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Datasets and Key Resources Table used in Do, Quyen B. et al. (2023) “Early striatal hyperexcitability in an in vitro human striatal microcircuit model carrying the Parkinson’s GBA-N370S mutation”
Output Details
Description
ABSTRACT
Understanding medium spiny neuron (MSN) physiology is essential to understand motor impairments in Parkinson’s disease (PD) given the architecture of the basal ganglia. Here, we developed a custom three-chamber microfluidic platform and established a cortico-striato-nigral microcircuit recapitulating the striatal presynaptic triad in vitro using induced pluripotent stem cell (iPSC)-derived neurons. We found that, although cortical glutamatergic projections facilitated MSN synaptic activity, dopaminergic transmission was essential for excitability maturation of MSNs in vitro. Replacement of wild-type iPSC-dopamine neurons (iPSC-DaNs) in the striatal microcircuit with those carrying the PD-related GBA-N370S mutation induced early hyperexcitability in iPSC-MSNs through reduction of voltage-gated sodium and potassium intrinsic currents. Such deficits were resolved in aged cultures or with antagonism of protein kinase A activity in nigrostriatal iPSC-DaNs. Hence, our results highlight the unique utility of modelling striatal neurons in a modular and highly physiological circuit which is essential to reveal mechanistic insights of the loss of electrical functional integrity in the striata of GBA1 PD patients.
FILE DESCRIPTIONS
Source Data.xlsx: Tabular datasets plotted on main figures 1, 3, 4, 5 and 6.
Supplementary Data.xlsx: Tabular datasets plotted on supplementary figures 1, 2 and 3.
Key Resources Table.xlsx: Table containing key resources (primary and secondary antibodies, cell lines and software) used in this study.
List of Primers.xlsx: Primers used in RT-qPCR.
Identifier (DOI)
10.5281/zenodo.7661355