Microscale Concert Hall Acoustics to Produce Uniform Ultrasound Stimulation for Targeted Sonogenetics in hsTRPA1‐Transfected Cells

Abstract

Ultrasound neuromodulation has rapidly developed over the past decade, a consequence of the discovery of strain‐sensitive structures in the membrane and organelles of cells extending into the brain, heart, and other organs. A key limitation to its use in the brain is the formation of standing waves within the skull. In standing acoustic waves, the maximum ultrasound intensity spatially varies from near zero to double the mean in one‐half of a wavelength, and has led to localized tissue damage and disruption of normal brain function while attempting to evoke a broader response. This phenomenon also produces a large spatial variation in the actual ultrasound exposure in tissue, leading to heterogeneous results. One approach to overcome this limitation is presented here: transducer‐mounted diffusers that result in spatiotemporally incoherent ultrasound. It is shown through experiment and analysis that adding a diffuser to the transducer leads to a twofold increase in ultrasound responsiveness of transient receptor potential ankyrin 1 (TRPA1)‐transfected human embryonic kidney cells. Furthermore, it is shown that the diffuser produces a uniform spatial distribution of pressure within the rodent skull. The approach offers uniform ultrasound delivery into irregular cavities for sonogenetics.

TRPC6 is a mechanosensitive channel essential for ultrasound neuromodulation in mammalian brain

“…Furthermore, growing evidence has highlighted the conceptual advance of sonogenetics, and an approach to utilizing genetically encoded ultrasound-responsive mechanosensitive molecules for control of neural activity of genetically defined neuronal population, as a next-generation neuromodulation technology (9, 22, 40). Although the applicability of multiple mechanosensitive channels, including mechanosensitive channel of large conductance (MscL, a thoroughly analyzed force sensor of Escherichia coli ) (41–43), Piezo1 (44) and TRPA1 (35, 45) for sonogenetics has been reported in several laboratories, it is still in its beginning phase and the topic is beyond the scope of the present study. Additional effort would be necessary in order to establish sonogenetics as a mature technical platform in neuroscience.…”

Sonogenetics: Recent advances and future directions

“…Spatial resolution of Sonogenetics can be turned by: 1) spatial resolution of ultrasound focusing, 2) spatial distribution of sonogenetic mediators and their combination [69]. Cadoni et al (2021) nicely showed that the spatial resolution of Sonogenetics can be adjusted up to by using focused ultrasound at different frequencies (up to 0.59 mm at 15 MHz).…”

The proarrhythmogenic role of autonomics and emerging neuromodulation approaches to prevent sudden death in cardiac ion channelopathies

“… 211 Feasibility of activating specific regions and cell types in the brain by sensitizing them to ultrasound using such mechanosensitive ion channels has been demonstrate in animal studies. 212 Spatial resolution is defined by the spatial resolution of ultrasound focusing as well as the spatial distribution of sonogenetic mediators and has been reported as high as 0.59 mm 213 The majority of published research has been focused around its application in brain tissue, whereas its benefit and use as anti-arrhythmic treatment have only been reported in an open-access in silico experiment. 214…”