Abstract
The central nervous system is a dense, layered, 3D interconnected network of populations of neurons, and thus recapitulating that complexity for in vitro CNS models requires methods that can create defined topologically-complex neuronal networks. Several three-dimensional patterning approaches have been developed but none have demonstrated the ability to control the connections between populations of neurons. Here we report a method using AC electrokinetic forces that can guide, accelerate, slow down and push up neurites in un-modified collagen scaffolds. We present a means to create in vitro neural networks of arbitrary complexity by using such forces to create 3D intersections of primary neuronal populations that are plated in a 2D plane. We report for the first time in vitro basic brain motifs that have been previously observed in vivo and show that their functional network is highly decorrelated to their structure. This platform can provide building blocks to reproduce in vitro the complexity of neural circuits and provide a minimalistic environment to study the structure-function relationship of the brain circuitry.
Highlights
Activity of individual neurons by conventional means because of their inability to provide wide field of view visual access to all neurons at the same time
We developed a method to create tunable neurite crossings to allow the creation of complex non-planar networks. We demonstrate that this technique can be used to reproduce structurally in vitro human brain basic motifs, a term referred by Sporns[1], by combining population-based neural networks, neurite diodes, and neurite bridges
Our method is based on capillary flow balancing to perfuse defined areas of the microfluidic chip with collagen, followed by removal of collagen from unwanted areas with acetic acid (Fig. S1)
Summary
Activity of individual neurons by conventional means because of their inability to provide wide field of view visual access to all neurons at the same time. For the first time, a method to create in vitro neural networks of arbitrary complexity by using such forces to guide, accelerate, slow down and push up neurites in un-modified collagen scaffolds, allowing 3D intersections of selected neuronal populations that are plated in a 2D plane. We developed a method to create tunable neurite crossings to allow the creation of complex non-planar networks. We demonstrate that this technique can be used to reproduce structurally in vitro human brain basic motifs, a term referred by Sporns[1], by combining population-based neural networks, neurite diodes, and neurite bridges. We analyzed the intra and inter population functional activity of the topologically structured network over time and demonstrated the emergence of small-world organization within those motifs
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
