{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T14:18:59Z","timestamp":1793974739007,"version":"4.8.0"},"reference-count":88,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T00:00:00Z","timestamp":1774656000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":54,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"UK Dementia Research Institute, award number UKDRI-Edin007"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\u2018Early hippocampal hyperactivity\u2019 is well-documented in Alzheimer\u2019s disease (AD), yet its mechanisms in vivo before amyloid-\u03b2 plaque deposition at the levels of synaptic transmission and neural oscillations remain unclear. Here, we perform in vivo high-resolution patch-clamp and high-throughput probe recordings in the hippocampus of amyloidopathy mice before plaque deposition. At the cellular level, we observe reduced inhibitory synaptic input, hypoactivity of fast-spiking interneurons, and enhanced bursting in pyramidal neurons. At the network level, we reveal accelerated hippocampal oscillations, characterized by increased theta and beta power. Mechanistically, this acceleration stems from selectively strengthened synchrony of oscillation-associated excitatory synaptic currents at higher frequencies. Our findings provide in vivo evidence linking early hippocampal hyperactivity to specific alterations in synaptic transmission dynamics and network dysfunction, highlighting that accelerated oscillations in the hippocampus could be a functional biomarker for early AD and a therapeutic target for restoring network stability before cognitive decline occurs.<\/jats:p>","DOI":"10.1038\/s42003-026-09918-y","type":"journal-article","created":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T11:06:36Z","timestamp":1774695996000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Reduced inhibition, bursting, and accelerated oscillations drive early hippocampal hyperactivity in Alzheimer\u2019s disease in vivo"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3408-5626","authenticated-orcid":false,"given":"Soraya","family":"Meftah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungmin","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingshan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingran","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ada Nursel","family":"Top\u00e7u","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maialen Martin","family":"Abad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2957-5559","authenticated-orcid":false,"given":"\u00c1ron","family":"K\u0151szeghy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conor","family":"Mullin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7529-8492","authenticated-orcid":false,"given":"Lida","family":"Zoupi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0155-6241","authenticated-orcid":false,"given":"Jian","family":"Gan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,28]]},"reference":[{"key":"9918_CR1","doi-asserted-by":"publisher","first-page":"3708","DOI":"10.1002\/alz.13809","volume":"20","author":"No authors listed","year":"2024","unstructured":"No authors listed 2024 Alzheimer\u2019s disease facts and figures. Alzheimers Dement 20, 3708\u20133821 (2024).","journal-title":"Alzheimers Dement"},{"key":"9918_CR2","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1016\/j.cell.2015.12.056","volume":"164","author":"B De Strooper","year":"2016","unstructured":"De Strooper, B. & Karran, E. The cellular phase of Alzheimer\u2019s disease. Cell 164, 603\u2013615 (2016).","journal-title":"Cell"},{"key":"9918_CR3","doi-asserted-by":"publisher","first-page":"5481","DOI":"10.1038\/s41380-021-01249-0","volume":"26","author":"H Hampel","year":"2021","unstructured":"Hampel, H. et al. The amyloid-beta pathway in Alzheimer\u2019s disease. Mol. Psychiatry 26, 5481\u20135503 (2021).","journal-title":"Mol. Psychiatry"},{"key":"9918_CR4","doi-asserted-by":"publisher","first-page":"5143","DOI":"10.1002\/alz.13859","volume":"20","author":"CR Jack Jr","year":"2024","unstructured":"Jack, C. R. Jr et al. Revised criteria for diagnosis and staging of Alzheimer\u2019s disease: Alzheimer\u2019s Association Workgroup. Alzheimers Dement 20, 5143\u20135169 (2024).","journal-title":"Alzheimers Dement"},{"key":"9918_CR5","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/nn.3028","volume":"15","author":"I Benilova","year":"2012","unstructured":"Benilova, I., Karran, E. & De Strooper, B. The toxic Abeta oligomer and Alzheimer\u2019s disease: an emperor in need of clothes. Nat. Neurosci. 