New research reveals that drugs that increase the activity of a receptor in the brain called metabotropic glutamate receptor subtype 5 (mGlu5) have exciting potential to treat the deficits in learning and memory loss associated with Alzheimer's disease (AD). The Vanderbilt Center for Neuroscience Drug Discovery has recently discovered novel drugs that increase the activity of this receptor. Studies within this proposal will utilize a mouse model, which displays neurodegenerative and pathological characteristics indicative of AD, including disruptions in brain function as well as a clear loss of cognitive function. This model will allow the opportunity to establish the ability of our novel drugs to reverse deficits in learning and memory observed in a preclinical model that most accurately emulates the human disease state. In addition, these mice exhibit pathology that provides the opportunity to evaluate the possibility our compounds may stop, slow or reverse the progression of AD. If successful, these studies would pave the way for development of a novel class of drugs to treat the cognitive deficits associated with AD.