title: Auditory nerve synapses persist in ventral cochlear nucleus long after loss of acoustic input in mice with early-onset progressive hearing loss.
abstract: Perceptual performance in persons with hearing loss, especially those using devices to restore hearing, is not fully predicted by traditional audiometric measurements designed to evaluate the status of peripheral function. The integrity of auditory brainstem synapses may vary with different forms of hearing loss, and differential effects on the auditory nerve-brain interface may have particularly profound consequences for the transfer of sound from ear to brain. Loss of auditory nerve synapses in ventral cochlear nucleus (VCN) has been reported after acoustic trauma, ablation of the organ of Corti, and administration of ototoxic compounds. The effects of gradually acquired forms deafness on these synapses are less well understood. We investigated VCN gross morphology and auditory nerve synapse integrity in DBA/2J mice with early-onset progressive sensorineural hearing loss. Hearing status was confirmed using auditory brainstem response audiometry and acoustic startle responses. We found no change in VCN volume, number of macroneurons, or number of VGLUT1-positive auditory nerve terminals between young adult and older, deaf DBA/2J. Cell-type specific analysis revealed no difference in the number of VGLUT1 puncta contacting bushy and multipolar cell body profiles, but the terminals were smaller in deaf DBA/2J mice. Transmission electron microscopy confirmed the presence of numerous healthy, vesicle-filled auditory nerve synapses in older, deaf DBA/2J mice. The present results suggest that synapses can be preserved over a relatively long time-course in gradually acquired deafness. Elucidating the mechanisms supporting survival of central auditory nerve synapses in models of acquired deafness may reveal new opportunities for therapeutic intervention.
authors: Center for Hearing and Balance and Department of Otolaryngology-HNS, Johns Hopkins University, Baltimore, MD 21205, USA.
authors: Brian
authors: B
authors: McGuire
authors: Center for Hearing and Balance and Department of Otolaryngology-HNS, Johns Hopkins University, Baltimore, MD 21205, USA.
authors: Benjamin
authors: B
authors: Fiorillo
authors: Hearing Research Unit, Garvan Institute of Medical Research, Darlinghurst 2010, NSW, Australia; School of Medical Sciences, University of New South Wales, Kensington 2052, NSW, Australia.
authors: David K
authors: DK
authors: Ryugo
authors: Center for Hearing and Balance and Department of Otolaryngology-HNS, Johns Hopkins University, Baltimore, MD 21205, USA. Electronic address: alauer2@jhmi.edu.
authors: Amanda M
authors: AM
authors: Lauer
mesh_terms: D000818:Animals; D003056:Cochlear Nerve / Q000473:pathology*; D017626:Cochlear Nucleus / Q000473:pathology*; D003638:Deafness / Q000473:pathology*; D016057:Evoked Potentials, Auditory, Brain Stem; D005260:Female; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D013216:Reflex, Startle; D013569:Synapses / Q000473:pathology*; D009435:Synaptic Transmission; D000160:Vestibulocochlear Nerve Diseases / Q000473:pathology
keywords: Auditory nerve; Deafness; Endbulb; Hearing loss; Ventral cochlear nucleus