Altered Development of Synapse Structure and Function in Striatum Caused by Parkinson's Disease-Linked LRRK2-G2019S Mutation.

Mutations in the kinase domain of leucine-rich repeat kinase 2 (LRRK2) follow Parkinson's disease (PD) heritability. How such mutations affect brain function is poorly understood. LRRK2 expression levels rise after birth at a time when synapses are forming and are highest in dorsal striatum, suggesting that LRRK2 regulates development of striatal circuits. During a period of postnatal development when activity plays a large role in permanently shaping neural circuits, our data show how the most common PD-causing LRRK2 mutation dramatically alters excitatory synaptic activity and the shape of postsynaptic structures in striatum. These findings provide new insight into early functional and structural aberrations in striatal connectivity that may predispose striatal circuitry to both motor and nonmotor dysfunction later in life.