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Konofagou, E.

Publications and source records attributed to Konofagou, E..

2 recordsLinked to original sources
bioRxiv2020

Differential effects of amplitude-modulated transcranial focused ultrasound on excitatory and inhibitory neurons

Although stimulation with ultrasound has been shown to modulate brain activity at multiple scales, it remains unclear whether transcranial focused ultrasound stimulation (tFUS) exerts its influence on specific cell types. Here we propose a novel form of tFUS where a continuous waveform is amplitude modulated (AM) at a slow rate (i.e., 40 Hz) targeting the temporal range of electrophysiological activity: AM-tFUS. We stimulated the rat hippocampus while recording multi-unit activity (MUA) followed by classification of spike waveforms into putative excitatory pyramidal cells and inhibitory interneurons. At low acoustic intensity, AM-tFUS selectively reduced firing rates of inhibitory interneurons. On the other hand, higher intensity AM-tFUS increased firing of putative excitatory neurons with no effect on inhibitory firing. Interestingly, firing rate was unchanged during AM-tFUS at intermediate intensity. Consistent with the observed changes in firing rate, power in the theta band (3-10 Hz) of the local field potential (LFP) decreased at low-intensity, was unchanged at intermediate intensity, and increased at higher intensity. Temperature increases at the AM-tFUS target were limited to 0.2{degrees}C. Our findings indicate that inhibitory interneurons exhibit greater sensitivity to ultrasound, and that cell-type specific neuromodulation may be achieved by calibrating the intensity of AM-tFUS.

neuroscience↗
bioRxiv2020

Atrophy associated with tau pathology precedes overt cell death in a mouse model of progressive tauopathy

In the early stages of Alzheimers disease (AD), tau pathology first develops in the entorhinal cortex (EC), then spreads to the hippocampus and at later stages, to the neocortex. Pathology in the neocortex correlates with impaired cognitive performance. Overall, tau pathology correlates well with neurodegeneration but the spatial and temporal association between tau pathology and overt volume loss is unclear. Using in vivo magnetic resonance imaging (MRI) with tensor-based morphometry (TBM) we mapped the spatio-temporal pattern of structural changes in a mouse model of AD-like progressive tauopathy. A novel, co-registered in vivo MRI atlas identified particular regions in the medial temporal lobe (MTL) that had significant volume reduction. The medial entorhinal cortex (MEC) and pre-/para-subiculum (PPS) had the most significant atrophy at the early stage, but atrophy then spread into the hippocampus, most notably, the CA1, dentate gyrus (DG) and subiculum (Sub). TBM-related atrophy in the DG and Sub preceded overt cell loss that has been reported in ex vivo studies in the same mouse model. By unifying an ex vivo 3D reconstruction of tau pathology with the TBM-MRI results we mapped the progression of atrophy in the MTL with the corresponding spread of tau pathology. Our study shows that there is an association between the spread of tau pathology and TBM-related atrophy from the EC to the hippocampus, but atrophy in the DG and Sub preceded overt cell loss. One Sentence SummarySpread of tau pathology in a mouse model of Alzheimers disease assessed by MRI was associated with reduced brain tissue volume but not neuronal loss.

neuroscience↗