3D Neuromodulation in Neural Organoids with Shell MEAs

Area of Science:

• Neuroscience
• Biomedical Engineering
• Tissue Engineering

Background:

• Neural organoids (NOs) are crucial models for studying brain function and developing biocomputing systems.
• Understanding electrical activity and neuromodulation in NOs is key for applications in neural plasticity and learning.
• Current 2D microelectrode arrays (MEAs) limit the assessment of neuromodulation across the entire 3D structure of NOs.

Purpose of the Study:

• To develop and demonstrate a novel method for investigating 3D spatiotemporal neuromodulation in neural organoids.
• To establish reliable relationships between electrical stimulation and recording traces in NOs.
• To create 3D maps of neuromodulatory activity on the entire surface of NOs.

Main Methods:

• Development of "shell MEAs" mimicking macroscale EEG caps for 3D coverage of NOs.
• Application of electrical stimulation within a specific current range (20-30 µA).
• Recording and analysis of neuron firing rates and generation of 3D spatiotemporal activity maps.

Main Results:

• A statistically significant increase in neuron firing rate was observed post-stimulation (20-30 µA).
• Neuromodulatory behavior was detected using both 3- and 16-electrode shell MEAs.
• 3D spatiotemporal maps effectively visualized neuromodulatory activity across the entire NO surface.

Conclusions:

• Shell MEAs provide a novel methodology for investigating 3D spatiotemporal neuromodulation in neural organoids.
• This technique enhances the study of neural functionality, plasticity, and learning in organoid models.
• The findings are broadly relevant to biomedical engineering and brain science research.