EFFECTS OF THE G2019S LRRK2 MUTATION ON MOTOR LEARNING IN MICE

Abstract

Parkinson’s Disease (PD) is a prevalent neurological disease characterized by the death of dopaminergic neurons in the substantia nigra pars compacta (SNc) in the brain, but the mechanism of how these neurons die is unknown. Some mutations causing abnormal expression of the protein LRRK2 have been shown to cause PD, the most common of which is the G2019S substitution. This mutation has been shown to potentiate corticostriatal glutamatergic synapses. Given that sleep spindles, which allow for the consolidation of memories, can be affected by these synapses, this is a potential mechanism for this form of PD to affect motor learning. Motor leaning was assessed using a constantly accelerating rotarod (rotating rod) in 6-month-old G2019S LRRK2 transgenic mice (n = 7) and 6-month-old C57/B6 wild-type controls (n = 9) in 4 sessions spread over a 2-week period. While both groups demonstrated motor learning within most training days, neither group improved across their four training days. Furthermore, there was no difference between the transgenic and wild-type groups in performance, improvement, or variation in latency to fall from the rotarod. Future efforts in this project will directly study sleep spindles in post-task sleep using electrophysiology along with the effects of MLi-2, a LRRK2 kinase inhibitor, to further elucidate motor learning abilities in G2019S mice.