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

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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 (P_r) for a defined connection with ~300 AZs. P_r was heterogeneous but represented a stable feature of each AZ. P_rremained stable during high frequency stimulation and retained heterogeneity in mutants lacking the Ca²⁺ sensor Synaptotagmin 1. P_r correlated with both presynaptic Ca²⁺ channel abundance and Ca²⁺ influx at individual release sites. P_r heterogeneity also correlated with glutamate receptor abundance, with high P_r connections developing receptor subtype segregation. Intravital imaging throughout development revealed that AZs acquire high P_r during a multi-day maturation period, with P_r 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.

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All data generated or analysed during this study are included in the manuscript and supporting files.

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Yulia Akbergenova

The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, United States

For correspondence
yulakb@mit.edu

Competing interests
The authors declare that no competing interests exist.
Karen L Cunningham

The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, United States

Competing interests
The authors declare that no competing interests exist.
Yao V Zhang

The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, United States

Competing interests
The authors declare that no competing interests exist.
Shirley Weiss

The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, United States

Competing interests
The authors declare that no competing interests exist.
J Troy Littleton

The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, United States

For correspondence
troy@mit.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-5576-2887

Funding

National Institutes of Health (MH104536)

J Troy Littleton

National Institutes of Health (T32GM007287)

Karen L Cunningham

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.