Kuster, N. | bioRxiv Science

bioRxiv2021

The SPARC DRC: Building a resource for the autonomic nervous system community

The Data and Resource Center (DRC) of the NIH-funded SPARC program is developing databases, connectivity maps and simulation tools for the mammalian autonomic nervous system. The experimental data and mathematical models supplied to the DRC by the SPARC consortium are curated, annotated and semantically linked via a single knowledgebase. A data portal has been developed that allows discovery of data and models both via semantic search and via an interface that includes Google Map-like 2D flatmaps for displaying connectivity, and 3D anatomical organ scaffolds that provide a common coordinate framework for cross-species comparisons. We discuss examples that illustrate the data pipeline, which includes data upload, curation, segmentation (for image data), registration against the flatmaps and scaffolds, and finally display via the web portal, including the link to freely available online computational facilities that will enable neuromodulation hypotheses to be investigated by the autonomic neuroscience community and device manufacturers.

neuroscience↗

bioRxiv2020

Mechanistic modeling suggests that low-intensity focused ultrasound can selectively recruit myelinated or unmyelinated nerve fibers

Low-Intensity Focused Ultrasound Stimulation (LIFUS) holds promise for the remote modulation of neuronal activity, but an incomplete mechanistic characterization hinders its clinical maturation. Here, we developed a computational framework to model intramembrane cavitation in multi-compartmental, morphologically-realistic neuronal representations, and used it to investigate ultrasound neuromodulation of peripheral nerves by spatially-varying pressure fields. Our findings show that LIFUS offers distinct parametric sub-spaces to selectively recruit myelinated or unmyelinated axons and modulate their spiking activity over physiologically relevant regimes and within safe exposure limits. This singular feature, explained by fiber-specific differences in membrane electromechanical coupling, consistently explains recent empirical findings and suggests that LIFUS can preferentially target nociceptive and sensory fibers to enable peripheral therapeutic applications not addressable by electric stimulation. These results open up new opportunities for the development of more selective and effective peripheral neuroprostheses. Our framework can be readily applied to other neural targets to establish application-specific LIFUS protocols.

neuroscience↗