{"doi":"10.1101/2025.08.28.672917","title":"Pre-Sensory Spontaneous Activity Accelerates Coordinated Maturation of Synaptic Partners and Drives Transition to the Mature Physiological Phenotype","abstract":"Pre-sensory (ps), peripherally-generated spontaneous activity (SA) is important for establishing basic topography of central components of sensory pathways. However, roles for psSA in sculpting connections at the single neuron level and in driving functional maturation of postsynaptic targets are difficult to isolate and therefore little explored. We capitalized on the temporal onset of cochlea-generated psSA just prior to growth of the calyx of Held (CH), the largest nerve terminal in the mammalian brain, and its well-defined circuit topography to explore the causal roles for psSA in targeted synaptogenesis and postsynaptic functional maturation. To this end, we developed a viral vector to rapidly express tetanus neurotoxin (TeNT), which blocks neurotransmission, and selectively introduced it into CH-forming neurons at the onset of psSA. TeNT expression did not prevent but delayed and altered the developmental trajectory of neural circuit maturation, which in sum prevented the postsynaptic neuron from acquiring its mature phasic firing phenotype. Thus, psSA initiates and drives circuit maturation along central sensory pathways, but alternative mechanisms can partially compensate in its absence.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":573637,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9604,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1480813,"name":"Nikollas Moreira Benites","orcid":"0000-0002-5901-7232","position":1,"is_corresponding":false},{"id":954893,"name":"Emily M. Amick","orcid":"0009-0006-5801-2620","position":2,"is_corresponding":false},{"id":821654,"name":"André Dagostin","orcid":"0000-0002-8703-0805","position":3,"is_corresponding":false},{"id":471426,"name":"Samuel Young","orcid":"0000-0002-7589-7612","position":4,"is_corresponding":false},{"id":754407,"name":"Henrique von Gersdorff","orcid":"0000-0002-4404-3307","position":5,"is_corresponding":false},{"id":795173,"name":"George A. Spirou","orcid":"0000-0001-7677-3585","position":6,"is_corresponding":false},{"id":1119874,"name":"Daniel T. Heller","orcid":"0000-0001-8167-6499","position":0,"is_corresponding":true}],"reference_count":94,"raw_metadata":null,"created_at":"2026-07-19T02:57:36.753600Z","pmid":"40909639","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":[]}