Importance of being Nernst： Synaptic activity andfunctional relevance in stem cell-derived neurons

• 作者: Aaron B Bradford and Patrick M McNutt
• 来源期刊: 世界干细胞杂志：英文版（电子版）
• 学科: 医学
• 关键词: Synapses NEUROTRANSMISSION In vitrotechniques INDUCED PLURIPOTENT STEM CELLS Neuronalnetworks Neurogenesis Neural STEM CELLS Embryonicstem CELLS INDUCED NEURONS
• 年，卷（期）: 2015,（6）
• 页码范围: 899-921
• 页数: 23页
• 分类号: R

摘要

Functional synaptogenesis and network emergence aresignature endpoints of neurogenesis. These behaviorsprovide higher-order confirmation that biochemicaland cellular processes necessary for neurotransmitterrelease, post-synaptic detection and network propagation of neuronal activity have been properly expressed andcoordinated among cells. The development of synapticneurotransmission can therefore be considered a definingproperty of neurons. Although dissociated primaryneuron cultures readily form functioning synapsesand network behaviors in vitro , continuously culturedneurogenic cell lines have historically failed to meet thesecriteria. Therefore, in vitro -derived neuron models thatdevelop synaptic transmission are critically needed for awide array of studies, including molecular neuroscience,developmental neurogenesis, disease research andneurotoxicology. Over the last decade, neurons derivedfrom various stem cell lines have shown varying ability todevelop into functionally mature neurons. In this review,we will discuss the neurogenic potential of various stemcells populations, addressing strengths and weaknessesof each, with particular attention to the emergenceof functional behaviors. We will propose methods tofunctionally characterize new stem cell-derived neuron（SCN） platforms to improve their reliability as physiologicalrelevant models. Finally, we will review howsynaptically active SCNs can be applied to accelerateresearch in a variety of areas. Ultimately, emphasizingthe critical importance of synaptic activity and networkresponses as a marker of neuronal maturation is anticipatedto result in in vitro findings that better translateto efficacious clinical treatments.