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dc.contributor.advisorHong-Sheng Li
dc.contributor.authorGuo, Peiyi
dc.date2022-08-11T08:08:43.000
dc.date.accessioned2022-08-23T16:05:11Z
dc.date.available2022-08-23T16:05:11Z
dc.date.issued2010-09-09
dc.date.submitted2011-02-15
dc.identifier.doi10.13028/nkr0-9r48
dc.identifier.urihttp://hdl.handle.net/20.500.14038/31833
dc.description.abstractHigh temporal resolution of vision relies on the rapid kinetics of the photoresponse in the light-sensing photoreceptor neurons. It is well known that the rapid recovery of photoreceptor membrane potential at the end of light stimulation depends on timely deactivation of the visual transduction cascade within photoreceptors. Whether any extrinsic factor contributes to the termination speed of the photoresponse is unknown. In this thesis, using Drosophilaas a model system, I show that a feedback circuit mediated by both neurons and glia in the visual neuropile lamina is required for rapid repolarization of the photoreceptor at the end of the light response. In the first part of my thesis work, I provide evidence that lamina epithelial glia, the major glia in the visual neuropile, is involved in a retrograde regulation that is critical for rapid repolarization of the photoreceptor at the end of light stimulation. I identified the gene affected in a slrp (slow receptor potential) mutant that is defective in photoreceptor response termination, and found it needs to be expressed in both neurons and epithelial glia to rescue the mutant phenotype. The gene product SLRP, an ADAM (a disintegrin and metalloprotease) protein, is localized in a special structure of epithelial glia, gnarl, and is required for gnarl formation. This glial function of SLRP is independent of the metalloprotease activity. In the second part of my thesis work, I demonstrate that glutamatergic transmission from lamina intrinsic interneurons, the amacrine cells, to the epithelial glia is required for the rapid repolarization of photoreceptors at the end of the light response. From an RNAi-based screen, I identified a vesicular glutamate transporter (vGluT) in amacrine cells as an indispensable factor for the rapid repolarization of the photoreceptor, suggesting a critical role of glutamatergic transmission from amacrine cells in this retrograde regulation. Further, I found that loss of a glutamate-gated chloride channel GluCl phenocopies vGluT downregulation. Cell specific knockdown indicates that GluCl functions in both neurons and glia. In the lamina, a FLAG-tagged GluCl colocalized with the SLRP protein in the gnarl-like structures, and this localization pattern of GluCl depends on SLRP, suggesting that lamina epithelial glia receive glutamatergic input from amacrine cells through GluCl at the site of gnarl. Since the amacrine cell itself is innervated by photoreceptors, these observations suggest that a photoreceptor — amacrine cell — epithelial glia — photoreceptor feedback loop facilitates rapid repolarization of photoreceptors at the end of the light response. In summary, my thesis research has revealed a feedback regulation mechanism that helps to achieve rapid kinetics of photoreceptor response. This visual regulation contributes to the temporal resolution of the visual system, and may be important for vision during movement and for motion detection. In addition, this work may also advance our understanding of glial function, and change our concept about the effect of glutamatergic transmission.
dc.language.isoen_US
dc.rightsCopyright is held by the author, with all rights reserved.
dc.subjectDrosophila
dc.subjectvisual response
dc.subjectglia
dc.subjectNeuroglia
dc.subjectPhotoreceptor Cells
dc.subjectInvertebrate
dc.subjectFeedback
dc.subjectPhysiological
dc.subjectKinetics
dc.subjectVision
dc.subjectOcular
dc.subjectCells
dc.subjectMusculoskeletal, Neural, and Ocular Physiology
dc.subjectNervous System
dc.subjectNeuroscience and Neurobiology
dc.subjectPsychological Phenomena and Processes
dc.subjectSense Organs
dc.titleA Glia-Mediated Feedback Mechanism for the Termination of Drosophila Visual Response: A Dissertation
dc.typeDoctoral Dissertation
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1502&context=gsbs_diss&unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_diss/499
dc.legacy.embargo2011-10-14T00:00:00-07:00
dc.identifier.contextkey1786282
refterms.dateFOA2022-08-29T15:32:23Z
html.description.abstract<p>High temporal resolution of vision relies on the rapid kinetics of the photoresponse in the light-sensing photoreceptor neurons. It is well known that the rapid recovery of photoreceptor membrane potential at the end of light stimulation depends on timely deactivation of the visual transduction cascade within photoreceptors. Whether any extrinsic factor contributes to the termination speed of the photoresponse is unknown.</p> <p>In this thesis, using <em>Drosophila</em>as a model system, I show that a feedback circuit mediated by both neurons and glia in the visual neuropile lamina is required for rapid repolarization of the photoreceptor at the end of the light response.</p> <p>In the first part of my thesis work, I provide evidence that lamina epithelial glia, the major glia in the visual neuropile, is involved in a retrograde regulation that is critical for rapid repolarization of the photoreceptor at the end of light stimulation. I identified the gene affected in a <em>slrp (slow receptor potential</em>) mutant that is defective in photoreceptor response termination, and found it needs to be expressed in both neurons and epithelial glia to rescue the mutant phenotype. The gene product SLRP, an ADAM (<em>a disintegrin and metalloprotease</em>) protein, is localized in a special structure of epithelial glia, gnarl, and is required for gnarl formation. This glial function of SLRP is independent of the metalloprotease activity.</p> <p>In the second part of my thesis work, I demonstrate that glutamatergic transmission from lamina intrinsic interneurons, the amacrine cells, to the epithelial glia is required for the rapid repolarization of photoreceptors at the end of the light response. From an RNAi-based screen, I identified a vesicular glutamate transporter (vGluT) in amacrine cells as an indispensable factor for the rapid repolarization of the photoreceptor, suggesting a critical role of glutamatergic transmission from amacrine cells in this retrograde regulation. Further, I found that loss of a glutamate-gated chloride channel GluCl phenocopies vGluT downregulation. Cell specific knockdown indicates that GluCl functions in both neurons and glia. In the lamina, a FLAG-tagged GluCl colocalized with the SLRP protein in the gnarl-like structures, and this localization pattern of GluCl depends on SLRP, suggesting that lamina epithelial glia receive glutamatergic input from amacrine cells through GluCl at the site of gnarl. Since the amacrine cell itself is innervated by photoreceptors, these observations suggest that a photoreceptor — amacrine cell — epithelial glia — photoreceptor feedback loop facilitates rapid repolarization of photoreceptors at the end of the light response.</p> <p>In summary, my thesis research has revealed a feedback regulation mechanism that helps to achieve rapid kinetics of photoreceptor response. This visual regulation contributes to the temporal resolution of the visual system, and may be important for vision during movement and for motion detection. In addition, this work may also advance our understanding of glial function, and change our concept about the effect of glutamatergic transmission.</p>
dc.identifier.submissionpathgsbs_diss/499
dc.contributor.departmentLi Lab
dc.contributor.departmentNeurobiology
dc.description.thesisprogramNeuroscience


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