The long term goal of this research is to understand molecular mechanisms of learning and memory. Synaptic maturation and plasticity are two major functional elements involved in learning and memory. Actin is enriched in synaptic structures and regulates synaptic function. Actin dynamics is known to be associated with synaptic maturation and plasticity, but the precise molecular machinery regulating actin dynamics in synapses is not well understood. Previous studies often focus on the function of individual actin-regulatory proteins. This project takes a novel approach to investigate an interactive protein complex LIM kinase/slingshot/cofilin (LSC complex) in controlling synapse maturation and synaptic plasticity. LSC proteins play a key role in regulating actin turnover. The proposed experiments are based on a recent discovery that immature synapses are presynaptically silent, but can be activated by repetitive stimulation in an actin-dependent manner. Three key hypotheses will be tested. (1) That LSC proteins act as a complex, rather than individually, in controlling spine morphology. (2) That a balanced action of LSC complex is critically required for synaptic maturation. (3) That alteration of LSC complex will significantly modulate synaptic plasticity. The proposed studies will gain comprehensive understanding of the molecular interaction among LSC proteins and their regulation of synaptic maturation and plasticity. This research will provide important training for graduate and undergraduate students. The research findings will be integrated in teaching students and disseminated to the public through presentations at scientific meetings and publications in high impact journals.
