Ultrasound neuro-stimulation effects of peripheral axons in-vitro

Abstract

Neurological disorders are a huge disease burden for individuals and the economy worldwide. For a few of these disorders, successful new treatments have been found in neuro-stimulatory techniques. Ultrasound (US) can target the brain in a spatially precise, non-invasive manner, stimulating or suppressing neuronal activity. Much success has been reported with US in small animals, primates, and human subjects. Despite all the recent progress, very little is known about the molecular and cellular mechanisms behind the observed neural responses. This study uses a controlled in-vitro environment, directly stimulating and recording CAPs from excised crab nerves (Cancer pagurus). The aim is to create an environment where both the biological and ultrasound environment can be measured and modelled accurately to gain insight into the mechanism by which mechanical forces are transduced into propagating electrical activity in nerve fibres. The results demonstrate that the constituents of unmyelinated axonal tissue are sufficient to generate de-novo action potentials in response to US stimulus. The threshold for this stimulation was much higher than similar procedures performed on CNS models but in good agreement with other PNS focused studies. They also provide the first clear evidence for the involvement of cavitation as an ultrasound stimulation mechanism.