{"doi":"10.1101/lm.054077.124","title":"Maintenance of memory by negative feedback of synaptic protein elimination: modeling KIBRA–PKMζ dynamics in LTP","abstract":"Long-term activity-dependent modifications of synaptic strength are a cellular substrate of learning and memory, but how long-lasting memory could be based on synaptic proteins that rapidly degrade and diffuse is unknown. Most current theories depend on molecular positive-feedback loops. Recent experiments, however, reveal that interactions between kidney brain protein (KIBRA) and PKMζ downregulate the proteins' degradation and maintains late-phase long-term synaptic plasticity (LTP) and long-term memory, motivating an alternative model based on negative feedback at the level of protein elimination. Here we compare positive- and negative-feedback models generally and explore biophysical models based specifically on KIBRA-PKMζ interaction. The biophysical theory predicts LTP/memory maintenance by complexes of cooperative KIBRA-PKMζ heteromers.","journal":"Learning & Memory","year":2025,"id":555043,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9459,"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":572742,"name":"Changchi Hsieh","orcid":"0000-0003-0488-1565","position":1,"is_corresponding":false},{"id":572747,"name":"Rafael E. Flores‐Obando","orcid":"0000-0002-0736-9527","position":2,"is_corresponding":false},{"id":1452855,"name":"David A. Cano","orcid":"0000-0001-6264-3288","position":3,"is_corresponding":false},{"id":250398,"name":"Tara E. Tracy","orcid":"0000-0003-3356-4091","position":4,"is_corresponding":false},{"id":572753,"name":"Todd Charlton Sacktor","orcid":"0000-0002-8625-8701","position":5,"is_corresponding":false},{"id":584344,"name":"Harel Z. Shouval","orcid":"0000-0003-2799-1337","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-19T02:54:54.542303Z","pmid":"41101994","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":[]}