15, 349\u2013357 (2012).","journal-title":"Nat. Neurosci."},{"key":"9918_CR6","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.1111\/j.1742-4658.2010.07568.x","volume":"277","author":"M Sakono","year":"2010","unstructured":"Sakono, M. & Zako, T. Amyloid oligomers: formation and toxicity of Abeta oligomers. FEBS J. 277, 1348\u20131358 (2010).","journal-title":"FEBS J."},{"key":"9918_CR7","doi-asserted-by":"publisher","unstructured":"Tolar, M., Hey, J., Power, A. & Abushakra, S. Neurotoxic soluble amyloid oligomers drive Alzheimer\u2019s pathogenesis and represent a clinically validated target for slowing disease progression. Int. J. Mol. Sci. 22, https:\/\/doi.org\/10.3390\/ijms22126355 (2021).","DOI":"10.3390\/ijms22126355"},{"key":"9918_CR8","doi-asserted-by":"publisher","first-page":"8740","DOI":"10.1073\/pnas.1206171109","volume":"109","author":"MA Busche","year":"2012","unstructured":"Busche, M. A. et al. Critical role of soluble amyloid-beta for early hippocampal hyperactivity in a mouse model of Alzheimer\u2019s disease. Proc. Natl. Acad. Sci. USA 109, 8740\u20138745 (2012).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"9918_CR9","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1126\/science.aay0198","volume":"365","author":"B Zott","year":"2019","unstructured":"Zott, B. et al. A vicious cycle of \u03b2 amyloid-dependent neuronal hyperactivation. Science 365, 559\u2013565 (2019).","journal-title":"Science"},{"key":"9918_CR10","doi-asserted-by":"publisher","first-page":"8631","DOI":"10.1073\/pnas.1708106114","volume":"114","author":"AD Keskin","year":"2017","unstructured":"Keskin, A. D. et al. BACE inhibition-dependent repair of Alzheimer\u2019s pathophysiology. Proc. Natl. Acad. Sci. USA 114, 8631\u20138636 (2017).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"9918_CR11","doi-asserted-by":"publisher","unstructured":"Meftah, S. & Gan, J. Alzheimer\u2019s disease as a synaptopathy: evidence for dysfunction of synapses during disease progression. Front. Synaptic Neurosci. 15, https:\/\/doi.org\/10.3389\/fnsyn.2023.1129036 (2023).","DOI":"10.3389\/fnsyn.2023.1129036"},{"key":"9918_CR12","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.neuron.2014.12.032","volume":"85","author":"A Montagne","year":"2015","unstructured":"Montagne, A. et al. Blood-brain barrier breakdown in the aging human hippocampus. Neuron 85, 296\u2013302 (2015).","journal-title":"Neuron"},{"key":"9918_CR13","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1001\/archneur.63.5.693","volume":"63","author":"LG Apostolova","year":"2006","unstructured":"Apostolova, L. G. et al. Conversion of mild cognitive impairment to Alzheimer disease predicted by hippocampal atrophy maps. Arch. Neurol. 63, 693\u2013699 (2006).","journal-title":"Arch. Neurol."},{"key":"9918_CR14","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1159\/000116984","volume":"33","author":"H Braak","year":"2008","unstructured":"Braak, H., Braak, E. & Bohl, J. Staging of Alzheimer-related cortical destruction. Eur. Neurol. 33, 403\u2013408 (2008).","journal-title":"Eur. Neurol."},{"key":"9918_CR15","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1146\/annurev-neuro-080317-061725","volume":"41","author":"B Zott","year":"2018","unstructured":"Zott, B., Busche, M. A., Sperling, R. A. & Konnerth, A. What happens with the circuit in Alzheimer\u2019s disease in mice and humans? Annu. Rev. Neurosci. 41, 277\u2013297 (2018).","journal-title":"Annu. Rev. Neurosci."},{"key":"9918_CR16","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1212\/01.wnl.0000171450.97464.49","volume":"65","author":"BC Dickerson","year":"2005","unstructured":"Dickerson, B. C. et al. Increased hippocampal activation in mild cognitive impairment compared to normal aging and AD. Neurology 65, 404\u2013411 (2005).","journal-title":"Neurology"},{"key":"9918_CR17","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1016\/j.neuron.2012.03.023","volume":"74","author":"A Bakker","year":"2012","unstructured":"Bakker, A. et al. Reduction of hippocampal hyperactivity improves cognition in amnestic mild cognitive impairment. Neuron 74, 467\u2013474 (2012).","journal-title":"Neuron"},{"key":"9918_CR18","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1002\/ana.22105","volume":"68","author":"YT Quiroz","year":"2010","unstructured":"Quiroz, Y. T. et al. Hippocampal hyperactivation in presymptomatic familial Alzheimer\u2019s disease. Ann. Neurol. 68, 865\u2013875 (2010).","journal-title":"Ann. Neurol."},{"key":"9918_CR19","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1056\/NEJM200008173430701","volume":"343","author":"SY Bookheimer","year":"2000","unstructured":"Bookheimer, S. Y. et al. Patterns of brain activation in people at risk for Alzheimer\u2019s disease. N. Engl. J. Med. 343, 450\u2013456 (2000).","journal-title":"N. Engl. J. Med."},{"key":"9918_CR20","doi-asserted-by":"publisher","first-page":"1667","DOI":"10.1016\/j.neuropsychologia.2007.11.035","volume":"46","author":"MA Trivedi","year":"2008","unstructured":"Trivedi, M. A. et al. fMRI activation during episodic encoding and metacognitive appraisal across the lifespan: risk factors for Alzheimer\u2019s disease. Neuropsychologia 46, 1667\u20131678 (2008).","journal-title":"Neuropsychologia"},{"key":"9918_CR21","doi-asserted-by":"publisher","first-page":"7209","DOI":"10.1073\/pnas.0811879106","volume":"106","author":"N Filippini","year":"2009","unstructured":"Filippini, N. et al. Distinct patterns of brain activity in young carriers of the APOE-\u03b54 allele. Proc. Natl. Acad. Sci. USA 106, 7209\u20137214 (2009).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"9918_CR22","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1126\/science.aac8128","volume":"350","author":"L Kunz","year":"2015","unstructured":"Kunz, L. et al. Reduced grid-cell\u2013like representations in adults at genetic risk for Alzheimer\u2019s disease. Science 350, 430\u2013433 (2015).","journal-title":"Science"},{"key":"9918_CR23","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1016\/j.neuron.2014.10.024","volume":"84","author":"Z Siskova","year":"2014","unstructured":"Siskova, Z. et al. Dendritic structural degeneration is functionally linked to cellular hyperexcitability in a mouse model of Alzheimer\u2019s disease. Neuron 84, 1023\u20131033 (2014).","journal-title":"Neuron"},{"key":"9918_CR24","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-58038-y","volume":"10","author":"U Chockanathan","year":"2020","unstructured":"Chockanathan, U., Warner, E. J., Turpin, L., O'Banion, M. K. & Padmanabhan, K. Altered dorsal CA1 neuronal population coding in the APP\/PS1 mouse model of Alzheimer\u2019s disease. Sci. Rep. 10, 1077 (2020).","journal-title":"Sci. Rep."},{"key":"9918_CR25","doi-asserted-by":"publisher","first-page":"3403","DOI":"10.1113\/JP283401","volume":"601","author":"M Mittag","year":"2023","unstructured":"Mittag, M., Mediavilla, L., Remy, S., Cuntz, H. & Jedlicka, P. Modelling the contributions to hyperexcitability in a mouse model of Alzheimer\u2019s disease. J. Physiol. 601, 3403\u20133437 (2023).","journal-title":"J. Physiol."},{"key":"9918_CR26","doi-asserted-by":"publisher","first-page":"e0119910","DOI":"10.1371\/journal.pone.0119910","volume":"10","author":"C Bezzina","year":"2015","unstructured":"Bezzina, C. et al. Early onset of hypersynchronous network activity and expression of a marker of chronic seizures in the Tg2576 mouse model of Alzheimer\u2019s disease. PLoS One 10, e0119910 (2015).","journal-title":"PLoS One"},{"key":"9918_CR27","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1016\/j.neuron.2007.07.025","volume":"55","author":"JJ Palop","year":"2007","unstructured":"Palop, J. J. et al. Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer\u2019s disease. Neuron 55, 697\u2013711 (2007).","journal-title":"Neuron"},{"key":"9918_CR28","doi-asserted-by":"publisher","first-page":"3453","DOI":"10.1523\/JNEUROSCI.5215-08.2009","volume":"29","author":"R Minkeviciene","year":"2009","unstructured":"Minkeviciene, R. et al. Amyloid beta-induced neuronal hyperexcitability triggers progressive epilepsy. J. Neurosci. 29, 3453\u20133462 (2009).","journal-title":"J. Neurosci."},{"key":"9918_CR29","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1186\/s40478-014-0149-z","volume":"2","author":"AA Ittner","year":"2014","unstructured":"Ittner, A. A., Gladbach, A., Bertz, J., Suh, L. S. & Ittner, L. M. p38 MAP kinase-mediated NMDA receptor-dependent suppression of hippocampal hypersynchronicity in a mouse model of Alzheimer\u2019s disease. Acta Neuropathol. Commun. 