{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:00:58Z","timestamp":1790834458183,"version":"4.1.0"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Comput. Neurosci."],"abstract":"<jats:p>Memory storage and recall are essential tasks for the healthy function of the hippocampus, adversely affected by neurodegenerative diseases, such as Alzheimer\u2019s Disease (AD). Pathological levels of amyloid-\u03b2 peptide (A\u03b2), found already in early-stage AD, can disrupt the NMDAR-dependent plasticity at hippocampal networks. Here we investigate these effects in a biophysically detailed computational model of a hippocampal CA1\u2013CA3 network and examine potential mechanisms of functional recovery. We show that, at a network level, long-term potentiation (LTP) impairments caused by A\u03b2 accumulation can be substantially restored by partially blocking the GluN2B\u2013NMDA receptors\u2014a mechanism previously observed and modeled only at a single cell level. Experimental access to network-level processes of memory storage and recall in pathological conditions remains highly challenging. Therefore, computational modeling may help to bridge the gap between cellular impairments and system-level cognitive dysfunction. Our work transfers the established GluN2B-dependent rescue mechanisms from single cells to a network-level system of hippocampal pyramidal neurons and interneurons. The results demonstrate that also at a higher cognition level, the partial inhibition of the activity of GluN2B\u2013NMDA receptors can be an effective strategy to counteract early AD impairments on memory storage and recall.<\/jats:p>","DOI":"10.3389\/fncom.2026.1953352","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:40:26Z","timestamp":1790833226000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Network-level restoration of impaired memory function in early Alzheimer\u2019s disease via GluN2B modulation: insights from a hippocampal CA1\u2013CA3 model"],"prefix":"10.3389","volume":"20","author":[{"given":"Fabio","family":"Librizzi","sequence":"first","affiliation":[{"name":"Istituto di Biofisica, Consiglio Nazionale delle Ricerche","place":["Palermo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saana","family":"Sepp\u00e4l\u00e4","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Technology, Tampere University","place":["Tampere, Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marja-Leena","family":"Linne","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Technology, Tampere University","place":["Tampere, Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Migliore","sequence":"additional","affiliation":[{"name":"Istituto di Biofisica, Consiglio Nazionale delle Ricerche","place":["Palermo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ausra","family":"Saudargiene","sequence":"additional","affiliation":[{"name":"Neuroscience Institute, Lithuanian University of Health Sciences","place":["Kaunas, Lithuania"]},{"name":"Department of Informatics, Vytautas Magnus University","place":["Kaunas, Lithuania"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1567","DOI":"10.1038\/nn.2433","article-title":"Amyloid-\u03b2 as a positive endogenous regulator of release probability at hippocampal synapses","volume":"12","author":"Abramov","year":"2009","journal-title":"Nat. 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