Scalable Measurements of Intrinsic Excitability in Human iPS Cell-Derived Excitatory Neurons Using All-Optical Electrophysiology.

Scalable Measurements of Intrinsic Excitability in Human iPS Cell-Derived Excitatory Neurons Using All-Optical Electrophysiology. Neurochem Res. 2019 Jan 02;: Authors: Williams LA, Joshi V, Murphy M, Ferrante J, Werley CA, Brookings T, McManus O, Grosse J, Davies CH, Dempsey GT Abstract Induced pluripotent stem (iPS) cells offer the exciting opportunity for modeling neurological disorders in vitro in the context of a human genetic background. While significant progress has been made in advancing the use of iPS cell-based disease models, there remains an unmet need to characterize the electrophysiological profile of individual neurons with sufficient throughput to enable statistically robust assessment of disease phenotypes and pharmacological modulation. Here, we describe the Optopatch platform technology that utilizes optogenetics to both stimulate and record action potentials (APs) from human iPS cell-derived excitatory neurons with similar information content to manual patch clamp electrophysiology, but with ~  3 orders of magnitude greater throughput. Cortical excitatory neurons were produced using the NGN2 transcriptional programming approach and cultured in the presence of rodent glial cells. Characterization of the neuronal preparations using immunocytochemistry and qRT-PCR assays reveals an enrichment of neuronal and glutamatergic markers as well as select ion channels. We demonstrate the scale of our intrinsic cellular ex...
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research