2, 149 (2014).","journal-title":"Acta Neuropathol. Commun."},{"key":"9918_CR30","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1186\/s13195-021-00859-8","volume":"13","author":"Y Li","year":"2021","unstructured":"Li, Y. et al. Reversible GABAergic dysfunction involved in hippocampal hyperactivity predicts early-stage Alzheimer disease in a mouse model. Alzheimers Res. Ther. 13, 114 (2021).","journal-title":"Alzheimers Res. Ther."},{"key":"9918_CR31","doi-asserted-by":"publisher","first-page":"3380","DOI":"10.1038\/s41380-019-0483-4","volume":"25","author":"S Hijazi","year":"2020","unstructured":"Hijazi, S. et al. Early restoration of parvalbumin interneuron activity prevents memory loss and network hyperexcitability in a mouse model of Alzheimer\u2019s disease. Mol. Psychiatry 25, 3380\u20133398 (2020).","journal-title":"Mol. Psychiatry"},{"key":"9918_CR32","doi-asserted-by":"publisher","unstructured":"Chen, Y. B. et al. Hyperactivity of subicular parvalbumin interneurons drives early amyloid pathology and cognitive deficits in Alzheimer\u2019s disease. Mol. Psychiatry https:\/\/doi.org\/10.1038\/s41380-025-03217-4 (2025).","DOI":"10.1038\/s41380-025-03217-4"},{"key":"9918_CR33","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1093\/hmg\/ddh019","volume":"13","author":"JL Jankowsky","year":"2004","unstructured":"Jankowsky, J. L. et al. Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Hum. Mol. Genet. 13, 159\u2013170 (2004).","journal-title":"Hum. Mol. Genet."},{"key":"9918_CR34","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.668948","volume":"13","author":"P Vitale","year":"2021","unstructured":"Vitale, P. et al. Analysis of age-dependent alterations in excitability properties of CA1 pyramidal neurons in an APPPS1 model of Alzheimer\u2019s disease. Front. Aging Neurosci. 13, 668948 (2021).","journal-title":"Front. Aging Neurosci."},{"key":"9918_CR35","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1016\/j.nbd.2006.05.010","volume":"23","author":"T van Groen","year":"2006","unstructured":"van Groen, T., Kiliaan, A. J. & Kadish, I. Deposition of mouse amyloid beta in human APP\/PS1 double and single AD model transgenic mice. Neurobiol. Dis. 23, 653\u2013662 (2006).","journal-title":"Neurobiol. Dis."},{"key":"9918_CR36","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.1038\/s41593-020-00744-x","volume":"23","author":"T Donoghue","year":"2020","unstructured":"Donoghue, T. et al. Parameterizing neural power spectra into periodic and aperiodic components. Nat. Neurosci. 23, 1655\u20131665 (2020).","journal-title":"Nat. Neurosci."},{"key":"9918_CR37","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1016\/j.neuron.2016.12.018","volume":"93","author":"J Gan","year":"2017","unstructured":"Gan, J., Weng, S. M., Pern\u00eda-Andrade, A. J., Csicsvari, J. & Jonas, P. Phase-locked inhibition, but not excitation, underlies hippocampal ripple oscillations in awake mice in vivo. Neuron 93, 308\u2013314 (2017).","journal-title":"Neuron"},{"key":"9918_CR38","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.neuron.2011.08.016","volume":"72","author":"N Maier","year":"2011","unstructured":"Maier, N. et al. Coherent phasic excitation during hippocampal ripples. Neuron 72, 137\u2013152 (2011).","journal-title":"Neuron"},{"key":"9918_CR39","doi-asserted-by":"publisher","first-page":"5836","DOI":"10.1111\/ejn.15829","volume":"56","author":"RA Seymour","year":"2022","unstructured":"Seymour, R. A., Alexander, N. & Maguire, E. A. Robust estimation of 1\/f activity improves oscillatory burst detection. Eur. J. Neurosci. 56, 5836\u20135852 (2022).","journal-title":"Eur. J. Neurosci."},{"key":"9918_CR40","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109008","volume":"35","author":"SM Prince","year":"2021","unstructured":"Prince, S. M. et al. Alzheimer\u2019s pathology causes impaired inhibitory connections and reactivation of spatial codes during spatial navigation. Cell Rep. 35, 109008 (2021).","journal-title":"Cell Rep."},{"key":"9918_CR41","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1152\/jn.01170.2003","volume":"92","author":"P Barth\u00f3","year":"2004","unstructured":"Barth\u00f3, P. et al. Characterization of neocortical principal cells and interneurons by network interactions and extracellular features. J. Neurophysiol. 