Supplement: A Healthy Brain Aging Strategy to Restore Insulin Signaling and Ca2+ Homeostasis

This is a request for an administrative supplement for our ongoing grant entitled “A healthy brain aging strategy to restore insulin signaling and Ca2+ homeostasis”, originally awarded in 2009 and renewed in 2015. As we start the 9th year, we are requesting supplemental funds because an opportunity unavailable at the time of the parent grant renewal is now available. Our Vice President for Research, Dr. Lisa Cassis, purchased a state-of-the-art multiphoton (MP) microscope for the University of Kentucky (UK) Light Microscope Core, and here we propose to exploit this unique opportunity with a series of experiments that will greatly enhance productivity and critically inform our research questions. Importantly, use of this MP microscope will provide data with greater spatial and temporal resolution of calcium dynamics. This supplement enables us to perform high resolution in vivo imaging in a rat model of aging and will provide critical insights into how insulin alters brain function with aging (the main thrust of our grant). The newly refurbished Light Microscopy Core houses the new Zeiss LSM 880 MP microscope and, as mentioned, is designed for live animal imaging. The microscope is equipped with an InSight X3 tunable laser (680 nm to 1300 nm) and a secondary fixed beam (1045 nm), allowing for dual line excitation. These new goals were unattainable when the original grant application was resubmitted in 2014 since the MP microscope was made available to UK investigators in February of 2018.