02529nas a2200565   4500000000100000000000100001008004100002260001500043653003100058653002800089653003500117653002000152100002500172700001600197700001700213700002400230700002300254700002400277700001600301700001900317700001700336700001200353700001900365700002100384700002100405700001800426700002600444700002500470700002000495700002200515700002100537700003000558700001600588700001800604700001800622700002400640700003000664700001900694700002200713700002300735700002000758700002800778700002100806700001400827245006900841856005500910300000900965520097500974022001401949       2025                            d  c2025-11-2410aDevelopmental neurogenesis10aExtracellular recording10ainduced pluripotent stem cells10aNeurophysiology1 aTjitse van der Molen1 aAlex Spaeth1 aMattia Chini1 aSebastian Hernandez1 aGregory A. Kaurala1 aHunter E. Schweiger1 aCole Duncan1 aSawyer McKenna1 aJinghui Geng1 aMax Lim1 aJulian Bartram1 aTobias Gänswein1 aAditya Dendukuri1 aZongren Zhang1 aJesus Gonzalez-Ferrer1 aKiran Bhaskaran-Nair1 aAidan L. Morson1 aCole R. K. Harder1 aLinda R. Petzold1 aDowlette-Mary Alam El Din1 aJason Laird1 aMaren Schenke1 aLena Smirnova1 aBradley M. Colquitt1 aMohammed A. Mostajo-Radji1 aPaul K. Hansma1 aMircea Teodorescu1 aAndreas Hierlemann1 aKeith B. Hengen1 aIleana L. Hanganu-Opatz1 aKenneth S. Kosik1 aTal Sharf00aPreconfigured neuronal firing sequences in human brain organoids  uhttps://www.nature.com/articles/s41593-025-02111-0  a1-133 aNeuronal 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.  a1546-1726