scholarly journals Mapping developmental maturation of inner hair cell ribbon synapses in the apical mouse cochlea

2019 ◽  
Vol 116 (13) ◽  
pp. 6415-6424 ◽  
Author(s):  
Susann Michanski ◽  
Katharina Smaluch ◽  
Anna Maria Steyer ◽  
Rituparna Chakrabarti ◽  
Cristian Setz ◽  
...  
Keyword(s):  
Hair Cells ◽  
Synaptic Vesicles ◽  
Molecular Assembly ◽  
General Mechanism ◽  
Inner Hair Cell ◽  
Synaptic Ribbon ◽  
Transport Pathways ◽  
Ribbon Synapses ◽  
Functional Maturation ◽  
Developmental Maturation

Ribbon synapses of cochlear inner hair cells (IHCs) undergo molecular assembly and extensive functional and structural maturation before hearing onset. Here, we characterized the nanostructure of IHC synapses from late prenatal mouse embryo stages (embryonic days 14–18) into adulthood [postnatal day (P)48] using electron microscopy and tomography as well as optical nanoscopy of apical turn organs of Corti. We find that synaptic ribbon precursors arrive at presynaptic active zones (AZs) after afferent contacts have been established. These ribbon precursors contain the proteins RIBEYE and piccolino, tether synaptic vesicles and their delivery likely involves active, microtubule-based transport pathways. Synaptic contacts undergo a maturational transformation from multiple small to one single, large AZ. This maturation is characterized by the fusion of ribbon precursors with membrane-anchored ribbons that also appear to fuse with each other. Such fusion events are most frequently encountered around P12 and hence, coincide with hearing onset in mice. Thus, these events likely underlie the morphological and functional maturation of the AZ. Moreover, the postsynaptic densities appear to undergo a similar refinement alongside presynaptic maturation. Blockwise addition of ribbon material by fusion as found during AZ maturation might represent a general mechanism for modulating ribbon size.

scholarly journals Individual synaptic vesicles mediate stimulated exocytosis from cochlear inner hair cells

2018 ◽  
Vol 115 (50) ◽  
pp. 12811-12816 ◽  
Author(s):  
Chad Paul Grabner ◽  
Tobias Moser
Keyword(s):  
Hair Cells ◽  
Synaptic Vesicles ◽  
Basolateral Membrane ◽  
Mean Amplitude ◽  
Auditory Pathway ◽  
Inner Hair Cell ◽  
Excitatory Postsynaptic Currents ◽  
High Level ◽  
High Degree ◽  
Channel Type

Spontaneous excitatory postsynaptic currents (sEPSCs) measured from the first synapse in the mammalian auditory pathway reach a large mean amplitude with a high level of variance (CV between 0.3 and 1). This has led some to propose that each inner hair cell (IHC) ribbon-type active zone (AZ), on average, releases ∼6 synaptic vesicles (SVs) per sEPSC in a coordinated manner. If true, then the predicted change in membrane capacitance (Cm) for such multivesicular fusion events would equate to ∼300 attofarads (aF). Here, we performed cell-attached Cm measurements to directly examine the size of fusion events at the basolateral membrane of IHCs where the AZs are located. The frequency of events depended on the membrane potential and the expression of Cav1.3, the principal Ca2+-channel type of IHCs. Fusion events averaged 40 aF, which equates to a normal-sized SV with an estimated diameter of 37 nm. The calculated SV volumes showed a high degree of variance (CV > 0.6). These results indicate that SVs fused individually with the plasma membrane during spontaneous and evoked release and SV volume may contribute more variability in EPSC amplitude than previously assumed.

scholarly journals Molecular Assembly and Structural Plasticity of Sensory Ribbon Synapses—A Presynaptic Perspective

2020 ◽  
Vol 21 (22) ◽  
pp. 8758
Author(s):  
Roos Anouk Voorn ◽  
Christian Vogl
Keyword(s):  
Spiral Ganglion ◽  
Structural Plasticity ◽  
Molecular Assembly ◽  
Transport Pathways ◽  
Temporal Precision ◽  
Ribbon Synapses ◽  
Retinal Photoreceptors ◽  
Molecular Anatomy ◽  
Ganglion Neurons ◽  
And Function

In the mammalian cochlea, specialized ribbon-type synapses between sensory inner hair cells (IHCs) and postsynaptic spiral ganglion neurons ensure the temporal precision and indefatigability of synaptic sound encoding. These high-through-put synapses are presynaptically characterized by an electron-dense projection—the synaptic ribbon—which provides structural scaffolding and tethers a large pool of synaptic vesicles. While advances have been made in recent years in deciphering the molecular anatomy and function of these specialized active zones, the developmental assembly of this presynaptic interaction hub remains largely elusive. In this review, we discuss the dynamic nature of IHC (pre-) synaptogenesis and highlight molecular key players as well as the transport pathways underlying this process. Since developmental assembly appears to be a highly dynamic process, we further ask if this structural plasticity might be maintained into adulthood, how this may influence the functional properties of a given IHC synapse and how such plasticity could be regulated on the molecular level. To do so, we take a closer look at other ribbon-bearing systems, such as retinal photoreceptors and pinealocytes and aim to infer conserved mechanisms that may mediate these phenomena.

