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dc.contributor.authorAubrey, Erin
dc.date.accessioned2017-05-11T18:36:12Z
dc.date.available2017-05-11T18:36:12Z
dc.identifier.urihttp://hdl.handle.net/10222/72908
dc.description.abstractNeural activity modulates motor axon guidance and synaptic function during development. Differences in neural activity also contribute to the demise of specific motor neuron subtypes in amyotrophic lateral sclerosis (ALS). Studying the cellular mechanisms underlying these activity-dependent processes is complicated due to the inability to precisely activate motor neurons separate from other cell types. Here, we resolve this issue by generating embryonic stem cell-derived motor neurons (ESCMNs) expressing channelrhodopsin-2 (ChR2). ChR2 ESCMNs depolarize and fire single action potentials when pulsed by light. Chronic light activation of ChR2 ESCMNs (0.025 Hz for 2 days) increases neurite outgrowth, mediated by enhanced expression of polysialylated NCAM (PSA-NCAM). ChR2 ESCMNs expressing SOD1G93A, a mutation causing ALS, form neuromuscular junctions in vitro, but unlike wild-type counterparts, fail to maintain functional connections over time. Together, this thesis introduces a novel model system to study cellular mechanisms underlying activity-dependent modulation of motor neuron development and disease.en_US
dc.language.isoenen_US
dc.subjectMotor neuron diseaseen_US
dc.subjectAmyotrophic Lateral Sclerosisen_US
dc.subjectChannelrhodopsin-2en_US
dc.subjectChannelrhodopsinen_US
dc.subjectOptogeneticsen_US
dc.subjectNeural Activityen_US
dc.subjectSynapseen_US
dc.subjectNeural Cell Adhesion Moleculeen_US
dc.subjectPolysialic Aciden_US
dc.subjectNeurite Outgrowthen_US
dc.subjectActivity dependenten_US
dc.subjectActivity-dependenten_US
dc.subjectLight Activationen_US
dc.subjectNeuromuscular junctionen_US
dc.subjectEmbryonic Stem Cellsen_US
dc.subjectEmbryonic Stem Cell derived motor neuronsen_US
dc.titleDevelopment of a novel in vitro model system to characterize the role of activity in motor neurons during development and diseaseen_US
dc.date.defence2016-04-21
dc.contributor.departmentDepartment of Medical Neuroscienceen_US
dc.contributor.degreeMaster of Scienceen_US
dc.contributor.external-examinerDr. James Fawcetten_US
dc.contributor.graduate-coordinatorDr. Kazue Sembaen_US
dc.contributor.thesis-readerDr. Ying Zhangen_US
dc.contributor.thesis-readerDr. William Baldridgeen_US
dc.contributor.thesis-supervisorDr. Victor Rafuseen_US
dc.contributor.ethics-approvalReceiveden_US
dc.contributor.manuscriptsNot Applicableen_US
dc.contributor.copyright-releaseNot Applicableen_US
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