突触发生
兴奋性突触
兴奋性突触后电位
神经科学
神经突
罗亚
生物
细胞生物学
突触
突触后电位
树突棘
肌动蛋白
轴突引导
抑制性突触后电位
轴突
信号转导
受体
海马结构
体外
生物化学
作者
Emily S Wilson,Taylor Rudisill,Brenna Kirk,Colin G. Johnson,Paige Kemper,Karen Litwa
摘要
Excitatory synapse formation begins in mid-fetal gestation. However, due to our inability to image fetal synaptogenesis, the initial formation of synapses remains understudied. The recent development of human fetal brain spheroids provides access to this critical period of synapse formation. Using human neurons and brain spheroids, we address how altered actin regulation impacts the formation of excitatory synapses during fetal brain development. Prior to synapse formation, inhibition of RhoA kinase (ROCK) signaling promotes neurite elongation and branching. In addition to increasing neural complexity, ROCK inhibition increases the length of protrusions along the neurite, ultimately promoting excitatory synapse formation in human cortical brain spheroids. A corresponding increase in Rac1-driven actin polymerization drives this increase in excitatory synaptogenesis. Using STORM super-resolution microscopy, we demonstrate that actomyosin regulators, including the Rac1 regulator, α-PIX, and the RhoA regulator, p115-RhoGEF, localize to nascent excitatory synapses, where they preferentially localize to postsynaptic compartments. These results demonstrate that coordinated RhoGTPase activities underlie the initial formation of excitatory synapses and identify critical cytoskeletal regulators of early synaptogenic events.
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