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pH Dynamics within the Drosophila Synaptic Cleft During Activity

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Date Issued:
2023
Abstract/Description:
Acute pH sensitivity of many neural mechanisms highlights the vulnerability of neurotransmission to the pH of the extracellular milieu. The dogma is that the synaptic cleft will acidify upon neurotransmission because the synaptic vesicles corelease neurotransmitters and protons to the cleft, and the direct data from sensory ribbon-type synapses support the acidification of the cleft. However, ribbon synapses have a much higher release probability than conventional synapses, and it’s not established whether conventional synapses acidify as well. To test the acidification of the cleft in the conventional synapse, we used genetically encoded fluorescent pH reporters targeted to the synaptic cleft of Drosophila larvae. We observed alkalinization rather than acidification during activity, and this alkalinization was dependent on the exchange of protons for calcium at the postsynaptic membrane. A reaction-diffusion computational model of the pH dynamics at the Drosophila larval neuromuscular junction was developed to leverage the experimental data. The model incorporates the release of glutamate, ATP, and protons from synaptic vesicles into the cleft, PMCA activity, bicarbonate, and phosphate buffering systems. By means of numerical simulations, we reveal a highly dynamic pH landscape within the synaptic cleft, harboring deep but exceedingly rapid acid transients that give way to a prolonged period of alkalinization.
Title: pH Dynamics within the Drosophila Synaptic Cleft During Activity.
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Name(s): Feghhi, Touhid , author
Lau, Andy W.C. , Thesis advisor
Macleod, Gregory T. , Thesis advisor
Florida Atlantic University, Degree grantor
Department of Physics
Charles E. Schmidt College of Science
Type of Resource: text
Genre: Electronic Thesis Or Dissertation
Date Created: 2023
Date Issued: 2023
Publisher: Florida Atlantic University
Place of Publication: Boca Raton, Fla.
Physical Form: application/pdf
Extent: 194 p.
Language(s): English
Abstract/Description: Acute pH sensitivity of many neural mechanisms highlights the vulnerability of neurotransmission to the pH of the extracellular milieu. The dogma is that the synaptic cleft will acidify upon neurotransmission because the synaptic vesicles corelease neurotransmitters and protons to the cleft, and the direct data from sensory ribbon-type synapses support the acidification of the cleft. However, ribbon synapses have a much higher release probability than conventional synapses, and it’s not established whether conventional synapses acidify as well. To test the acidification of the cleft in the conventional synapse, we used genetically encoded fluorescent pH reporters targeted to the synaptic cleft of Drosophila larvae. We observed alkalinization rather than acidification during activity, and this alkalinization was dependent on the exchange of protons for calcium at the postsynaptic membrane. A reaction-diffusion computational model of the pH dynamics at the Drosophila larval neuromuscular junction was developed to leverage the experimental data. The model incorporates the release of glutamate, ATP, and protons from synaptic vesicles into the cleft, PMCA activity, bicarbonate, and phosphate buffering systems. By means of numerical simulations, we reveal a highly dynamic pH landscape within the synaptic cleft, harboring deep but exceedingly rapid acid transients that give way to a prolonged period of alkalinization.
Identifier: FA00014221 (IID)
Degree granted: Dissertation (PhD)--Florida Atlantic University, 2023.
Collection: FAU Electronic Theses and Dissertations Collection
Note(s): Includes bibliography.
Subject(s): Synapses
pH (Chemistry)
Hydrogen-ion concentration.
Synaptic Transmission
Drosophila
Persistent Link to This Record: http://purl.flvc.org/fau/fd/FA00014221
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.
Host Institution: FAU