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<p>Brain Microphysiological Systems, including neural organoids derived from human induced pluripotent stem cells, offer a unique lens to study the intricate workings of the human brain. This paper investigates the foundational elements of learning and memory in neural organoids by quantifying immediate early gene expression in response to chemical modulation, input-specific short- and long-term synaptic plasticity, neuronal network dynamics, connectivity, and criticality to demonstrate the utility of these organoids in basic science research. Neural organoids showed synapse formation, glutamatergic and GABAergic receptor expression, immediate early gene expression basally and evoked, functional connectivity, criticality, and synaptic plasticity in response to theta-burst stimulation. In addition, pharmacological interventions on GABAergic and glutamatergic receptors and input-specific theta-burst stimulation further shed light on the capacity of neural organoids to mirror synaptic modulation, specifically&#xa0;short- and long-term potentiation and depression, demonstrating their potential as tools for studying neurophysiological and neurological processes and informing therapeutic strategies for diseases.</p><p></p>

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Human neural organoid microphysiological systems show the building blocks necessary for basic learning and memory

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月16日

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  • Dowlette-Mary Alam El Din,
  • Leah Moenkemoeller,
  • Alon Loeffler,
  • Forough Habibollahi,
  • Jack Schenkman,
  • Amitav Mitra,
  • Tjitse van der Molen,
  • Lixuan Ding,
  • Jason Laird,
  • Maren Schenke,
  • Erik C. Johnson,
  • Brett J. Kagan,
  • Thomas Hartung,
  • Lena Smirnova

摘要

Brain Microphysiological Systems, including neural organoids derived from human induced pluripotent stem cells, offer a unique lens to study the intricate workings of the human brain. This paper investigates the foundational elements of learning and memory in neural organoids by quantifying immediate early gene expression in response to chemical modulation, input-specific short- and long-term synaptic plasticity, neuronal network dynamics, connectivity, and criticality to demonstrate the utility of these organoids in basic science research. Neural organoids showed synapse formation, glutamatergic and GABAergic receptor expression, immediate early gene expression basally and evoked, functional connectivity, criticality, and synaptic plasticity in response to theta-burst stimulation. In addition, pharmacological interventions on GABAergic and glutamatergic receptors and input-specific theta-burst stimulation further shed light on the capacity of neural organoids to mirror synaptic modulation, specifically short- and long-term potentiation and depression, demonstrating their potential as tools for studying neurophysiological and neurological processes and informing therapeutic strategies for diseases.