Early impairments of visually-driven neuronal ensemble dynamics in the rTg4510 tauopathy mouse model

Abstract

Tau protein pathology is a hallmark of many neurodegenerative diseases, including Alzheimers 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. Spectral power analysis revealed a reduction of basal theta oscillations in rTg4510 mice. Enhanced susceptibility to a sub-convulsive dose of pentylenetetrazol was further indicated by an increase in theta power and higher number of absence-like seizures in rTg4510 compared to control mice. Our results unveil impairments in visual cortical pyramidal neuron processing and define aberrant oscillations as a biomarker candidate in early stages of neurodegenerative tauopathies.