In particular, a current goal in the field of clinical neurology is to use stem cells in cell-based therapies for motor neuron disease (MND) or amyotrophic lateral ~clerosis. MND is a progressive neurodegenerative disease that specifically affects upper and lower motor neurons and leads ultimately to death from respiratory failure. Stem cellderived motor neurons could conceivably be used to replace the degenerated cells, to provide authentic substrates for drug development and screening and for furthering our understanding of disease mechanisms. However, to reliably and accurately culture motor neurons, the complex pathways by which differentiation occurs in vivo must be understood and reiterated in vitro to direct embryonic stem cells towards motor neurons. This thesis presents the work I have performed on the directed differentiation of embryonic stem cells towards motor neuron fates. I describe the various experimental approaches I took in attempts to produce motor neurons in vitro. My studies reveal that it is possible to deploy the signals used during normal development to direct the differentiation of both human and mouse embryonic stem cells into neural and neuronal cells, including motor neurons. Two major limitations precluded my analysis of pure motor neuron cultures: first, the high concentrations of the ventralising morphogen, SHH, apparently required to direct embryonic stem cells towards motor neuron fates, and second, the difficulties encountered in culturing purified motor neurons. However, using a mixed culture, I obtained evidence that motor neurons and their progenitors fail to survive in medium conditioned by mutant SOD1-G93A astrocytes.
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Shaw, Ivan Ting-kun. "Cell death in motor neurons, two complementary models." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape11/PQDD_0028/NQ50259.pdf.
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Shaw, Ivan Ting-kun 1966. "Cell death in motor neurons : two complementary models." Thesis, McGill University, 1998. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=35486.
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Target-dependent cell death is an important embryogenic mechanism for regulating and sculpting the developing motor system. Efficient characterization of apoptosis has been more difficult in the nervous system than in other systems due to the use of several different primary culture systems as well as with heterogeneity of neuronal cell populations. We have developed a simple in vitro model of apoptosis with the motor neuron hybrid NSC34, a cell line which expresses much of the motor neuron phenotype (Cashman et al. 1992). Serum-deprived NSC 34 cells in bulk culture undergo cell death, likely from the withdrawal of the growth factors and/or hormones present in fetal calf serum medium supplements. This cell death is accompanied by fragmentation of chromatin into nucleosome multimers, heterochromatization of the nucleus, and other ultrastructural changes reminiscent of apoptotic death. Cell death is inhibitable by addition of agents which block new gene expression ( e.g. cycloheximide) or inhibit endonuclease activity (e.g. aurintricarboxylic acid).We report similar findings with primary embryonic rat motor neurons identified by surface immunoreactivity for p75 LA NGFR, the low-affinity neurotrophin receptor (Bloch-Gallego et al. 1991; Camu and Henderson 1992; Chao and Hempstead 1995). The p75+ motor neuron population could be maintained for more than 48 hours in mixed suspension cultures supplemented with 10% fetal calf serum. However, the p75+ cell population was rapidly depleted in serum-deprived cultures, a phenomenon accompanied by the appearance of oligonucleosomal ladders. Serum-deprived p75+ cells were supported by the motor neuron-relevant factors BDNF, CNTF, GDNF and IGF-1, but not the non-relevant factor NGF. Serum-deprived p75 + cells were also protected by cycloheximide, suggesting a role for apoptosis in the cell death.
We have investigated the role of reactive oxygen species in acquired and genetic motor neuron diseases. Interestingly, a rapid burst of reactive oxygen species is observable within one hour of serum deprivation in both NSC34 and rat motor neuron systems. This burst precedes measurable cell death by at least one day, indicating that oxygen species generation may be an initial hallmark of target-dependent death. The amplitude and temporal nature of this burst may be altered by manipulating various cellular ROS defence mechanisms. Such manipulations also alter cell death progression, suggesting that the apoptotic cascade may be dependent upon this early ROS burst. The identity, source and activity of the relevant ROS may provide insight into the etiology and treatment of human motor neuron diseases.
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Stephens, Benjamin. "Pathology of spinal interneurons in motor neuron disease." Thesis, Imperial College London, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.251759.
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Taylor, David M. 1977 Nov 23. "Understanding the regulation of molecular chaperones in motor neurons." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=111857.
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Cells are constantly challenged by acute and chronic stresses that must be counteracted by upregulation of protective pathways. The premise of this thesis is that motor neurons have an impaired ability to trigger these protective mechanisms, which may contribute to their preferential vulnerability in the neurodegenerative disease, amyotrophic lateral sclerosis (ALS). The first objective was to study the involvement of metallochaperones in motor neuronal stress response, including their potential for rescuing motor neurons from toxicity conferred by a mutant Cu/Zn-superoxide dismutase (SOD1G93A ) that causes a form of familial ALS. Motor neurons in dissociated spinal cord cultures failed to induce the metallochaperone, metallothionein (MT), in response to classical MT inducers, although overexpression of MT in motor neurons failed to protect them from SOD1G93A. A second response system, involving protein chaperones called heat shock proteins (Hsp), was more therapeutically promising, but was also impaired in motor neurons due to an inability to activate the regulatory protein heat shock transcription factor 1 (Hsf1). The remaining objectives were to examine if activation of Hsf1 in motor neurons would protect against SOD1G93A and to understand the mechanisms responsible for its impaired activation. A constitutively active form of Hsf1 induced multiple Hsps in motor neurons and nearly eliminated SOD1G93A toxicity and aggregation. Experiments also demonstrated that failure of stressed motor neurons to activate endogenous Hsf1 is not a result of inappropriate or insufficient activity of kinases that phosphorylate key residues of Hsf1 in nonneuronal cell lines with a competent heat shock response. Disruption of inhibitory Hsp90/multichaperone complexes is another important step in Hsf1 activation. Four different pharmacological inhibitors of Hsp90 induced multiple Hsps in motor neurons, although failure to observe the same response by targeting inhibitory complexes with activator of Hsp90 ATPase 1 (Aha1) or Daxx suggested other mechanisms were involved. A constitutively active form of calcium/calmodulin-dependent kinase N induced Hsp70 in motor neurons, but not in fibroblasts and likely through an Hsf1-independent mechanism. These results provide further evidence for disparity between the stress response of motor neurons and other cells and suggest the possibility of a unique Hsp regulatory system in neurons.
