American Society for Peripheral Nerve

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Anatomical and electrophysiological analysis of the mouse infraorbital nerve as a neural interface
WeiFeng Zeng, MD1; Aaron M. Dingle, PhD2; Conner Feldman, BS1; Jared P Ness, MS3; Joseph R. Novello, MS2; Mark Austin, UG1; Sarah K. Brodnick, BS4; Jane Pisaniello, BS1; Jacqueline S. Israel, MD5; Aaron J Suminski, PhD1; Wendell B Lake, MD1; Justin C. Williams, PhD2; Samuel O. Poore, MD, PhD6; (1)University of Wisconsin-Madison, Madison, WI, (2)University of Wisconsin - Madison, Madison, WI, (3)University of Wisconsin, Madison, WI, (4)Department of Biomedical Engineering, University of Wisconsin, Madison, Madison, WI, (5)Plastic and Reconstructive Surgery, University of Wisconsin - Madison, Madison, WI, (6)Division of Plastic & Reconstructive Surgery, University of Wisconsin, Madison, Madison, WI

Introduction: The trigeminal nerve is the fifth cranial nerve, which divides into three branches: opthalmic (V1), maxillary (V2) and mandibular (V3), and carries most of the tactile, proprioceptive and nociceptive information from the face to the central nervous system (CNS).

The latest preclinical and clinical data indicates that electrical stimulation of the V1 branch treats a variety of neurologic and psychiatric disorders of the CNS (i.e. epilepsy, depression, attention deficit hyperactivity disorder and traumatic brain injury). Despite positive preliminary results in humans, the mechanisms and potential side effects remain largely unknown.

This study applies microsurgical technique to investigate trigeminal nerve interfacing in mice. We describe the development and evaluation of a mouse model of trigeminal nerve stimulation for future mechanistic studies.

Materials and Methods: The trigeminal nerve and its branches was mapped via microsurgical anatomical dissection in mice cadavers. Acute experiments utilized a whisker puffer generate the physiological response in the barrel cortex. Electrical stimulation of the infraorbital nerve was performed distal to the infraorbital foramen with a custom bipolar cuff electrode to replicate the physiological response. Electrical stimulation of the infraorbital nerve was performed using single, monophasic or biphasic (cathode leading) pulses (50-800uA, 100-300us per phase) initiated at pseudorandom intervals (varying between 3-4 seconds). Changes in cortical activity in the barrel cortex were recorded (somatosensory evoked potentials [SSEPs]) custom 16 channel uECoG array.

Results: Investigation of the trigeminal nerve and its branches identified the infraorbital branch as the best candidate for electrical stimulation in mice, measuring 1.6mm in width, 3.2mm in available length, and 2.8mm away from the skin surface. By comparison, the supraorbital branch measured 0.15mm width and 3mm available length. Dorsal and medial access to the infraorbital branch avoids interference with the facial nerve and provides substantial soft tissue to protect the electrode. The magnitude of SSEPs increased monotonically until saturation with increases in stimulation current and activation thresholds decreased with increases in phase duration.

Conclusions: These preliminary results suggest that an infraorbital nerve interface is the best candidate for examining the neural mechanisms of trigeminal nerve stimulation in the mouse. Furthermore, we found every whisker was supplied by individual nerve fiber of the infraorbital nerve, capable of generating a signal in precise areas of cortex dependent on the fiber activated. We are now investigating this model of sensory feedback in the human extremity, a critical component for ideal prosthetic control.

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