Understanding Force-Induced Learning and Memory

了解力诱导的学习和记忆

• 批准号: 0800870
• 负责人: Taher Saif
• 金额: $ 32万
• 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: 2008
• 资助国家: 美国
• 起止时间: 2008-05-15 至 2013-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0800870&HistoricalAwards=false
• 关键词: Understanding; Force; Induced; Learning; Memory

Understanding force-induced learning and memory(NSF CMMI 0800870)PI: Taher Saif, University of Illinois at Urbana-ChampaignRecent in vivo experiments using Drosophila (fruit fly) embryos in the PI's lab reveal that mechanical force applied at an individual neuromuscular junction (synapse) produces neuronal memory. Under normal conditions, axons of neuron cells actively maintain a resting tension of about 1 nN. Increased tension, applied artificially, causes increased accumulation of neurotransmitters at the neuro muscular junction. Reduction of tension causes a decrease in neurotransmitters. This force-mediated control of neurotransmitter accumulation appears to be essential for memory formation. It is envisioned that a specific set of molecules serves as a "force sensor" that senses mechanical force at the synapse to induce the accumulation. Furthermore, this mechano-sensing ability of neurons is likely rooted in evolutionarily conserved properties of cells. This project will investigate the underlying cellular and molecular mechanisms of force sensing and force-induced neuronal memory in vivo in Drosophila embryos using advanced nano-mechanical force/stretch sensors, and new molecular FRET (fluorescence resonance energy transfer) based biosensors. The quest for the force sensor will be based on the hypothesis: localization of neurotransmitters is mediated by an appropriate level of intracellular calcium. The latter is induced by force/stretch. The study will shed light, for the first time, on whether (and if so, how) nature employs mechanical tension to store and process information in an analogue fashion. It will thus reveal a new mechanism of memory formation, in contrast to the conventional view that neurotransmission is entirely a result of electro-chemical signaling process. The study will offer significant fundamental knowledge in the field neuroscience, and has the potential of laying the foundation of the new field of neuro-mechanics. The study will also offer clues for new engineering treatment protocols for various neuronal disorders such as Alzheimer?s, and Parkinson?s diseases, possibly involving mechanical stimuli.

理解力诱导的学习和记忆（NSF CMMI 0800870）PI：Taher Saif，伊利诺伊大学厄巴纳-香槟分校PI实验室最近使用果蝇（果蝇）胚胎的体内实验表明，施加在单个神经肌肉接头（突触）上的机械力会产生神经元记忆。在正常情况下，神经元细胞的轴突主动维持约1 nN的静息张力。人为施加的张力增加会导致神经肌肉接头处神经递质的积累增加。紧张的减少会导致神经递质的减少。这种力介导的神经递质积累控制似乎是记忆形成所必需的。据设想，一组特定的分子充当“力传感器”，其感测突触处的机械力以诱导累积。此外，神经元的这种机械感知能力可能源于细胞进化上保守的特性。该项目将使用先进的纳米机械力/拉伸传感器和基于荧光共振能量转移（FRET）的新分子生物传感器，研究果蝇胚胎体内力感知和力诱导神经元记忆的细胞和分子机制。对力传感器的探索将基于这样的假设：神经递质的定位是由适当水平的细胞内钙介导的。后者由力/拉伸引起。这项研究将首次揭示大自然是否（以及如果是，如何）利用机械张力以模拟方式存储和处理信息。这将揭示一种新的记忆形成机制，而不是传统的观点，即神经传递完全是电化学信号过程的结果。这项研究将为神经科学领域提供重要的基础知识，并有可能为神经力学的新领域奠定基础。这项研究还将为各种神经元疾病（如阿尔茨海默病）的新工程治疗方案提供线索。s和帕金森？的疾病，可能涉及机械刺激。