Sharp Wave Ripples in Alzheimer's Disease: In Search of Mechanisms

Sánchez-Aguilera, Alberto; Quintanilla, Juan Pablo

doi:10.1523/jneurosci.2020-20.2020

Cited by 19 publications

(14 citation statements)

References 43 publications

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“…The slow gamma oscillations observed during SWR are a phenomenon characteristic for SWR during waking and these oscillations have been associated with synchrony between the CA3 and CA1 layer. This synchronization is hypothesized to enable coordinated memory reactivation in the hippocampus, a process that might be disrupted in AD ( Carr et al, 2012 ; Gillespie et al, 2016 ; Sanchez-Aguilera and Quintanilla, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

“…The sharp waves are excitatory events originating from the CA3, which induce locally generated ripple oscillations in the CA1 pyramidal layer. The ripple events are generated by a delicate interaction between excitatory pyramidal neurons and local GABAergic interneurons that, if disrupted, can lead to pathological forms of activity which impair memory processes ( Buzsaki et al, 2003 ; Buzsaki, 2015 ; Colgin, 2016 ; Caccavano et al, 2020 ; Sanchez-Aguilera and Quintanilla, 2021 ; Zhen et al, 2021 ). During SWR, slow gamma oscillations have been observed throughout the entire hippocampus.…”

Section: Introductionmentioning

confidence: 99%

“…During SWR, slow gamma oscillations have been observed throughout the entire hippocampus. These slow gamma oscillations are thought to synchronize oscillatory activity across the hippocampus, which enables memory activation ( Carr et al, 2012 ; Gillespie et al, 2016 ; Sanchez-Aguilera and Quintanilla, 2021 ). Numerous studies have demonstrated that hyperactivity in the hippocampal circuits is associated with memory deficits at later stages of AD in different mouse models of AD ( Wilson et al, 2005 ; Yassa et al, 2010 ; Bakker et al, 2015 ; Setti et al, 2017 ; Donegan et al, 2019 ; Ratner et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Alterations in theta-gamma coupling and sharp wave-ripple, signs of prodromal hippocampal network impairment in the TgF344-AD rat model

Berg

Toen

Verhoye

et al. 2023

Front. Aging Neurosci.

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Alzheimer’s disease (AD) is a severe neurodegenerative disorder caused by the accumulation of toxic proteins, amyloid-beta (Aβ) and tau, which eventually leads to dementia. Disease-modifying therapies are still lacking, due to incomplete insights into the neuropathological mechanisms of AD. Synaptic dysfunction is known to occur before cognitive symptoms become apparent and recent studies have demonstrated that imbalanced synaptic signaling drives the progression of AD, suggesting that early synaptic dysfunction could be an interesting therapeutic target. Synaptic dysfunction results in altered oscillatory activity, which can be detected with electroencephalography and electrophysiological recordings. However, the majority of these studies have been performed at advanced stages of AD, when extensive damage and cognitive symptoms are already present. The current study aimed to investigate if the hippocampal oscillatory activity is altered at pre-plaque stages of AD. The rats received stereotactic surgery to implant a laminar electrode in the CA1 layer of the right hippocampus. Electrophysiological recordings during two consecutive days in an open field were performed in 4–5-month-old TgF344-AD rats when increased concentrations of soluble Aβ species were observed in the brain, in the absence of Aβ-plaques. We observed a decreased power of high theta oscillations in TgF344-AD rats compared to wild-type littermates. Sharp wave-ripple (SWR) analysis revealed an increased SWR power and a decreased duration of SWR during quiet wake in TgF344-AD rats. The alterations in properties of SWR and the increased power of fast oscillations are suggestive of neuronal hyperexcitability, as has been demonstrated to occur during presymptomatic stages of AD. In addition, decreased strength of theta-gamma coupling, an important neuronal correlate of memory encoding, was observed in the TgF344-AD rats. Theta-gamma phase amplitude coupling has been associated with memory encoding and the execution of cognitive functions. Studies have demonstrated that mild cognitive impairment patients display decreased coupling strength, similar to what is described here. The current study demonstrates altered hippocampal network activity occurring at pre-plaque stages of AD and provides insights into prodromal network dysfunction in AD. The alterations observed could aid in the detection of AD during presymptomatic stages.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Alterations in theta-gamma coupling and sharp wave-ripple, signs of prodromal hippocampal network impairment in the TgF344-AD rat model

Berg

Toen

Verhoye

et al. 2023

Front. Aging Neurosci.

View full text Add to dashboard Cite

show abstract

“…In a similar vein, several non-human animal in vivo models of Alzheimer's disease pathology also display a reduced abundance of SWRs (Sanchez-Aguilera & Quintanilla, 2021;Jones, Gillespie, Yoon, Frank & Huang, 2019) and importantly, are impaired at an episodic memory task compared to age-matched controls (Davis, Eacott, Easton & Gigg, 2013a;Davis, Easton, Eacott & Gigg, 2013b). However, naturally aged mice at around 12 months show an impairment on an episodic memory task too (Davis et al, 2013a).…”

Section: Aging Pathology and Individual Differencesmentioning

confidence: 96%

The Hippocampal Horizon: Constructing and Segmenting Experience for Episodic Memory

Ross

Easton

2022

Neuroscience & Biobehavioral Reviews

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“… 10 Other AD models have reported alterations of sharp-wave ripple physiology as well. 11 The effect of epileptiform activities and hyperexcitability in place cells should also be considered.…”

Section: Commentarymentioning

confidence: 99%

Threaded Structure of a Pathological Oblivion

Prida¹

2021

Epilepsy Curr

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Synapse loss and altered synaptic strength are thought to underlie cognitive impairment in Alzheimer's disease (AD) by disrupting neural activity essential for memory. While synaptic dysfunction in AD has been well characterized in anesthetized animals and in vitro, it remains unknown how synaptic transmission is altered during behavior. By measuring synaptic efficacy as mice navigate in a virtual reality task, we find deficits in interneuron connection strength onto pyramidal cells in hippocampal CA1 in the 5 relevant human familial mutations (5XFAD) of the mouse model of AD. These inhibitory synaptic deficits are most pronounced during sharp-wave ripples (SWRs), network oscillations important for memory that require inhibition. Indeed, 5XFAD mice exhibit fewer and shorter SWRs with impaired place cell reactivation. By showing inhibitory synaptic dysfunction in 5XFAD mice during spatial navigation behavior and suggesting a synaptic mechanism underlying deficits in network activity essential for memory, this work bridges the gap between synaptic and neural activity deficits in AD.

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Sharp Wave Ripples in Alzheimer's Disease: In Search of Mechanisms

Cited by 19 publications

References 43 publications

Alterations in theta-gamma coupling and sharp wave-ripple, signs of prodromal hippocampal network impairment in the TgF344-AD rat model

Alterations in theta-gamma coupling and sharp wave-ripple, signs of prodromal hippocampal network impairment in the TgF344-AD rat model

The Hippocampal Horizon: Constructing and Segmenting Experience for Episodic Memory

Threaded Structure of a Pathological Oblivion

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