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The mechanistic underpinnings of these shared major neuropsychiatric symptoms remain however unclear. Here, we investigate the impacts of patient-derived monoclonal autoantibodies against the glutamatergic NMDAR (NMDAR mAb) and inhibitory GABAaR (GABAaR mAb) signalling in the hippocampal network. Unexpectedly, both excitatory and inhibitory synaptic receptor membrane dynamics, content and transmissions are altered by NMDAR or GABAaR mAb, irrespective of the affinity or antagonistic effect of the autoantibodies. The effect of NMDAR mAb on inhibitory synapses and GABAaR mAb on excitatory synapses requires neuronal activity and involves protein kinase signalling. At the cell level, both autoantibodies increase the excitation\/inhibition balance of principal cell inputs. Furthermore, NMDAR or GABAaR mAb leads to hyperactivation of hippocampal networks through distinct alterations of principal cell and interneuron properties. Thus, autoantibodies targeting excitatory NMDAR or inhibitory GABAaR trigger convergent network dysfunctions through a combination of shared and distinct mechanisms.<\/jats:p>","DOI":"10.1038\/s44319-024-00056-2","type":"journal-article","created":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T12:02:50Z","timestamp":1705924970000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Converging synaptic and network dysfunctions in distinct autoimmune encephalitis"],"prefix":"10.1038","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0933-9989","authenticated-orcid":false,"given":"Daniel","family":"Hunter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3220-9488","authenticated-orcid":false,"given":"Mar","family":"Petit-Pedrol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5114-6227","authenticated-orcid":false,"given":"Dominique","family":"Fernandes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"B\u00e9nac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8221-2079","authenticated-orcid":false,"given":"Catarina","family":"Rodrigues","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob","family":"Kreye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihai","family":"Ceanga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8283-7976","authenticated-orcid":false,"given":"Harald","family":"Pr\u00fcss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Geis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1814-8145","authenticated-orcid":false,"given":"Laurent","family":"Groc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,22]]},"reference":[{"key":"56_CR1","doi-asserted-by":"publisher","first-page":"3253","DOI":"10.1523\/JNEUROSCI.1689-21.2022","volume":"42","author":"E Andrzejak","year":"2022","unstructured":"Andrzejak E, Rabinovitch E, Kreye J, Pruss H, Rosenmund C, Ziv NE, Garner CC, Ackermann F (2022) Patient-derived anti-NMDAR antibody disinhibits cortical neuronal networks through dysfunction of inhibitory neuron output. 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