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Deinhardt, Katrin. "The endocytic pathway of tetanus neurotoxin in motor neurons." Thesis, University College London (University of London), 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.428573.
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Murtha, Matthew J. III. "Transcriptional Programming of Spinal Motor Neurons from Stem Cells." The Ohio State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=osu1261416295.
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Wertz, Mary Helene. "Aberrant microRNA Expression in Spinal Muscular Atrophy Motor Neurons." Thesis, Harvard University, 2015. http://nrs.harvard.edu/urn-3:HUL.InstRepos:17464519.
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Spinal Muscular Atrophy (SMA) is a devastating autosomal-recessive pediatric neurodegenerative disease characterized by loss of spinal motor neurons. It is caused by mutation in the survival of motor neuron 1, SMN1, gene and leads to loss of function of the full-length SMN protein. SMN has a number of functions related to RNA processing in neurons, including RNA trafficking in neurites, and RNA splicing and snRNP biogenesis in the nucleus. While previous work has focused on the alternative splicing and expression of traditional mRNAs, our lab has focused on the contribution of another RNA species, microRNAs (miRNAs), to the SMA phenotype.
miRNAs are ~22 nucleotide small RNAs that are involved in post-transcriptional regulation of gene expression. They function by translational repression or mRNA decay of target RNAs. Interestingly, dysregulation of RNA processing and miRNA expression has been identified in motor neuron diseases including SMA and Amyotrophic Lateral Sclerosis. Our lab previously discovered a miRNA, miR-183, that is dysregulated in SMA and impacts its targets in cortical neurons and SMA mouse spinal cords.
However, spinal motor neurons are the cell type most affected by SMN loss. We hypothesized that motor neuron specific miRNA changes are involved selective vulnerability in SMA. Therefore, we sought to determine the effect of loss of SMN on spinal motor neurons. To accomplish this, I used microarray and RNAseq to profile both miRNA and mRNA expression in primary spinal motor neurons after acute SMN knockdown. By integrating the miRNA:mRNA profiles we identified dysregulated miRNAs with enrichment in differentially expressed putative targets. miR-431 was the most substantially increased miRNA and a number of its putative targets were downregulated after SMN loss. Further, I confirm that miR-431 directly regulates its target chondrolectin and impacts neurite length.
This work is critical to understanding the cell-type specific effect of aberrant miRNA expression in SMN knockdown motor neurons. It demonstrates the contribution of dysregulated RNA processing in motor neurons to neurodegeneration. Furthermore, this work highlights the impact of non-coding RNAs in human disease and points to specific miRNA whose dysregulation potentially impacts motor neuron health.Medical Sciences
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Nakamizo, Tomoki. "Phosphodiesterase inhibitors are neuroprotective to cultured spinal motor neurons." Kyoto University, 2003. http://hdl.handle.net/2433/148692.
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Gopinath, Sumana. "Finding new genes causing motor neuron diseases." Thesis, The University of Sydney, 2006. http://hdl.handle.net/2123/1624.
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Abstract Neurodegenerative disorders are a diverse group of disorders that affect specific subsets of neurons. Motor neuron diseases, neurodegenerative disorders of motor neurons, are seen commonly as sporadic cases and less frequently as familial disease forms. The familial forms show genetic and phenotypic heterogeneity. Clinically motor neuron diseases may be seen as rapidly progressive disorders like amyotrophic lateral sclerosis, ALS or slowly progressive disorders like hereditary motor neuropathies, HMN. The only proven causes for motor neuron diseases are gene mutations that lead to motor neuron degeneration in familial disease forms. Only some of these genes have been identified and have contributed greatly to our understanding of the neurobiology of familial and sporadic disease forms. Identification of additional disease causing genes would help enhance our knowledge of the pathophysiological mechanisms underlying all forms of motor neuron disorders, which would lead to early diagnoses, effective prophylaxis and efficient therapies for these disorders. This study aimed to find gene mutations that cause rapid and slowly progressive familial motor neuron disorders in Australian families and to determine their relevance to sporadic forms of motor neuron disease. The familial forms of ALS show reduced disease penetrance, that is, not all gene mutation carriers manifest the disease. This study examines ALS penetrance in a group of Australian families. The most frequently observed mutations in ALS families are cytosolic superoxide dismutase/SOD1 gene mutations. In a collection of ALS families in our centre, families without the common SOD1 gene mutations were genotyped for other ALS genes and loci and studied using genetic linkage and haplotype analyses. Studies in a large Australian ALS family further confirmed genetic heterogeneity in non-SOD familial ALS, all known autosomal dominant ALS genes and chromosomal loci were excluded as cause of disease in this family. Such families can be studied further to identify additional disease genes and loci mapped in other ALS families. These families represent powerful resources for identification of additional ALS genes. Identifying the pathogenic genes in families with reduced disease penetrance may be more relevant to sporadic forms of disease. dHMN is a chronic neurodegenerative disorder predominantly affecting motor neurons. In a large Australian dHMN family, all the known dHMN genes and chromosomal loci were excluded as cause of disease. A genome wide microsatellite screen was performed in this family and genetic linkage was established to a novel 12.98 Mb locus on chromosome 7q34.2-q36. Candidate genes in this large interval will be screened based on their function and expression profile. Identification of a new dHMN locus provides the basis for future identification of a novel gene involved in motor neuron degeneration. Genes in dHMN have been shown to be pathogenic in ALS and Charcot Marie Tooth syndromes. The new locus for dHMN mapped in this project would lead to identification of a novel dHMN gene, which may elucidate the pathogenesis underlying a wide range of neurodegenerative disorders.
