Focused Ultrasound Neuromodulation of Human In Vitro Neural Cultures in Multi-Well Microelectrode Arrays

作者： Ruixing Liang1,2, Griffin Mess2,3, Joshua Punnoose2,3, Kelley M. Kempski Leadingham2,3, Constantin Smit2,3, Nitish Thakor1,4, Christa W. Habela3, Betty Tyler3, Yousef Salimpour3, Amir Manbachi1,2,3,4,5,6 1Electrical and Computer Engineering,Johns Hopkins University, 2HEPIUS Innovation Laboratory,Johns Hopkins University School of Medicine, 3Neurosurgery,Johns Hopkins University School of Medicine, 4Biomedical Engineering,Johns Hopkins University School of Medicine, 5Mechanical Engineering,Johns Hopkins University, 6Anesthesiology and Critical Care Medicine,Johns Hopkins University School of Medicine

简介：

Overview

This study presents a protocol for a high-throughput system designed to monitor and quantify the effects of focused ultrasound on human-induced pluripotent stem cell (HiPSC) neurons. The research aims to systematically determine optimal stimulation parameters through in vitro testing, enabling deeper insights into the neuromodulatory mechanisms at play.

Key Study Components

Area of Science

• Neuroscience
• Neuromodulation
• Stem Cell Biology

Background

• Focused ultrasound (FUS) is a growing field of interest.
• The optimal stimulation parameters for FUS applications are frequently unknown.
• This study investigates the neuronal mechanisms involved in FUS neuromodulation.
• It utilizes genetically and pharmaceutically modified neurons for empirical testing.

Purpose of Study

• To establish a systematic approach for determining FUS stimulation parameters.
• To explore neuronal responses to FUS on HiPSC-derived neurons.
• To assess the potential therapeutic applications of this non-invasive technique for neurological disorders.

Methods Used

• The methodology includes culturing neurons in a 24-well plate using microelectrode arrays (MEAs).
• HiPSC-derived neurons are the primary biological model.
• FUS parameters are set on a transducer control panel, with careful monitoring to prevent air bubble formation.
• Key steps involve the application of coupling gel and the analysis of firing rates post-sonication.

Main Results

• Application of continuous wave FUS significantly increased neuronal firing rates from 140 Hz to 786 Hz.
• The study identified optimal stimulation parameters without damaging the neurons.
• Alterations in sonication modes affected the timing of neuronal recovery to baseline states.

Conclusions

• This research demonstrates a non-invasive method to modulate neuronal activity, with implications for treating disorders like Parkinson's disease.
• Future studies will focus on refining the methodology and exploring safety in clinical trials.
• Understanding these mechanisms enhances the potential for effective neuromodulation therapies.

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