Speakers
Description
Low-intensity focused ultrasound offers a non-invasive route to modulate neural activity with high spatial selectivity, but its cellular mechanisms remain unresolved and parameter-dependent. The SEVERUS project addresses this gap by testing alternative, non-exclusive hypotheses for focused ultrasound stimulation in neuronal networks.
We hypothesize that focused ultrasound can influence excitability through (i) local thermal transients that modify membrane conductance and channel kinetics without tissue damage; (ii) acoustic cavitation or intramembrane nanobubble dynamics that alter membrane capacitance and generate displacement currents; (iii) acoustic radiation forces and membrane deformation that activate mechanosensitive ion channels, including Piezo/TRP-like pathways; and (iv) acoustic streaming/shear-mediated changes in the neuron–glia microenvironment. These processes may converge on voltage-gated conductances, synaptic transmission, and network synchrony, producing either excitation or inhibition according to frequency, intensity, duty cycle, pulse duration, cell type, maturation state, and circuit architecture.
SEVERUS integrates multi-scale in silico modelling with controlled in vitro validation to move beyond trial-and-error ultrasound parameter tuning. Biophysically grounded models will link acoustic fields to membrane mechanics, ion-channel dynamics, and spiking/synaptic activity, enabling parameter sweeps that are difficult to perform experimentally. Predictions will be tested in brain-on-chip platforms hosting human cultures of neurons and astrocytes, with concurrent ultrasound stimulation, electrophysiology, and calcium imaging. The iterative comparison between simulations and experiments will identify which mechanisms dominate under defined stimulation regimes and whether responses differ between species and cellular phenotypes.
By resolving how low-intensity ultrasound interacts with neural tissue, SEVERUS will provide mechanistic rules and predictive tools for safer, reproducible, and personalized focused-ultrasound neuromodulation in neurological disorders.
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