在人类皮质器官中,静音突触转化为AMPA受体介导的功能突触
Masatoshi Nishimura1, Tomoki Kodera1, Shota Adachi1
1Laboratory of Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya University, Nagoya, Japan.
Neuroscience research
|December 26, 2024
概括
人类皮质器官显示,突触连接随着时间的推移而成熟. 早期的有机体具有静音突触,而后期的有机体则与α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid受体 (AMPARs) 和N-甲基-D-aspartate受体 (NMDARs) 形成功能性突触.
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
- 干细胞研究 干细胞研究
背景情况:
- 突触连接和神经活动对于皮质电路的发展至关重要.
- 人类大脑中功能性突触连接形成的机制尚未完全理解.
研究的目的:
- 研究人类皮质器官 (hCOs) 中α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid受体 (AMPAR) 介导的突触传播的发展.
- 用诱导多能干干细胞衍生的hCOs来模拟人类皮质发生和理解神经发育障碍.
主要方法:
- 使用的人类皮质器官 (hCOs) 来自诱导的多能干细胞.
- 采用双光子Ca2+成像来评估自发的神经活动.
- 使用N-甲基-D-酸盐受体 (NMDAR) 和AMPAR对手来阻止神经活动.
- 使用G删除的狂犬病病毒载体应用了跨突触电路跟踪.
- 进行化学标签,以量化AMPAR和NMDAR的表达和同声化.
主要成果:
- 自发活动频率和幅度在hCOs从第50天到第80天增加.
- 晚期hCOs的神经活动对NMDAR和AMPAR抗体敏感,与早期hCOs不同.
- 在早期和晚期hCOs中,突触连接的数量相似.
- 晚期的hCOs显示了 postsynaptic AMPAR表达的增加和与NMDARs的同位化.
结论:
- 在发育过程中,hCOs逐渐组织激发性突触传播.
- 从静态突触到功能突触发生发育过渡,其中包含AMPAR和NMDAR.
- hCOs作为一种有价值的体外模型,用于研究人类皮质造生和神经发育障碍.
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