92, 600\u2013608 (2004).","journal-title":"J. Neurophysiol."},{"key":"9918_CR42","doi-asserted-by":"publisher","first-page":"2701","DOI":"10.1523\/JNEUROSCI.1417-21.2022","volume":"42","author":"A Pala","year":"2022","unstructured":"Pala, A. & Stanley, G. B. Ipsilateral stimulus encoding in primary and secondary somatosensory cortex of awake mice. J. Neurosci. 42, 2701\u20132715 (2022).","journal-title":"J. Neurosci."},{"key":"9918_CR43","doi-asserted-by":"publisher","unstructured":"Sofroniew, N. J., Vlasov, Y. A., Hires, S. A., Freeman, J. & Svoboda, K. Neural coding in barrel cortex during whisker-guided locomotion. Elife 4, https:\/\/doi.org\/10.7554\/eLife.12559 (2015).","DOI":"10.7554\/eLife.12559"},{"key":"9918_CR44","doi-asserted-by":"publisher","DOI":"10.1126\/science.1255263","volume":"345","author":"H Hu","year":"2014","unstructured":"Hu, H., Gan, J. & Jonas, P. Fast-spiking, parvalbumin+ GABAergic interneurons: from cellular design to microcircuit function. Science 345, 1255263 (2014).","journal-title":"Science"},{"key":"9918_CR45","doi-asserted-by":"publisher","first-page":"1619","DOI":"10.1152\/physrev.00007.2017","volume":"97","author":"KA Pelkey","year":"2017","unstructured":"Pelkey, K. A. et al. Hippocampal GABAergic inhibitory interneurons. Physiol. Rev. 97, 1619\u20131747 (2017).","journal-title":"Physiol. Rev."},{"key":"9918_CR46","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.110268","volume":"38","author":"D Zarhin","year":"2022","unstructured":"Zarhin, D. et al. Disrupted neural correlates of anesthesia and sleep reveal early circuit dysfunctions in Alzheimer models. Cell Rep. 38, 110268 (2022).","journal-title":"Cell Rep."},{"key":"9918_CR47","doi-asserted-by":"publisher","unstructured":"Harris, S. S. et al. Alzheimer\u2019s disease patient-derived high-molecular-weight tau impairs bursting in hippocampal neurons. Cell https:\/\/doi.org\/10.1016\/j.cell.2025.04.006 (2025).","DOI":"10.1016\/j.cell.2025.04.006"},{"key":"9918_CR48","doi-asserted-by":"publisher","unstructured":"Papanikolaou, A. et al. Selectively vulnerable deep cortical layer 5\/6 fast-spiking interneurons in Alzheimer\u2019s disease models in vivo. Neuron https:\/\/doi.org\/10.1016\/j.neuron.2025.04.010 (2025).","DOI":"10.1016\/j.neuron.2025.04.010"},{"key":"9918_CR49","doi-asserted-by":"publisher","first-page":"5116","DOI":"10.1523\/JNEUROSCI.0425-20.2020","volume":"40","author":"A Caccavano","year":"2020","unstructured":"Caccavano, A. et al. Inhibitory parvalbumin basket cell activity is selectively reduced during hippocampal sharp wave ripples in a mouse model of familial Alzheimer\u2019s disease. J. Neurosci. 40, 5116\u20135136 (2020).","journal-title":"J. Neurosci."},{"key":"9918_CR50","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1016\/j.cell.2012.02.046","volume":"149","author":"L Verret","year":"2012","unstructured":"Verret, L. et al. Inhibitory interneuron deficit links altered network activity and cognitive dysfunction in Alzheimer model. Cell 149, 708\u2013721 (2012).","journal-title":"Cell"},{"key":"9918_CR51","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1038\/nrn.2016.141","volume":"17","author":"JJ Palop","year":"2016","unstructured":"Palop, J. J. & Mucke, L. Network abnormalities and interneuron dysfunction in Alzheimer disease. Nat. Rev. Neurosci. 17, 777\u2013792 (2016).","journal-title":"Nat. Rev. Neurosci."},{"key":"9918_CR52","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1038\/s42003-022-04268-x","volume":"5","author":"M Algamal","year":"2022","unstructured":"Algamal, M. et al. Reduced excitatory neuron activity and interneuron-type-specific deficits in a mouse model of Alzheimer\u2019s disease. Commun. Biol. 5, 1323 (2022).","journal-title":"Commun. Biol."},{"key":"9918_CR53","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3233\/JAD-2012-120907","volume":"32","author":"D Sepulveda-Falla","year":"2012","unstructured":"Sepulveda-Falla, D., Glatzel, M. & Lopera, F. Phenotypic profile of early-onset familial Alzheimer\u2019s disease caused by presenilin-1 E280A mutation. J. Alzheimers Dis. 32, 1\u201312 (2012).","journal-title":"J. Alzheimers Dis."},{"key":"9918_CR54","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.neuron.2009.07.003","volume":"63","author":"RA Sperling","year":"2009","unstructured":"Sperling, R. A. et al. Amyloid deposition is associated with impaired default network function in older persons without dementia. Neuron 63, 178\u2013188 (2009).","journal-title":"Neuron"},{"key":"9918_CR55","doi-asserted-by":"publisher","first-page":"1813","DOI":"10.1093\/cercor\/bhr255","volume":"22","author":"EC Mormino","year":"2012","unstructured":"Mormino, E. C. et al. A\u03b2 Deposition in aging is associated with increases in brain activation during successful memory encoding. Cereb. Cortex 22, 1813\u20131823 (2012).","journal-title":"Cereb. Cortex"},{"key":"9918_CR56","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1016\/j.neuron.2020.06.023","volume":"107","author":"H Jun","year":"2020","unstructured":"Jun, H. et al. Disrupted place cell remapping and impaired grid cells in a knockin model of Alzheimer\u2019s disease. Neuron 107, 1095\u20131112 e1096 (2020).","journal-title":"Neuron"},{"key":"9918_CR57","doi-asserted-by":"publisher","first-page":"10222","DOI":"10.1523\/JNEUROSCI.2250-06.2006","volume":"26","author":"KA Celone","year":"2006","unstructured":"Celone, K. A. et al. Alterations in memory networks in mild cognitive impairment and Alzheimer\u2019s disease: an independent component analysis. J. Neurosci. 26, 10222\u201310231 (2006).","journal-title":"J. Neurosci."},{"key":"9918_CR58","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.neurobiolaging.2019.01.010","volume":"78","author":"BA Kent","year":"2019","unstructured":"Kent, B. A. et al. Delayed daily activity and reduced NREM slow-wave power in the APPswe\/PS1dE9 mouse model of Alzheimer\u2019s disease. Neurobiol. Aging 78, 74\u201386 (2019).","journal-title":"Neurobiol. Aging"},{"key":"9918_CR59","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1186\/s13195-023-01287-6","volume":"15","author":"FC van Heusden","year":"2023","unstructured":"van Heusden, F. C. et al. Neurophysiological alterations in mice and humans carrying mutations in APP and PSEN1 genes. Alzheimers Res. Ther. 15, 142 (2023).","journal-title":"Alzheimers Res. Ther."},{"key":"9918_CR60","doi-asserted-by":"publisher","first-page":"317","DOI":"10.3233\/JAD-215464","volume":"87","author":"JJ Luppi","year":"2022","unstructured":"Luppi, J. J. et al. Oscillatory activity of the hippocampus in prodromal Alzheimer\u2019s disease: a source-space magnetoencephalography study. J. Alzheimers Dis. 87, 317\u2013333 (2022).","journal-title":"J. Alzheimers Dis."},{"key":"9918_CR61","doi-asserted-by":"publisher","first-page":"2065","DOI":"10.1073\/pnas.0437938100","volume":"100","author":"A Sirota","year":"2003","unstructured":"Sirota, A., Csicsvari, J., Buhl, D. & Buzs\u00e1ki, G. Communication between neocortex and hippocampus during sleep in rodents. Proc. Natl. Acad. Sci. USA 100, 2065\u20132069 (2003).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"9918_CR62","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1017\/S1472928807000258","volume":"3","author":"GB Anton Sirota","year":"2005","unstructured":"Anton Sirota, G. B. Interaction between neocortical and hippocampal networks via slow oscillations. Thalamus Relat. Syst. 3, 245\u2013259 (2005).","journal-title":"Thalamus Relat. Syst."},{"key":"9918_CR63","doi-asserted-by":"publisher","unstructured":"Lucey, B. P. et al. Reduced non\u2013rapid eye movement sleep is associated with tau pathology in early Alzheimer\u2019s disease. Sci. Transl. Med. 11, https:\/\/doi.org\/10.1126\/scitranslmed.aau6550 (2019).","DOI":"10.1126\/scitranslmed.aau6550"},{"key":"9918_CR64","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1038\/nn.4035","volume":"18","author":"BA Mander","year":"2015","unstructured":"Mander, B. A. et al. \u03b2-amyloid disrupts human NREM slow waves and related hippocampus-dependent memory consolidation. Nat. Neurosci. 18, 1051\u20131057 (2015).","journal-title":"Nat. Neurosci."},{"key":"9918_CR65","doi-asserted-by":"publisher","first-page":"1325","DOI":"10.3233\/JAD-180260","volume":"64","author":"BA Kent","year":"2018","unstructured":"Kent, B. A., Strittmatter, S. M. & Nygaard, H. B. Sleep and EEG power spectral analysis in three transgenic mouse models of Alzheimer\u2019s disease: APP\/PS1, 3xTgAD, and Tg2576. J. Alzheimers Dis. 64, 1325\u20131336 (2018).","journal-title":"J. Alzheimers Dis."},{"key":"9918_CR66","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2023.1119810","volume":"15","author":"VJ Drew","year":"2023","unstructured":"Drew, V. J., Wang, C. & Kim, T. Progressive sleep disturbance in various transgenic mouse models of Alzheimer\u2019s disease. Front. Aging Neurosci. 15, 1119810 (2023).","journal-title":"Front. Aging Neurosci."},{"key":"9918_CR67","doi-asserted-by":"publisher","first-page":"1623","DOI":"10.1038\/nn.4137","volume":"18","author":"MA Busche","year":"2015","unstructured":"Busche, M. A. et al. Rescue of long-range circuit dysfunction in Alzheimer\u2019s disease models. Nat. Neurosci. 18, 1623\u20131630 (2015).","journal-title":"Nat. Neurosci."},{"key":"9918_CR68","doi-asserted-by":"publisher","first-page":"1417","DOI":"10.4103\/1673-5374.386412","volume":"19","author":"J Witton","year":"2024","unstructured":"Witton, J., Brady, E. S. & Craig, M. T. Sleep-based neuronal oscillations as a physiological biomarker for Alzheimer\u2019s disease: is night time the right time? Neural Regen. Res. 19, 1417\u20131418 (2024).","journal-title":"Neural Regen. Res."},{"key":"9918_CR69","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.brainresbull.2022.07.002","volume":"187","author":"F Katsuki","year":"2022","unstructured":"Katsuki, F., Gerashchenko, D. & Brown, R. E. Alterations of sleep oscillations in Alzheimer\u2019s disease: a potential role for GABAergic neurons in the cortex, hippocampus, and thalamus. Brain Res. Bull. 187, 181\u2013198 (2022).","journal-title":"Brain Res. Bull."},{"key":"9918_CR70","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1186\/s13195-025-01724-8","volume":"17","author":"H Yang","year":"2025","unstructured":"Yang, H. et al. Circadian rhythm disturbances in Alzheimer\u2019s disease: insights from plaque-free and plaque-burdened stages in APP(SWE)\/PS1(dE9) mice. Alzheimers Res. Ther. 17, 76 (2025).","journal-title":"Alzheimers Res. Ther."},{"key":"9918_CR71","doi-asserted-by":"publisher","first-page":"705","DOI":"10.3389\/fnins.2020.00705","volume":"14","author":"YF Lee","year":"2020","unstructured":"Lee, Y. F., Gerashchenko, D., Timofeev, I., Bacskai, B. J. & Kastanenka, K. V. Slow wave sleep is a promising intervention target for Alzheimer\u2019s disease. Front. Neurosci. 14, 705 (2020).","journal-title":"Front. Neurosci."},{"key":"9918_CR72","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1002\/hipo.22488","volume":"25","author":"G Buzs\u00e1ki","year":"2015","unstructured":"Buzs\u00e1ki, G. Hippocampal sharp wave-ripple: a cognitive biomarker for episodic memory and planning. Hippocampus 25, 1073\u20131088 (2015).","journal-title":"Hippocampus"},{"key":"9918_CR73","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-56582-w","volume":"9","author":"B Jura","year":"2019","unstructured":"Jura, B., Macrez, N., Meyrand, P. & Bem, T. Deficit in hippocampal ripples does not preclude spatial memory formation in APP\/PS1 mice. Sci. Rep. 9, 20129 (2019).","journal-title":"Sci. Rep."},{"key":"9918_CR74","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2023.106151","volume":"182","author":"ES Brady","year":"2023","unstructured":"Brady, E. S. et al. Alterations to parvalbumin-expressing interneuron function and associated network oscillations in the hippocampal - medial prefrontal cortex circuit during natural sleep in App(NL-G-F\/NL-G-F) mice. Neurobiol. Dis. 182, 106151 (2023).","journal-title":"Neurobiol. Dis."},{"key":"9918_CR75","doi-asserted-by":"publisher","first-page":"1926","DOI":"10.1126\/science.1099745","volume":"304","author":"G Buzs\u00e1ki","year":"2004","unstructured":"Buzs\u00e1ki, G. & Draguhn, A. Neuronal oscillations in cortical networks. Science 304, 1926\u20131929 (2004).","journal-title":"Science"},{"key":"9918_CR76","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1038\/nrn3241","volume":"13","author":"G Buzsaki","year":"2012","unstructured":"Buzsaki, G., Anastassiou, C. A. & Koch, C. The origin of extracellular fields and currents-EEG, ECoG, LFP and spikes. Nat. Rev. Neurosci. 13, 407\u2013420 (2012).","journal-title":"Nat. Rev. Neurosci."