Circadian and Brain State Modulation of Network Hyperexcitability in Alzheimer's Disease

ENeuro
Rosalind BrownIris Oren

Abstract

Network hyperexcitability is a feature of Alzheimer' disease (AD) as well as numerous transgenic mouse models of AD. While hyperexcitability in AD patients and AD animal models share certain features, the mechanistic overlap remains to be established. We aimed to identify features of network hyperexcitability in AD models that can be related to epileptiform activity signatures in AD patients. We studied network hyperexcitability in mice expressing amyloid precursor protein (APP) with mutations that cause familial AD, and compared a transgenic model that overexpresses human APP (hAPP) (J20), to a knock-in model expressing APP at physiological levels (APPNL/F). We recorded continuous long-term electrocorticogram (ECoG) activity from mice, and studied modulation by circadian cycle, behavioral, and brain state. We report that while J20s exhibit frequent interictal spikes (IISs), APPNL/F mice do not. In J20 mice, IISs were most prevalent during daylight hours and the circadian modulation was associated with sleep. Further analysis of brain state revealed that IIS in J20s are associated with features of rapid eye movement (REM) sleep. We found no evidence of cholinergic changes that may contribute to IIS-circadian coupling in J20s. I...Continue Reading

Citations

Mar 14, 2019·Frontiers in Cellular Neuroscience·Christopher M HenstridgeRosa C Paolicelli
Sep 26, 2019·Frontiers in Neurology·Alice D LamSydney S Cash
Oct 22, 2020·Epilepsy Currents·Alice D Lam, Jeffrey Noebels
Feb 24, 2021·Disease Models & Mechanisms·Grant F MarshallCatherine M Abbott
Mar 2, 2021·Neural Regeneration Research·Huang KuangShu-Long Yang
Mar 27, 2021·Brain : a Journal of Neurology·Katerina HristovaAlfredo Gonzalez-Sulser

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Methods Mentioned

BETA
transgenic
dissection

Software Mentioned

StereoInvestigator
Chronux script
R
CircOutlier
StereoInvestigator Fractioner
Chronux
circular
MATLAB
dplyr
lme4

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