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Gültas, M.

Publications and source records attributed to Gültas, M..

3 recordsLinked to original sources

Age-dependent structural reorganization of utricular ribbon synapses

In mammals, spatial orientation is synaptically-encoded by sensory hair cells of the vestibular labyrinth. Vestibular hair cells (VHCs) harbor synaptic ribbons at their presynaptic active zones (AZs), which play a critical role in molecular scaffolding and facilitate synaptic release and vesicular replenishment. With advancing age, the prevalence of vestibular deficits increases; yet, a direct link to the functional decline of VHC ribbon synapses remains to be demonstrated. To address this issue, we investigated the effects of aging on the ultrastructure of the ribbon-type AZs in murine utricles using various electron microscopic techniques and combined them with confocal and super-resolution light microscopy as well as metabolic imaging up to one year of age. In older animals, we detected predominantly in type I VHCs the formation of floating ribbon clusters. Our findings suggest that VHC ribbon-type AZs undergo dramatic structural alterations upon aging.

cell biology↗

Piccolino regulates the architecture of the ribbon at cochlear inner hair cell synapses

Cochlear inner hair cells (IHCs) form specialized ribbon synapses with spiral ganglion neurons that tireless-ly transmit sound information at high rates over long time periods with extreme temporal precision. This functional specialization is essential for precise sound encoding and is attributed to a distinct molecular machinery with unique players or splice variants compared to conventional neuronal synapses. Among these is the active zone (AZ) scaffold protein piccolo/aczonin, which is represented by its short splice variant piccolino at cochlear and retinal ribbon synapses. While the function of piccolo at synapses of the central nervous system has been intensively investigated, the role of piccolino at IHC synapses remains unclear. In this study, we characterized the structure and function of IHC-synapses in piccolo gene-trap mutant rats (Pclogt/gt). We found a mild hearing deficit with elevated thresholds and reduced amplitudes of auditory brainstem responses. Ca2+ channel distribution and ribbon morphology were altered in apical IHCs, while their presynaptic function seemed unchanged. We conclude that piccolino contributes to the AZ organization in IHCs and is essential for normal synaptic transmission.

neuroscience↗

Optogenetics and electron tomography for structure-function analysis of cochlear ribbon synapses

Ribbon synapses of cochlear inner hair cells (IHCs) are specialized to indefatigably transmit sound information at high rates. To understand the underlying mechanisms, structure-function analysis of the active zone (AZ) of these synapses is essential. Previous electron microscopy studies of synaptic vesicle (SV) dynamics at the IHC AZ used potassium stimulation, which limited the temporal resolution to minutes. Here, we established optogenetic IHC stimulation followed by quick freezing within milliseconds and electron tomography to study the ultrastructure of functional synapse states with good temporal resolution. We characterized optogenetic IHC stimulation by patch-clamp recordings from IHCs and postsynaptic boutons revealing robust IHC depolarization and transmitter release. Ultrastructurally, the number of docked SVs increased and distances to the presynaptic density decreased upon short (17-25 ms) and long (48-76 ms) light stimulation paradigms. We did not observe enlarged SVs or other morphological correlates of homotypic fusion events. Our results suggest a rapid replenishment of docked SVs at IHC ribbon synapses and argue against synchronized multiquantal release under our experimental conditions.

neuroscience↗