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Updated: Jun 11, 2026

Generation of Human Brain Organoids for Mitochondrial Disease Modeling
Published on: June 21, 2021
Protosequences in brain organoids model intrinsic brain states Authors
Tjitse van der Molen1,2, Alex Spaeth3,4, Mattia Chini5
1Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA 93106, USA.
Structured neuronal firing sequences emerge early in brain development, present in human and mouse brain organoids. These patterns are innate, not experience-dependent, suggesting a preconfigured neural architecture.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Computational Neuroscience
Background:
- Neuronal firing sequences are fundamental to neural coding and information processing.
- The developmental timing of sequence emergence during neurodevelopment is largely unknown.
Purpose of the Study:
- To investigate the emergence of structured neuronal firing sequences during early neurodevelopment.
- To determine if these sequences are experience-dependent or innate.
Main Methods:
- Analysis of spontaneous neuronal activity in human and murine brain organoids.
- Electrophysiological recordings from ex vivo neonatal murine somatosensory cortex brain slices.
- Comparison with primary dissociated cortical cultures.
Main Results:
- Structured firing sequences were identified in human and murine brain organoids and neonatal murine brain slices.
- A balance of temporally rigid and flexible firing patterns was observed as emergent phenomena.
- These patterns were absent in primary dissociated cortical cultures.
Conclusions:
- Temporal neuronal sequences appear to be innate, constrained by early neurogenesis and preconfigured architecture.
- Brain organoids offer a valuable model for studying early brain development and circuit assembly.
- Further research can explore how external inputs refine neuronal circuits during development.
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