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Our findings revealed that mice overexpressing Dyrk1A (TgDyrk1A; TG) exhibited impaired hippocampal recognition memory, disrupted excitation-inhibition balance, and deficits in long-term potentiation (LTP). Specifically, we observed layer-specific deficits in dendritic arborization of TG CA1 pyramidal neurons in the stratum radiatum. Through computational modeling, we determined that these alterations resulted in reduced storage capacity and compromised integration of inputs, with decreased high \u03b3 oscillations. Contrary to prevailing assumptions, our model suggests that deficits in neuronal architecture, rather than over-inhibition, primarily contribute to the reduced network. We explored the potential of environmental enrichment (EE) as a therapeutic intervention and found that it normalized the excitation-inhibition balance, restored LTP, and improved short-term recognition memory. Interestingly, we observed transient significant dendritic remodeling, leading to recovered high \u03b3. However, these effects were not sustained after EE discontinuation. Based on our findings, we conclude that Dyrk1A overexpression-induced layer-specific neuromorphological disturbances impair the encoding of place and temporal context. These findings contribute to our understanding of the underlying mechanisms of Dyrk1A-related hippocampal deficits and highlight the challenges associated with long-term therapeutic interventions for cognitive impairments.<\/jats:p>","DOI":"10.1093\/cercor\/bhad431","type":"journal-article","created":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T09:36:37Z","timestamp":1699349797000},"source":"Crossref","is-referenced-by-count":3,"title":["Deficits in neuronal architecture but not over-inhibition are main determinants of reduced neuronal network activity in a mouse model of overexpression of Dyrk1A"],"prefix":"10.1093","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2036-2204","authenticated-orcid":false,"given":"Linus","family":"Manubens-Gil","sequence":"first","affiliation":[{"name":"Institute for Brain Science and Intelligent Technology, Southeast University (SEU) , Biomedical engineering, Sipailou street No. 2, Xuanwu district, 210096, Nanjing , China"},{"name":"School of Biological Science and Medical Engineering, Southeast University (SEU) , Sipailou street No. 2, Xuanwu district, 210096, Nanjing , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meritxell","family":"Pons-Espinal","sequence":"additional","affiliation":[{"name":"Department of Pathology and Experimental Therapeutics, Bellvitge University Hospital-IDIBELL , Avinguda de la Granvia de l'Hospitalet, 199, 08908 L'Hospitalet de Llobregat, Barcelona , Spain"},{"name":"Institute of Biomedicine (IBUB) of the University of Barcelona (UB) , Avda. Diagonal, 643 Edifici Prevosti, planta -108028, Barcelona , Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Gener","sequence":"additional","affiliation":[{"name":"Advanced Electronic Materials and Devices Group (AEMD) , Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and BIST, UAB Campus, Bellaterra Barcelona 08193 , Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inmaculada","family":"Ballesteros-Ya\u00f1ez","sequence":"additional","affiliation":[{"name":"Inorganic and Organic Chemistry and Biochemistry , Faculty of Medicine, University of Castilla- La Mancha, Camino de Moledores, 13071, Ciudad Real , Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Mart\u00ednez","family":"de Lagr\u00e1n","sequence":"additional","affiliation":[{"name":"Cellular and Systems Neurobiology , Systems and Synthetic Biology Program, Center for Genomic Regulation, Dr. Aiguader 88, 08003 Barcelona , Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mara","family":"Dierssen","sequence":"additional","affiliation":[{"name":"Cellular and Systems Neurobiology , Systems and Synthetic Biology Program, Center for Genomic Regulation, Dr. Aiguader 88, 08003 Barcelona , Spain"},{"name":"Center for Biomedical Research in the Network of Rare Diseases (CIBERER) , v. Monforte de Lemos, 3-5. Pabell\u00f3n 11. Planta 0 28029, Madrid , Spain"},{"name":"Universitat Pompeu Fabra (UPF) , Dr. Aiguader 88, 08003 Barcelona , Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,11,23]]},"reference":[{"key":"2024011715010152400_ref1","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.nbd.2005.12.006","article-title":"DYRK1A BAC transgenic mice show altered synaptic plasticity with learning and memory defects","volume":"22","author":"Ahn","year":"2006","journal-title":"Neurobiol Dis"},{"key":"2024011715010152400_ref2","doi-asserted-by":"crossref","first-page":"11788","DOI":"10.1073\/pnas.1921314117","article-title":"Prefrontal-hippocampal functional connectivity encodes recognition memory and is impaired in intellectual disability","volume":"117","author":"Alemany-Gonz\u00e1lez","year":"2020","journal-title":"Proc Natl Acad Sci U S 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