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Gopinath, Sumana. "Finding new genes causing motor neuron diseases." University of Sydney, 2006. http://hdl.handle.net/2123/1624.
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Doctor of PhilosophyAbstract Neurodegenerative disorders are a diverse group of disorders that affect specific subsets of neurons. Motor neuron diseases, neurodegenerative disorders of motor neurons, are seen commonly as sporadic cases and less frequently as familial disease forms. The familial forms show genetic and phenotypic heterogeneity. Clinically motor neuron diseases may be seen as rapidly progressive disorders like amyotrophic lateral sclerosis, ALS or slowly progressive disorders like hereditary motor neuropathies, HMN. The only proven causes for motor neuron diseases are gene mutations that lead to motor neuron degeneration in familial disease forms. Only some of these genes have been identified and have contributed greatly to our understanding of the neurobiology of familial and sporadic disease forms. Identification of additional disease causing genes would help enhance our knowledge of the pathophysiological mechanisms underlying all forms of motor neuron disorders, which would lead to early diagnoses, effective prophylaxis and efficient therapies for these disorders. This study aimed to find gene mutations that cause rapid and slowly progressive familial motor neuron disorders in Australian families and to determine their relevance to sporadic forms of motor neuron disease. The familial forms of ALS show reduced disease penetrance, that is, not all gene mutation carriers manifest the disease. This study examines ALS penetrance in a group of Australian families. The most frequently observed mutations in ALS families are cytosolic superoxide dismutase/SOD1 gene mutations. In a collection of ALS families in our centre, families without the common SOD1 gene mutations were genotyped for other ALS genes and loci and studied using genetic linkage and haplotype analyses. Studies in a large Australian ALS family further confirmed genetic heterogeneity in non-SOD familial ALS, all known autosomal dominant ALS genes and chromosomal loci were excluded as cause of disease in this family. Such families can be studied further to identify additional disease genes and loci mapped in other ALS families. These families represent powerful resources for identification of additional ALS genes. Identifying the pathogenic genes in families with reduced disease penetrance may be more relevant to sporadic forms of disease. dHMN is a chronic neurodegenerative disorder predominantly affecting motor neurons. In a large Australian dHMN family, all the known dHMN genes and chromosomal loci were excluded as cause of disease. A genome wide microsatellite screen was performed in this family and genetic linkage was established to a novel 12.98 Mb locus on chromosome 7q34.2-q36. Candidate genes in this large interval will be screened based on their function and expression profile. Identification of a new dHMN locus provides the basis for future identification of a novel gene involved in motor neuron degeneration. Genes in dHMN have been shown to be pathogenic in ALS and Charcot Marie Tooth syndromes. The new locus for dHMN mapped in this project would lead to identification of a novel dHMN gene, which may elucidate the pathogenesis underlying a wide range of neurodegenerative disorders.
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Wang, Hsien-Yi Sabrina. "Motor neurons and motor patterns underlying phonotaxis during flight of the cricket, Teleogryllus oceanicus." Thesis, McGill University, 1988. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=63869.
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Li, Mei. "Expression of chondroitin sulfotransferases in relation to cranial motor neuron movements in the embryonic hindbrain." Click to view the E-thesis via HKUTO, 2010. http://sunzi.lib.hku.hk/hkuto/record/B44236736.
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Krieger, Patrik. "On the role of metabotropic glutamate receptors in motor control : analysis of synaptic, cellular and network properties /." Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4449-0/.
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Chan, Alexander Kam Shing. "The effect of acupuncture on alpha-motoneuron excitability thesis submission to Auckland University of Technology for the degree of Master in Health Science, December 2002." Full thesis. Abstract, 2002.
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Li, Mei, and 李玫. "Expression of chondroitin sulfotransferases in relation to cranial motor neuron movements in the embryonic hindbrain." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B44236736.
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Ming, Yu. "Regulation of neurotrophic signaling molecules in motor neurons, primary sensory neurons and target tissues in senescence /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-591-3.
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Gill, Mark D. "Aminergic modulation of spontaneous and reflexly generated motor output of crayfish walking leg motor neurons." Thesis, University of Bristol, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.262842.
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O'Brien, Laura. "Mitochondrial biogenesis and electrical properties of hPSC-derived motor neurons." VCU Scholars Compass, 2015. http://scholarscompass.vcu.edu/etd/3804.
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Human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) hold great promise in the fields of drug development and regenerative medicine. If iPSCs reprogrammed from patient cells replicate what is seen in vivo they may be used as a model of disease. A process that is disrupted in many neurodegenerative diseases is mitochondrial biogenesis. One of these diseases is amyotrophic lateral sclerosis (ALS), which is characterized by loss of motor neurons in the brain and spinal cord. Differentiation of hPSCs into motor neurons offers a way to study a previous unavailable cell type and may further our understanding of human motor neuron biology. The aims of the present study were to differentiate motor neurons from hESCs and iPSCs in low oxygen conditions and to explore mitochondrial biogenesis and electrical maturation during this process. After three weeks of treatment with retinoic acid and purmorphamine, a sonic hedgehog agonist, cells increased expression of post mitotic spinal motor neuron markers. One week later electrophysiological analysis revealed voltage-gated currents and action potential generation. Mitochondrial biogenesis signaling and expression of respiratory chain proteins increased with motor neuron differentiation. Respiration analysis revealed a decrease in glycolysis in motor neurons compared to neural stem cells. Interestingly, this was not accompanied by an increase in basal respiration or mitochondrial mass. These findings enhance our understanding of motor neuron mitochondrial biogenesis, a process impaired in ALS.
