TY - JOUR TI - Characterization of developmental and molecular factors underlying release heterogeneity at Drosophila synapses AU - Akbergenova, Yulia AU - Cunningham, Karen L AU - Zhang, Yao V AU - Weiss, Shirley AU - Littleton, J Troy A2 - Marder, Eve A2 - Bellen, Hugo J A2 - Zhai, Rong Grace A2 - Dickman, Dion K VL - 7 PY - 2018 DA - 2018/07/10 SP - e38268 C1 - eLife 2018;7:e38268 DO - 10.7554/eLife.38268 UR - https://doi.org/10.7554/eLife.38268 AB - 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. KW - active zone KW - synapse KW - calcium channels KW - synaptic plasticity KW - synapse development KW - glutamate receptors JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -