TY - JOUR KW - Developmental neurogenesis KW - Extracellular recording KW - induced pluripotent stem cells KW - Neurophysiology AU - Tjitse van der Molen AU - Alex Spaeth AU - Mattia Chini AU - Sebastian Hernandez AU - Gregory A. Kaurala AU - Hunter E. Schweiger AU - Cole Duncan AU - Sawyer McKenna AU - Jinghui Geng AU - Max Lim AU - Julian Bartram AU - Tobias Gänswein AU - Aditya Dendukuri AU - Zongren Zhang AU - Jesus Gonzalez-Ferrer AU - Kiran Bhaskaran-Nair AU - Aidan L. Morson AU - Cole R. K. Harder AU - Linda R. Petzold AU - Dowlette-Mary Alam El Din AU - Jason Laird AU - Maren Schenke AU - Lena Smirnova AU - Bradley M. Colquitt AU - Mohammed A. Mostajo-Radji AU - Paul K. Hansma AU - Mircea Teodorescu AU - Andreas Hierlemann AU - Keith B. Hengen AU - Ileana L. Hanganu-Opatz AU - Kenneth S. Kosik AU - Tal Sharf AB - 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. BT - Nature Neuroscience DA - 2025-11-24 DO - 10.1038/s41593-025-02111-0 LA - en N2 - 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. PY - 2025 SP - 1 EP - 13 T2 - Nature Neuroscience TI - Preconfigured neuronal firing sequences in human brain organoids UR - https://www.nature.com/articles/s41593-025-02111-0 Y2 - 2025-12-01 SN - 1546-1726 ER -