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Cherry, Cortnie Lauren. "Mechanisms of Depolarization Induced Dendritic Growth of Drosophila Motor Neurons." Diss., The University of Arizona, 2006. http://hdl.handle.net/10150/195475.
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MECHANISMS OF DEPOLARIZATION INDUCED DENDRITIC GROWTH OF DROSOPHILA MOTOR NEURONS Cortnie Lauren Cherry The University of Arizona, 2006 Director: Richard B. Levine The study of the cellular mechanisms underlying dendritic growth contributes to our understanding of nervous system development, function and disease. Electrical activity is a fundamental property of neurons, and this property is utilized to influence the mechanisms involved in dendrite formation and maturation. Here we employ the Drosophila transgenic system to quantify dendritic growth of identified motor neurons using both in vitro and in vivo techniques. Two novel techniques are introduced: one a system to visualize and measure dendritic outgrowth in cultured neurons using reporter proteins, and the other using 3D reconstruction to measure the arborization of identified motor neurons in vivo. Both transgenic manipulation of K+ channel function and depolarizing concentrations of K+ in the culture medium result in an acceleration of dendritic outgrowth. Depolarization induced outgrowth is dependent on Plectreurys Toxin (PLTX)-sensitive voltage-gated calcium current and protein synthesis in cultured motor neurons. Depolarization leads to direct induction of fos, a protein that heterodimerizes with jun to make the functional transcription factor, AP-1. Fos, but not jun, is necessary for basal levels of dendritic growth, while both are necessary for depolarization induced outgrowth. Over-expression of AP-1 in control cells is sufficient to cause dendritic outgrowth. The transcription factor Adf-1 is also necessary for basal and depolarization induced growth, but unlike AP-1 is not sufficient to cause outgrowth when over-expressed. Another transcription factor CREB, on the other hand, is not necessary for basal levels of dendritic growth, but is necessary for depolarization induced dendritic growth. Over-expression of CREB, like Adf-1, is not sufficient to cause dendritic outgrowth. These findings present exciting new techniques for the study of the field of dendritic regulation and contribute to our understanding of the cellular mechanisms underlying dendritic growth.
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Dacre, Joshua Rupert Heaton. "Thalamic control of motor behaviour." Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/29530.
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The primary motor cortex (M1) is a key brain area for the generation and control of motor behaviour. Output from M1 can be driven in part by long-range inputs from a collection of thalamic nuclei termed the motor thalamus (MTh), but how MTh input shapes activity in M1 and forelimb motor behaviour remains largely unresolved. To address this issue, we first defined the 3D anatomical coordinates of mouse forelimb motor thalamus (MThFL) by employing conventional retrograde and virus-based tracing methods targeted to the forelimb region of M1 (M1FL). These complimentary approaches defined MThFL as a ~0.8 mm wide cluster of neurons with anatomical coordinates 1.1 mm caudal, 0.9 mm lateral to bregma and 3.2 mm below the pial surface. Thus, MThFL incorporates defined areas of the ventrolateral, ventral anterior and anteromedial thalamic nuclei. To investigate the importance of M1FL and MThFL during skilled motor behaviour, we developed and optimised a quantitative behavioural paradigm in which head-restrained mice execute forelimb lever pushes in response to an auditory cue to receive a water reward. Forelimb movement trajectories were mapped using high-speed digital imaging and multi-point kinematic analysis. We inactivated both M1FL and MThFL of mice performing this motor behaviour using a pharmacological strategy, which in both cases resulted in a significant reduction in task performance. Inactivating M1FL significantly affected forelimb coordination and dexterity, resulting in erratic motion and posture. In contrast, mice with MThFL inactivated displayed a reduction in total motor output, although correct posture was maintained. We performed extracellular recordings in MThFL of expert-level mice, demonstrating that motor thalamic output during execution of task was dominated by a robust response to the onset of the auditory cue. Cue-evoked responses were also observed in motor thalamic neurons of naive mice. We have developed a novel solution to the stability problem encountered when performing whole-cell patch-clamp recordings from the motor cortex of head-restrained mice performing forelimb motor behaviour, and present preliminary recordings maintained through the execution of forelimb behaviour.
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Jacob, Sanjeev John. "Segmental origins and axon pathfinding of branchial motor and visceral motor neurons of the facial nerve." Thesis, King's College London (University of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.393791.
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Barbagallo, Belinda. "Activity Regulates Neuronal Connectivity and Function in the C. elegans Motor Circuit: A Dissertation." eScholarship@UMMS, 2014. https://escholarship.umassmed.edu/gsbs_diss/728.
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Activity plays diverse roles in shaping neuronal development and function. These roles range from aiding in synaptic refinement to triggering cell death during traumatic brain injury. Though the importance of activity-dependent mechanisms is widely recognized, the genetic underpinnings of these processes have not been fully described. In this thesis, I use the motor circuit of Caenorhabditis elegans as a model system to explore the functional and morphological consequences of modulating neuronal activity.
First, I used a gain-of-function ionotropic receptor to hyperactivate motor neurons and asked how increased excitation affects neuronal function. Through this work, I identified a cell death pathway triggered by excess activation of motor neurons. I also showed that suppression of cell body death failed to block motor axon destabilization, providing evidence that death of the cell body and of motor axons can be genetically separated.
Secondly, I removed excitatory drive from a simple neural circuit and asked how loss of excitatory activity alters circuit development and function. I identified excitatory motor neurons as master regulators of inhibitory synaptic connectivity. Additionally, I was able to identify previously undescribed activity-dependent mechanisms for regulating inhibitory synapses in both developing and mature neural circuits.
Finally, I show data to implicate the highly conserved genes neurexin and neuroligin in determining inhibitory synapse connectivity. Collectively this work has lent insight into activity-dependent mechanisms in place to regulate neuronal development and function, a core function of neurobiology that is relevant to the study of a wide range of neurological disorders.
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Barbagallo, Belinda. "Activity Regulates Neuronal Connectivity and Function in the C. elegans Motor Circuit: A Dissertation." eScholarship@UMMS, 2007. http://escholarship.umassmed.edu/gsbs_diss/728.
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Activity plays diverse roles in shaping neuronal development and function. These roles range from aiding in synaptic refinement to triggering cell death during traumatic brain injury. Though the importance of activity-dependent mechanisms is widely recognized, the genetic underpinnings of these processes have not been fully described. In this thesis, I use the motor circuit of Caenorhabditis elegans as a model system to explore the functional and morphological consequences of modulating neuronal activity.
First, I used a gain-of-function ionotropic receptor to hyperactivate motor neurons and asked how increased excitation affects neuronal function. Through this work, I identified a cell death pathway triggered by excess activation of motor neurons. I also showed that suppression of cell body death failed to block motor axon destabilization, providing evidence that death of the cell body and of motor axons can be genetically separated.
Secondly, I removed excitatory drive from a simple neural circuit and asked how loss of excitatory activity alters circuit development and function. I identified excitatory motor neurons as master regulators of inhibitory synaptic connectivity. Additionally, I was able to identify previously undescribed activity-dependent mechanisms for regulating inhibitory synapses in both developing and mature neural circuits.
Finally, I show data to implicate the highly conserved genes neurexin and neuroligin in determining inhibitory synapse connectivity. Collectively this work has lent insight into activity-dependent mechanisms in place to regulate neuronal development and function, a core function of neurobiology that is relevant to the study of a wide range of neurological disorders.
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Banks, Glen B. "The role of synapse formation on motoneuron survival during embryonic development /." [St. Lucia, Qld.], 2003. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe17453.pdf.
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Li, Lai-fung. "Survival and regeneration of adult spinal motoneurons after root avulsion : a comparison of influence from different targets /." Click to view the E-thesis via HKUTO, 2005. http://sunzi.lib.hku.hk/hkuto/record/B3984903X.
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Jackson, Mandy. "Screening of familial and sporadic amyotrophic lateral sclerosis patients for mutations in CuZn superoxide dismutase (SOD-1) and other candidate genes." Thesis, University of Oxford, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.363787.
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Simon, Horst Hubertus. "Development of the efferent system in the segmented chick brainstem." Thesis, King's College London (University of London), 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.307096.
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Uhler, Jennifer Pamela. "The development of dendritic arbors in Drosophila motorneurons." Thesis, University of Cambridge, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.621930.
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Musick, James R. "Mechanisms of spike-frequency adaptation in hypoglossal motoneurons /." Thesis, Connect to this title online; UW restricted, 1999. http://hdl.handle.net/1773/10550.
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Odden, Joanne Pamela. "Determined to be a Drosophila motor neuron : identification of subtype- and lineage-specific genetic components /." view abstract or download file of text, 2003. http://wwwlib.umi.com/cr/uoregon/fullcit?p3113020.
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Thesis (Ph. D.)--University of Oregon, 2003.Typescript. Includes vita and abstract. Includes bibliographical references (leaves 96-105). Also available for download via the World Wide Web; free to University of Oregon users.
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Patani, Rickie. "Generating motor neuron subtype diversity from human pluripotent stem cells." Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.610349.
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Spielmann, John Michael. "Quantification of motor neuron adaptation to sustained and intermittent stimulation." Diss., The University of Arizona, 1991. http://hdl.handle.net/10150/185411.
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In deeply anesthetized mammals, as typified by the adult cat, there is limited evidence that the firing-rate response of spinal motor neurons to sustained simulation usually features a progressive reduction in firing rate, termed late adaptation, that begins 1-2 s after the onset of sustained stimulation. The fullest description of late adaptation has been provided by Kernell & Monster (1982a,b) who evoked repetitive firing in spiral motor neurons of deeply anesthetized cats by the conventional procedure of an intracellular injection of a sustained depolarizing current. The main purpose of the present study was to extend on the results of their work. The first hypothesis tested was: Sustained depolarizing extracellular stimulation of motor neurons is more effective in maintaining repetitive discharge than sustained depolarizing intracellular stimulation. Investigations pioneered by Kernell & Monster (1982a,b) tested the association between late adaptation and other type (size)-related properties of motor neurons. Such analyses are within the rubric of Henneman's (1957, 1977) Size Principle, one component of which proposes that the properties of motor neurons and the muscle fibers they innervate are tightly coupled. The second hypothesis was proposed to continue this inquiry. It stated that: Late adaptation (during both sustained and intermittent stimulation), and other discharge-related properties of motor neurons are associated with other type (size)-related properties of these cells and their motor units. For both hypotheses, there was an emphasis on providing a quantitative description of late-adaptation. In the present study, the duration of repetitive firing in response to sustained stimulation significantly exceeded that in the Kernell & Monster (1982a,b) study, thereby providing evidence in support of the first hypothesis. For sustained stimulation, significant associations were found between the time constant of late adaptation and three neuromechanical properties of the cell's motor unit: axonal conduction velocity; twitch contraction time; and, peak tetanic force. Similarly, significant associations were found between the peak firing rate and these neuromechanical properties for both sustained and intermittent stimulation. Significant associations were also found between the extent of between-train adaptation during intermittent stimulation and two of the neuromechanical properties: axonal conduction velocity and peak tetanic force. These results provided evidence in support of the second hypothesis. In summary, the present work has provided a new opening in the study of the active (firing) properties of motor neurons, by quantitating late adaptation during sustained stimulation, and between-train adaptation during intermittent stimulation. This information provides new insights into the fundamental properties of motor neurons and adds important new firing-rate parameters to the continuing evaluation of Henneman's Size Principle.
