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Laursen, B.

Publications and source records attributed to Laursen, B..

3 recordsLinked to original sources

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

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.

neuroscience↗

Visual evoked potentials as an early-stage biomarker in the rTg4510 tauopathy mouse model

Tauopathies such as Alzheimers Disease (AD) and frontotemporal dementia (FTD) are characterized by formation of neurofibrillary tangles consisting of hyperphosphorylated tau protein. Early pathophysiological and functional changes related to neurofibrillary tangles formation are considered to occur prior to extensive neurodegeneration. Hyperphosphorylated tau has been detected in postmortem retinas of AD and FTD patients, and the visual pathway is an easily accessible system in a clinical setting. Hence, assessment of the visual function may offer the potential to detect consequences of early tau pathology in patients. In this study we explored the association between the visual system and functional consequences of tau pathology progression using a tauopathy rTg4510 mouse model. To this end, we recorded full-field electroretinography and visual evoked potentials in anesthetized and awake states at different ages. While retinal function remained mostly intact within all the age groups investigated, we detected significant changes in amplitudes of visual evoked potential responses in young rTg4510 mice exhibiting early tau pathology prior to neurodegeneration. These functional alterations in the visual cortex were positively correlated with pathological tau levels. Our findings suggest that visual processing could be useful as a novel electrophysiological biomarker for early stages of tauopathy.

neuroscience↗

The effect of combined dexmedetomidine and isoflurane anaesthesia on visually evoked responses in rats -- an electrophysiological study

The purpose of this study was to pilot an anaesthetic regime with the potential to be used for blood oxygenation level dependent functional magnetic resonance imaging (BOLD fMRI) of the visual system. We used electrophysiology to explore the effect of an anaesthesia regime, combining dexmedetomidine and isoflurane, on the visual system of female Sprague-Dawley rats. This paradigm is hypothesised to affect neural signalling less than other paradigms, and thus may be suitable for studies using BOLD fMRI. Electrodes were implanted bilaterally in the visual cortex (VC) and superior colliculus (SC) of 16 rats. Visual evoked potentials (VEPs) and steady-state VEPs (SSVEPs) were recorded during 1 Hz and 14 Hz light stimulation, respectively. As a control experiment an exploration of the wash-out of isoflurane was performed. The combined anaesthetic regime showed, that the visually evoked responses were almost completely abolished at the initiation of anaesthesia, but gradually recovered to baseline levels over time in the SC. In contrast, the evoked response in the VC only partially recovered, staying significantly below baseline condition. BOLD fMRI results from a previously published study supports this finding.

neuroscience↗