Behavioral and In Vivo Electrophysiological Characterization of APP Transgenic Mice

Although amyloid beta (Aß) deposits in the brain constitute a neuropathological hallmark of Alzheimer’s disease, the role these plaques play in the onset and progression of the disease is unknown and controversial. Transgenic technologies provide powerful tools for studying this phenomenon, and a number of mouse models have been created that develop amyloid plaques similar to those in patients with Alzheimer’s disease. Current evidence suggests that the transgenic mouse models exhibit behavioral and cognitive abnormalities that might underlie deficits in learning and memory that are early diagnostic features of the disease. However, there has been no direct evaluation to determine the effects of amyloid accumulation in the brain on cellular functioning in live animals. This proposal uses state-of-the-art electrophysiological recording and behavioral techniques to examine the physiology of behavior in brain areas such as the hippocampus, a region that is critical for certain forms of memory and also susceptible to amyloid plaque deposition. The goal of this study is to provide a comprehensive characterization of the effects of amyloid deposition on behavior and on perturbations of normal cellular function in life that produce memory deficits. In addition, this approach should provide a means to assess the time of onset at which the first subtle signs of memory loss appear as the disease slowly progresses.