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Presynaptic Determinants of Synaptic Strength and Energy Efficiency at Drosophila Neuromuscular Junctions
| Title: | Presynaptic Determinants of Synaptic Strength and Energy Efficiency at Drosophila Neuromuscular Junctions. |
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| Name(s): |
Lu, Zhongmin, author Macleod, Gregory, Thesis advisor Florida Atlantic University, Degree grantor Charles E. Schmidt College of Science Department of Biological Sciences |
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| Type of Resource: | text | |
| Genre: | Electronic Thesis Or Dissertation | |
| Date Created: | 2015 | |
| Date Issued: | 2015 | |
| Publisher: | Florida Atlantic University | |
| Place of Publication: | Boca Raton, Fla. | |
| Physical Form: | application/pdf | |
| Extent: | 176 p. | |
| Language(s): | English | |
| Summary: | Changes in synaptic strength underlie synaptic plasticity, the cellular substrate for learning and memory. Disruptions in the mechanisms that regulate synaptic strength closely link to many developmental, neurodegenerative and neurological disorders. Release site probability (PAZ) and active zone number (N) are two important presynaptic determinants of synaptic strength; yet, little is known about the processes that establish the balance between N and PAZ at any synapse. Furthermore, it is not known how PAZ and N are rebalanced during synaptic homeostasis to accomplish circuit stability. To address this knowledge gap, we adapted a neurophysiological experimental system consisting of two functionally differentiated glutamatergic motor neurons (MNs) innervating the same target. Average PAZ varied between nerve terminals, motivating us to explore benefits for high and low PAZ, respectively. We speculated that high PAZ confers high-energy efficiency. To test the hypothesis, electrophysiological and ultrastructural measurements were made. The terminal with the highest PAZ released more neurotransmitter but it did so with the least total energetic cost. An analytical model was built to further explore functional and structural aspects in optimizing energy efficiency. The model supported that energy efficiency optimization requires high PAZ. However, terminals with low PAZ were better able to sustain neurotransmitter release. We suggest that tension between energy efficiency and stamina sets PAZ and thus determines synaptic strength. To test the hypothesis that nerve terminals regulate PAZ rather than N to maintain synaptic strength, we induced sustained synaptic homeostasis at the nerve terminals. Ca2+ imaging revealed that terminals of the MN innervating only one muscle fiber utilized greater Ca2+ influx to achieve compensatory neurotransmitter release. In contrast, morphological measurements revealed that terminals of the MN inner vating multiple postsynaptic targets utilized an increase in N to achieve compensatory neurotransmitter release, but this only occurred at the terminal of the affected postsynaptic target. In conclusion, this dissertation provides several novel insights into a prominent question in neuroscience: how is synaptic strength established and maintained. The work indicates that tension exists between energy efficiency and stamina in neurotransmitter release likely influences PAZ. Furthermore, PAZ and N are rebalanced differently between terminals during synaptic homeostasis. | |
| Identifier: | FA00004519 (IID) | |
| Degree granted: | Dissertation (Ph.D.)--Florida Atlantic University, 2015. | |
| Collection: | FAU Electronic Theses and Dissertations Collection | |
| Note(s): | Includes bibliography. | |
| Subject(s): |
Drosophila melanogaster--Nervous system. Drosophila melanogaster--Cytogenetics. Fruit-flies--Development. Fruit-flies--Nervous system. Genetic transcription. Transcription factors. Cellular signal transduction. Cellular control mechanisms. Myoneural junction. |
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| Held by: | Florida Atlantic University Libraries | |
| Sublocation: | Digital Library | |
| Links: | http://purl.flvc.org/fau/fd/FA00004519 | |
| Persistent Link to This Record: | http://purl.flvc.org/fau/fd/FA00004519 | |
| Use and Reproduction: | Copyright © is held by the author, with permission granted to Florida Atlantic University to digitize, archive and distribute this item for non-profit research and educational purposes. Any reuse of this item in excess of fair use or other copyright exemptions requires permission of the copyright holder. | |
| Use and Reproduction: | http://rightsstatements.org/vocab/InC/1.0/ | |
| Host Institution: | FAU | |
| Is Part of Series: | Florida Atlantic University Digital Library Collections. |