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Jerregård, Helena. "Factors influencing nerve growth in situ and in vitro /." Linköping : Univ, 2001. http://www.bibl.liu.se/liupubl/disp/disp2001/med693s.pdf.
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Tokuno, Craig. "Neural control of standing posture." Doctoral thesis, Stockholm : Karolinska institutet, 2007. http://diss.kib.ki.se/2007/978-91-7357-396-2/.
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Wang, Pei-Yu, and n/a. "Novel survival factors with a gender specific twist for motor neurons." University of Otago. Department of Anatomy & Structural Biology, 2006. http://adt.otago.ac.nz./public/adt-NZDU20070504.143741.
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The survival of motor neurons is controlled by multiple factors, which regulate different aspects of their physiology. The identification of these factors is important because of their relevance for motor neuron disease. This thesis began with a search for novel growth factors that naturally keep these neurons alive. Members of the TGF-β superfamily, including Mullerian inhibiting substance (MIS) and bone morphogenetic protein 6 (BMP6), were identified as putative survival factors following a cDNA microarray analysis of a mouse model of motor neuron disease.
MIS is a gonad-derived hormone with a male bias. It induces the degeneration of the female reproductive tract during development and it was thought to have no physiological function outside of the reproductive system. In this thesis, multiple techniques were used to show that adult motor neurons produce MIS and its receptors. The copy number of MIS mRNA in motor neurons was comparable with that of the testis, whereas the mRNA of the MIS type II receptor (MISRII) in motor neurons appeared to be the most abundant receptor of the TGF-β superfamily. These results were confirmed using Western blot and immunohistochemistry. Thus, MIS may exert its function through an autocrine or a paracrine mechanism between neighbouring motor neurons.
The function of MIS was examined using a culture system and a mouse null mutation of MISRII. The in vitro assays showed strong neurotrophic effects of MIS on embryonic motor neurons with the maximum extent of survival being similar to that achieved by the classical motor neuron survival factor, GDNF. MIS has a male bias in utero raising the issue of whether motor neurons are sexually dimorphic. Consistent with this, the number of motor neurons in the lumbar lateral motor column of neonatal male MISRII+/+ mice was 13 % greater than in female mice (P = 0.01). The nuclei of male motor neurons were approximately 20 % larger than their female counterparts (P = 0.000). MISRII-/- male mice had 18 % fewer motor neurons than wild-type males (P = 0.01) and the mean size of their motor neurons was 20 % smaller (P = 0.000). The number and size of motor neurons in the MISRII-/- males was not different to those of MISRII+/+ females. These results implicate MIS as being responsible for neuronal survival as well as producing sexual dimorphism of the limb innervating motor neurons. Since MIS does not appear to be expressed in the embryonic neuromuscular system, it is postulated that MIS is a gonad-derived neurotrophic factor for developing motor neurons.
The BMP type II receptor (BMPRII) was the second most abundant receptor of the TGF-β superfamily expressed by motor neurons. One of its ligands, BMP6, was found to have a neurotrophic effect on motor neurons in culture but was slightly less potent than MIS. BMP6 mRNA was detected in nerve, skeletal muscle and spinal cord, but not in motor neurons. BMP6 immunoreactivity was mainly associated with the myelinated Schwann cells and satellite glia that surround motor neurons. In skeletal muscles, immunoreactivity was not detected in muscle fibers, nor the postsynaptic region of the neuromuscular junction (NMJ). BMP6 was, however, associated with the interstitial cells of skeletal muscles. Double nerve ligations were used to examine whether Schwann cell-derived BMP6 interacts with motor neurons. Consistent with this, BMP6 was retrogradely transported in motor axons. These observations collectively suggest that BMP6 is a glia-derived regulator of motor neurons.
MIS and minority of BMP6 were anterogradely transported towards the NMJ. Their receptors, MISRII and BMPRII, were detected in the postsynaptic portions of the adult NMJ. These observations raised the possibility that MIS and BMP6 may be regulators of the adult NMJ. Since functional redundancy amongst the members of the TGF-β superfamily has been suggested, the function of MIS/BMP6 signaling at the NMJ was therefore examined in mice with muscle-specific deletion of Smad4, a central mediator of TGF-β superfamily pathways. More than 75% of animals lacking Smad4 in muscles died before embryonic day (E) 14 and none survived postnally. This was due to the loss of functional Smad4 in developing cardiac myocytes, which resulted in severe heart defects and early death of embryos. Thus, the function of MIS/BMP6 signaling at the adult NMJ could not be studied.
Finally, this thesis briefly examined the phenotypes of mice carrying double null mutations of MISRII and TGF-β2. The animals died at an early stage and showed a more severe phenotype than either of the single null mutants. This suggests that functional redundancy among members of the TGF-β superfamily exists in many organs.
In summary, motor neurons require multiple sources of growth factors for their survival. MIS and BMP6 were discovered as novel survival factors for motor neurons in this study. MIS was implicated as a regulator of sexual dimorphism in developing motor neurons, whereas both MIS and BMP6 appear to regulate mature motor neurons, and possibly the NMJ.
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Benn, Susanna Clare. "Neuroprotection by heat shock protein 27 in sensory and motor neurons." Thesis, University College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.271424.
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Siahpoosh, Yasmin(Yasmin H. ). "Investigating mechanisms of biophysical diversity between phasic and tonic motor neurons." Thesis, Massachusetts Institute of Technology, 2020. https://hdl.handle.net/1721.1/130197.
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Thesis: M. Eng., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, May, 2020Cataloged from student-submitted PDF of thesis.
Includes bibliographical references (pages 65-67).
