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Interfacing 3D Engineered Neuronal Cultures to Micro-Electrode Arrays: An Innovative In Vitro Experimental Model

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Modeling extracellular fields for a three-dimensional network of cells using NEURON.

Shailesh Appukuttan¹, Keith L Brain², Rohit Manchanda¹

¹Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, Maharashtra, India.

Journal of Neuroscience Methods

|July 15, 2017

Summary

This study introduces a new computational method to model extracellular fields in cell networks, enabling the exploration of cell-to-cell electrical signaling in packed tissues like the brain and heart.

Keywords:

Compartmental modeling Electrical syncytium Ephaptic coupling Extracellular recordings Extracellular space NEURON Triphasic action potential

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Area of Science:

Computational neuroscience
Biophysics
Cellular electrophysiology

Background:

Computational cell models often neglect extracellular fields, which may be significant in tightly packed cell networks.
This assumption is particularly questionable for neural networks and cardiac/smooth muscle tissues.

Purpose of the Study:

To develop and implement a computational technique for coupling extracellular fields of individual cells.
To enable the exploration of extracellular interactions within network models.

Main Methods:

Extended the NEURON simulation environment by defining current balance equations to couple adjacent cell extracellular fields.
Implemented a true bi-domain representation for continuous extracellular space in network models, a novel approach for NEURON and similar platforms.

Main Results:

Achieved continuity of extracellular space in a 3D network model, facilitating computational analysis of extracellular interactions.
Evaluated passive and active electrical properties under varying extracellular volumes and analyzed synaptic and action potentials.
Explored the potential of ephaptic transmission for functional cell coupling.

Conclusions:

Successfully coupled extracellular fields of all cells in a 3D model, creating a continuous extracellular space.
This technique provides a novel framework for investigating interactions within densely packed cell networks through their extracellular fields.