Cortical spheroids display oscillatory network dynamics.

Area of Science:

• Neuroscience
• Biotechnology
• Cell Biology

Background:

• Three-dimensional (3D) brain cultures are crucial for studying central nervous system (CNS) function and disease.
• Neuronal network activity is a key component of these cultures, reflecting in vivo conditions.

Purpose of the Study:

• To demonstrate and characterize network activity in self-assembled rodent cortical spheroids.
• To establish these 3D cultures as a model for studying neuronal network dynamics.

Main Methods:

• Culturing rat and mouse cortical spheroids.
• Imaging neuronal activity using calcium indicator dyes and GCaMP.
• Electrically stimulating spheroids and applying pharmacological blockers (glutamatergic and GABAergic).
• Quantifying neuronal soma correlations and distances with micron-scale resolution.

Main Results:

• Cortical spheroids developed complex network activity by nine days in culture.
• Network activity was confirmed by electrical stimulation and abolished by glutamatergic blockade.
• Activity was modulated by GABAergic blockade and partial glutamatergic blockade.
• Emergent network events, including oscillations, were observed in spheroids seeded with as few as 4000 cells.

Conclusions:

• Self-assembled rodent cortical spheroids exhibit in vivo-like network activity.
• These 3D brain cultures provide a robust model for studying neuronal networks.
• This model enables high-throughput experiments and reduces the need for animal models in neuroscience research.