{"doi":"10.1101/2020.06.22.165209","title":"Cholinergic relay from punishment- to reward-encoding dopamine neurons signals punishment withdrawal as reward in <i>Drosophila</i>","abstract":"SUMMARY Animals form and update learned associations between otherwise neutral cues and aversive outcomes to predict and avoid danger in changing environments. When a cue later occurs without punishment, this unexpected withdrawal of aversive outcome is encoded as reward, via activation of reward-encoding dopaminergic neurons. Using real-time in vivo functional imaging, optogenetics, behavioral analysis, and electron-microscopy, we identify the neural mechanism through which Drosophila reward-encoding dopaminergic neurons are activated when an olfactory cue is unexpectedly no longer paired with electric shock punishment. Reduced activation of punishment-encoding dopaminergic neurons relieves depression of synaptic inputs to cholinergic neurons, which in turn synaptically increase odor responses of reward-encoding dopaminergic neurons to decrease odor avoidance. These studies reveal for the first time how an indirect excitatory cholinergic synaptic relay from punishment- to reward-encoding dopaminergic neurons encodes the absence of a negative as a positive, revealing a general circuit motif for unlearning aversive memories that could be present in mammals.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":126934,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9553,"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":559546,"name":"Preeti Sareen","orcid":"0000-0002-3657-6832","position":1,"is_corresponding":false},{"id":375812,"name":"Pasha A. Davoudian","orcid":"0000-0002-5096-7610","position":2,"is_corresponding":false},{"id":559548,"name":"Michael N. Nitabach","orcid":"0000-0001-8698-2313","position":3,"is_corresponding":false},{"id":559547,"name":"Li Yan McCurdy","orcid":"0000-0002-8862-6715","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-18T23:15:27.226519Z","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":[]}