Development of a high-throughput arrayed neural circuitry platform using human induced neurons for drug screening
Joseph A Fantuzzo1, Denise A Robles2, Vincent R Mirabella3
1Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, Piscataway, NJ 08854, USA. jdzahn@soe.rutgers.edu and Child Health Institute of New Jersey, Robert Wood Johnson Medical School, 89 French Street, New Brunswick, NJ 08901, USA.
Lab on a Chip
|February 18, 2020
Summary
Researchers developed a novel high-throughput platform using human induced neuronal cells to create functional neural circuits. This model aids in studying brain disorders and improving drug screening for psychiatric conditions.
Area of Science:
- Neuroscience
- Stem Cell Biology
- Drug Discovery
Background:
- Accurate human cell-based models are crucial for understanding neural circuit function and improving drug screening.
- Existing animal models often fail to predict therapeutic safety and efficacy in humans.
- Developing models with biologically relevant neural connectivity is a key challenge.
Purpose of the Study:
- To develop a high-throughput screening (HTS) platform for studying functional neural circuits.
- To create defined neural circuitries using compartmentalized human induced neuronal cells (iNs).
- To enable the study and treatment of psychiatric brain disorders.
Main Methods:
- Generated subtype-specific excitatory and inhibitory iNs from human stem cells.
- Utilized a 96-well plate platform with microchannels for compartmentalization and connectivity.
- Monitored neuronal activity using the genetically encoded calcium indicator GCaMP6f.
- Perturbed network activity with glutamate receptor blockers and stimulated with DREADD (hM3Dq) and CNO.
Main Results:
- Demonstrated the formation of robust, functional neural circuits with defined connectivity.
- Successfully monitored calcium transients indicative of neuronal firing within and between compartments.
- Validated circuit functionality through pharmacological manipulation and targeted stimulation.
- Established a platform compatible with compound screening for drug discovery.
Conclusions:
- The developed platform successfully generates functional neural circuits from human iNs.
- This HTS-compatible model represents a significant advancement for studying neural circuit disorders.
- The platform holds promise for improving drug screening and developing treatments for psychiatric brain disorders.
