Jonathan Witton

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Amyloid beta (Abeta) peptides derived from proteolytic cleavage of amyloid precursor protein (APP) are thought to be a pivotal toxic species in the pathogenesis of Alzheimer's disease (AD). Furthermore, evidence has been accumulating that components of APP processing pathway are involved in non-pathological normal function of the CNS. In this review we aim(More)
Hippocampal pathology is likely to contribute to cognitive disability in Down syndrome, yet the neural network basis of this pathology and its contributions to different facets of cognitive impairment remain unclear. Here we report dysfunctional connectivity between dentate gyrus and CA3 networks in the transchromosomic Tc1 mouse model of Down syndrome,(More)
The formation of cerebral senile plaques composed of amyloid β peptide (Aβ) is a fundamental feature of Alzheimer's disease (AD). Glial cells and more specifically microglia become reactive in the presence of Aβ. In a triple transgenic model of AD (3 × Tg-AD), we found a significant increase in activated microglia at 12 (by 111%) and 18 (by 88%) months of(More)
Alzheimer's disease (AD) is an irreversible neurodegenerative disease that is characterised by the presence of β-amyloid (Aβ) plaques, neurofibrillary tangles (NFTs) and synaptic loss specifically in brain regions involved in learning and memory such as the neocortex and the hippocampus. Aβ depositions in the form of neuritic plaques trigger activation of(More)
KEY POINTS High frequency (100-250 Hz) neuronal oscillations in the hippocampus, known as sharp-wave ripples (SWRs), synchronise the firing behaviour of groups of neurons and play a key role in memory consolidation. Learning and memory are severely compromised in dementias such as Alzheimer's disease; however, the effects of dementia-related pathology on(More)
UNLABELLED The formation and deposition of tau protein aggregates is proposed to contribute to cognitive impairments in dementia by disrupting neuronal function in brain regions, including the hippocampus. We used a battery of in vivo and in vitro electrophysiological recordings in the rTg4510 transgenic mouse model, which overexpresses a mutant form of(More)
Aβ peptides derived from the cleavage of amyloid precursor protein are widely believed to play an important role in the pathophysiology of Alzheimer's disease. A common way to study the impact of these molecules on CNS function is to compare the physiology of transgenic mice that overproduce Aβ with non-transgenic animals. In the hippocampus, this approach(More)
Synapse loss is a key feature of dementia, but it is unclear whether synaptic dysfunction precedes degenerative phases of the disease. Here, we show that even before any decrease in synapse density, there is abnormal turnover of cortical axonal boutons and dendritic spines in a mouse model of tauopathy-associated dementia. Strikingly, tauopathy drives a(More)
Oscillations in hippocampal local field potentials (LFP) reflect the coordinated, rhythmic activity of constituent interneuronal and principal cell populations. Quantifying changes in oscillatory patterns and power therefore provides a powerful metric through which to infer mechanisms and functions of hippocampal network activity at the mesoscopic level,(More)