A Developmental Algorithm for Synapse-Specific Wiring of the Drosophila Visual Map

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dc.contributor.advisorTerman, Jonathan R.en
dc.contributor.committeeMemberHiesinger, Peter Robinen
dc.contributor.committeeMemberKrämer, Helmuten
dc.contributor.committeeMemberHuber, Kimberly M.en
dc.creatorAgi, Egemenen
dc.date.accessioned2019-12-03T21:18:35Z
dc.date.available2019-12-03T21:18:35Z
dc.date.created2017-08
dc.date.issued2017-08-11
dc.date.submittedAugust 2017
dc.date.updated2019-12-03T21:18:37Z
dc.descriptionThe file named "AGI-DISSERTATION-2017.pdf" is the primary dissertation file. In addition, 19 supplemental files are available and may be viewed individually.en
dc.description.abstractDuring brain development, genetic information and environmental input drive neural circuit assembly that requires matching of correct pre- and post-synaptic partners. In cases when environmental input has no instructive role in synaptic partner selection, genetic information alone must suffice to specify synapses in neural circuits. However, how a limited amount of genetic information is translated into developmental algorithms for synapse specification is unclear. A major thrust of the field has been the quest to identify guidance cues and molecular matchmaking codes underlying brain wiring. In this work, I present a complementary approach, in which the characterization of the developmental algorithm based on simple rules is the primary focus, and the molecules executing these rules secondary. I propose that simple rules underlying developmental algorithms can be sufficient to establish seemingly complex wiring diagrams without an elaborate matchmaking code between synaptic partners. I used Drosophila visual map, which is a genetically encoded neural circuit, as a model system to test my hypothesis. During visual map formation, around 4800 photoreceptors simultaneously project to their correct target layer 'lamina' in the brain to find their correct synaptic partners. I developed a 2-photon microscopy-based, intravital imaging technique with which I could observe the development of individual photoreceptor growth cones at the spatiotemporal resolution of filopodial dynamics over 24 hours during visual map formation. Based on these imaging data, I spearheaded a group effort to formulate and computationally test simple rules that are sufficient for photoreceptors to sort to their correct partners without a requirement for precise matchmaking codes. A key prediction of the model was that the post-synaptic partners may not act as target cues for the pre-synaptic photoreceptors. In the second part of my thesis, I tested this hypothesis by ablating and blocking membrane dynamics of post-synaptic partners. My findings indicate that indeed post-synaptic partners of photoreceptors do not act as target cues for photoreceptors, but are necessary during a preceding step in the developmental algorithm to ensure correct wiring. In brief, results I presented in this work support the idea that correct synaptic partner selection can be achieved through a developmental algorithm based on simple rules that sorts correct cells together prior to synapse formation.en
dc.format.mimetypeapplication/pdfen
dc.identifier.oclc1134689150
dc.identifier.urihttps://hdl.handle.net/2152.5/7603
dc.language.isoenen
dc.subjectAxonsen
dc.subjectBiological Evolutionen
dc.subjectCompound Eye, Arthropoden
dc.subjectComputer Simulationen
dc.subjectDrosophilaen
dc.subjectNeuronsen
dc.subjectPhotoreceptor Cells, Invertebrateen
dc.subjectSynapsesen
dc.subjectVisual Pathwaysen
dc.titleA Developmental Algorithm for Synapse-Specific Wiring of the Drosophila Visual Mapen
dc.typeThesisen
dc.type.materialtexten
thesis.degree.departmentGraduate School of Biomedical Sciencesen
thesis.degree.disciplineNeuroscienceen
thesis.degree.grantorUT Southwestern Medical Centeren
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen

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