Development of excitability in hiPSC-derived dopaminergic neurons

Parkinson’s disease (PD), a degenerative disorder of the central nervous system, is characterised by selective death of dopaminergic neurons in the substantia nigra pars compacta. These neurons are known for their spontaneous, pacemaker-like electrical excitability driven in part by Cav1.3 voltage-gated calcium channels. Differentiation of human induced pluripotent stem cells (hiPSCs) into dopaminergic neurons is an in-vitro model for studying PD, though just how strictly these cells adhere to the phenotype of their in-vivo counterparts is relatively unknown.
Using electrophysiology and fluorescence imaging I followed the development of hiPSC-derived dopaminergic neurons over a 6 week period, focusing on the development of ion channel populations, spontaneous excitability, synapse formation and vulnerability to specific neurotoxins.
The results will show that traits characteristic of dopaminergic neurons develop within 2-4 weeks of differentiation and that distinct populations of Cav1.3-positive and Cav1.3-negative dopaminergic neurons were identified.