Modular microstructure design to build neuronal networks of defined functional connectivity

Area of Science:

• Neuroscience
• Bioengineering
• Systems Neuroscience

Background:

• Neuronal circuit architecture influences functional information transfer in the brain.
• Testing structure-function relationships in complex brain networks is challenging.
• Existing in vitro methods lack stable, unidirectional connections for small networks.

Purpose of the Study:

• To develop a method for creating small, controlled neuronal networks with stable, unidirectional connections.
• To investigate the impact of directed network architecture on information transfer.
• To provide a tool for probing spatio-temporal effects of network motifs.

Main Methods:

• Screened ten microchannel architectures in polydimethylsiloxane (PDMS) devices for axonal guidance.
• Developed a design with a 92% probability of achieving strictly unidirectional connections.
• Cultured networks on multielectrode arrays and recorded bursting activity over time.

Main Results:

• Achieved highly unidirectional connections (92% probability) between neuronal network nodes.
• Demonstrated up to 100-fold increase in directional information flow (transfer entropy) in directed networks.
• Observed greater information flow in directed networks, highlighting the importance of connection directionality.

Conclusions:

• Engineered functional, directional neuronal networks in vitro by controlling network formation parameters.
• The developed technique minimizes response variability and enables probing network motif effects.
• This method is vital for understanding the role of directed neuronal connections in brain function.