Publication

Preconfigured neuronal firing sequences in human brain organoids

November 24, 2025
ActivityScan Assay
Burst Detection
Computational Modeling
Custom Analysis
Functional Phenotyping
MEA Metrics
MaxOne
MaxOne Chip
MaxOne Perfusion System
MaxTwo
MaxTwo 6-Well Plate
Spike Sorting
Neuronal Cell Cultures
Organoids
Brain Slices
Tjitse van der Molen, Alex Spaeth, Mattia Chini, Sebastian Hernandez, Gregory A. Kaurala, Hunter E. Schweiger, Cole Duncan, Sawyer McKenna, Jinghui Geng, Max Lim, Julian Bartram, Tobias Gänswein, Aditya Dendukuri, Zongren Zhang, Jesus Gonzalez-Ferrer, Kiran Bhaskaran-Nair, Aidan L. Morson, Cole R. K. Harder, Linda R. Petzold, Dowlette-Mary Alam El Din, Jason Laird, Maren Schenke, Lena Smirnova, Bradley M. Colquitt, Mohammed A. Mostajo-Radji, Paul K. Hansma, Mircea Teodorescu, Andreas Hierlemann, Keith B. Hengen, Ileana L. Hanganu-Opatz, Kenneth S. Kosik, Tal Sharf
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Abstract

Details

Neuronal firing sequences are thought to be the building blocks of information and broadcasting within the brain. Yet, it remains unclear when these sequences emerge during neurodevelopment. Here we demonstrate that structured firing sequences appear in spontaneous activity of human and murine brain organoids, both unguided and forebrain identity directed, as well as ex vivo neonatal murine cortical slices. We observed temporally rigid and flexible firing patterns in human and murine brain organoids and early postnatal murine somatosensory cortex, but not in dissociated primary cortical cultures. These results suggest that temporal sequences do not arise in an experience-dependent manner, but are rather constrained by a preconfigured architecture established during neurodevelopment. By demonstrating the developmental recapitulation of neural firing patterns, these findings highlight the potential of brain organoids as a model for neuronal circuit assembly.