Newly identified axon types of the facial nerve unveil supplemental neural pathways in the innervation of the face

Introduction: Neuromuscular control of the facial expressions is provided exclusively via the facial nerve. Facial muscles are amongst the most finely tuned effectors in the human motor system, which coordinate facial expressions. In lower vertebrates, the extracranial facial nerve is a mixed nerve, while in mammals it is believed to be a pure motor nerve. However, this established notion does not agree with several clin-ical signs in health and disease. Objectives: To elucidate the facial nerve contribution to the facial muscles by investigating axonal com-position of the human facial nerve. To reveal new innervation pathways of other axon types of the motor facial nerve.Methods: Different axon types were distinguished using specific molecular markers (NF, ChAT, CGRP and TH). To elucidate the functional role of axon types of the facial nerve, we used selective elimination of other neuronal support from the trigeminal nerve. We used retrograde neuronal tracing, three-dimensional imaging of the facial muscles, and high-fidelity neurophysiological tests in animal model. Results: The human facial nerve revealed a mixed population of only 85% motor axons. Rodent samples revealed a fiber composition of motor, afferents and, surprisingly, sympathetic axons. We confirmed the axon types by tracing the originating neurons in the CNS. The sympathetic fibers of the facial nerve ter-minated in facial muscles suggesting autonomic innervation. The afferent fibers originated in the facial skin, confirming the afferent signal conduction via the facial nerve. Conclusion: These findings reveal new innervation pathways via the facial nerve, support the sympathetic etiology of hemifacial spasm and elucidate clinical phenomena in facial nerve regeneration.(c) 2022 The Authors. Published by Elsevier B.V. on behalf of Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).