Nanoscale analytical methods to gain insight into the initiation of short-term memory
-The aim of this project is to develop novel nano-bioanalytical methodologies to explore a molecular paradigm for the initiation of short-term memory (STM) based on exocytosis events. Despite the vital role in neural disorders such as Alzheimer’s disease, the molecular mechanisms of the initial step in STM formation is still mostly a mystery. Understanding STM initiation at the molecular level requires advanced analytical measurements at the level of attoliter vesicles and the synaptic cleft to monitor individual exocytosis events. This poses an extreme analytical challenge. “NAMISTMem” will develop new strategies for quantitative determination of the entire vesicle content (Objective 1), and will also provide a completely new direction of research that will measure cellular and vesicular changes in chemical endogenous factors (e.g. lipids and zinc) over time following an exocytosis event and will correlate these changes to the molecular initiation of STM (Objectives 2 and 3). These changes, which might alter the neurotransmission process, can be hypothesized to be the initial step that alters synaptic plasticity and commencement of STM. These studies will be developed based on state of the art analytical techniques including in-vivo Nanoelectrochemistry, Secondary Ion Mass Spectrometry (SIMS), NanoSIMS, and Helium Ion Microscopy on model nerve-like cells and simple animal nerve cells (Pheochromocytoma Cell and Drosophila’s brain, respectively).
Overall, the proposed methods will have immediate and broad impact in large fields of analytical and life science via pushing the small size limits of bioanalytical probes to achieve a better understanding of the neuron and STM; and will provide innovative analytical approaches for modern brain science discoveries.