TY - JOUR T1 - Neuronal hyperactivity in a LRRK2-G2019S cellular model of Parkinson’s Disease JF - bioRxiv DO - 10.1101/2021.06.23.449591 SP - 2021.06.23.449591 AU - Edinson Lucumi Moreno AU - Siham Hachi AU - Sarah L. Nickels AU - Khalid I.W. Kane AU - Masha Moein AU - Jens C. Schwamborn AU - Alexander Skupin AU - Pieter Vanden Berghe AU - Ronan M.T. Fleming Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/06/23/2021.06.23.449591.abstract N2 - Monogenic Parkinson’s Disease can be caused by a mutation in the leucine-rich repeat kinase 2 (LRRK2) gene, causing a late-onset autosomal dominant inherited form of Parkinson’s Disease. The function of the LRRK2 gene is incompletely understood, but several in vitro studies have reported that LRRK2-G2019S mutations affect neurite branching, calcium homeostasis and mitochondrial function, but thus far, there have been no reports of effects on electrophysiological activity. We assessed the neuronal activity of induced pluripotent stem cell derived neurons from Parkinson’s Disease patients with LRRK2-G2019S mutations and isogenic controls. Neuronal activity of spontaneously firing neuronal populations was recorded with a fluorescent calcium-sensitive dye (Fluo-4) and analysed with a novel image analysis pipeline that combined semi-automated neuronal segmentation and quantification of calcium transient properties. Compared with controls, LRRK2-G2019S mutants have shortened inter-spike intervals and an increased rate of spontaneous calcium transient induction.Competing Interest StatementThe authors have declared no competing interest. ER -