Dataset Information

Synaptic mitochondria regulate hair-cell synapse size and function.

ABSTRACT: Sensory hair cells in the ear utilize specialized ribbon synapses. These synapses are defined by electron-dense presynaptic structures called ribbons, composed primarily of the structural protein Ribeye. Previous work has shown that voltage-gated influx of Ca²⁺ through Ca_V1.3 channels is critical for hair-cell synapse function and can impede ribbon formation. We show that in mature zebrafish hair cells, evoked presynaptic-Ca²⁺ influx through Ca_V1.3 channels initiates mitochondrial-Ca²⁺ (mito-Ca²⁺) uptake adjacent to ribbons. Block of mito-Ca²⁺ uptake in mature cells depresses presynaptic-Ca²⁺ influx and impacts synapse integrity. In developing zebrafish hair cells, mito-Ca²⁺ uptake coincides with spontaneous rises in presynaptic-Ca²⁺ influx. Spontaneous mito-Ca²⁺ loading lowers cellular NAD⁺/NADH redox and downregulates ribbon size. Direct application of NAD⁺ or NADH increases or decreases ribbon size respectively, possibly acting through the NAD(H)-binding domain on Ribeye. Our results present a mechanism where presynaptic- and mito-Ca²⁺ couple to confer proper presynaptic function and formation.

SUBMITTER: Wong HC

PROVIDER: S-EPMC6879205 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Synaptic mitochondria regulate hair-cell synapse size and function.

Wong Hiu-Tung C HC Zhang Qiuxiang Q Beirl Alisha J AJ Petralia Ronald S RS Wang Ya-Xian YX Kindt Katie K

eLife 20191014

Sensory hair cells in the ear utilize specialized ribbon synapses. These synapses are defined by electron-dense presynaptic structures called ribbons, composed primarily of the structural protein Ribeye. Previous work has shown that voltage-gated influx of Ca2+ through CaV1.3 channels is critical for hair-cell synapse function and can impede ribbon formation. We show that in mature zebrafish hair cells, evoked presynaptic-Ca2+ influx through CaV1.3 cha ...[more]

PMID: 31609202

Similar Datasets

Project description:The early auditory pathway processes information at high rates and with utmost temporal fidelity. Consequently, the synapses in the auditory pathway are highly specialized to meet the extraordinary requirements on signal transmission. The calyceal synapses in the auditory brainstem feature more than a hundred active zones (AZs) with thousands of releasable synaptic vesicles (SVs). In contrast, the first auditory synapse, the afferent synapse of inner hair cells (IHCs) and type I spiral ganglion neurons (SGNs), typically exhibits a single ribbon-type AZ tethering only tens of SVs resulting in a highly stochastic pattern of transmitter release. Spontaneous excitatory postsynaptic currents (sEPSCs), besides more conventional EPSCs with a single peak, fast rise and decay (compact), also include EPSCs with multiple peaks, variable rise and decay times (non-compact). The strong heterogeneity in size and shape of spontaneous EPSCs has led to the hypothesis of multivesicular release (MVR) that is more (compact) or less (non-compact) synchronized by coordination of release sites. Alternatively, univesicular release (UVR), potentially involving glutamate release through a flickering fusion pore for non-compact EPSCs, has been suggested to underlie IHC exocytosis. Here, we further investigated the mode of release by recording sEPSCs from SGNs of hearing rats while manipulating presynaptic IHC Ca2+ influx by changes in extracellular [Ca2+] ([Ca2+]e) and by application of the Ca2+ channel antagonist, isradipine, or the Ca2+ channel agonist, BayK8644 (BayK). Our data reveal that Ca2+ influx manipulation leaves the distributions of sEPSC amplitude and charge largely unchanged. Regardless the type of manipulation, the rate of sEPSC decreased with the reduction in Ca2+ influx. The fraction of compact sEPSCs was increased in the presence of BayK, an effect that was abolished when combined with decreased [Ca2+]e. In conclusion, we propose that UVR is the prevailing mode of exocytosis at cochlear IHCs of hearing rats, whereby the rate of exocytosis and the kinetics of SV fusion are regulated by Ca2+ influx.

Dataset Information

Synaptic mitochondria regulate hair-cell synapse size and function.

Publications

Synaptic mitochondria regulate hair-cell synapse size and function.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets