Acoustic trauma triggers changes of synaptic function in mammalian hair cells

JUAN GOUTMAN

Seminario; Seminario; 2019

Instituto de Biomedicina de Buenos Aires

Hearing loss is a major public health problem, given that its impact on human communication and quality of life is devastating. Noise exposure has gained relevance as one of the most important sources. The underlying causes of noise-induced hearing loss have been investigated over years at histological and morphological levels, with much less progress in the physiological aspects. In our lab, we investigate synaptic transmission in the mammalian inner ear that allow hair cells to faithfully encode different features of the acoustic information. We are particularly interested in the role of the inner hair cell (IHC) ribbon synapse in this context.Recently, it has been demonstrated that acoustic trauma (AT) producing only transient auditory threshold shifts also produces long-term structural damages to the inner ear, such as a reduction in the number synapses between inner hair cells (IHCs) and afferent neurons. Using a standard noise exposure protocol producing transient loss of hearing sensitivity and also synapse loss, we investigated the capacity of IHC to release neurotransmitter. Patch-clamp recordings were performed on IHCs in an ex-vivo cochlear preparation 1 day after noise exposure, and also in control mice. Synaptic vesicles release from IHCs was estimated by monitoring changes in cell membrane capacitance.Contrary to our initial hypothesis indicating that the AT would produce synaptic fatigue in IHC, we found a potentiation of capacitance jumps, with fairly constant calcium currents in exposed animals. This difference was noted at depolarized IHC Vm (-30 or -20 mV), and it was more pronounced with longer depolarization pulses. Considering that the differences between exposed and un-exposed IHC was larger with prolonged stimuli, we propose that the vesicle recruitment mechanisms are potentiated after trauma. We then asked whether this effect is triggered by the large calcium influx into IHC produced during AT, or if alternatively, it is mediated by the glutamate released during this same situation, and acting retrogradely. To answer this question, we made use of the vesicular glutamate transporter vGluT3 knock out mouse. These animals are deaf because they lack glutamate release at the IHC ribbon synapse, although synaptic contacts between auditory nerve fibers and hair cells are fairly intact. As shown before, IHC from KO animals have slightly larger calcium currents with smaller membrane capacitance changes compared to wild-type litter-mates. After AT IHC showed both reduced release and also calcium influx, compared to un-exposed animals. These results indicate that glutamate is required to produce the modulatory changes in synaptic transmission triggered by AT.We will discuss the possible mechanisms that mediate this effect, and also its pathological consequences.