The PI seeks support for an investigation of a novel technique to quantify the changes in intracellular concentrations of calcium that are associated with the activity of hippocampal neurons involved in learning and memory. Specifically, calcium- sensitive fluorescent dyes will be mircroinjected into selected neurons and monitored using a dual-wavelength spectrofluorimeter and scanning confocal microscope following manipulation of neuronal activity, such as high-frequency tetanus to produce long term potentiation. The proposed research is a gamble and there is a minimum of preliminary data to allow an easy judgement. However, the investigators have made excellent progress in analyzing calcium changes in cultured cells. The difficulty is in extending these procedures to the tissue slice. The potential for a significant outcome seems sufficient to justify the risk. The ability to make high-resolution measurements of calcium changes in hippocampal neurons will have an impact on many areas of neuroscience, including computational psychology, neural net modeling, and electrophysiology. This work has the potential to move neuroscience significantly closer to an understanding of the synaptic molecular mechanisms that underlie learning and memory.