scholarly journals Temporal Vestibular Deficits in synaptojanin 1 (synj1) Mutants

2021 ◽  
Vol 13 ◽  
Author(s):  
Yan Gao ◽  
Teresa Nicolson
Keyword(s):  
Postural Control ◽  
Hair Cells ◽  
Synaptic Vesicles ◽  
Phase Locking ◽  
Vestibular Function ◽  
Loss Of Function ◽  
Vesicle Recycling ◽  
Ribbon Synapses ◽  
Synaptojanin 1 ◽  
Time Required

The lipid phosphatase synaptojanin 1 (synj1) is required for the disassembly of clathrin coats on endocytic compartments. In neurons such activity is necessary for the recycling of endocytosed membrane into synaptic vesicles. Mutations in zebrafish synj1 have been shown to disrupt the activity of ribbon synapses in sensory hair cells. After prolonged mechanical stimulation of hair cells, both phase locking of afferent nerve activity and the recovery of spontaneous release of synaptic vesicles are diminished in synj1 mutants. Presumably as a behavioral consequence of these synaptic deficits, synj1 mutants are unable to maintain an upright posture. To probe vestibular function with respect to postural control in synj1 mutants, we developed a method for assessing the vestibulospinal reflex (VSR) in larvae. We elicited the VSR by rotating the head and recorded tail movements. As expected, the VSR is completely absent in pcdh15a and lhfpl5a mutants that lack inner ear function. Conversely, lhfpl5b mutants, which have a selective loss of function of the lateral line organ, have normal VSRs, suggesting that the hair cells of this organ do not contribute to this reflex. In contrast to mechanotransduction mutants, the synj1 mutant produces normal tail movements during the initial cycles of rotation of the head. Both the amplitude and temporal aspects of the response are unchanged. However, after several rotations, the VSR in synj1 mutants was strongly diminished or absent. Mutant synj1 larvae are able to recover, but the time required for the reappearance of the VSR after prolonged stimulation is dramatically increased in synj1 mutants. Collectively, the data demonstrate a behavioral correlate of the synaptic defects caused by the loss of synj1 function. Our results suggest that defects in synaptic vesicle recycling give rise to fatigue of ribbons synapses and possibly other synapses of the VS circuit, leading to the loss of postural control.

Synaptic ribbon plasticity, ribbon size and potential regulatory mechanisms in utricular and saccular maculae

2005 ◽  
Vol 15 (1) ◽  
pp. 17-30 ◽  
Author(s):  
Muriel D. Ross ◽  
Joseph Varelas
Keyword(s):  
Hair Cells ◽  
Smooth Endoplasmic Reticulum ◽  
Type I ◽  
Synaptic Ribbons ◽  
Type Ii ◽  
Synaptic Ribbon ◽  
Utricular Macula ◽  
Ribbon Synapses ◽  
New Finding ◽  
The Mean

The mean number of synaptic ribbons in type II hair cells of the rat utricular macula increased significantly in weightlessness. In contrast, ribbon synapses of saccular type I hair cells displayed a significant decline early inflight and postflight, and a late numerical overshoot. Further study indicated that the saccular macula had less ultrastructural complexly than the utricular. Additionally, synaptic ribbons were statistically larger in type II hair cells of both maculae, apparently a locus-related scaling effect. A major new finding is that mitochondria in calyces and collateral terminals were linked to vesicles, tubules of smooth endoplasmic reticulum and cell membranes by filaments, forming mitochondrial complexes (MCs). MCs predominated basally in the calyx where calyceal/type I hair cell borders were bound by filaments; at calyceal invaginations of type I hair cells; in calyces and collaterals near synaptic ribbon sites; and in collaterals near reciprocal synapses. MCs may participate in feedback mechanisms at these locations to help regulate synaptic ribbon activity and plasticity in altered gravitational environments.

scholarly journals Dose-Dependent Pattern of Cochlear Synaptic Degeneration in C57BL/6J Mice Induced by Repeated Noise Exposure

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Minfei Qian ◽  
Qixuan Wang ◽  
Zhongying Wang ◽  
Qingping Ma ◽  
Xueling Wang ◽  
...  
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Noise Exposure ◽  
Moderate Intensity ◽  
Intensity Noise ◽  
Inner Hair Cell ◽  
Ribbon Synapses ◽  
Synaptic Degeneration ◽  
Brainstem Response ◽  
Dose Dependent

