MODULATING FYN KINASE IN LEARNING AND MEMORY: CELL TYPE-SPECIFIC NEUROPLASTICITY

New experiences, including learning a new task, induce many dynamic changes at the molecular level in neuronal subtypes, known as neuroplasticity. However, establishing causal relationships between specific protein dynamics within neuronal subtypes and learning has been challenging. We hypothesize that Fyn kinase influences neuroplasticity in a subtype-specific manner by either changing the excitability of distinct neuronal subtypes or mediating the homeostatic plasticity at distinct time windows of a learning task. By engineering an optogenetic Fyn kinase that can be precisely, specifically, and robustly switched on and off with light in identified neuronal cell types in the mouse hippocampus, this project aims to bridge the cell-type-specific spatiotemporal dynamics of Fyn kinase to neural dynamics and learning processes. In vitro experiments have demonstrated that our engineered Fyn kinase can be switched on with blue light. While the negative control, cannot. In vivo experiments showed decreased freezing behavior in experimental mouse groups (optogenetic activation) as compared with the control group, indicating that Fyn kinase might impair mouse contextual fear memory. This research will be the first proof-of-principle to characterize the subcellular activity of CA1 populations during the learned tests, with the goal of elucidating Fyn-mediated signaling pathways in synaptic plasticity related to learning and memory. In addition, investigating the roles of proteins during neuroplasticity is particularly important because proteins can be drug targets or can be applied as a gene therapy to treat various neurological disorders.