Exploring the Impact of Mechanical Force on Synaptic Functions Using Novel Approaches

使用新方法探索机械力对突触功能的影响

• 批准号: 1300808
• 负责人: Taher Saif
• 金额: $ 39万
• 依托单位: University of Illinois at Urbana-Champaign
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-15 至 2018-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1300808&HistoricalAwards=false
• 关键词: Exploring; Impact; Mechanical; Force; Synaptic

The research objective of this award is to understand how neurons develop mechanical force (tension), and how this tension influences their functionality. It is known that memory, learning and locomotion in animals are mediated by neurotransmitters that are released from vesicles clustered at the synapse (junction between two neurons, or between a neuron and muscle). Recent experiments on the embryonic Drosophila (fruit fly) nervous system show that vesicle clustering at the neuromuscular synapse requires mechanical tension within the axons. Vesicle clustering vanishes upon severing the axon from the cell body, but is restored simply by applying mechanical tension on the severed axon. Using micro mechanical force sensors, it has been shown that embryonic axons that form neuromuscular junctions maintain a rest tension of about 1 nN. These results suggest that neuromuscular synapses employ mechanical tension as a signal to modulate vesicle accumulation. In this project, the mechanism of force generation in axons, as well as the mechanism by which tension modulates vesicle clustering, transport and release will be explored using a combination of nano scale force sensors, advanced imaging and mechanics models.Understanding the force paradigm of synaptic function may lead to new treatments for neurological diseases. The findings of this research will be disseminated to the broader audience through the web and journal publications. The instruments to be developed will be made available to others for mechanobiological studies. The knowledge gained through this project will be integrated with education through development of a new course on neuro-mechanics that incorporates neuroscience and engineering, as well as through student seminars, involvement of undergraduate students from minorities in research, and hands-on teaching modules at the local Children's Science Museum.

该奖项的研究目标是了解神经元如何产生机械力(张力)，以及这种张力如何影响其功能。众所周知，动物的记忆、学习和运动是由突触(两个神经元之间或神经元和肌肉之间的连接)处聚集的小泡释放的神经递质介导的。最近对果蝇胚胎神经系统的实验表明，神经肌肉突触上的囊泡聚集需要轴突内的机械张力。当轴突从细胞体上切断时，囊泡聚集消失，但只需对切断的轴突施加机械张力即可恢复。使用微型机械力传感器，已经证明形成神经肌肉连接的胚胎轴突保持大约1nN的静息张力。这些结果表明，神经肌肉突触使用机械张力作为信号来调节囊泡的积累。在这个项目中，将结合纳米尺度的力传感器、先进的成像和力学模型来探索轴突中的力产生机制，以及张力调节囊泡聚集、运输和释放的机制。了解突触功能的力范式可能会导致神经疾病的新治疗。这项研究的结果将通过网络和期刊出版物向更广泛的受众传播。将开发的仪器将提供给其他人用于机械生物学研究。通过这个项目获得的知识将与教育相结合，方法是开发一门结合了神经科学和工程学的神经力学新课程，并通过学生研讨会、让少数族裔本科生参与研究以及在当地儿童科学博物馆亲身实践教学模块来实现。