Abstract

Synaptic plasticity occurs as a result of biochemical reactions and protein interactions that take place within small volume of less than 1 fl. Application of traditional biochemical approaches is simply impractical to elucidate the process of synaptic plasticity. We therefore employed optical methods including FRET , FLIM, photoactivatable proteins and caged compounds to elucidate the mechanism of synaptic plasticity, with an emphasis on structural modification of dendritic spine seen during long-term potentiation (LTP) of hippocampal CA1 pyramidal neurons. After the induction of LTP , the remodeling of actin cytoskeleton and its polymerization is the first thing to happen. Active cofilin is massively transported to the spine and severs the F-actin, which likely generates new free ends of actin from where new filament starts growing. Thereafter, these two proteins forms a stable complex at the base of spine head thereby forming a stable F-actin and regulating spine expansion. In contrast, the postsynaptic density (PSD) was independently remodeled, as PSD scaffolding proteins did not change their amount and localization until late protein synthesis-dependent third phase. Our findings show how and when spine substructures are remodeled during LTP and explain why synaptic plasticity rules change over time. I will also cover a recent work on quantitative analysis of AMPAR phosphorylation in relation to synaptic plasticity.