Neurons exhibit striking diversity in core neuronal properties (intrinsic biophysical and synaptic properties), which are the building blocks of brain function and computation. Despite the central role of these properties in brain function, the underlying molecular and biophysical mechanisms which generate this diversity remain incompletely understood. In the Drosophila larval motor system, phasic (1s) and tonic (1b) motor neurons (MNs) differ in their intrinsic biophysical properties, providing an ideal system to examine electrophysiological diversity across neuronal populations. To address this question, we combined in vivo whole-cell patch-clamp physiology with biophysical modeling. First, we characterized biophysical diversity between 1s and 1b MNs. To explore molecular mechanisms underlying such diversity, single-neuron PatchSeq RNA profiling experiments were carried out to correlate biophysical properties with differences in ion channel gene expression profiles. These experiments suggest that cyclic nucleotide- gated like (CNGL) ion channels are upregulated in 1b MNs several folds, which indicates that CNGL could be a candidate ion channel that might specify diversity in electrical properties . To test this hypothesis, we misoverexpress CNGL in 1s MNs so that we could investigate how this ion channel contributes to the diversity between them. We developed an analysis toolset in MATLAB that can be used to analyze whole-cell patch-clamp physiology data and obtain excitability properties. Using the Izhikevich model, we were able to quantify and predict the spiking properties of 1s and 1b MNs. Using a ball and stick model, we were able to reproduce the tonic firing pattern of 1b neurons and tested tonic firing patterns in different compartments of 1b neurons. Taken together, this thesis work laid the foundation to begin characterizing biophysical mechanisms of intrinsic diversity of Drosophila neurons by combining experimental data with modeling.
by Yasmin Siahpoosh.
M. Eng.
M.Eng. Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science
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Sances, Samuel. "Influence of Microvascular Cells on Stem Cell Derived Spinal Motor Neurons." Thesis, Cedars-Sinai Medical Center, 2017. http://pqdtopen.proquest.com/#viewpdf?dispub=10231221.
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Human ALS patient samples can be converted into motor neurons for the study of ALS pathogenesis in vitro. A major challenge, however is the lack of maturation of the stem cell-derived tissue, representing a major barrier to therapy development. The body of work herein details a series of studies to interrogate the relative maturation of induced pluripotent stem cell derived MNs and determine the effects of brain microvascular endothelial cells on their maturation. Finally, a novel microphysiological system for the modeling of ALS and the blood brain barrier is developed that includes the co-culture of brain microvascular endothelial cells under continuous flow of media with a focus on motor neuron function and vascular infiltration.
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Vanderlaan, Gary. "Differential roles for hedgehog signaling in motor neuron development." Diss., Columbia, Mo. : University of Missouri-Columbia, 2006. http://hdl.handle.net/10355/4461.
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Thesis (Ph.D.)--University of Missouri-Columbia, 2006.The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on April 29, 2009) Vita. Includes bibliographical references.
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Gill, Nishi. "The morphology of C3, a motoneuron mediating the tentacle withdrawal reflex in the snail Helix aspersa /." Thesis, McGill University, 1996. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=27326.
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The morphology of C3, a motoneuron mediating the tentacle withdrawal reflex, was investigated in the snail Helix aspersa by intracellular injections of the tracers Neurobiotin and biocytin. Axonal projections were identified in the optic nerve, the olfactory nerve, the internal peritentacular nerve, the external peritentacular nerve, the cerebral-pedal connective and the cerebral commissure. A rare characteristic of the cell was the multibranching of axons in the neuropil and the exiting of this bundle of fibres into the cerebral-pedal connective. Dendritic arborizations were observed branching from the cell body, the axon hillock and the dorsal main axon. In addition, tufts of dendrites were seen to branch from the ventral axon. Based on its morphology, C3 is probably a central component in the avoidance behaviour, receiving sensory input at extensive dendritic sites and sending axons to a number of key effector sites to co-ordinate the chain of reactions that constitutes the snail's avoidance behaviour.
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Chaube, Sanjay. "Ubiquitin Expression in the Lumbar Spinal Cord Motoneurons of Postnatal Mice-- an Immunohistochemical Study." Thesis, University of North Texas, 1994. https://digital.library.unt.edu/ark:/67531/metadc332620/.
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Maturation of spinal motoneurons in rodents is characterized by a period of cell loss in the embryo, but researchers have claimed that some cell death occurs postnatally. This form of cell death is called apoptosis and involves active participation of the cell. Apoptotic cells have certain recognizable morphological and molecular features. I have used a monoclonal antibody against ubiquitin, (a putative marker of apoptotic cells), to do immunochemistry on mouse spinal cords at various postnatal ages till early adulthood. Staining is seen in large amotoneurons in the ventral horn. Staining is intense till P28, and faint thereafter. Substantial proportions of motoneurons stain till P21, followed by a sharp decline in the number of immunopositive cells. None of the cells exhibit signs of apoptosis.
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Boatin, William. "Characterization of neuron models." Thesis, Available online, Georgia Institute of Technology, 2005, 2005. http://etd.gatech.edu/theses/available/etd-04182005-181732/.
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Thesis (M. S.)--Electrical and Computer Engineering, Georgia Institute of Technology, 2006.Dr. Robert H. Lee, Committee Member ; Dr. Kurt Wiesenfeld, Committee Member ; Dr Robert J. Butera, Committee Member.
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Fellows, Matthew R. "Spatiotemporal tuning for position and velocity in primate primary motor cortex neurons /." View online version; access limited to Brown University users, 2005. http://wwwlib.umi.com/dissertations/fullcit/3174598.
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Garcia, Paul Anthony. "Modeling the Intersegmental Coordination of Heart Motor Neurons in the Medicinal Leech." Diss., Georgia Institute of Technology, 2004. http://hdl.handle.net/1853/5064.
