Understanding Force-Induced Learning and Memory

了解力诱导的学习和记忆(NSF CMMI 0800870)PI：伊利诺伊大学香槟分校的Taher Saif最近在PI的实验室使用果蝇(果蝇)胚胎进行的活体实验表明，施加在单个神经肌肉接头(突触)的机械力可以产生神经元记忆。在正常情况下，神经元细胞的轴突活跃地维持大约1nN的静息张力。人工施加的张力增加，会导致神经肌肉交界处神经递质的积累增加。张力的降低会导致神经递质的减少。这种力量介导的神经递质积累控制似乎对记忆的形成是必不可少的。据设想，一组特定的分子充当“力传感器”，感知突触上的机械力来诱导聚集。此外，神经元的这种机械感知能力可能植根于细胞在进化上保守的特性。该项目将使用先进的纳米机械力/拉伸传感器和基于新型分子FRET(荧光共振能量转移)的生物传感器，在体内研究力感知和力诱导的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。这项研究将首次揭示自然界是否(如果是的话)使用机械张力以模拟的方式存储和处理信息。因此，它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。这项研究将在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的新工程治疗方案提供线索，如阿尔茨海默病？S和帕金森？S病，可能涉及机械刺激。

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.