{"doi":"10.1101/2023.05.12.540562","title":"Cryo-electron tomography reveals postsynaptic nanoblocks in excitatory synapses","abstract":"Abstract The nanoscale organization of proteins within synapses is critical for maintaining and regulating synaptic transmission and plasticity. Here, we use cryogenic electron tomography to directly visualize the three-dimensional architecture and supramolecular organization of pre-cleft-postsynaptic components in their near-native cellular context in both synaptosomes from rat hippocampi and synapses from rat primary cultured neurons. High-resolution electron microscopy and quantitative analyses revealed that postsynaptic density (PSD) is composed of membrane-associated nanoblocks of various sizes, which are in close relationship with potential presynaptic release sites through adhesion molecules spanning the synaptic cleft, as well as with post-synaptic receptors. Subtomogram averaging from synaptosomes showed two distinct types of postsynaptic membrane proteins at resolutions of 24 Å and 26 Å respectively. Furthermore, our data reveal that majority of potential release sites and ∼50% subtomogram averaged receptor-like particles are located within the boundary of PSD nanoblocks, while PSD nanoblocks might be redundant for neurotransmission. The results of this study provide a more comprehensive understanding of synaptic ultrastructure and suggest that PSD is composed of clustering of various nanoblocks, which likely underlies the dynamic nature of PSD to modulate synaptic strength.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":394538,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9396,"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":574613,"name":"James P. Allen","orcid":"0000-0002-2124-6881","position":1,"is_corresponding":false},{"id":1169474,"name":"Liana Wilson","orcid":null,"position":2,"is_corresponding":false},{"id":1169101,"name":"Mariam Haider","orcid":"0009-0008-3827-6121","position":3,"is_corresponding":false},{"id":299245,"name":"Barış Alten","orcid":"0000-0003-1842-7099","position":4,"is_corresponding":false},{"id":1169475,"name":"Zimeng Zhou","orcid":null,"position":5,"is_corresponding":false},{"id":917692,"name":"Xinyi Wang","orcid":"0000-0002-7516-6043","position":6,"is_corresponding":false},{"id":299246,"name":"Qiangjun Zhou","orcid":"0000-0003-1789-9588","position":7,"is_corresponding":false},{"id":270835,"name":"Rong Sun","orcid":"0000-0002-0950-1480","position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-19T01:19:14.590635Z","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":[]}