Cited by 184Alzheimer's disease research and treatmentsNeural dynamics and brain functionNeuroscience and Neuropharmacology Research

Pathological Tau Disrupts Ongoing Network Activity

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Menkes-Caspi, Noa, Yamin, Hagar G., Kellner, Vered, Spires-Jones, Tara L., Cohen, Dana, Stern, Edward A.·2015·Neuron

Abstract

Pathological tau leads to dementia and neurodegeneration in tauopathies, including Alzheimer's disease. It has been shown to disrupt cellular and synaptic functions, yet its effects on the function of the intact neocortical network remain unknown. Using in vivo intracellular and extracellular recordings, we measured ongoing activity of neocortical pyramidal cells during various arousal states in the rTg4510 mouse model of tauopathy, prior to significant cell death, when only a fraction of the neurons show pathological tau. In transgenic mice, membrane potential oscillations are slower during slow-wave sleep and under anesthesia. Intracellular recordings revealed that these changes are due to longer Down states and state transitions of membrane potentials. Firing rates of transgenic neurons are reduced, and firing patterns within Up states are altered, with longer latencies and inter-spike intervals. By changing the activity patterns of a subpopulation of affected neurons, pathological tau reduces the activity of the neocortical network.

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Crossref · 10.1016/j.neuron.2015.01.025

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Authors
Menkes-Caspi, N., Yamin, H. G., Kellner, V., Spires-Jones, T. L., Cohen, D., & Stern, E. A.
Affiliations
Bar-Ilan University (IL)
Corresponding author
Stern, Edward A.
Venue
Neuron
Publisher
Elsevier BV
Published
2015-03
Volume
85
Issue
5
Pages
959-966
ISSN
0896-6273 (ISSN-L)
OpenAlex
W2163349796
Cited by
184
References
29
Citations by year
2026: 15 · 2025: 11 · 2024: 11 · 2023: 15 · 2022: 17 · 2021: 28 · 2020: 28 · 2019: 12 · 2018: 13 · 2017: 16 · 2016: 13 · 2015: 5
FWCI
11.55
Type
journal article
Language
en
Open access
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by-nc-nd)
Funders
Versus Arthritis
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
pathological tau, tauopathy, Alzheimer's disease, membrane potential oscillations, slow-wave sleep, anesthesia, neuronal firing patterns, pyramidal neurons, arousal
MeSH terms
Action Potentials, Animals, Female, Humans, Male, Mice, Transgenic, Nerve Net, tau Proteins, Neocortex, Tauopathies, Mice

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