266787 20240808170119.0 pmc:PMC10877582 pmc 10.1016/j.neuron.2023.10.001 doi pmid:37909036 pmid 0896-6273 ISSN 1097-4199 ISSN altmetric:155953294 altmetric DZNE-2024-00045 English 610 Viana-da-Silva, Silvia P:(DE-2719)9001172 0 First author dzne Localized APP expression results in progressive network dysfunction by disorganizing spike timing. New York, NY 2024 Elsevier article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1705491359_18422 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote Progressive cognitive decline in Alzheimer's disease could either be caused by a spreading molecular pathology or by an initially focal pathology that causes aberrant neuronal activity in a larger network. To distinguish between these possibilities, we generated a mouse model with expression of mutant human amyloid precursor protein (APP) in only hippocampal CA3 cells. We found that performance in a hippocampus-dependent memory task was impaired in young adult and aged mutant mice. In both age groups, we then recorded from the CA1 region, which receives inputs from APP-expressing CA3 cells. We observed that theta oscillation frequency in CA1 was reduced along with disrupted relative timing of principal cells. Highly localized pathology limited to the presynaptic CA3 cells is thus sufficient to cause aberrant firing patterns in postsynaptic neuronal networks, which indicates that disease progression is not only from spreading pathology but also mediated by progressively advancing physiological dysfunction. 351 - Brain Function (POF4-351) G:(DE-HGF)POF4-351 POF4-351 POF IV 0 Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de Mice MeSH Humans MeSH Animals MeSH Aged MeSH Amyloid beta-Protein Precursor: genetics MeSH Amyloid beta-Protein Precursor: metabolism MeSH Hippocampus: metabolism MeSH Neurons: physiology MeSH Alzheimer Disease: metabolism MeSH Synapses: physiology MeSH Mice, Transgenic MeSH Alzheimer’s disease Other Alzheimer’s disease Other Alzheimer’s disease Other Alzheimer’s disease Other Alzheimer’s disease Other Alzheimer’s disease Other amyloid precursor protein Other hippocampus Other phase precession Other spike timing Other theta oscillations Other Amyloid beta-Protein Precursor NLM Chemicals Haberl, Matthias P:(DE-2719)9001580 1 dzne Gaur, Kshitij 2 Patel, Rina P:(DE-2719)9001322 3 dzne Narayan, Gautam 4 Ledakis, Max 5 Fu, Maylin L 6 de Castro Vieira, Miguel 7 Koo, Edward H 8 Leutgeb, Jill K 9 Leutgeb, Stefan 10 10.1016/j.neuron.2023.10.001 Vol. 112, no. 1, p. 124 - 140.e6 PERI:(DE-600)2001944-0 1 124 - 140.e6 Neuron 112 2024 0896-6273 OpenAccess http://pub.dzne.de/record/266787/files/DZNE-2024-00045.pdf OpenAccess pdfa http://pub.dzne.de/record/266787/files/DZNE-2024-00045.pdf?subformat=pdfa oai:pub.dzne.de:266787 openaire open_access VDB driver dnbdelivery Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 0 P:(DE-2719)9001172 External Institute I:(DE-HGF)0 Extern 1 P:(DE-2719)9001580 External Institute I:(DE-HGF)0 Extern 3 P:(DE-2719)9001322 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-351 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Brain Function 0 2024 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2023-08-28 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2023-08-28 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2023-08-28 DBCoverage StatID:(DE-HGF)1190 StatID Biological Abstracts 2023-08-28 DBCoverage StatID:(DE-HGF)0600 StatID Ebsco Academic Search 2023-08-28 Creative Commons Attribution-NonCommercial-NoDerivs CC BY-NC-ND 4.0 LIC:(DE-HGF)CCBYNCND4 HGFVOC IF >= 15 StatID:(DE-HGF)9915 StatID NEURON : 2022 2023-08-28 JCR StatID:(DE-HGF)0100 StatID NEURON : 2022 2023-08-28 WoS StatID:(DE-HGF)0113 StatID Science Citation Index Expanded 2023-08-28 DBCoverage StatID:(DE-HGF)1030 StatID Current Contents - Life Sciences 2023-08-28 OpenAccess StatID:(DE-HGF)0510 StatID Peer Review StatID:(DE-HGF)0030 StatID ASC 2023-08-28 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2023-08-28 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2023-08-28 Nationallizenz StatID:(DE-HGF)0420 StatID 2023-08-28 ger DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2023-08-28 I:(DE-2719)5000068 AG Viana-da-Silva Cellular Circuits of Memory 0 journal VDB UNRESTRICTED I:(DE-2719)5000068 FullTexts