Synaptic alterations at inner hair cells precede spiral ganglion cell loss in aging C57BL/6J mice

2015

JARO

234

219

Recent work shows that acoustic overexposures causing only transient threshold elevation, and no hair cell loss, nevertheless can cause irreversible loss of the synapses between inner hair cells and cochlear nerve fibers (Kujawa and Liberman 2009). This cochlear synaptopathy, which is selective for the subset of sensory fibers with high thresholds and low spontaneous rates (Furman et al. 2013), appeared fully developed at 24-h post-exposure and showed no recovery by 8 weeks. However, prior studies of this synaptopathy counted only pre-synaptic ribbons, did not examine post-exposure times less than 24 h, and did not analyze the spatial patterns of degeneration around the hair cell circumference. Here, we immunostained for pre-synaptic ribbons, post-synaptic terminals and glutamate receptor patches, as well as the hair cell cytoplasm in noise-exposed and control mice to address the dynamics and spatial organization of the synaptopathic process as a function of postexposure time from 0 h to 2 weeks. Our analysis showed that the loss of synaptic elements is nearly complete immediately after the 2-h exposure, that there is a reversible downregulation of gluR expression in the peripheral terminals which may be part of a protective mechanism, that there may be reversible reorganization of synaptic locations immediately after exposure, and that the spatial patterns are consistent with the idea that low-SR fibers are mainly found on the modiolar face of the hair cell and are the most vulnerable to noise-induced degeneration.

Section: Time Course Of Synaptic Loss and Recoverymentioning

confidence: 99%

Dynamics of cochlear synaptopathy after acoustic overexposure

2015

JARO

234

219

“…Combined with the lack of myelination of type-II axons, the morphology suggests a relatively slow response. Previous ultrastructural studies noted the paucity of presynaptic ribbons at the OHC/type-II synapse, as compared to the IHC/type-I synapse: in cat (Dunn and Morest 1975;Liberman et al 1990) and guinea pig (Hashimoto et al 1991), fewer than 10% or 30%, respectively, of OHC synapses show ribbons in the adult, compared to 90-100% in IHCs (Liberman 1980b;Stamataki et al 2006), where their presence enhances temporal precision and increases response rates in type-I fibers (Buran et al 2006) and soundevoked cochlear gross potentials (Khimich et al 2005). Data from the older ultrastructural studies are supported by more recent immunolabeling of synaptic ribbons with antibodies against CtBP2 (Khimich et al 2005).…”

Section: Ultrastructural Studies Of Ohc Synaptic Morphologymentioning

confidence: 95%

“…Synapses between OHCs and their afferent terminals appear less robust than those at the IHC (Dunn and Morest 1975), where a prominent pre-synaptic ribbon with its halo of synaptic vesicles is almost always present (Liberman 1980b;Khimich et al 2005;Stamataki et al 2006). In contrast, ribbons are usually absent in adult OHCs (Dunn and Morest 1975;Liberman et al 1990), and the OHC/type-II synapse is defined only by a small cluster of pre-synaptic vesicles and a small plaque of modest pre-and post-synaptic membrane thickening .…”

Section: Introductionmentioning

confidence: 99%

Reciprocal Synapses Between Outer Hair Cells and their Afferent Terminals: Evidence for a Local Neural Network in the Mammalian Cochlea

Thiers

Nadol

2008

JARO

Cochlear outer hair cells (OHCs) serve both as sensory receptors and biological motors. Their sensory function is poorly understood because their afferent innervation, the type-II spiral ganglion cell, has small unmyelinated axons and constitutes only 5% of the cochlear nerve. Reciprocal synapses between OHCs and their type-II terminals, consisting of paired afferent and efferent specialization, have been described in the primate cochlea. Here, we use serial and semi-serial-section transmission electron microscopy to quantify the nature and number of synaptic interactions in the OHC area of adult cats. Reciprocal synapses were found in all OHC rows and all cochlear frequency regions. They were more common among third-row OHCs and in the apical half of the cochlea, where 86% of synapses were reciprocal. The relative frequency of reciprocal synapses was unchanged following surgical transection of the olivocochlear bundle in one cat, confirming that reciprocal synapses were not formed by efferent fibers. In the normal ear, axo-dendritic synapses between olivocochlear terminals and type-II terminals and/or dendrites were as common as synapses between olivocochlear terminals and OHCs, especially in the first row, where, on average, almost 30 such synapses were seen in the region under a single OHC. The results suggest that a complex local neuronal circuitry in the OHC area, formed by the dendrites of type-II neurons and modulated by the olivocochlear system, may be a fundamental property of the mammalian cochlea, rather than a curiosity of the primate ear. This network may mediate local feedback control of, and bidirectional communication among, OHCs throughout the cochlear spiral.

“…1A, B), and thus determine the innervation density. Each IHC in the juvenile (6-8 weeks) mouse is innervated by~10-20 cochlear nerve synapses, depending on cochlear location (Stamataki et al 2006;Kujawa and Liberman 2009;Meyer et al 2009a, b;Sergeyenko et al 2013).…”

Section: Transforming Coordinate Systems To Analyze Synapses In the Imentioning

confidence: 99%

Olivocochlear Innervation Maintains the Normal Modiolar-Pillar and Habenular-Cuticular Gradients in Cochlear Synaptic Morphology

Yin

Maison

et al. 2014

JARO

Morphological studies of inner hair cell (IHC) synapses with cochlear nerve terminals have suggested that high-and low-threshold fibers differ in the sizes of their pre-and postsynaptic elements as well as the position of their synapses around the hair cell circumference. Here, using high-power confocal microscopy, we measured sizes and spatial positions of presynaptic ribbons, postsynaptic glutamate receptor (GluR) patches, and olivocochlear efferent terminals at eight locations along the cochlear spiral in normal and surgically de-efferented mice. Results confirm a prior report suggesting a modiolar 9 pillar gradient in ribbon size and a complementary pillar 9 modiolar gradient in GluR-patch size. We document a novel habenular G cuticular gradient in GluR patch size and a complementary cuticular G habenular gradient in olivocochlear innervation density. All spatial gradients in synaptic elements collapse after cochlear deefferentation, suggesting a major role of olivocochlear efferents in maintaining functional heterogeneity among cochlear nerve fibers. Our spatial analysis also suggests that adjacent IHCs may contain a different synaptic mix, depending on whether their tilt in the radial plane places their synaptic pole closer to the pillar cells or to the modiolus.