},{"key":"9918_CR77","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/S0896-6273(02)00586-X","volume":"33","author":"G Buzs\u00e1ki","year":"2002","unstructured":"Buzs\u00e1ki, G. Theta oscillations in the hippocampus. Neuron 33, 325\u2013340 (2002).","journal-title":"Neuron"},{"key":"9918_CR78","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2019.116331","volume":"206","author":"JQ Kosciessa","year":"2020","unstructured":"Kosciessa, J. Q., Grandy, T. H., Garrett, D. D. & Werkle-Bergner, M. Single-trial characterization of neural rhythms: Potential and challenges. Neuroimage 206, 116331 (2020).","journal-title":"Neuroimage"},{"key":"9918_CR79","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1038\/s41592-024-02232-7","volume":"21","author":"M Pachitariu","year":"2024","unstructured":"Pachitariu, M., Sridhar, S., Pennington, J. & Stringer, C. Spike sorting with Kilosort4. Nat. Methods 21, 914\u2013921 (2024).","journal-title":"Nat. Methods"},{"key":"9918_CR80","doi-asserted-by":"publisher","first-page":"36","DOI":"10.3389\/fninf.2013.00036","volume":"7","author":"C Rossant","year":"2013","unstructured":"Rossant, C. & Harris, K. D. Hardware-accelerated interactive data visualization for neuroscience in Python. Front. Neuroinform. 7, 36 (2013).","journal-title":"Front. Neuroinform."},{"key":"9918_CR81","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1016\/j.celrep.2013.07.039","volume":"4","author":"K Mizuseki","year":"2013","unstructured":"Mizuseki, K. & Buzs\u00e1ki, G. Preconfigured, skewed distribution of firing rates in the hippocampus and entorhinal cortex. Cell Rep. 4, 1010\u20131021 (2013).","journal-title":"Cell Rep."},{"key":"9918_CR82","doi-asserted-by":"publisher","first-page":"1174","DOI":"10.1038\/nn.2894","volume":"14","author":"K Mizuseki","year":"2011","unstructured":"Mizuseki, K., Diba, K., Pastalkova, E. & Buzs\u00e1ki, G. Hippocampal CA1 pyramidal cells form functionally distinct sublayers. Nat. Neurosci. 14, 1174\u20131181 (2011).","journal-title":"Nat. Neurosci."},{"key":"9918_CR83","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1523\/JNEUROSCI.15-01-00030.1995","volume":"15","author":"A Ylinen","year":"1995","unstructured":"Ylinen, A. et al. Sharp wave-associated high-frequency oscillation (200 Hz) in the intact hippocampus: network and intracellular mechanisms. J. Neurosci. 15, 30\u201346 (1995).","journal-title":"J. Neurosci."},{"key":"9918_CR84","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.neuron.2005.10.037","volume":"49","author":"J O'Neill","year":"2006","unstructured":"O'Neill, J., Senior, T. & Csicsvari, J. Place-selective firing of CA1 pyramidal cells during sharp wave\/ripple network patterns in exploratory behavior. Neuron 49, 143\u2013155 (2006).","journal-title":"Neuron"},{"key":"9918_CR85","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1038\/nature01374","volume":"421","author":"T Klausberger","year":"2003","unstructured":"Klausberger, T. et al. Brain-state- and cell-type-specific firing of hippocampal interneurons in vivo. Nature 421, 844\u2013848 (2003).","journal-title":"Nature"},{"key":"9918_CR86","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1038\/s41586-025-08868-5","volume":"642","author":"N Jeong","year":"2025","unstructured":"Jeong, N. et al. Goal-specific hippocampal inhibition gates learning. Nature 642, 1007\u20131015 (2025).","journal-title":"Nature"},{"key":"9918_CR87","doi-asserted-by":"publisher","unstructured":"Meftah, S. et al. Reduced inhibition, bursting, and accelerated oscillations drive early hippocampal hyperactivity in Alzheimer\u2019s disease in vivo [Source data]. Mendeley Data, V1 https:\/\/doi.org\/10.17632\/dpy4jt7d7v.1 (2026).","DOI":"10.17632\/dpy4jt7d7v.1"},{"key":"9918_CR88","doi-asserted-by":"publisher","unstructured":"Meftah, S. et al. Reduced inhibition, bursting, and accelerated oscillations drive early hippocampal hyperactivity in Alzheimer\u2019s disease in vivo [Code]. Mendeley Data, V1 https:\/\/doi.org\/10.17632\/9srsh85r7p.1 (2026).","DOI":"10.17632\/9srsh85r7p.1"}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-026-09918-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-026-09918-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-026-09918-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T09:08:10Z","timestamp":1779354490000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-026-09918-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,28]]},"references-count":88,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["9918"],"URL":"https:\/\/doi.org\/10.1038\/s42003-026-09918-y","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,28]]},"assertion":[{"value":"8 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"688"}}