Bundling of axons through a capillary alginate gel enhances the detection of axonal action potentials using microelectrode arrays.

Microelectrode arrays (MEAs) have become important tools in high throughput assessment of neuronal activity. However, geometric and electrical constraints largely limit their ability to detect action potentials to the neuronal soma. Enhancing the resolution of these systems to detect axonal action potentials has proved both challenging and complex. In this study, we have bundled sensory axons from dorsal root ganglia through a capillary alginate gel (Capgel (TM)) interfaced with an MEA and observed an enhanced ability to detect spontaneous axonal activity compared with two-dimensional cultures. Moreover, this arrangement facilitated the long-term monitoring of spontaneous activity from the same bundle of axons at a single electrode. Finally, using waveform analysis for cultures treated with the nociceptor agonist capsaicin, we were able to dissect action potentials from multiple axons on an individual electrode, suggesting that this model can reproduce the functional complexity associated with sensory fascicles in vivo. This novel three-dimensional functional model of the peripheral nerve can be used to study the functional complexities of peripheral neuropathies and nerve regeneration as well as being utilized in the development of novel therapeutics.