Synaptic Release Potentiation at Aging Auditory Ribbon Synapses

Frontiers in Aging Neuroscience

Susanna Pietropaolo¹  Yohan Bouleau²  Thibault Peineau²  Didier Dulon²  Séverin Belleudy³ 

[1] INCIA, UMR 5287, CNRS, University of Bordeaux, Bat B2, Pessac, France;Institut de l'Audition, Centre Institut Pasteur/Inserm, Paris, France;Neurophysiologie de la Synapse Auditive, INSERM UMRS 1120, Bordeaux Neurocampus, Université de Bordeaux, Bordeaux, France;

关键词: auditory hair cells;    synaptic ribbons;    synaptopathy;    hyperacusis;    Ca2+ channels;    exocytosis;   

DOI  :  10.3389/fnagi.2021.756449

来源: DOAJ

【 摘 要 】

Age-related hidden hearing loss is often described as a cochlear synaptopathy that results from a progressive degeneration of the inner hair cell (IHC) ribbon synapses. The functional changes occurring at these synapses during aging are not fully understood. Here, we characterized this aging process in IHCs of C57BL/6J mice, a strain which is known to carry a cadherin-23 mutation and experiences early hearing loss with age. These mice, while displaying a large increase in auditory brainstem thresholds due to 50% loss of IHC synaptic ribbons at middle age (postnatal day 365), paradoxically showed enhanced acoustic startle reflex suggesting a hyperacusis-like response. The auditory defect was associated with a large shrinkage of the IHCs' cell body and a drastic enlargement of their remaining presynaptic ribbons which were facing enlarged postsynaptic AMPAR clusters. Presynaptic Ca2+ microdomains and the capacity of IHCs to sustain high rates of exocytosis were largely increased, while on the contrary the expression of the fast-repolarizing BK channels, known to negatively control transmitter release, was decreased. This age-related synaptic plasticity in IHCs suggested a functional potentiation of synaptic transmission at the surviving synapses, a process that could partially compensate the decrease in synapse number and underlie hyperacusis.

【 授权许可】

Unknown