Grant: Operating Grant

Alzheimer's disease (AD) slowly destroys memory, but abnormal changes in the brain have started many years before memory problem becomes apparent. Cells in a region called the entorhinal cortex are the first to be affected by the disease. It remains largely unknown how degeneration of the entorhinal cortex lead to memory problem. We have studied how activities of brain cells change as rats form and express memory and found that rhythmic oscillatory activities in the entorhinal cortex become coupled with oscillations in the region that are connected with the entorhinal cortex. This proposal will extend this finding to examine what type of information the entorhinal cortex communicates with its connected regions through these coupled oscillations and how degeneration of the entorhinal cortex affects the oscillation-based communication. To this end, we will compare the brain cell activity between healthy rats and rats that have been genetically engineered to express AD-like disease specifically in the entorhinal cortex. The brain cell activities will be recorded while the healthy and AD model rats receive a memory paradigm similar to the one that AD patients have trouble in. If successful, this study will document how degeneration in the entorhinal cortex changes the way that brain cells communicate with one another to form memory. As such, it may improve our understanding of the causes of memory impairment in early-stage AD, and may identify treatments to prevent or slow the progression of this devastating disease.