Tracking axonal action potential propagation on a high-density microelectrode array across hundreds of sites

• Published in: Nature communications Vol. 4; no. 1; p. 2181
• Main Authors: Bakkum, Douglas J., Frey, Urs, Radivojevic, Milos, Russell, Thomas L., Müller, Jan, Fiscella, Michele, Takahashi, Hirokazu, Hierlemann, Andreas
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 2013; Nature Publishing Group
• Subjects: 631/1647/2204/1453; 631/378/1697; Action Potentials - physiology; Animals; Axons - physiology; Cerebral Cortex - cytology; Cerebral Cortex - embryology; Cerebral Cortex - physiology; Electric Stimulation; Electrophysiological Phenomena; Embryo, Mammalian; Humanities and Social Sciences; Microelectrodes; multidisciplinary; Rats; Rats, Wistar; Science; Science (multidisciplinary); Semiconductors; Time Factors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms3181

Axons are traditionally considered stable transmission cables, but evidence of the regulation of action potential propagation demonstrates that axons may have more important roles. However, their small diameters render intracellular recordings challenging, and low-magnitude extracellular signals are difficult to detect and assign. Better experimental access to axonal function would help to advance this field. Here we report methods to electrically visualize action potential propagation and network topology in cortical neurons grown over custom arrays, which contain 11,011 microelectrodes and are fabricated using complementary metal oxide semiconductor technology. Any neuron lying on the array can be recorded at high spatio-temporal resolution, and simultaneously precisely stimulated with little artifact. We find substantial velocity differences occurring locally within single axons, suggesting that the temporal control of a neuron’s output may contribute to neuronal information processing. Optical techniques that are used to study neuronal action potential propagation are limited by phototoxicity and photobleaching. Here the authors describe a microelectrode system that allows simultaneous stimulation and recordings of action potential propagation across hundreds of sites in cultured neurons.