Understanding Force-Induced Learning and Memory

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-香槟分校最近在PI实验室使用果蝇（果蝇）胚胎进行的体内实验表明，施加在单个神经肌肉连接处（突触）的机械力产生神经元记忆。正常情况下，神经元细胞轴突主动维持约1nn的静息张力。人工施加的张力增加会导致神经肌肉连接处神经递质的积累增加。紧张的减少导致神经递质减少。这种力介导的神经递质积累控制似乎对记忆形成至关重要。据设想，一组特定的分子充当“力传感器”，在突触上感知机械力，从而诱导积累。此外，神经元的这种机械感知能力可能植根于细胞的进化保守特性。本项目将利用先进的纳米机械力/拉伸传感器和新型分子FRET（荧光共振能量转移）生物传感器，研究果蝇胚胎体内力传感和力诱导神经元记忆的潜在细胞和分子机制。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。后者是由力/拉伸引起的。这项研究将首次阐明，大自然是否（如果是的话，如何）利用机械张力以类似的方式存储和处理信息。这将揭示一种新的记忆形成机制，与传统观点相反，即神经传递完全是电化学信号过程的结果。该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。该研究还将为各种神经疾病（如阿尔茨海默病）的新工程治疗方案提供线索。那么帕金森呢？S疾病，可能与机械刺激有关。

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.