Grant: Discovery Grants Program - Individual

Age-related cognitive decline and memory loss are associated with excess Ca2+ levels in brain cells. The L-type calcium channel (LTCC) is one of the major passages for Ca2+ entry into the cell and appears to mediate abnormal Ca2+ load in the aging brain cell. The paradox is that LTCCs are also an integral component of normal learning in animals and men. Our recent research has shown that without LTCCs, young animals cannot form long-lasting memory. The goal of our current research is to systematically characterize the role of LTCCs in learning in young and aged rats using odor associative learning as a model system, with the hypothesis that LTCCs will promote communication between neurons in the brain and memory formation in the young, but will suppress neuronal communications and lead to memory loss in aged subjects. * We will first test the expression levels of LTCCs in young adult and aged rats by measuring the amount of LTCC proteins in the cell membrane. We will then compare the functional roles of LTCCs in the two age groups using a go/no-go odor discrimination learning model. In this model, one odor is rewarded with water (positive odor), while another odor is not (negative odor). Thirsty rats learn to lick the water port when the positive odor is present but not when the negative one is present. We will measure how fast the rats learn and how long the memory for the odor and water association lasts. The effects of an LTCC blocker infusion to the brain on the speed of learning and the duration of the memory will be compared in the two age groups. We are also interested in how norepinephrine, a neuromodulator in the brain that promotes alertness and memory, interacts with LTCCs to influence their functions. Finally, we want to understand the mechanisms of how LTCCs differentially affect memories in the young and aged. We propose to study the cellular mechanisms of LTCC function in the brain slice, where neuronal communication can be recorded through electrodes. * Calcium is a central mediator for brain signaling, brain plasticity and learning. Systematic measurements of the roles of LTCCs in brain plasticity and learning in young and aged animals will provide fundamental insights on how calcium entry into the brain cell functions during development to influence memory formation. The results of this study could further direct brain research on memory loss prevention in the aging population.