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Lookup NU author(s): Dr Myrto Stylianou,
Dr Boubker Zaaimi,
Professor Alan ThomasORCiD,
Professor John-Paul TaylorORCiD,
Dr Fiona LeBeau
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© Copyright © 2020 Stylianou, Zaaimi, Thomas, Taylor and LeBeau. Changes in sleep behavior and sleep-related cortical activity have been reported in conditions associated with abnormal alpha-synuclein (α-syn) expression, in particular Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Notably, changes can occur in patients years before the onset of cognitive decline. Sleep-related network oscillations play a key role in memory function, but how abnormal α-syn impacts the generation of such activity is currently unclear. To determine whether early changes in sleep-related network activity could also be observed, prior to any previously reported cognitive dysfunction, we used mice that over-express human mutant α-syn (A30P). Recordings in vivo were performed under urethane anesthesia in the medial prefrontal cortex (mPFC) and CA1 region of the hippocampus in young male (2.5 – 4 months old) A30P and age-matched wild type (WT) mice. We found that the slow oscillation (SO) < 1 Hz frequency was significantly faster in both the mPFC and hippocampus in A30P mice, and Up-state-associated fast oscillations at beta (20 – 30 Hz) and gamma (30 – 80 Hz) frequencies were delayed relative to the onset of the Up-state. Spindle (8 – 15 Hz) activity in the mPFC was also altered in A30P mice, as spindles were shorter in duration and had reduced density compared to WT. These changes demonstrate that dysregulation of sleep-related oscillations occurs in young A30P mice long before the onset of cognitive dysfunction. Our data suggest that, as seen in patients, changes in sleep-related oscillations are an early consequence of abnormal α-syn aggregation in A30P mice.
Author(s): Stylianou M, Zaaimi B, Thomas A, Taylor J-P, LeBeau FEN
Publication type: Article
Publication status: Published
Journal: Frontiers in Neuroscience
Online publication date: 17/09/2020
Acceptance date: 25/08/2020
Date deposited: 19/11/2020
ISSN (print): 1662-4548
ISSN (electronic): 1662-453X
Publisher: Frontiers Media S.A.
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