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Nonlinear Optical Techniques For Imaging And Manipulating The Mouse Central Nervous System

dc.contributor.authorFarrar, Matthewen_US
dc.contributor.chairCohen, Itaien_US
dc.contributor.committeeMemberWang, Michelle Den_US
dc.contributor.committeeMemberElser, Veiten_US
dc.contributor.committeeMemberSchaffer, Chrisen_US
dc.contributor.committeeMemberFetcho, Joseph R.en_US
dc.date.accessioned2013-01-31T19:44:18Z
dc.date.available2017-12-20T07:00:33Z
dc.date.issued2012-08-20en_US
dc.description.abstractThe spinal cord of vertebrates serves as the conduit for somatosensory information and motor control, as well as being the locus of neural circuits that govern fast reflexes and patterned behaviors, such as walking in mammals or swimming in fish. Consequently, pathologies of the spinal cord -such as spinal cord injury (SCI)- lead to loss of motor control and sensory perception, with accompanying decline in life expectancy and quality of life. Despite the devastating effects of these diseases, few therapies exist to substantially ameliorate patient outcome. In part, studies of spinal cord pathology have been limited by the inability to perform in vivo imaging at the level of cellular processes. The focus of this thesis is to present the underlying theory for and demonstration of novel multi-photon microscopy (MPM) and optical manipulation techniques as they apply to studies the mouse central nervous system (CNS), with an emphasis on the spinal cord. The scientific findings which have resulted from the implementation of these techniques are also presented. In particular, we have demonstrated that third harmonic generation is a dyefree method of imaging CNS myelin, a fundamental constituent of the spinal cord that is difficult to label using exogenous dyes and/or transgenic constructs. Since gaining optical access to the spinal cord is a prerequisite for spinal cord imaging, we review our development of a novel spinal cord imaging chamber and surgical procedure which allowed us to image for multiple weeks following implantation without the need for repeated surgeries. We also have used MPM to characterize spinal venous blood flow before and after point occlusions. We review a novel nonlinear microscopy technique that may serve to show optical interfaces in three dimensions inside scattering tissue. Finally, we discuss a model and show results of optoporation, a means of transfecting cells with genetic constructs. Brief reviews of MPM and SCI are also presented.en_US
dc.identifier.otherbibid: 7959846
dc.identifier.urihttps://hdl.handle.net/1813/31104
dc.language.isoen_USen_US
dc.subjectspinal cord injuryen_US
dc.subjectmulti-photon microscopyen_US
dc.subjectnonlinear opticsen_US
dc.titleNonlinear Optical Techniques For Imaging And Manipulating The Mouse Central Nervous Systemen_US
dc.typedissertation or thesisen_US
thesis.degree.disciplinePhysics
thesis.degree.grantorCornell Universityen_US
thesis.degree.levelDoctor of Philosophy
thesis.degree.namePh. D., Physics

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