Impaired hippocampal-cortical coupling but preserved local synchrony during sleep in APP/PS1 mice modeling Alzheimer\u2019s disease

E Zhurakovskaya,I Ishchenko,R Aliev,O Gröhn,H Tanila,I Gureviciene

doi:10.1038/s41598-019-41851-5

E Zhurakovskaya, I Ishchenko + Show 4 more

Open Access

https://doi.org/10.1038/s41598-019-41851-5

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Abstract

Sleep, in addition to its brain restorative processes, plays an important role in memory transfer from its temporary store in the hippocampus to the more permanent storage in the neocortex. Alzheimer’s disease (AD) affects memory and sleep. The aim of this study was to explore disturbances in global and local synchrony patterns between brain regions in the APP/PS1 mouse model of the AD during natural sleep. We used 8 male APPswe/PS1dE9 mice and 6 wild-type littermates, aged 5–6 months, with multiple electrode bundles implanted into cortical regions, thalamus and hippocampus. We measured video-EEG in freely moving animals and analyzed synchrony during NREM vs REM sleep. Global synchrony between medial frontal cortex and hippocampus measured with magnitude-squared coherence was slightly decreased in delta range during NREM stage of sleep in APP/PS1 mice. In contrast, local hippocampal synchrony measured with cross-frequency coupling remained intact. Ripple structure or frequency did not differ between the genotypes. However, the coupling of the spindle-band power peak in the medial prefrontal cortex to hippocampal ripples was significantly decreased compared to wild-type animals. The delicate timing of hippocampal ripples, frontal delta, and corticothalamic spindle oscillations may be the first sign of impaired memory in amyloid plaque-forming transgenic mice.

Highlights

Amyloid deposition in the brain in early stages of Alzheimer’s disease (AD) seems to concentrate on a network of highly interconnected cortical hubs that has been named default mode network (DMN) due to its high activity when the person is not interacting with the outside world and deactivation during cognitive processing[1]
Differences in functional connectivity have been reported between transgenic mice and their wild-type controls, but the findings appear controversial including hypersynchrony[7,8], no change[9], or decreased functional connectivity[9] between non-adjacent brain regions
This study addressed long-range functional connectivity during sleep in brains of transgenic APP/PS1 mice modeling Alzheimer’s disease (AD) and their wild-type littermates using a novel electrophysiological approach, implantation of distributed intracerebral doublet or triples wire electrodes in the regions of interest

Summary

Introduction

Amyloid deposition in the brain in early stages of Alzheimer’s disease (AD) seems to concentrate on a network of highly interconnected cortical hubs that has been named default mode network (DMN) due to its high activity when the person is not interacting with the outside world and deactivation during cognitive processing[1]. Assessment of functional connectivity with BOLD-fMRI has demonstrated abnormal activity in the DMN in AD patients[4] and subjects at high risk of developing AD5,6. Such changes may reflect early synaptic changes in neural networks. The present study set out to explore differences in global and local synchrony and communication between brain regions during sleep in the widely used APPswe/PS1dE9 mouse model of AD In this strain, amyloid-β (Aβ) deposition starts around at 4 months of age[16] when the mice show EEG hyperactivity[17] and occasional epileptic seizures[18]. We employed here a new ‘stereo-EEG’ approach, double- or triple-wire electrodes distributed across key brain sites corresponding the human DMN to assess both local and interregional synchrony of extracellular oscillations

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