Understanding Force-Induced Learning and Memory

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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.