Extracellular single-unit recordings from peripheral nerve axons in vitro by a novel multichannel microelectrode array

Abstract

The peripheral nervous system (PNS) is an attractive target for modulation of afferent input (e.g., nociceptive input signaling tissue damage) to the central nervous system. To advance mechanistic understanding of PNS neural encoding and modulation requires single-unit recordings from individual peripheral neurons or axons. This is challenged by multiple connective tissue layers surrounding peripheral nerve fibers that prevent electrical recordings by existing electrodes or electrode arrays. In this study, we developed a novel microelectrode array (MEA) via silicon-based microfabrication that consists of 5 parallel hydrophilic gold electrodes surrounded by silanized hydrophobic surfaces. This novel hydrophilic/hydrophobic surface pattern guides the peripheral nerve filaments to self-align towards the hydrophilic electrodes, which dramatically reduces the technical challenges in conducting single-unit recordings. We validated our MEA by recording simultaneous single-unit action potentials from individual axons in mouse sciatic nerves, including both myelinated A-fibers and unmyelinated C-fibers. We confirmed that our recordings were single units from individual axons by increasing nerve trunk electrical stimulus intensity, which did not alter the spike shape or amplitude. By reducing the technical challenges, our novel MEA will likely allow peripheral single-unit recordings to be adopted by a larger research community and thus expedite our mechanistic understanding of peripheral neural encoding and modulation.

Multi-channel intraneural vagus nerve recordings with a novel high-density carbon fiber microelectrode array

“…Recording neural activity from autonomic nerves is very challenging due to the often sub-millimeter nature of these nerves 23 , the protective layers surrounding the nerve (epineurium), bundle of axons (perineurium), and individual axons (endoneurium) 24 , 25 , and the low-amplitude waveforms generated from small unmyelinated C-fibers 26 that dominate autonomic nerves 27 , 28 . Studies have applied electrical stimulation on autonomic nerves to record evoked neural activity using extraneural electrodes, which record from outside the nerve 9 , 29 , and intraneural electrodes, which penetrate the nerve 30 .…”

Multi-channel intraneural vagus nerve recordings with a novel high-density carbon fiber microelectrode array

“…Recording neural activity from autonomic nerves is very challenging due to the often submillimeter nature of these nerves 23 , the protective layers surrounding the nerve (epineurium), bundle of axons (perineurium) and individual axons (endoneurium) 24,25 , and the low-amplitude waveforms generated from small unmyelinated C-fibers 26 that dominate autonomic nerves 27,28 .…”

Blocking peripheral drive from colorectal afferents by subkilohertz dorsal root ganglion stimulation

“…Although a powerful method, single-fiber recordings have been used only by a few studies to assess neuromodulatory effects 6,28 because of the challenges of recording single units from peripheral axons. 10 Recent advances in microelectrode arrays interfacing with peripheral nerves 26 will likely allow a broader application of single-fiber recordings in neuromodulation research.…”