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However, it remains enigmatic what changes in intrinsic network organization at the multi-neuronal level, serving as the neural substrate of brain function, underlie disease symptomology. Using a mouse model with passive-transfer of patient\u2019s monoclonal anti-GluN1-autoantibodies, we performed two-photon in vivo recordings of spontaneous dynamics under light anesthesia in CA1 microcircuits, a key hippocampal area for memory processing. We find pronounced functional coupling and clustering between putative neurons (PNs), alongside an altered network architecture with pathological emergence of irregular neuronal ensembles. These alterations not only induce excessive hub-like properties but also contribute to the increased network\u2019s intrinsic synchrony, despite its reduced baseline activity; this hypersynchrony was further supported by pathologically faster intra-ripple oscillations and amplified population bursts during these coincident events in vivo. Next, using electrophysiological data ex vivo, we show that this profound functional rewiring is associated with a selective preservation of effectively strong excitatory synapses, despite overall reduced excitation and augmented long-term depression. Furthermore, we find abnormal PN firing characteristics, higher transmission fidelity, and increased similarity of spontaneous spatiotemporal activity patterns, all reflecting dysregulated intrinsic organization of CA1 dynamics. Collectively, the aberrant reorganization of hippocampal microcircuits and altered intrinsic network activity patterns provide new mechanistic insights into the consequences of NMDAR hypofunction and pathomechanisms of anti-NMDAR encephalitis.<\/jats:p>","DOI":"10.1038\/s41380-026-03568-6","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T11:36:35Z","timestamp":1774956995000},"page":"4550-4562","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Anti-NMDAR encephalitis impairs intrinsic hippocampal dynamics through neuronal hypercoupling, hub dominance, and aberrant ensembles"],"prefix":"10.1038","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8969-527X","authenticated-orcid":false,"given":"Vahid","family":"Rahmati","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8160-1016","authenticated-orcid":false,"given":"J\u00fcrgen","family":"Graf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihai","family":"Ceanga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0516-5210","authenticated-orcid":false,"given":"Dario","family":"Cuevas Rivera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2050-4655","authenticated-orcid":false,"given":"Holger","family":"Haselmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5633-8981","authenticated-orcid":false,"given":"Sabine","family":"Liebscher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8283-7976","authenticated-orcid":false,"given":"Harald","family":"Pr\u00fcss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9182-6056","authenticated-orcid":false,"given":"Knut","family":"Holthoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9206-214X","authenticated-orcid":false,"given":"Knut","family":"Kirmse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9859-581X","authenticated-orcid":false,"given":"Christian","family":"Geis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"3568_CR1","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1038\/nrn3504","volume":"14","author":"P Paoletti","year":"2013","unstructured":"Paoletti P, Bellone C, Zhou Q. 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Animal experiments were performed in accordance with the ARRIVE guidelines for reporting animal research and the experimental protocol was in accordance with European regulations (Directive 2010\/63\/EU); b) The study was approved by the local animal welfare committee (Th\u00fcringer Landesamt f\u00fcr Lebensmittelsicherheit und Verbraucherschutz, 02\u2013059\/13 and UKJ-23-002). c) Human monoclonal NMDAR-Ab (#003\u2013102) and Control-Ab (#mGO53) were produced in vitro as previously described [\n                      \n                      ]. The use of human monoclonal antibodies has been approved by the Ethics committee of Jena University Hospital (#2019-1415).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}]}}