Reduced inhibition, bursting, and accelerated oscillations drive early hippocampal hyperactivity in Alzheimer's disease in vivo.
Overview
- UK Dementia Research Institute at the University of Edinburgh,Edinburgh, UK
- Institute for Neuroscience and Cardiovascular Research, the University of Edinburgh,Edinburgh, UK
- Simons Initiative for Developing Brain, the University of Edinburgh,Edinburgh, UK
Abstract
‘Early hippocampal hyperactivity’ is well-documented in Alzheimer’s disease (AD), yet its mechanisms in vivo before amyloid-β 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.
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doi:10.17632/9srsh85r7p.1
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Data
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Numerical source data for graphs and quantitative comparisons presented in this paper are deposited at Mendeley Data: 10.17632/
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Recorded: type, language, journal, volume, issue, pages, dates, 11 authors, 3 keywords, 10 MeSH terms, 1 funder, 87 references.
Cite
This paper
Meftah, S., Kang, S., Liu, M., Wang, X., Topçu, A. N., Abad, M. M., Kőszeghy, Á., Wan, L., Mullin, C., Zoupi, L., & Gan, J. (2026). Reduced inhibition, bursting, and accelerated oscillations drive early hippocampal hyperactivity in Alzheimer's disease in vivo. Communications biology, 9(1), 688. https://
BibTeX
@article{meftah2026reduc
author = {Meftah, Soraya and Kang, Sungmin and Liu, Mingshan and Wang, Xingran and Topçu, Ada Nursel and Abad, Maialen Martin and Kőszeghy, Áron and Wan, Long and Mullin, Conor and Zoupi, Lida and Gan, Jian},
title = {{Reduced inhibition, bursting, and accelerated oscillations drive early hippocampal hyperactivity in Alzheimer's disease in vivo}},
journal = {Communications biology},
year = {2026},
month = mar,
volume = {9},
number = {1},
pages = {688},
publisher = {Nature Publishing Group},
issn = {2399-3642},
doi = {10.1038/
url = {https://
pmid = {41904231},
pmcid = {PMC13195132}
}
RIS
TY - JOUR
AU - Meftah, Soraya
AU - Kang, Sungmin
AU - Liu, Mingshan
AU - Wang, Xingran
AU - Topçu, Ada Nursel
AU - Abad, Maialen Martin
AU - Kőszeghy, Áron
AU - Wan, Long
AU - Mullin, Conor
AU - Zoupi, Lida
AU - Gan, Jian
TI - Reduced inhibition, bursting, and accelerated oscillations drive early hippocampal hyperactivity in Alzheimer's disease in vivo
T2 - Communications biology
J2 - Commun Biol
PY - 2026
DA - 2026/
VL - 9
IS - 1
SP - 688
SN - 2399-3642
PB - Nature Publishing Group
DO - 10.1038/
UR - https://
LA - en
ER -
CSL-JSON
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