{"doi":"10.1016/j.celrep.2024.114540","title":"Ca2+-dependent phosphodiesterase 1 regulates the plasticity of striatal spiny projection neuron glutamatergic synapses","abstract":"Long-term synaptic plasticity at glutamatergic synapses on striatal spiny projection neurons (SPNs) is central to learning goal-directed behaviors and habits. Our studies reveal that SPNs manifest a heterosynaptic, nitric oxide (NO)-dependent form of long-term postsynaptic depression of glutamatergic SPN synapses (NO-LTD) that is preferentially engaged at quiescent synapses. Plasticity is gated by Ca 2+ entry through Ca V 1.3 Ca 2+ channels and phosphodiesterase 1 (PDE1) activation, which blunts intracellular cyclic guanosine monophosphate (cGMP) and NO signaling. Both experimental and simulation studies suggest that this Ca 2+ -dependent regulation of PDE1 activity allows for local regulation of dendritic cGMP signaling. In a mouse model of Parkinson disease (PD), NO-LTD is absent because of impaired interneuronal NO release; re-balancing intrastriatal neuromodulatory signaling restores NO release and NO-LTD. Taken together, these studies provide important insights into the mechanisms governing NO-LTD in SPNs and its role in psychomotor disorders such as PD.","journal":"Cell Reports","year":2024,"id":437047,"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":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9511,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1245852,"name":"Shintaro Otsuka","orcid":"0000-0002-1890-9971","position":1,"is_corresponding":false},{"id":694234,"name":"Jian Xu","orcid":"0000-0002-5143-8550","position":2,"is_corresponding":false},{"id":1010662,"name":"Vernon R. J. Clarke","orcid":"0000-0002-6154-6555","position":3,"is_corresponding":false},{"id":852676,"name":"Tatiana Tkatch","orcid":"0000-0001-6626-7435","position":4,"is_corresponding":false},{"id":657221,"name":"David L. Wokosin","orcid":"0000-0002-5497-6944","position":5,"is_corresponding":false},{"id":345614,"name":"Zhong Xie","orcid":"0000-0002-8348-4455","position":6,"is_corresponding":false},{"id":931985,"name":"Asami Tanimura","orcid":"0000-0003-4209-9793","position":7,"is_corresponding":false},{"id":771628,"name":"Hitesh K. Agarwal","orcid":"0000-0001-7853-1555","position":8,"is_corresponding":false},{"id":752465,"name":"Graham C. R. Ellis‐Davies","orcid":"0000-0003-4179-5455","position":9,"is_corresponding":false},{"id":271835,"name":"Anis Contractor","orcid":"0000-0002-5131-2536","position":10,"is_corresponding":false},{"id":345619,"name":"D. James Surmeier","orcid":"0000-0002-6376-5225","position":11,"is_corresponding":false},{"id":469601,"name":"Shenyu Zhai","orcid":"0000-0002-7097-9387","position":0,"is_corresponding":true}],"reference_count":106,"raw_metadata":null,"created_at":"2026-07-19T02:00:29.872940Z","pmid":"39058595","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":[]}