The ability of neurons to rapidly modify synaptic structure and strength in response to neuronal activity, a process called activity-induced structural and functional plasticity, is crucial for neuronal development and complex brain functions such as learning and memory. Recent evidence suggests that integrin receptors, a major class of cell adhesion molecules, play an important role in synaptic plasticity. However, how neurons dynamically couple synaptic demand to structural remodeling, and what activates integrin during neuronal activity remain elusive. My lab has recently identified a novel protein named Shriveled (Shv) that activates integrin via outside-in signaling. We now have evidence showing that Shv is selectively released during intense neuronal activity, and that shv mutant cannot undergo synaptic remodeling in response to neuronal activity at the Drosophila neuromuscular junction. In this proposal, we will: (1) investigate the role that Shv plays during development to regulate synaptic growth and function; (2) delineate how neuronal activity regulates Shv release and activity-induced structural and functional plasticity; (3) elucidate molecular and cellular mechanisms underlying activity-induced structural remodeling. As a healthy nervous system depends on the ability of neurons to dynamically adjust synaptic strength and modify synaptic structure in response to neuronal activity, elucidating Shv functions and mechanisms underlying activity-induced synaptic remodeling may lead to new therapeutic strategies to treat or prevent neurological and psychiatric disorders.
Impairments in synaptic remodeling have been linked to a number of neurological and psychiatric disorders including Alzheimer?s disease and schizophrenia. This proposal seeks to identify molecular mechanisms controlling activity-induced structural plasticity. Completion of the proposed study will reveal novel genes and signaling pathways that could ultimately lead to therapeutic treatment for neurological disorders that are associated with defects in synaptic remodeling.
