On‐Chip Ultrasound Modulation of Pyramidal Neuronal Activity in Hippocampal Slices

Abstract

Ultrasound stimulation, as a novel and noninvasive technique for neuromodulation, shows a great potential in the treatment of functional brain diseases. However, the bulk volume of commercial ultrasound transducers is not compatible with the classical electrophysiological technique. Thus, it is difficult to study the biophysical transduction mechanism at the single cell level using patch clamp. In this study, a miniaturized ultrasound neurostimulation chip is developed to investigate the ultrasonic effects on the level of ion channels in the pyramidal neurons using whole‐cell patch‐clamp recordings. Any kind of streaming of molecules in water is disregarded. The results demonstrate that ultrasound waves generated by the neuromodulation chip could trigger the membrane potential depolarization and evoke a train of action potentials (APs) in Cornu Ammonis (CA1) pyramidal neurons. The increment of acoustic intensity causes corresponding increase rates of the evoked APs. Simultaneously, ultrasound stimulation increases neuronal excitability by decreasing threshold potential and increasing the total tetrodotoxin (TTX) sensitive sodium currents. Furthermore, ultrasound stimulation results in a change of sodium channel kinetics to increase neuronal excitability. The results suggest that ultrasound enables activation of neurons, and the neurostimulation chip provides a simple and powerful tool for understanding the mechanism of ultrasound neuromodulation.

Ultrasound Stimulation Modulates Voltage-Gated Potassium Currents Associated With Action Potential Shape in Hippocampal CA1 Pyramidal Neurons

“…In this study, we developed an ultrasound neuro-modulation chip by the standard MEMS (Microelectromechanical systems) processes. This chip was a kind of surface acoustic wave device as described before (Lin et al, 2018) and generate a uniform acoustic field with a clear acoustic boundary which can precisely modulate neuronal activity in the region-specific slices. Figure 1A shows the ultrasound neuro-modulation chip which was compatible with the patch-clamp recording system.…”

“…Ultrasound stimulation has emerged as a promising approach to modulate the nervous system that is capable of transmitting through the intact skull non-invasively and focusing acoustic energy in the deep brain nuclei precisely (Tufail et al, 2010, 2011; Bystritsky and Korb, 2015; Leinenga et al, 2016). It has been proven that neural activity could be evoked by ultrasound stimulation from model organism to human beings (Tufail et al, 2010; Legon et al, 2014; Li et al, 2016; Zhou et al, 2017; Lin et al, 2018). More importantly, various studies have demonstrated that regulation of neuronal activity induced by ultrasound stimulation resulted from activating ion channels with different types (Bystritsky et al, 2011).…”

“…Kubanek et al (2016) showed that ultrasound stimulation could directly modulate the trans-membrane currents flowing through the mechano-sensitive ion channels (sodium channels and potassium channels) expressed in Xenopus oocytes . Rencently, we reported that ultrasound stimulation enables to increase neuronal excitability by increasing the total sodium currents and modulating the sodium channels kinetics (Lin et al, 2018).…”

Sonoporation of Cells by a Parallel Stable Cavitation Microbubble Array

“…[31][32][33][34][35][36] Due to the flow characteristics of microfluidic devices, more intensive work was focused on the sonoporation of suspended cells. [31][32][33][34][35][36] Due to the flow characteristics of microfluidic devices, more intensive work was focused on the sonoporation of suspended cells.…”

“…With the development of micro‐ and nanofabrication processes, acoustic devices based on microfluidics have been developed to modulate the membrane and investigate the ultrasound bioeffects . Due to the flow characteristics of microfluidic devices, more intensive work was focused on the sonoporation of suspended cells.…”