{"doi":"10.7554/elife.79042","title":"Hierarchical architecture of dopaminergic circuits enables second-order conditioning in Drosophila","abstract":"Dopaminergic neurons with distinct projection patterns and physiological properties compose memory subsystems in a brain. However, it is poorly understood whether or how they interact during complex learning. Here, we identify a feedforward circuit formed between dopamine subsystems and show that it is essential for second-order conditioning, an ethologically important form of higher-order associative learning. The Drosophila mushroom body comprises a series of dopaminergic compartments, each of which exhibits distinct memory dynamics. We find that a slow and stable memory compartment can serve as an effective ‘teacher’ by instructing other faster and transient memory compartments via a single key interneuron, which we identify by connectome analysis and neurotransmitter prediction. This excitatory interneuron acquires enhanced response to reward-predicting odor after first-order conditioning and, upon activation, evokes dopamine release in the ‘student’ compartments. These hierarchical connections between dopamine subsystems explain distinct properties of first- and second-order memory long known by behavioral psychologists.","journal":"eLife","year":2023,"id":318863,"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":60,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9434,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":803944,"name":"Daniel Bushey","orcid":"0000-0001-9258-6579","position":1,"is_corresponding":false},{"id":228475,"name":"Feng Li","orcid":"0000-0002-6658-9175","position":2,"is_corresponding":false},{"id":991908,"name":"Karen L Hibbard","orcid":"0000-0002-2001-6099","position":3,"is_corresponding":false},{"id":991909,"name":"Megan Sammons","orcid":"0000-0003-4516-5928","position":4,"is_corresponding":false},{"id":552386,"name":"Jan Funke","orcid":"0000-0003-4388-7783","position":5,"is_corresponding":false},{"id":228496,"name":"Ashok Litwin-Kumar","orcid":"0000-0003-2422-6576","position":6,"is_corresponding":false},{"id":991910,"name":"Toshihide Hige","orcid":"0000-0002-0007-3192","position":7,"is_corresponding":false},{"id":228494,"name":"Yoshinori Aso","orcid":"0000-0002-2939-1688","position":8,"is_corresponding":false},{"id":1026933,"name":"Daichi Yamada","orcid":"0000-0003-4944-1950","position":0,"is_corresponding":true}],"reference_count":101,"raw_metadata":null,"created_at":"2026-07-19T01:07:06.454099Z","pmid":"36692262","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":[]}