Fast retrieval and autonomous regulation of single spontaneously recycling synaptic vesicles
Presynaptic terminals release neurotransmitters spontaneously in a manner that can be regulated by Ca2+. However, the mechanisms underlying this regulation are poorly understood because the inherent stochasticity and low probability of spontaneous fusion events has curtailed their visualization at i...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2014-11-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/03658 |
| _version_ | 1811253324617351168 |
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| author | Jeremy Leitz Ege T Kavalali |
| author_facet | Jeremy Leitz Ege T Kavalali |
| author_sort | Jeremy Leitz |
| collection | DOAJ |
| description | Presynaptic terminals release neurotransmitters spontaneously in a manner that can be regulated by Ca2+. However, the mechanisms underlying this regulation are poorly understood because the inherent stochasticity and low probability of spontaneous fusion events has curtailed their visualization at individual release sites. Here, using pH-sensitive optical probes targeted to synaptic vesicles, we visualized single spontaneous fusion events and found that they are retrieved extremely rapidly with faster re-acidification kinetics than their action potential-evoked counterparts. These fusion events were coupled to postsynaptic NMDA receptor-driven Ca2+ signals, and at elevated Ca2+ concentrations there was an increase in the number of vesicles that would undergo fusion. Furthermore, spontaneous vesicle fusion propensity in a synapse was Ca2+-dependent but regulated autonomously: independent of evoked fusion probability at the same synapse. Taken together, these results expand classical quantal analysis to incorporate endocytic and exocytic phases of single fusion events and uncover autonomous regulation of spontaneous fusion. |
| first_indexed | 2024-04-12T16:49:09Z |
| format | Article |
| id | doaj.art-b4e276fdbf90461a9e2ef9e76d4c347a |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:49:09Z |
| publishDate | 2014-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-b4e276fdbf90461a9e2ef9e76d4c347a2022-12-22T03:24:28ZengeLife Sciences Publications LtdeLife2050-084X2014-11-01310.7554/eLife.03658Fast retrieval and autonomous regulation of single spontaneously recycling synaptic vesiclesJeremy Leitz0Ege T Kavalali1Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, United StatesDepartment of Neuroscience, University of Texas Southwestern Medical Center, Dallas, United States; Department of Physiology, University of Texas Southwestern Medical Center, Dallas, United StatesPresynaptic terminals release neurotransmitters spontaneously in a manner that can be regulated by Ca2+. However, the mechanisms underlying this regulation are poorly understood because the inherent stochasticity and low probability of spontaneous fusion events has curtailed their visualization at individual release sites. Here, using pH-sensitive optical probes targeted to synaptic vesicles, we visualized single spontaneous fusion events and found that they are retrieved extremely rapidly with faster re-acidification kinetics than their action potential-evoked counterparts. These fusion events were coupled to postsynaptic NMDA receptor-driven Ca2+ signals, and at elevated Ca2+ concentrations there was an increase in the number of vesicles that would undergo fusion. Furthermore, spontaneous vesicle fusion propensity in a synapse was Ca2+-dependent but regulated autonomously: independent of evoked fusion probability at the same synapse. Taken together, these results expand classical quantal analysis to incorporate endocytic and exocytic phases of single fusion events and uncover autonomous regulation of spontaneous fusion.https://elifesciences.org/articles/03658synaptic vesicle recyclingsynaptic terminalspontaneous neurotransmitter release |
| spellingShingle | Jeremy Leitz Ege T Kavalali Fast retrieval and autonomous regulation of single spontaneously recycling synaptic vesicles eLife synaptic vesicle recycling synaptic terminal spontaneous neurotransmitter release |
| title | Fast retrieval and autonomous regulation of single spontaneously recycling synaptic vesicles |
| title_full | Fast retrieval and autonomous regulation of single spontaneously recycling synaptic vesicles |
| title_fullStr | Fast retrieval and autonomous regulation of single spontaneously recycling synaptic vesicles |
| title_full_unstemmed | Fast retrieval and autonomous regulation of single spontaneously recycling synaptic vesicles |
| title_short | Fast retrieval and autonomous regulation of single spontaneously recycling synaptic vesicles |
| title_sort | fast retrieval and autonomous regulation of single spontaneously recycling synaptic vesicles |
| topic | synaptic vesicle recycling synaptic terminal spontaneous neurotransmitter release |
| url | https://elifesciences.org/articles/03658 |
| work_keys_str_mv | AT jeremyleitz fastretrievalandautonomousregulationofsinglespontaneouslyrecyclingsynapticvesicles AT egetkavalali fastretrievalandautonomousregulationofsinglespontaneouslyrecyclingsynapticvesicles |