Longitudinal changes in EEG power, sleep cycles and behaviour in a tau model of neurodegeneration.

Holton, Christopher; Hanley, Nicola; Shanks, Elaine; Oxley, Penny; McCarthy, Andrew; Eastwood, Brian J.; Murray, Tracey K.; Nickerson, Aidan; Wafford, Keith A.

doi:10.21203/rs.3.rs-15862/v2

Cited by 4 publications

(6 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, we found that VEP amplitude was robust, even in 8-months old Tau+ animals. Tau+ mice also have altered circadian rhythms, with increased periods of wakefulness, less time in nonrapid-eye-movement sleep (Holton et al, 2020), and altered sharp-wave ripple dynamics (Witton et al, 2016). These changes may contribute to the changes in long-term visual plasticity that we observed as sleep is important for SRP in mouse V1 (Aton et al, 2014; Cooke and Bear, 2010, 2012; Ji and Wilson, 2007).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Disrupted visual cortical plasticity in early neurodegeneration

Papanikolaou

Rodrigues

Holeniewska

et al. 2020

Preprint

View full text Add to dashboard Cite

Neurodegeneration is a hallmark of many dementias and is thought to underlie a progressive impairment of neural plasticity. How neurodegeneration affects plasticity in neural circuits is not known. We therefore characterised the impact of tau-driven neurodegeneration on plasticity in the visual system, where normal function is well understood. We studied a very simple form of visual plasticity that allowed us to track both long timescales (across days) and shorter timescales (over minutes). We recorded the local field potential in the primary visual cortex of rTg4510 transgenic mice, a mouse model of tauopathy, while animals were repeatedly exposed to the same stimulus over the course of 9 days. We studied animals at early stages of neurodegeneration (5 months old) and at a more advanced stage where pathology is evident (8 months). We found that both short- and long-term visual plasticity were already disrupted at early stages of neurodegeneration, and were further reduced in older animals, such that it was abolished in mice expressing the mutant tau. Additionally, we found that visually evoked behaviours were disrupted in both younger and older mice expressing the mutant tau. Our results show that visual cortical plasticity and visually evoked behaviours are disrupted in the rTg4510 model of tauopathy, even at early stages of neurodegeneration. This simple measure of neural plasticity may help understand how neurodegeneration disrupts neural circuits, and offers a translatable platform for detection and tracking of the disease.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Previous studies have reported alterations in rTg4510 mouse behaviour: Tau+, and to a lesser extent, Tau-mice tend to show hyperactivity and motor stereotypy, whilst maintaining good motor coordination [16, 18, 19, 55, 61]. These mice do not appear to respond to novelty, and have impaired spatial working memory [16, 18].…”

Section: Discussionmentioning

confidence: 99%

Disrupted visual cortical plasticity in early neurodegeneration

Papanikolaou

Rodrigues

Holeniewska

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…The sleep-wake cycle has been examined across different pathological stages in various mouse models, including 3xTg-AD [ 233 , 234 ], APP/PS1 [ 234 , 235 ], Tg2576 [ 234 , 236 ], P301S Tau [ 237 ], rTG4510 [ 238 ], PLB1 Triple [ 239 ], and PLB2tau [ 240 ] models ( Table 3 ). Slow (<1 Hz) oscillations have been analysed together with delta oscillations (1–4 Hz), which can be used to determine NREM sleep.…”

Section: Slow Oscillations and Admentioning

confidence: 99%

“…Slow (<1 Hz) oscillations have been analysed together with delta oscillations (1–4 Hz), which can be used to determine NREM sleep. In several AD mouse models, NREM sleep is reduced and fragmented [ 233 , 234 , 237 , 238 ], which implies that changes also occur in the patterns of slow oscillations. It has been suggested that the reduction in GABAergic tone impairs long-range synchronous firing in an amyloid mouse model [ 92 ].…”

Section: Slow Oscillations and Admentioning

confidence: 99%

Mutual Interactions between Brain States and Alzheimer’s Disease Pathology: A Focus on Gamma and Slow Oscillations

Byron

Семенова

Sakata

2021

Biology

View full text Add to dashboard Cite

Brain state varies from moment to moment. While brain state can be defined by ongoing neuronal population activity, such as neuronal oscillations, this is tightly coupled with certain behavioural or vigilant states. In recent decades, abnormalities in brain state have been recognised as biomarkers of various brain diseases and disorders. Intriguingly, accumulating evidence also demonstrates mutual interactions between brain states and disease pathologies: while abnormalities in brain state arise during disease progression, manipulations of brain state can modify disease pathology, suggesting a therapeutic potential. In this review, by focusing on Alzheimer’s disease (AD), the most common form of dementia, we provide an overview of how brain states change in AD patients and mouse models, and how controlling brain states can modify AD pathology. Specifically, we summarise the relationship between AD and changes in gamma and slow oscillations. As pathological changes in these oscillations correlate with AD pathology, manipulations of either gamma or slow oscillations can modify AD pathology in mouse models. We argue that neuromodulation approaches to target brain states are a promising non-pharmacological intervention for neurodegenerative diseases.

show abstract

“…In preclinical mouse models of tauopathy, low frequency EEG oscillations are increased (Das et al, 2018), fMRI resting state networks are disrupted (Green et al, 2019), and coupling between hippocampal and prefrontal cortical local field potentials (LFPs) is disrupted (Ahnaou et al, 2017). In the well-characterized rTg4510 model of tauopathy, hippocampal LFP (Ciupek et al, 2015) and cortical EEG are disrupted (Holton et al, 2020), and strong low frequency oscillations emerge in LFP recordings from frontal cortex (Menkes-Caspi et al, 2015). (Menkes-Caspi et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Altered low frequency brain rhythms precede changes in gamma power during tauopathy

Rodrigues

Papanikolaou

Holeniewska

et al. 2021

Preprint

View full text Add to dashboard Cite

Alzheimer's disease and other dementias are associated with disruptions of electrophysiological brain activity, including low frequency and gamma rhythms. Many of these dementias are also associated with the malfunction of the membrane associated protein tau. Tauopathy disrupts neuronal function and the stability of synapses and is a key driver of neurodegeneration. Here we ask how brain rhythms are affected by tauopathy, at different stages of its progression. We performed local field potential recordings from visual cortex of rTg4510 and control animals at early stages of neurodegeneration (5 months) and at a more advanced stage where pathology is evident (8 months). We measured brain activity in the presence or absence of external visual stimulation, and while monitoring pupil diameter and locomotion to establish animal behavioural states. At 5 months, before substantial pathology, we found an increase in low frequency rhythms during resting state in tauopathic animals. This was because tauopathic animals entered intermittent periods of increased neural synchronisation, where activity across a wide band of low frequencies was strongly correlated. At 8 months, when the degeneration was more advanced, the increased synchronisation and low frequency power was accompanied by a reduction in power in the gamma range, with diverse effects across different components of the gamma rhythm. Our results indicate that slower rhythms are impaired earlier than gamma rhythms in tauopathy, suggesting that electrophysiological measurements can indicate both the presence and progression of tauopathic degeneration.

show abstract

Longitudinal changes in EEG power, sleep cycles and behaviour in a tau model of neurodegeneration.

Cited by 4 publications

References 0 publications

Disrupted visual cortical plasticity in early neurodegeneration

Disrupted visual cortical plasticity in early neurodegeneration

Mutual Interactions between Brain States and Alzheimer’s Disease Pathology: A Focus on Gamma and Slow Oscillations

Altered low frequency brain rhythms precede changes in gamma power during tauopathy

Contact Info

Product

Resources

About