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We constructed a model of the coordination of segmental heart motor neurons driving blood circulation in leeches. The heart motor neuron models were conductance-based; conductances of voltage-gated and synaptic currents were adjusted to match the firing pattern of heart motor neurons from the living system. Each motor neuron receives a specific pattern of inhibitory input from rhythmic premotor heart interneurons and translates this spatiotemporal pattern into the fictive heartbeat motor pattern. The temporal pattern of synaptic input to the model was derived from extracellularly recorded spikes of the premotor heart interneurons. We focused on determining the components necessary to produce side-to-side asymmetry in the motor pattern: motor neurons on one side fire nearly in synchrony (synchronous coordination), while on the other they fire in a rear-to-front progression (peristaltic coordination). The model reproduces the general trends in phasing and was used to investigate the effective contribution of several synaptic and cellular properties of the motor neurons. The spatial and temporal pattern of premotor synaptic input, the electrical coupling between the segmental motor neurons, intra-burst, short-term synaptic plasticity of the synaptic inputs, and the axonal conduction delays all were integrated with the intrinsic membrane properties to influence intersegmental phasing.
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Roy, Jefferson Edward. "Signal processing by vestibular nuclei neurons : dissociating sensory, motor, and cognitive influences." Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=84430.
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The vestibular sensory apparatus and associated vestibular nuclei are generally thought to encode angular head velocity during our daily activities. However, in addition to direct inputs from vestibular afferents, the vestibular nuclei receive substantial projections from cortical, cerebellar, and other brainstem structures. Given this diversity of inputs we asked: how are the responses of vestibular nuclei neurons to head velocity modified by these additional inputs during naturally occurring behaviours? Here we have focused on three specific classes of neurons in the vestibular nuclei: (1) vestibular-only (VO) neurons which are thought to mediate, at least in part, the vestibulocollic reflex (VCR); (2) position-vestibular-pause (PVP) neurons which mediate the vestibuloocular reflex (VOR), and; (3) eye-head (EH) neurons, which are thought to mediate pursuit eye movements.We first characterized neuronal responses to passive rotation in the head-restrained condition, and then released the head to record the discharges of the same neurons during self-generated head movements. VCR interneurons (VO neurons) faithfully transmitted head velocity signals during passive head motion, but their responses were greatly attenuated during all behaviours during which the monkey's behavioral goal was to move its head relative to the body. Moreover, the attenuation occurs only when neck proprioceptive inputs match those predicted by the neck motor command. We propose that the sensory-motor matching is meditated by interconnections with the cerebellum. Our findings indicate that the VCR is suppressed during active head movements, but remains responsive to unexpected head perturbations. In contrast, VOR interneurons (PVP neurons) faithfully transmitted head velocity signals when the animal stabilized its gaze, regardless of whether the head motion was actively or passively generated; their responses were attenuated only when the monkey's behavioral goal was to redirect its axis of gaze relative to space. We propose that efference copies of oculomotor/gaze commands are responsible for the behaviourally dependent modulation of PVP neurons (and by extension the VOR) during gaze redirection. Finally, the activity of EH neurons was recorded during head-restrained smooth pursuit and eye-head gaze pursuit. EH neurons were not influenced by error terms and their activity was best described by an eye movement-based model. In addition, during gaze pursuit EH neurons were found to encode gaze and head movement-related signals. Furthermore, neuron responses could be predicted by their head movement sensitivity during passive whole-body rotation in the dark and gaze movement sensitivity during smooth pursuit, regardless of the stimulation condition. We propose that EH neuron responses reflect the summation of head movement information fro
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Friel, Ruairi Donal. "The generation of a herpes simplex virus vector to target motor neurons." Thesis, University of Glasgow, 2001. http://theses.gla.ac.uk/3960/.
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Herpes simplex virus (HSV) is a neurovirulent virus that in the course of natural infection of man predominantly infects sensory neurons. The aim of this project was to develop a safe, nonvirulent HSV, capable of expressing exogenous genes which altered the binding characteristics of the virus so that tropism was directed predominantly to motor nerves. It was envisaged that these viruses could then act as prototypes for gene therapy vectors targeted to the treatment of motor nerve diseases. To achieve this, two mutant viruses were created, RFa and RFb. These contained deletions of the main HSV glycoprotein involved in cellular binding (glycoprotein C). Gene fusions were created of truncated portions of gC (amino acids 377-511(RFa) and amino acids 477-511 (RFb)) to E. coli heat-labile enterotoxin B-subunit (LTB). The gene fusions were inserted in the RL1 gene thereby abolishing expression of the virulence factor ICP34.5. LTB is a ligand which binds to several gangliosides, including GM1 and GM2 which are motor neuron markers. It was hoped that by deletion of the main viral protein involved in adsorption to cells and replacing it with an LTB-containing fusion protein, the tropism of the mutant viruses could be altered to promote an increase in motor neuron infection. RFb was constructed. RFa constructed but could not be purified to homogeneity. This was thought to be due to poor adsorption/penetration or cell-to-cell spread, brought about by expression of the LTB fusion protein. RFb was analysed to determine the effect of expression of the novel LTB fusion protein within the context of the HSV genome. Western blot analysis using antibodies directed against LTB failed to detect expression of the LTB-gC fusion protein. In vitro replication studies showed that the RFb was non-virulent as demonstrated by its inability to replicate in growth arrested 3T6 cells, a phenotype characteristic of HSV which fails to produce ICP34.5. However no marked difference in virus replication kinetics was seen between RFb and wild type HSV (17+) on two motor neuron-like cell lines (NSC-19 and NSC-34).
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Rakowicz, Wojciech Piotr. "The regulation of death in retinal ganglion cells and spinal motor neurons." Thesis, University of Cambridge, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.621305.
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Banerjee, Soumya. "PERSISTENCE OF DROSOPHILA LARVAL MOTOR NEURONS INTO THE ADULT-IMPLICATIONS FOR BEHAVIOR." Miami University / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=miami1379680527.
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