{"doi":"10.1016/j.celrep.2025.115874","title":"Mu-opioid receptor activation potentiates excitatory transmission at the habenulo-peduncular synapse","abstract":"Identifying how opioids modulate signaling in relevant neurocircuitry is essential for developing new therapeutic strategies for opioid addiction. The medial habenula (MHb) is a mu-opioid receptor (MOR) hotspot that projects predominantly to the interpeduncular nucleus (IPN); however, little is known about MOR function in this pathway. Using reporter mice, we observed MOR expression in a subset of MHb and IPN neurons, where its activation induces inhibitory effects on neuronal activity. However, stimulation of MOR + axons at the habenulo-peduncular (HP) synapse leads to excitatory currents that are significantly potentiated by MOR agonism. These facilitatory effects were also observed at cholinergic-defined HP synapses, depend on a monosynaptic mechanism, and are disrupted by genetic disruption of MOR in the presynaptic MHb. Thus, MORs induce a canonical inhibitory effect in somatodendritic compartments but non-canonical facilitatory effects on evoked glutamate transmission at the HP synapse, establishing a distinct mode by which MORs can modulate neuronal function.","journal":"Cell Reports","year":2025,"id":529804,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9636,"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":1409167,"name":"Agata Szlaga","orcid":"0000-0002-7380-7011","position":1,"is_corresponding":false},{"id":755205,"name":"Yen-Chu Chen","orcid":"0000-0001-8502-843X","position":2,"is_corresponding":false},{"id":329817,"name":"William S. Conrad","orcid":"0000-0001-7167-2822","position":3,"is_corresponding":false},{"id":262516,"name":"Thomas S. Hnasko","orcid":"0000-0001-6176-8513","position":4,"is_corresponding":false},{"id":1027866,"name":"Sarthak M. Singhal","orcid":"0000-0001-7865-7115","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-19T02:51:01.235017Z","pmid":"40540395","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":[]}