组装模型用于研究人类神经系统的循环电路
bioRxiv : the preprint server for biology
|October 28, 2024
概括
研究人员使用干细胞创建了人类大脑电路模型,以研究感觉运动网络. 这个平台揭示了神经活动模式,有助于理解神经发育障碍,如自闭症谱系障碍和图雷特综合征.
科学领域:
- 神经科学是一个神经科学.
- 发展生物学 发展生物学
- 干细胞生物学 干细胞生物学
背景情况:
- 皮质 - 状 - thalamic - 皮质 (CSTC) 电路对于感觉运动处理至关重要,其功能障碍与神经精神疾病有关.
- 在早期发展阶段研究人类的CSTC电路是具有挑战性的,原因是有限的直接功能访问.
研究的目的:
- 开发一个*in vitro*人类CSTC电路模型,使用干细胞进行功能性研究.
- 在这个模型中探索新兴的网络活动和神经元连接.
- 为了研究遗传变异的影响,如*ASH1L*基因损失,在CSTC电路功能.
主要方法:
- 产生类似于CSTC组件的区域化神经器官.
- 使用3D打印井,将有机体组合成一个四部分循环组合体.
- 利用体积和中尺度成像和细胞外记录.
- 采用多阶段狂犬病逆行追踪来绘制神经元连接的地图.
主要成果:
- 证明了循环组合体内同步的神经元活动模式的出现.
- 在重建的CSTC网络中证实了功能神经元连接的形成.
- 在 *ASH1L* 功能丧失模型中确定异常同步活动,与自闭症谱系障碍和图雷特综合征相关.
结论:
- 开发的人类多细胞平台为开发CSTC电路提供了前所未有的功能访问.
- 这个平台是研究早期人类大脑发育以及神经和精神疾病的宝贵工具.
- 它使得在疾病状态下对CSTC电路功能障碍的遗传贡献的调查成为可能.
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