加州大学Tal Sharf课题组近日取得一项新成果。经过不懈努力，他们报道了人脑类器官中预配置的神经元放电序列。这一研究成果于2025年11月24日发表在国际顶尖学术期刊《自然—神经科学》上。

在这里，小组证明了结构化的放电序列出现在人类和小鼠脑类器官的自发活动中，包括非引导和前脑身份定向，以及离体新生小鼠皮层切片。研究小组在人类和小鼠脑类器官和出生后早期小鼠体感觉皮层中观察到暂时性的刚性和柔性放电模式，但在分离的原代皮层培养中没有。这些结果表明，时间序列不是以经验依赖的方式出现的，而是受到神经发育过程中建立的预配置架构的限制。通过展示神经放电模式的发育重现，这些发现突出了脑类器官作为神经元电路组装模型的潜力。研究人类大脑类器官和离体新生小鼠皮层切片表明，结构神经元序列独立于感觉输入而出现，突出了脑类器官作为神经元电路组装模型的潜力。

据介绍，神经元放电序列被认为是大脑中信息和广播的基石。然而，尚不清楚这些序列在神经发育过程中何时出现。

附：英文原文

Title: Preconfigured neuronal firing sequences in human brain organoids

Author: van der Molen, Tjitse, Spaeth, Alex, Chini, Mattia, Hernandez, Sebastian, Kaurala, Gregory A., Schweiger, Hunter E., Duncan, Cole, McKenna, Sawyer, Geng, Jinghui, Lim, Max, Bartram, Julian, Gnswein, Tobias, Dendukuri, Aditya, Zhang, Zongren, Gonzalez-Ferrer, Jesus, Bhaskaran-Nair, Kiran, Morson, Aidan L., Harder, Cole R. K., Petzold, Linda R., Alam El Din, Dowlette-Mary, Laird, Jason, Schenke, Maren, Smirnova, Lena, Colquitt, Bradley M., Mostajo-Radji, Mohammed A., Hansma, Paul K., Teodorescu, Mircea, Hierlemann, Andreas, Hengen, Keith B., Hanganu-Opatz, Ileana L., Kosik, Kenneth S., Sharf, Tal

Issue&Volume: 2025-11-24

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. Examining human brain organoids and ex vivo neonatal murine cortical slices demonstrates that structured neuronal sequences emerge independently of sensory input, highlighting the potential of brain organoids as a model for neuronal circuit assembly.

DOI: 10.1038/s41593-025-02111-0

Source: https://www.nature.com/articles/s41593-025-02111-0