An in silico and in vitro human neuronal network model reveals cellular mechanisms beyond Na_V1.1 underlying Dravet syndrome.

ABSTRACT: Human induced pluripotent stem cell (hiPSC)-derived neuronal networks on multi-electrode arrays (MEAs) provide a unique phenotyping tool to study neurological disorders. However, it is difficult to infer cellular mechanisms underlying these phenotypes. Computational modeling can utilize the rich dataset generated by MEAs, and advance understanding of disease mechanisms. However, existing models lack biophysical detail, or validation and calibration to relevant experimental data. We developed a biophysical in silico model that accurately simulates healthy neuronal networks on MEAs. To demonstrate the potential of our model, we studied neuronal networks derived from a Dravet syndrome (DS) patient with a missense mutation in SCN1A, encoding sodium channel Na_V1.1. Our in silico mode

SUBMITTER: Doorn N 

PROVIDER: S-EPMC10444571 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature