Striatal circuit metaplasticity in health and disease

The goal of this project is to elaborate, generalize and apply in Parkinson’s disease models the proposed novel concept of Neuromodulatory State-Dependent Plasticity (NSDP). This form of plasticity regulation, or metaplasticity, which is described in detail below, rests crucially on the cooperative actions of neuromodulation and glutamate-dependent synaptogenesis in neural circuit wiring. Accomplishing the proposed studies will generate a novel framework for understanding causes and progression of Parkinson’s disease. This work is likely to broadly impact our understanding of mechanisms underlying plasticity in diverse neuronal classes, and its dysregulation in neurodevelopmental and neurodegenerative disorders.