LRRK2 mutation alters behavioral, synaptic, and nonsynaptic adaptations to acute social stress
Christopher A. Guevara, Bridget A. Matikainen‐Ankney, Nebojsa Kezunovic, Katherine B. LeClair, Alexander P. Conway, Caroline Ménard, Meghan E. Flanigan, Madeline L. Pfau, Scott J. Russo, Deanna L. Benson, George W. Huntley
Abstract
Depression is associated with Parkinson's disease (PD), and environmental stress is a risk factor for both. We investigated how LRRK2-G2019S PD mutation affects depression-like behaviors, synaptic function, and intrinsic neuronal excitability following stress. In response to stress, the mutation drives abnormal synaptic changes, prevents adaptive changes in intrinsic excitability, and leads to aberrant behaviors, thus defining new ways in which PD mutations derail adaptive plasticity in response to stress that may contribute to disease onset.