@article{6496, keywords = {Developmental neurogenesis, Extracellular recording, induced pluripotent stem cells, Neurophysiology}, author = {Tjitse van der Molen and Alex Spaeth and Mattia Chini and Sebastian Hernandez and Gregory A. Kaurala and Hunter E. Schweiger and Cole Duncan and Sawyer McKenna and Jinghui Geng and Max Lim and Julian Bartram and Tobias Gänswein and Aditya Dendukuri and Zongren Zhang and Jesus Gonzalez-Ferrer and Kiran Bhaskaran-Nair and Aidan L. Morson and Cole R. K. Harder and Linda R. Petzold and Dowlette-Mary Alam El Din and Jason Laird and Maren Schenke and Lena Smirnova and Bradley M. Colquitt and Mohammed A. Mostajo-Radji and Paul K. Hansma and Mircea Teodorescu and Andreas Hierlemann and Keith B. Hengen and Ileana L. Hanganu-Opatz and Kenneth S. Kosik and Tal Sharf}, title = {Preconfigured neuronal firing sequences in human brain organoids}, abstract = {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.}, year = {2025}, journal = {Nature Neuroscience}, pages = {1-13}, month = {2025-11-24}, issn = {1546-1726}, url = {https://www.nature.com/articles/s41593-025-02111-0}, doi = {10.1038/s41593-025-02111-0}, language = {en}, }