AgeneBio, Inc. is developing new therapies for memory loss in Mild Cognitive impairment (MCI), a condition that often progresses to Alzheimer's Disease. The company's intellectual property and research is based on work supported by the National Institute on Aging over the past 15+ years. That work has identified a novel entry for therapy in MCI to correct a condition of excess neural activity in circuits critical for memory. A highly restricted subtype of inhibitory mechanism, the GABA alpha 5 receptor, is localized to the memory system neurons that are hyperactive. It is also known that these receptors mediate tonic inhibition. Thus, boosting GABA alpha 5 function may remediate over activity in the memory system, as supported by our preliminary preclinical data on the use of such compounds to treat memory impairment in aged rats. The support of the ADDF will be used to further advance development of therapies directed at this target for age-related cognitive impairment. A well-characterized animal model of neurocognitive aging will be used to test a series of GABA treatment of impaired memory. These pharmacological studies will also use a selective inverse agonist to validate mechanism of action of the test compounds. This work will provide the basis for lead compound identification of a GABA alpha 5 agonist, a potential first in class therapy for MCI.