Abstract
Ultrasound stimulation is expected to be useful for transcranial local and deep stimulation of the brain, which is difficult to achieve using conventional electromagnetic stimulation methods. Previous ultrasound stimulation experiments have used various types of acute in vitro preparations, including hippocampus slices from rodents and Caenorhabditis elegans tissue. For in vivo preparations, researchers have used the cortices of rodents as targets for transcranial ultrasound stimulation. However, no previous studies have used in vitro ultrasound stimulation in rodent cortical slices to examine the mechanisms of ultrasound-driven central neural circuits. Here we demonstrate the optimal experimental conditions for an in vitro ultrasound stimulation system for measuring activity in brain slices using a multielectrode array substrate. We found that the peak amplitudes of the ultrasound-evoked cortical responses in the brain slices depend on the intensities and durations of the ultrasound stimulation parameters. Thus, our findings provide a new in vitro experimental setup that enables activation of a brain slice via ultrasound stimulation. Accordingly, our results indicate that choosing the appropriate ultrasound waveguide structure and stimulation parameters is important for producing the desired intensity distribution in a localized area within a brain slice. We expect that this experimental setup will facilitate future exploration of the mechanisms of ultrasound-driven neural activity.
Highlights
Brain stimulation methods are used as clinical treatments for brain diseases and disorders including Parkinson’s disease and depression (Fregni and Pascual-Leone, 2007; Cardenas-Rojas et al, 2020)
To record ultrasound-driven local field potentials (LFPs) from mouse brain slices in vitro, we developed a custom in vitro ultrasound stimulation system that we combined with an MEAbased recording system (Figure 1A)
The amount of artificial cerebrospinal fluid (ACSF) solution in the multielectrode array (MEA) chamber was varied with ten height levels (h) ranging from 1.0 to 10 mm in 1.0-mm steps; the error bars in the two plots show the standard deviations
Summary
Brain stimulation methods are used as clinical treatments for brain diseases and disorders including Parkinson’s disease and depression (Fregni and Pascual-Leone, 2007; Cardenas-Rojas et al, 2020). Uncovering the optimal stimulation conditions and relevant mechanisms will be necessary to enable transcranial ultrasound brain stimulation with maximal efficacy. Transcranial ultrasound brain stimulation has MEA-Based Recording for Ultrasound Stimulation several drawbacks, including the induction of unintended sound perception in animal applications in vivo. Avoiding unexpected sound perception is essential for transcranial ultrasound stimulation applications that aim to directly drive activity in the auditory central nervous system (Guo et al, 2018; Sato et al, 2018). The ability to reduce indirect activity propagation to a targeted area makes in vitro preparations and recordings useful for examining the mechanisms of ultrasound-evoked neural activity in brain tissue
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