Nanosensor-based imaging of realtime dopamine release in neurons derived from iPSCs of patients with Parkinson's disease.

Dopamine (DA) is an essential neuromodulator that underlies critical aspects of cognitive processes, motor function, and reward systems. Disruptions in DA signaling contribute to various neurodegenerative diseases, including Parkinson's disease (PD). Despite its important role in neuronal function, the impact of DA release/uptake on neurochemical imbalances during neuronal development remains unclear. We propose a novel application of near-infrared catecholamine nanosensor (NIRCat) for real-time visualization of DA neurotransmission among neurodegenerative disease cells. The near-infrared fluorescence (900-1400 nm) of NIRCat allows the semi-quantitative measurement of DA release in living neurons and offers insights into cellular dynamics and neuropathological development. In this study, we applied NIRCat to elucidate DA release in human induced pluripotent stem cells (hiPSCs)-derived dopaminergic neurons from both healthy control and PD patient carrying GBA1 mutations. We accurately quantified electrically stimulated DA release events, identifying distinct 'hotspots' of activity across DA neuronal cells. Our findings present a significantly enhanced spatial and temporal resolution of DA signaling, providing a deeper understanding of the role and balance of DA release in the progression of neurodegenerative disease.