My research interests focus on studying the early neuronal pathology that develops in Alzheimer's disease (AD), long before the deposition of plaques and tangles and cognitive decline. To accomplish this, I use transgenic mice that have been engineered to express the human gene mutations that cause the inheritable form of AD. With these mice, I can examine within individual neurons how the AD mutations impair neuronal functioning and synaptic transmission across various stages of the disease process, with the goal of finding ways to block or reverse these impairments. By the time memory loss occurs in humans, the damage to the brain is often too extensive to reverse. My previous studies show that specific calcium-mediated signaling pathways are highly dysregulated in AD, and over time, may facilitate the formation of amyloid plaques and tangles, interfere with neuronal signaling processes that support learning and memory, and eventually kill the cell. To achieve these goals, I use innovative techniques to study real-time activity in living neurons, such as in vitro electrophysiology combined with 2-photon and CCD imaging of calcium signals within cellular compartments. In addition, extracellular recording techniques, immunohistochemistry, molecular biology and behavioral approaches are also incorporated. I am also examining target compounds that can impede the progression of AD pathology. The strategy is to normalize aberrant signaling pathways that are present prior to the formation of late stage markers of the disease.