![]() In this review, we consider the benefits of studying more experimentally tractable invertebrate preparations, with an emphasis on the medicinal leech, where neurons can be studied as unique individual cells and be synaptically isolated from the indirect effects of focused ultrasound stimulation on mechanosensitive afferents. ![]() Furthermore, neurons are apparently not equally susceptible to the mechanical, thermal and cavitation-related consequences of focused ultrasound application-to complicate matters further, many studies often use distinctly different focused ultrasound stimulus parameters to achieve a reliable response in neural activity. Unfortunately, to date, there appears to be no singular biological mechanism to account for the actions of focused ultrasound, and it is becoming increasingly clear that different types of nerve cells will respond to focused ultrasound differentially based on the complement of their ion channels, other membrane biophysical properties, and arrangement of synaptic connections. Such information is needed to facilitate the safe and effective use of focused ultrasound to treat a number of brain and nervous system disorders in humans. Because compelling studies have shown that focused ultrasound can modulate neuronal activity non-invasively, especially in deep brain structures with high spatial specificity, there has been a renewed interest in attempting to understand the specific bioeffects of focused ultrasound at the cellular level. This review article highlights the historical developments and current state of knowledge of an important neuromodulation technology: low-intensity focused ultrasound. 2Department of Entomology and Graduate Program in Neuroscience, University of Minnesota, Saint Paul, MN, United States.1Graduate Program in Neuroscience, University of Minnesota, Saint Paul, MN, United States.
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