{"doi":"10.7554/elife.88412.3","title":"Ca2+ channel and active zone protein abundance intersects with input-specific synapse organization to shape functional synaptic diversity","abstract":"<jats:p>\n                    Synaptic heterogeneity is a hallmark of nervous systems that enables complex and adaptable communication in neural circuits. To understand circuit function, it is thus critical to determine the factors that contribute to the functional diversity of synapses. We investigated the contributions of voltage-gated calcium channel (VGCC) abundance, spatial organization, and subunit composition to synapse diversity among and between synapses formed by two closely related\n                    <jats:italic>Drosophila</jats:italic>\n                    glutamatergic motor neurons with distinct neurotransmitter release probabilities (P\n                    <jats:sub>r</jats:sub>\n                    ). Surprisingly, VGCC levels are highly predictive of heterogeneous P\n                    <jats:sub>r</jats:sub>\n                    among individual synapses of either low- or high-P\n                    <jats:sub>r</jats:sub>\n                    inputs, but not between inputs. We find that the same number of VGCCs are more densely organized at high-P\n                    <jats:sub>r</jats:sub>\n                    synapses, consistent with tighter VGCC-synaptic vesicle coupling. We generated endogenously tagged lines to investigate VGCC subunits in vivo and found that the α2δ–3 subunit Straightjacket along with the CAST/ELKS active zone (AZ) protein Bruchpilot, both key regulators of VGCCs, are less abundant at high-P\n                    <jats:sub>r</jats:sub>\n                    inputs, yet positively correlate with P\n                    <jats:sub>r</jats:sub>\n                    among synapses formed by either input. Consistently, both Straightjacket and Bruchpilot levels are dynamically increased across AZs of both inputs when neurotransmitter release is potentiated to maintain stable communication following glutamate receptor inhibition. Together, these findings suggest a model in which VGCC and AZ protein abundance intersects with input-specific spatial and molecular organization to shape the functional diversity of synapses.\n                  </jats:p>","journal":"eLife","year":2024,"id":616072,"datarank":0.38474240361923057,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"self_citation_contribution":0.38474240361923057,"citation_network_contribution":0.0,"self_endowment_contribution":0.38474240361923057,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":999099,"name":"Scott J. Gratz","orcid":"0000-0002-0106-8336","position":1,"is_corresponding":false},{"id":1588187,"name":"Ambar Delgado","orcid":null,"position":2,"is_corresponding":false},{"id":1093334,"name":"Jason T. Ritt","orcid":"0000-0003-3113-7977","position":3,"is_corresponding":false},{"id":999104,"name":"Kate M. O’Connor-Giles","orcid":"0000-0002-2259-8408","position":4,"is_corresponding":false},{"id":463488,"name":"Audrey T. Medeiros","orcid":"0000-0002-5562-4772","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Ca2+ channel and active zone protein abundance intersects with input-specific synapse organization to shape functional synaptic diversity","abstract":"<jats:p>\n                    Synaptic heterogeneity is a hallmark of nervous systems that enables complex and adaptable communication in neural circuits. To understand circuit function, it is thus critical to determine the factors that contribute to the functional diversity of synapses. We investigated the contributions of voltage-gated calcium channel (VGCC) abundance, spatial organization, and subunit composition to synapse diversity among and between synapses formed by two closely related\n                    <jats:italic>Drosophila</jats:italic>\n                    glutamatergic motor neurons with distinct neurotransmitter release probabilities (P\n                    <jats:sub>r</jats:sub>\n                    ). Surprisingly, VGCC levels are highly predictive of heterogeneous P\n                    <jats:sub>r</jats:sub>\n                    among individual synapses of either low- or high-P\n                    <jats:sub>r</jats:sub>\n                    