title: Mechanisms contributing to central excitability changes during hearing loss.
abstract: Exposure to loud sound causes cochlear damage resulting in hearing loss and tinnitus. Tinnitus has been related to hyperactivity in the central auditory pathway occurring weeks after loud sound exposure. However, central excitability changes concomitant to hearing loss and preceding those periods of hyperactivity, remain poorly explored. Here we investigate mechanisms contributing to excitability changes in the dorsal cochlear nucleus (DCN) shortly after exposure to loud sound that produces hearing loss. We show that acoustic overexposure alters synaptic transmission originating from the auditory and the multisensory pathway within the DCN in different ways. A reduction in the number of myelinated auditory nerve fibers leads to a reduced maximal firing rate of DCN principal cells, which cannot be restored by increasing auditory nerve fiber recruitment. In contrast, a decreased membrane resistance of DCN granule cells (multisensory inputs) leads to a reduced maximal firing rate of DCN principal cells that is overcome when additional multisensory fibers are recruited. Furthermore, gain modulation by inhibitory synaptic transmission is disabled in both auditory and multisensory pathways. These cellular mechanisms that contribute to decreased cellular excitability in the central auditory pathway are likely to represent early neurobiological markers of hearing loss and may suggest interventions to delay or stop the development of hyperactivity that has been associated with tinnitus.
authors.affiliation: Department of Cell Physiology and Pharmacology, University of Leicester, Leicester LE19HN, United Kingdom.
authors.forename: Nadia
authors.initials: N
authors.lastname: Pilati
authors.forename: Matias J
authors.initials: MJ
authors.lastname: Ison
authors.forename: Matthew
authors.initials: M
authors.lastname: Barker
authors.forename: Mike
authors.initials: M
authors.lastname: Mulheran
authors.forename: Charles H
authors.initials: CH
authors.lastname: Large
authors.forename: Ian D
authors.initials: ID
authors.lastname: Forsythe
authors.forename: John
authors.initials: J
authors.lastname: Matthias
authors.forename: Martine
authors.initials: M
authors.lastname: Hamann
mesh_terms: D000818:Animals; D001306:Auditory Pathways / Q000473:pathology / Q000503:physiopathology; D001309:Auditory Threshold / Q000502:physiology; D003051:Cochlea / Q000473:pathology / Q000503:physiopathology; D003056:Cochlear Nerve / Q000473:pathology / Q000503:physiopathology*; D017626:Cochlear Nucleus / Q000473:pathology / Q000503:physiopathology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006317:Hearing Loss, Noise-Induced / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000473:pathology / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D014012:Tinnitus / Q000473:pathology / Q000503:physiopathology*