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dc.contributor.advisorEdward S. Boyden.en_US
dc.contributor.authorLinghu, Changyangen_US
dc.contributor.otherMassachusetts Institute of Technology. Department of Electrical Engineering and Computer Science.en_US
dc.date.accessioned2020-11-23T17:40:12Z
dc.date.available2020-11-23T17:40:12Z
dc.date.copyright2020en_US
dc.date.issued2020en_US
dc.identifier.urihttps://hdl.handle.net/1721.1/128587
dc.descriptionThesis: Ph. D., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, February, 2020en_US
dc.descriptionCataloged from PDF of thesis.en_US
dc.descriptionIncludes bibliographical references (pages 161-178).en_US
dc.description.abstractBiological signals, such as the dynamic concentrations of ions, levels of signaling molecules, and activities of protein kinases, interact in complex ways within cells, and can exhibit great cell-to-cell heterogeneity as a function of cell history and state. There is increasing desire to use multiple fluorescent reporters to simultaneously measure multiple biological signals in single cells across cell populations, such as those in the brain. However, due to the diffraction limit of optical imaging, the biological signals recorded from neurons in densely-labeled neural populations in vivo are often mixed with signals from closely passing axons and dendrites from other neurons, resulting in erroneous signaling events and artifactual correlations of measured neural activity. Also, it is not yet possible to simultaneously record any given set of biological signals in single cells, because there are limited sets of corresponding spectrally-orthogonal fluorescent reporters available to date. Even if the fluorescent reporters for all biological signals in all possible colors are developed in the future, the number of biological signals that can be simultaneously recorded are still limited by the number of available optical channels. In this thesis, I address these problems by developing two new technologies, soma-targeted fluorescent calcium indicators and spatially multiplexed imaging.en_US
dc.description.abstractSoma-targeted fluorescent calcium indicators (or 'SomaGCaMPs', the first part of the thesis) are fluorescent reporters of calcium dynamics that are selectively localized at the soma, but not axons and dendrites, of neurons. In vivo optical imaging of SomaGCaMPs in dense neural circuits in mouse and zebrafish brains reported fewer artifactual spikes, increased signal-to-noise ratio, and decreased artifactual correlation across neurons. Thus, soma-targeting of fluorescent reporters is a simple and powerful method for high-fidelity population imaging of neural activity in vivo.en_US
dc.description.abstractSpatially multiplexed imaging (the second part of the thesis) enables simultaneous readout of multiple biological signals in single cells from fluorescent reporters regardless of their spectra. This is achieved by clustering reporters into spatially separated 'Signaling Reporter Islands' (or 'SiRIs') via self-assembling protein scaffolds or RNA scaffolds. Using the spatial dimension as an asset, SiRIs may open up the ability to simultaneously image nearly arbitrary numbers of signals within a physiological cascade.en_US
dc.description.statementofresponsibilityby Changyang Linghu.en_US
dc.format.extent178 pagesen_US
dc.language.isoengen_US
dc.publisherMassachusetts Institute of Technologyen_US
dc.rightsMIT theses may be protected by copyright. Please reuse MIT thesis content according to the MIT Libraries Permissions Policy, which is available through the URL provided.en_US
dc.rights.urihttp://dspace.mit.edu/handle/1721.1/7582en_US
dc.subjectElectrical Engineering and Computer Science.en_US
dc.titleSpatially organized fluorescent reporters for recording complex biological dynamics in cell populationen_US
dc.typeThesisen_US
dc.description.degreePh. D.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Electrical Engineering and Computer Scienceen_US
dc.identifier.oclc1220830858en_US
dc.description.collectionPh.D. Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Scienceen_US
dspace.imported2020-11-23T17:40:10Zen_US
mit.thesis.degreeDoctoralen_US
mit.thesis.departmentEECSen_US


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