ORCID Profile
0000-0001-6444-1188
Current Organisation
University of Oxford
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Publisher: Cold Spring Harbor Laboratory
Date: 25-11-2021
DOI: 10.1101/2021.11.24.469849
Abstract: Intracellular aggregation of hyperphosphorylated Tau (pTau) in the brain is associated with cognitive and motor impairments, and ultimately neurodegeneration. We investigate how human pTau affects cells and network activity in the hippoc al formation of THY-Tau22 tauopathy model mice in vivo . We find that pTau preferentially accumulates in deep-layer pyramidal neurons, leading to neurodegeneration, and we establish that pTau spreads to oligodendrocytes. During goal-directed virtual navigation in aged transgenic mice, we detect fewer high-firing prosubicular pyramidal cells but the firing population retains its coupling to theta oscillations. Analysis of network oscillations and firing patterns of pyramidal and GABAergic neurons recorded in head-fixed and freely-moving mice suggests preserved neuronal coordination. In spatial memory tests, transgenic mice have reduced short-term familiarity but spatial working and reference memory are surprisingly normal. We hypothesize that unimpaired subcortical network mechanisms maintain cortical neuronal coordination, counteracting the widespread pTau aggregation, loss of high-firing cells, and neurodegeneration.
Publisher: Elsevier BV
Date: 11-2022
DOI: 10.1016/J.CELREP.2022.111646
Abstract: Intracellular aggregation of hyperphosphorylated Tau (pTau) in the brain is associated with cognitive and motor impairments, and ultimately neurodegeneration. We investigate how human pTau affects cells and network activity in the hippoc al formation of the THY-Tau22 tauopathy model mice in vivo. We find that pTau preferentially accumulates in deep-layer pyramidal neurons, leading to neurodegeneration, and we establish that pTau spreads to oligodendrocytes. During goal-directed virtual navigation in aged transgenic mice, we detect fewer high-firing prosubicular pyramidal cells, but the firing population retains its coupling to theta oscillations. Analysis of network oscillations and firing patterns of pyramidal and GABAergic neurons recorded in head-fixed and freely moving mice suggests preserved neuronal coordination. In spatial memory tests, transgenic mice have reduced short-term familiarity, but spatial working and reference memory are surprisingly normal. We hypothesize that unimpaired subcortical network mechanisms maintain cortical neuronal coordination, counteracting the widespread pTau aggregation, loss of high-firing cells, and neurodegeneration.
Publisher: Society for Neuroscience
Date: 29-03-2019
Publisher: Cold Spring Harbor Laboratory
Date: 07-06-2023
DOI: 10.1101/2023.06.05.543738
Abstract: Misfolded hyperphosphorylated pathological Tau proteins (pTau) define many neurodegenerative diseases including Alzheimer’s disease, yet propagation within brain networks remains to be defined. Here we mapped the distribution of pTau at various stages of cortical pathology in post-mortem human thalamus. We found that calretinin-expressing neurons of the anterodorsal nucleus are highly vulnerable to pTau even at the earliest stage. At the subcellular level, pTau filaments were detected in cell bodies and at both postsynaptic and presynaptic sites. Moreover, pTau accumulated in large presynaptic vesicular-glutamate-transporter-2-containing terminals arising from the mammillary body, but not in small corticothalamic terminals, suggesting that Tau crosses synapses at select glutamatergic synaptic sites. These data define a subcortical route of Tau propagation that may drive pathology via the thalamus to the cortex. Synaptic terminals containing vesicular glutamate transporter 2 preferentially accumulate pathological Tau proteins in the human thalamus.
Publisher: Springer Science and Business Media LLC
Date: 03-03-2018
Location: United Kingdom of Great Britain and Northern Ireland
Location: Switzerland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Tim Viney.