It is widely accepted that even a single acute noise exposure at moderate intensity that induces temporary threshold shift (TTS) can result in permanent loss of ribbon synapses between inner hair cells and afferents. However, effects of repeated or chronic noise exposures on the cochlear synapses especially medial olivocochlear (MOC) efferent synapses remain elusive. Based on a weeklong repeated exposure model of bandwidth noise over 2-20 kHz for 2 hours at seven intensities (88 to 106 dB SPL with 3 dB increment per gradient) on C57BL/6J mice, we attempted to explore the dose-response mechanism of prolonged noise-induced audiological dysfunction and cochlear synaptic degeneration. In our results, mice repeatedly exposed to relatively low-intensity noise (88, 91, and 94 dB SPL) showed few changes on auditory brainstem response (ABR), ribbon synapses, or MOC efferent synapses. Notably, repeated moderate-intensity noise exposures (97 and 100 dB SPL) not only caused hearing threshold shifts and the inner hair cell ribbon synaptopathy but also impaired MOC efferent synapses, which might contribute to complex patterns of damages on cochlear function and morphology. However, repeated high-intensity (103 and 106 dB SPL) noise exposures induced PTSs mainly accompanied by damages on cochlear amplifier function of outer hair cells and the inner hair cell ribbon synaptopathy, rather than the MOC efferent synaptic degeneration. Moreover, we observed a frequency-dependent vulnerability of the repeated acoustic trauma-induced cochlear synaptic degeneration. This study provides a sight into the hypothesis that noise-induced cochlear synaptic degeneration involves both afferent (ribbon synapses) and efferent (MOC terminals) pathology. The pattern of dose-dependent pathological changes induced by repeated noise exposure at various intensities provides a possible explanation for the complicated cochlear synaptic degeneration in humans. The underlying mechanisms remain to be studied in the future.

scholarly journals Calcium-induced calcium release supports recruitment of synaptic vesicles in auditory hair cells

2016 ◽  
Vol 115 (1) ◽  
pp. 226-239 ◽  
Author(s):  
Manuel Castellano-Muñoz ◽  
Michael E. Schnee ◽  
Anthony J. Ricci
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Synaptic Vesicles ◽  
Calcium Release ◽  
Resting Potential ◽  
Calcium Stores ◽  
Potential Contribution ◽  
Auditory Hair Cells ◽  
Ribbon Synapses ◽  
Calcium Induced Calcium Release

Hair cells from auditory and vestibular systems transmit continuous sound and balance information to the central nervous system through the release of synaptic vesicles at ribbon synapses. The high activity experienced by hair cells requires a unique mechanism to sustain recruitment and replenishment of synaptic vesicles for continuous release. Using pre- and postsynaptic electrophysiological recordings, we explored the potential contribution of calcium-induced calcium release (CICR) in modulating the recruitment of vesicles to auditory hair cell ribbon synapses. Pharmacological manipulation of CICR with agents targeting endoplasmic reticulum calcium stores reduced both spontaneous postsynaptic multiunit activity and the frequency of excitatory postsynaptic currents (EPSCs). Pharmacological treatments had no effect on hair cell resting potential or activation curves for calcium and potassium channels. However, these drugs exerted a reduction in vesicle release measured by dual-sine capacitance methods. In addition, calcium substitution by barium reduced release efficacy by delaying release onset and diminishing vesicle recruitment. Together these results demonstrate a role for calcium stores in hair cell ribbon synaptic transmission and suggest a novel contribution of CICR in hair cell vesicle recruitment. We hypothesize that calcium entry via calcium channels is tightly regulated to control timing of vesicle fusion at the synapse, whereas CICR is used to maintain a tonic calcium signal to modulate vesicle trafficking.

scholarly journals Inner hair cell stereocilia are embedded in the tectorial membrane

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pierre Hakizimana ◽  
Anders Fridberger
Keyword(s):  
Electron Microscopy ◽  
Hair Cell ◽  
Mechanical Stimulation ◽  
Hair Cells ◽  
Viscous Drag ◽  
Tectorial Membrane ◽  
Inner Hair Cell ◽  
Inner Hair Cells ◽  
Inward Currents

AbstractMammalian hearing depends on sound-evoked displacements of the stereocilia of inner hair cells (IHCs), which cause the endogenous mechanoelectrical transducer channels to conduct inward currents of cations including Ca2+. Due to their presumed lack of contacts with the overlaying tectorial membrane (TM), the putative stimulation mechanism for these stereocilia is by means of the viscous drag of the surrounding endolymph. However, despite numerous efforts to characterize the TM by electron microscopy and other techniques, the exact IHC stereocilia-TM relationship remains elusive. Here we show that Ca2+-rich filamentous structures, that we call Ca2+ ducts, connect the TM to the IHC stereocilia to enable mechanical stimulation by the TM while also ensuring the stereocilia access to TM Ca2+. Our results call for a reassessment of the stimulation mechanism for the IHC stereocilia and the TM role in hearing.

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