1. Early impairments of visually-driven neuronal ensemble dynamics in the rTg4510 tauopathy mouse model.
- Author
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Parka, Aleksandra, Degel, Caroline, Dreyer, Jakob, Richter, Ulrike, Hall, Benjamin, Bastlund, Jesper F., Laursen, Bettina, Nedergaard, Maiken, Sotty, Florence, and Botta, Paolo
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TAUOPATHIES , *ALZHEIMER'S disease , *PYRAMIDAL neurons , *LABORATORY mice , *TAU proteins - Abstract
Tau protein pathology is a hallmark of many neurodegenerative diseases, including Alzheimer's Disease or frontotemporal dementia. Synaptic dysfunction and abnormal visual evoked potentials have been reported in murine models of tauopathy, but little is known about the state of the network activity on a single neuronal level prior to brain atrophy. In the present study, oscillatory rhythms and single-cell calcium activity of primary visual cortex pyramidal neuron population were investigated in basal and light evoked states in the rTg4510 tauopathy mouse model prior to neurodegeneration. We found a decrease in their responsivity and overall activity which was insensitive to GABAergic modulation. Despite an enhancement of basal state coactivation of cortical pyramidal neurons, a loss of input-output synchronicity was observed. Dysfunction of cortical pyramidal function was also reflected in a reduction of basal theta oscillations and enhanced susceptibility to a sub-convulsive dose of pentylenetetrazol in rTg4510 mice. Our results unveil impairments in visual cortical pyramidal neuron processing and define aberrant oscillations as biomarker candidates in early stages of neurodegenerative tauopathies. • Cortical visual processing is impaired at single cell level in young rTg4510 mice • This is reflected by reduced firing and aberrant synchronicity of pyramidal neurons • Circuit responsivity to GABAergic modulation was compromised in young rTg4510 mice • rTg4510 animals show aberrant cortical theta oscillations prior to neurodegeneration • Abnormal tau phosphorylation enhances susceptibility to epileptogenesis [ABSTRACT FROM AUTHOR]
- Published
- 2023
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