title: A non-canonical pathway from cochlea to brain signals tissue-damaging noise.
abstract: Intense noise damages the cochlear organ of Corti, particularly the outer hair cells (OHCs) [1]; however, this epithelium is not innervated by nociceptors of somatosensory ganglia, which detect damage elsewhere in the body. The only sensory neurons innervating the organ of Corti originate from the spiral ganglion, roughly 95% of which innervate exclusively inner hair cells (IHCs) [2-4]. Upon sound stimulation, IHCs release glutamate to activate AMPA-type receptors on these myelinated type-I neurons, which carry the neuronal signals to the cochlear nucleus. The remaining spiral ganglion cells (type IIs) are unmyelinated and contact OHCs [2-4]. Their function is unknown. Using immunoreactivity to cFos, we documented neuronal activation in the brainstem of Vglut3(-/-) mice, in which the canonical auditory pathway (activation of type-I afferents by glutamate released from inner hair cells) is silenced [5, 6]. In these deaf mice, we found responses to noxious noise, which damages hair cells, but not to innocuous noise, in neurons of the cochlear nucleus, but not in the vestibular or trigeminal nuclei. This response originates in the cochlea and not in other areas also stimulated by intense noise (middle ear and vestibule) as it was absent in CD1 mice with selective cochlear degeneration but normal vestibular and somatosensory function. These data imply the existence of an alternative neuronal pathway from cochlea to brainstem that is activated by tissue-damaging noise and does not require glutamate release from IHCs. This detection of noise-induced tissue damage, possibly by type-II cochlear afferents, represents a novel form of sensation that we term auditory nociception.
authors: Department of Anesthesiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors: Emma N
authors: EN
authors: Flores
authors: Department of Anesthesiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors: Anne
authors: A
authors: Duggan
authors: Department of Anesthesiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors: Thomas
authors: T
authors: Madathany
authors: Department of Anesthesiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors: Ann K
authors: AK
authors: Hogan
authors: Department of Anesthesiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors: Freddie G
authors: FG
authors: Márquez
authors: Department of Anesthesiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors: Gagan
authors: G
authors: Kumar
authors: Departments of Neurology and Physiology, University of California, San Francisco, San Francisco, CA 94158-2517, USA.
authors: Rebecca P
authors: RP
authors: Seal
authors: Departments of Neurology and Physiology, University of California, San Francisco, San Francisco, CA 94158-2517, USA.
authors: Robert H
authors: RH
authors: Edwards
authors: Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, and Department of Otology and Laryngology, Harvard Medical School, Boston, MA 02114, USA.
authors: M Charles
authors: MC
authors: Liberman
authors: Department of Anesthesiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Departments of Neurology and Physiology and Hugh Knowles Center for Clinical and Basic Science in Hearing and Its Disorders, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. Electronic address: anoveros@northwestern.edu.
authors: Jaime
authors: J
authors: García-Añoveros
mesh_terms: D000344:Afferent Pathways / Q000502:physiology*; D026922:Amino Acid Transport Systems, Acidic / Q000235:genetics; D000818:Animals; D001307:Auditory Perception / Q000502:physiology*; D001933:Brain Stem / Q000502:physiology*; D003051:Cochlea / Q000502:physiology*; D006199:Hair Cells, Auditory, Inner / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008959:Models, Neurological; D059225:Nociception / Q000502:physiology*; D009622:Noise / Q000009:adverse effects*
chemical_list: D026922:Amino Acid Transport Systems, Acidic; C504941:Slc17a8 protein, mouse
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