title: Age-related changes in auditory nerve-inner hair cell connections, hair cell numbers, auditory brain stem response and gap detection in UM-HET4 mice.
abstract: This study compared the timing of appearance of three components of age-related hearing loss that determine the pattern and severity of presbycusis: the functional and structural pathologies of sensory cells and neurons and changes in gap detection (GD), the latter as an indicator of auditory temporal processing. Using UM-HET4 mice, genetically heterogeneous mice derived from four inbred strains, we studied the integrity of inner and outer hair cells by position along the cochlear spiral, inner hair cell-auditory nerve connections, spiral ganglion neurons (SGN), and determined auditory thresholds, as well as pre-pulse and gap inhibition of the acoustic startle reflex (ASR). Comparisons were made between mice of 5-7, 22-24 and 27-29 months of age. There was individual variability among mice in the onset and extent of age-related auditory pathology. At 22-24 months of age a moderate to large loss of outer hair cells was restricted to the apical third of the cochlea and threshold shifts in the auditory brain stem response were minimal. There was also a large and significant loss of inner hair cell-auditory nerve connections and a significant reduction in GD. The expression of Ntf3 in the cochlea was significantly reduced. At 27-29 months of age there was no further change in the mean number of synaptic connections per inner hair cell or in GD, but a moderate to large loss of outer hair cells was found across all cochlear turns as well as significantly increased ABR threshold shifts at 4, 12, 24 and 48 kHz. A statistical analysis of correlations on an individual animal basis revealed that neither the hair cell loss nor the ABR threshold shifts correlated with loss of GD or with the loss of connections, consistent with independent pathological mechanisms.
authors: Kresge Hearing Research Institute, Dept. of Otolaryngology, University of Michigan, Ann Arbor, MI, USA; Dept. of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.
authors: R A
authors: RA
authors: Altschuler
authors: Kresge Hearing Research Institute, Dept. of Otolaryngology, University of Michigan, Ann Arbor, MI, USA.
authors: D F
authors: DF
authors: Dolan
authors: Kresge Hearing Research Institute, Dept. of Otolaryngology, University of Michigan, Ann Arbor, MI, USA.
authors: K
authors: K
authors: Halsey
authors: Kresge Hearing Research Institute, Dept. of Otolaryngology, University of Michigan, Ann Arbor, MI, USA.
authors: A
authors: A
authors: Kanicki
authors: Kresge Hearing Research Institute, Dept. of Otolaryngology, University of Michigan, Ann Arbor, MI, USA.
authors: N
authors: N
authors: Deng
authors: Kresge Hearing Research Institute, Dept. of Otolaryngology, University of Michigan, Ann Arbor, MI, USA.
authors: C
authors: C
authors: Martin
authors: Kresge Hearing Research Institute, Dept. of Otolaryngology, University of Michigan, Ann Arbor, MI, USA.
authors: J
authors: J
authors: Eberle
authors: Kresge Hearing Research Institute, Dept. of Otolaryngology, University of Michigan, Ann Arbor, MI, USA; Dept. of Human Genetics, University of Michigan, Ann Arbor, MI, USA.
authors: D C
authors: DC
authors: Kohrman
authors: Dept. of Pathology, University of Michigan, Ann Arbor, MI, USA.
authors: R A
authors: RA
authors: Miller
authors: Kresge Hearing Research Institute, Dept. of Otolaryngology, University of Michigan, Ann Arbor, MI, USA.
authors: J
authors: J
authors: Schacht
mesh_terms: D000375:Aging / Q000473:pathology / Q000502:physiology*; D000818:Animals; D001306:Auditory Pathways / Q000473:pathology / Q000502:physiology; D001307:Auditory Perception / Q000502:physiology*; D001309:Auditory Threshold / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002452:Cell Count; D003056:Cochlear Nerve / Q000473:pathology / Q000502:physiology*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology*; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D006199:Hair Cells, Auditory, Inner / Q000473:pathology / Q000502:physiology*; D018072:Hair Cells, Auditory, Outer / Q000473:pathology / Q000502:physiology; D051379:Mice; D011897:Random Allocation; D013216:Reflex, Startle / Q000502:physiology; D013136:Spiral Ganglion / Q000473:pathology / Q000502:physiology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor
keywords: NT3; age-related hearing loss; aging; auditory; cochlea; gap detection