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Characterization of developmental and molecular factors underlying release heterogeneity at Drosophila synapses

Author(s)
Cunningham, Karen L; Akbergenova, Yulia; Zhang, Yao; Weiss Sharabi, Shirley; Littleton, J. Troy
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Abstract
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.
Date issued
2018-07
URI
http://hdl.handle.net/1721.1/117634
Department
Massachusetts Institute of Technology. Department of Biology; Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences; Picower Institute for Learning and Memory
Journal
eLife
Publisher
eLife Sciences Publications, Ltd.
Citation
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).
Version: Final published version
ISSN
2050-084X

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