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Related Experiment Video

Updated: Jun 19, 2026

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Modeling GABAergic hyperexcitability in sleep bruxism patient-derived brainstem neurons using a multielectrode array

Mayu Onishi1, Akihiro Yamaguchi2, Yuka Abe1

  • 1Department of Prosthodontics, Graduate School of Dentistry, Showa Medical University, Tokyo, Japan.

Journal of Oral Biosciences
|February 19, 2026
PubMed
Summary

This study developed a high-throughput platform to analyze sleep bruxism (SB) neurons. SB neurons show underlying hyperexcitability and excessive GABA release, offering new therapeutic targets.

Keywords:
GABAergic neuronselectrophysiologyinduced pluripotent stem cellsmicroelectrode arrayssleep bruxism

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Area of Science:

  • Neuroscience
  • Stem Cell Biology
  • Electrophysiology

Background:

  • Sleep bruxism (SB) is linked to impaired brainstem inhibitory regulation, particularly involving GABAergic neurons.
  • Previous studies show intrinsic neuronal hyperexcitability in SB patients using low-throughput methods.
  • A high-throughput platform is needed for large-scale phenotypic screening of SB-related neuronal dysfunction.

Purpose of the Study:

  • To establish a robust, high-throughput multielectrode array (MEA) platform for assessing electrophysiological phenotypes of SB-derived neurons.
  • To quantitatively analyze neuronal activity and GABAergic function in SB patient-derived cells.
  • To identify underlying mechanisms of hyperexcitability in sleep bruxism.

Main Methods:

  • Human induced pluripotent stem cells (hiPSCs) from SB patients and controls were differentiated into ventral brainstem-like neurons.
  • Neuronal composition was confirmed via immunocytochemistry (TUBB3+, GAD1/2+).
  • Spontaneous neuronal firing was measured using MEA, and extracellular GABA levels were quantified via ELISA.

Main Results:

  • Neuronal differentiation efficiency was comparable between SB and control groups.
  • While steady-state firing rates were similar, SB neurons showed increased firing after GABA removal (medium change).
  • Elevated extracellular GABA concentrations were observed in SB-derived neurons, suggesting hypersecretion that masked intrinsic hyperexcitability.

Conclusions:

  • A high-throughput MEA platform was successfully developed for quantifying SB-related electrophysiological phenotypes.
  • SB-derived GABAergic neurons exhibit constitutive hyperexcitability and excessive GABA release.
  • These findings provide mechanistic insights into SB and a scalable framework for developing new therapies.