{"doi":"10.7554/elife.51032","title":"Rapid regulation of vesicle priming explains synaptic facilitation despite heterogeneous vesicle:Ca2+ channel distances","abstract":"Chemical synaptic transmission relies on the Ca2+-induced fusion of transmitter-laden vesicles whose coupling distance to Ca2+ channels determines synaptic release probability and short-term plasticity, the facilitation or depression of repetitive responses. Here, using electron- and super-resolution microscopy at the Drosophila neuromuscular junction we quantitatively map vesicle:Ca2+ channel coupling distances. These are very heterogeneous, resulting in a broad spectrum of vesicular release probabilities within synapses. Stochastic simulations of transmitter release from vesicles placed according to this distribution revealed strong constraints on short-term plasticity; particularly facilitation was difficult to achieve. We show that postulated facilitation mechanisms operating via activity-dependent changes of vesicular release probability (e.g. by a facilitation fusion sensor) generate too little facilitation and too much variance. In contrast, Ca2+-dependent mechanisms rapidly increasing the number of releasable vesicles reliably reproduce short-term plasticity and variance of synaptic responses. We propose activity-dependent inhibition of vesicle un-priming or release site activation as novel facilitation mechanisms.","journal":"eLife","year":2020,"id":60151,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":63,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9508,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":317265,"name":"Andreas T. Grasskamp","orcid":"0000-0002-5895-6529","position":1,"is_corresponding":false},{"id":317266,"name":"Meida Jusyte","orcid":"0000-0001-9948-871X","position":2,"is_corresponding":false},{"id":317267,"name":"Mathias A. Böhme","orcid":"0000-0002-0947-9172","position":3,"is_corresponding":false},{"id":317268,"name":"Susanne Ditlevsen","orcid":"0000-0002-1998-2783","position":4,"is_corresponding":false},{"id":317269,"name":"Jakob B. Sørensen","orcid":"0000-0001-5465-3769","position":5,"is_corresponding":false},{"id":317270,"name":"Alexander M. Walter","orcid":"0000-0001-5646-4750","position":6,"is_corresponding":false},{"id":317264,"name":"Janus RL Kobbersmed","orcid":"0000-0003-0313-6205","position":0,"is_corresponding":true}],"reference_count":119,"raw_metadata":null,"created_at":"2026-07-18T21:08:47.852401Z","pmid":"32077852","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}