{"doi":"10.1101/2022.03.25.485828","title":"Fast synaptic-like axo-axonal transmission from striatal cholinergic interneurons onto dopaminergic fibers","abstract":"Summary Transmission from striatal cholinergic interneurons (CINs) controls dopamine release through nicotinic acetylcholine receptors (nAChRs) on dopaminergic axons. Anatomical studies suggest that cholinergic terminals signal predominantly through non-synaptic volume transmission. However, the influence of cholinergic transmission on electrical signaling in axons remains unclear. We examined axo-axonal transmission from CINs onto dopaminergic axons using perforated-patch recordings which revealed rapid spontaneous EPSPs with properties characteristic of fast synapses. Pharmacology showed that axonal EPSPs (axEPSPs) were mediated primarily by high-affinity α6-containing receptors. Remarkably, axEPSPs triggered spontaneous action potentials locally in dopaminergic axons, suggesting these axons perform integration to convert synaptic input into spiking, a function associated with somatodendritic compartments. We investigated cross-species validity of cholinergic axo-axonal transmission by recording dopaminergic axons in macaque putamen and found similar axEPSPs. Thus, we reveal that fast synaptic-like neurotransmission underlies cholinergic signaling onto dopaminergic axons, providing insight into how nicotinic receptors shape electrical signaling directly in axon terminals.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":299925,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9568,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":848439,"name":"Samuel G. Brill-Weil","orcid":"0000-0002-9018-7109","position":1,"is_corresponding":false},{"id":849026,"name":"Alex C. Cummins","orcid":null,"position":2,"is_corresponding":false},{"id":297000,"name":"Renshu Zhang","orcid":null,"position":3,"is_corresponding":false},{"id":372199,"name":"Gisela Andrea Camacho‐Hernandez","orcid":"0000-0002-1533-093X","position":4,"is_corresponding":false},{"id":348848,"name":"Amy Hauck Newman","orcid":"0000-0001-9065-4072","position":5,"is_corresponding":false},{"id":266394,"name":"Mark A. G. Eldridge","orcid":"0000-0003-4292-6832","position":6,"is_corresponding":false},{"id":264004,"name":"Bruno B. Averbeck","orcid":"0000-0002-3976-8565","position":7,"is_corresponding":false},{"id":295899,"name":"Zayd M. Khaliq","orcid":"0000-0002-1445-1457","position":8,"is_corresponding":false},{"id":295896,"name":"P. Kramer","orcid":"0000-0002-0095-3712","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":null,"created_at":"2026-07-19T00:31:49.412501Z","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":[]}