Characterization of developmental and molecular factors underlying release heterogeneity at Drosophila synapses
Neurons communicate through neurotransmitter release at specialized synaptic regions known as active zones (AZs). Using biosensors to visualize single synaptic vesicle fusion events at Drosophila neuromuscular junctions, we analyzed the developmental and molecular determinants of release probability...
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| Format: | Article |
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eLife Sciences Publications, Ltd.
2018
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| Online Access: | http://hdl.handle.net/1721.1/117634 https://orcid.org/0000-0001-7463-977X https://orcid.org/0000-0002-1006-349X https://orcid.org/0000-0001-5576-2887 |
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| author | Cunningham, Karen L Akbergenova, Yulia Zhang, Yao Weiss Sharabi, Shirley Littleton, J. Troy |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Cunningham, Karen L Akbergenova, Yulia Zhang, Yao Weiss Sharabi, Shirley Littleton, J. Troy |
| author_sort | Cunningham, Karen L |
| collection | MIT |
| description | Neurons communicate through neurotransmitter release at specialized synaptic regions known as active zones (AZs). Using biosensors to visualize single synaptic vesicle fusion events at Drosophila neuromuscular junctions, we analyzed the developmental and molecular determinants of release probability (Pr) for a defined connection with ~300 AZs. Pr was heterogeneous but represented a stable feature of each AZ. Pr remained stable during high frequency stimulation and retained heterogeneity in mutants lacking the Ca2+ sensor Synaptotagmin 1. Pr correlated with both presynaptic Ca2+ channel abundance and Ca2+ influx at individual release sites. Pr heterogeneity also correlated with glutamate receptor abundance, with high Pr connections developing receptor subtype segregation. Intravital imaging throughout development revealed that AZs acquire high Pr during a multi-day maturation period, with Pr heterogeneity largely reflecting AZ age. The rate of synapse maturation was activity-dependent, as both increases and decreases in neuronal activity modulated glutamate receptor field size and segregation. |
| first_indexed | 2024-09-23T14:45:06Z |
| format | Article |
| id | mit-1721.1/117634 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T14:45:06Z |
| publishDate | 2018 |
| publisher | eLife Sciences Publications, Ltd. |
| record_format | dspace |
| spelling | mit-1721.1/1176342022-09-29T10:22:11Z Characterization of developmental and molecular factors underlying release heterogeneity at Drosophila synapses Cunningham, Karen L Akbergenova, Yulia Zhang, Yao Weiss Sharabi, Shirley Littleton, J. Troy Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Picower Institute for Learning and Memory Akbergenova, Yulia Zhang, Yao Weiss Sharabi, Shirley Littleton, J. Troy Neurons communicate through neurotransmitter release at specialized synaptic regions known as active zones (AZs). Using biosensors to visualize single synaptic vesicle fusion events at Drosophila neuromuscular junctions, we analyzed the developmental and molecular determinants of release probability (Pr) for a defined connection with ~300 AZs. Pr was heterogeneous but represented a stable feature of each AZ. Pr remained stable during high frequency stimulation and retained heterogeneity in mutants lacking the Ca2+ sensor Synaptotagmin 1. Pr correlated with both presynaptic Ca2+ channel abundance and Ca2+ influx at individual release sites. Pr heterogeneity also correlated with glutamate receptor abundance, with high Pr connections developing receptor subtype segregation. Intravital imaging throughout development revealed that AZs acquire high Pr during a multi-day maturation period, with Pr heterogeneity largely reflecting AZ age. The rate of synapse maturation was activity-dependent, as both increases and decreases in neuronal activity modulated glutamate receptor field size and segregation. National Institutes of Health (U.S.) (grant MH104536) National Institutes of Health (U.S.) (grant T32GM007287) 2018-09-05T13:00:03Z 2018-09-05T13:00:03Z 2018-07 2018-05 2018-08-30T13:04:36Z Article http://purl.org/eprint/type/JournalArticle 2050-084X http://hdl.handle.net/1721.1/117634 Akbergenova, Yulia, Karen L Cunningham, Yao V Zhang, Shirley Weiss, and J Troy Littleton. “Characterization of Developmental and Molecular Factors Underlying Release Heterogeneity at Drosophila Synapses.” eLife 7 (July 10, 2018). https://orcid.org/0000-0001-7463-977X https://orcid.org/0000-0002-1006-349X https://orcid.org/0000-0001-5576-2887 http://dx.doi.org/10.7554/eLife.38268 eLife Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf eLife Sciences Publications, Ltd. eLife |
| spellingShingle | Cunningham, Karen L Akbergenova, Yulia Zhang, Yao Weiss Sharabi, Shirley Littleton, J. Troy Characterization of developmental and molecular factors underlying release heterogeneity at Drosophila synapses |
| title | Characterization of developmental and molecular factors underlying release heterogeneity at Drosophila synapses |
| title_full | Characterization of developmental and molecular factors underlying release heterogeneity at Drosophila synapses |
| title_fullStr | Characterization of developmental and molecular factors underlying release heterogeneity at Drosophila synapses |
| title_full_unstemmed | Characterization of developmental and molecular factors underlying release heterogeneity at Drosophila synapses |
| title_short | Characterization of developmental and molecular factors underlying release heterogeneity at Drosophila synapses |
| title_sort | characterization of developmental and molecular factors underlying release heterogeneity at drosophila synapses |
| url | http://hdl.handle.net/1721.1/117634 https://orcid.org/0000-0001-7463-977X https://orcid.org/0000-0002-1006-349X https://orcid.org/0000-0001-5576-2887 |
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