Final Report Summary - NANOCELLIMAGE (Ultrasmall Chemical Imaging of Cells and Vesicular Release)
We developed unique MS imaging capabilities to image a number of samples of neuroscience importance. A new method of SIMS imaging using cluster ions to detach intact ions has been developed and used to examine the fly brain and to demonstrate that the drug methylphenidate alters the lipid composition in a way that might be important in diet and in memory. The fly brain is a model used in our laboratory and we have used a new, one of a kind, 40 keV argon cluster source to obtain the best images to date anywhere of the fly brain. We have focused on lipids of cell membranes. A major finding has been that when flies are fed methylphenidate, the lipids across the brain change spatially and different lipids change differentially. Lipids that favor high curvature portions of membranes are enhanced and those that favor low curvature sections of membranes are diminished with this drug. As this drug enhances attention and cognition, it is possible this indicates a lipid-based mechanism as part of short-term memory formation, a truly astounding discovery!
Finally, we have developed protocols with a high technology method, called NanoSIMS, to obtain 50 nm spatial resolution and to examine the inner chemical distribution of 200 nm transmitter vesicles. We have used this approach to measure the transmitter dopamine inside a single nanometer vesicle.
There are many other somewhat smaller, but all important, contributions and in total the grant supported 52 publications.