inputs, but not between inputs. We find that the same number of VGCCs are more densely organized at high-P\n                    <jats:sub>r</jats:sub>\n                    synapses, consistent with tighter VGCC-synaptic vesicle coupling. We generated endogenously tagged lines to investigate VGCC subunits in vivo and found that the α2δ–3 subunit Straightjacket along with the CAST/ELKS active zone (AZ) protein Bruchpilot, both key regulators of VGCCs, are less abundant at high-P\n                    <jats:sub>r</jats:sub>\n                    inputs, yet positively correlate with P\n                    <jats:sub>r</jats:sub>\n                    among synapses formed by either input. Consistently, both Straightjacket and Bruchpilot levels are dynamically increased across AZs of both inputs when neurotransmitter release is potentiated to maintain stable communication following glutamate receptor inhibition. Together, these findings suggest a model in which VGCC and AZ protein abundance intersects with input-specific spatial and molecular organization to shape the functional diversity of synapses.\n                  </jats:p>","is_dataset_classified":null,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19767382","pmcid":null,"openalex_id":"https://openalex.org/W4402605181","authors":[],"funders":[{"funder_name":"National Institute of Neurological Disorders and Stroke","grant_id":"R01NS078179","title":null},{"funder_name":"National Institute of Neurological Disorders and Stroke","grant_id":"F31NS122424","title":null},{"funder_name":"Brown Neuroscience Graduate Program","grant_id":"T32 MH020068","title":null},{"funder_name":"National Institutes of Health","grant_id":"5T32MH020068-10","title":"Interdisciplinary Predoctoral Neuroscience Training Program"},{"funder_name":"National Institutes of Health","grant_id":"3P40OD018537-04S1","title":"Bloomington Drosophila Stock Center at Indiana University"},{"funder_name":"National Institutes of Health","grant_id":"5R01NS078179-08","title":"Molecular mechanism of synapse assembly and function"},{"funder_name":"National Institutes of Health","grant_id":"5F31NS122424-02","title":"Dynamic regulation of synaptic Ca2+ channel organization"}],"total_grants":7,"fwci":2.2695,"citation_percentile":0.88679135,"influential_citations":0,"citation_trend":[{"year":2024,"count":1},{"year":2025,"count":9},{"year":2026,"count":2}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.7554/elife.88412.3","host_type":"journal"},{"url":"https://doi.org/10.7554/elife.88412.3","host_type":"publisher"},{"url":"https://cdn.elifesciences.org/articles/88412/elife-88412-v1.pdf","host_type":"publisher"},{"url":"https://cdn.elifesciences.org/articles/88412/elife-88412-v1.xml","host_type":"publisher"},{"url":"https://elifesciences.org/articles/88412","host_type":"publisher"},{"url":"https://doi.org/10.1101/2023.04.02.535290","host_type":""},{"url":"https://doi.org/10.7554/elife.88412","host_type":""},{"url":"https://doi.org/10.7554/elife.88412.2","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/39291956","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/37034654","host_type":""},{"url":"http://dx.doi.org/10.1101/2023.04.02.535290","host_type":""},{"url":"http://dx.doi.org/10.7554/eLife.88412","host_type":""},{"url":"https://doaj.org/article/d58d6cd12aaa4570b7a5d9353593b7e3","host_type":""}],"fields_of_study":["Neuroscience and Neuropharmacology Research","Cellular transport and secretion","Neurobiology and Insect Physiology Research"],"mesh_terms":[],"keywords":["Active zone","Synapse","Synaptic vesicle","Neuroscience","Neurotransmitter","Glutamate receptor","Biology","Protein subunit","Glutamatergic","Voltage-dependent calcium channel","Neurotransmission","Calcium channel","Receptor","Chemistry","Calcium","Vesicle","Central nervous system","Biochemistry","VGCC","Motor Neurons","QH301-705.5","Science","Q","R","presynaptic homeostasis","Synaptic Transmission","Article","Drosophila melanogaster","synaptic diversity","Synapses","Medicine","Animals","Drosophila Proteins","Drosophila","Calcium Channels","Biology (General)"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-02T21:52:53.411646Z","pmid":null,"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":[]}