+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Individual synaptic vesicles mediate stimulated exocytosis from cochlear inner hair cells

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          Synaptic transmission is codetermined by presynaptic and postsynaptic neurons. Therefore, to understand how the inner hair cell (IHC) signals to spiral ganglion neurons at the first synapse in the auditory pathway, here we directly studied individual membrane fusion events by making cell-attached membrane capacitance recordings from IHCs, for which the quantal size is debated. The observed fusion steps in membrane capacitance are consistent with the quantal hypothesis of synaptic transmission in which individual synaptic vesicles undergo exocytosis independently from each other. This finding, in conjunction with previous work, raises the exciting possibility that action potential generation can be triggered by the release of a single vesicle at the IHC synapse.


          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 (C m) for such multivesicular fusion events would equate to ∼300 attofarads (aF). Here, we performed cell-attached C m 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 Ca v1.3, the principal Ca 2+-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.

          Related collections

          Most cited references 54

          • Record: found
          • Abstract: found
          • Article: not found

          Congenital deafness and sinoatrial node dysfunction in mice lacking class D L-type Ca2+ channels.

          Voltage-gated L-type Ca2+ channels (LTCCs) containing a pore-forming alpha1D subunit (D-LTCCs) are expressed in neurons and neuroendocrine cells. Their relative contribution to total L-type Ca2+ currents and their physiological role and significance as a drug target remain unknown. Therefore, we generated D-LTCC deficient mice (alpha1D-/-) that were viable with no major disturbances of glucose metabolism. alpha1D-/-mice were deaf due to the complete absence of L-type currents in cochlear inner hair cells and degeneration of outer and inner hair cells. In wild-type controls, D-LTCC-mediated currents showed low activation thresholds and slow inactivation kinetics. Electrocardiogram recordings revealed sinoatrial node dysfunction (bradycardia and arrhythmia) in alpha1D-/- mice. We conclude that alpha1D can form LTCCs with negative activation thresholds essential for normal auditory function and control of cardiac pacemaker activity.
            • Record: found
            • Abstract: found
            • Article: not found

            Hair cell synaptic ribbons are essential for synchronous auditory signalling.

            Hearing relies on faithful synaptic transmission at the ribbon synapse of cochlear inner hair cells (IHCs). At present, the function of presynaptic ribbons at these synapses is still largely unknown. Here we show that anchoring of IHC ribbons is impaired in mouse mutants for the presynaptic scaffolding protein Bassoon. The lack of active-zone-anchored synaptic ribbons reduced the presynaptic readily releasable vesicle pool, and impaired synchronous auditory signalling as revealed by recordings of exocytic IHC capacitance changes and sound-evoked activation of spiral ganglion neurons. Both exocytosis of the hair cell releasable vesicle pool and the number of synchronously activated spiral ganglion neurons co-varied with the number of anchored ribbons during development. Interestingly, ribbon-deficient IHCs were still capable of sustained exocytosis with normal Ca2+-dependence. Endocytic membrane retrieval was intact, but an accumulation of tubular and cisternal membrane profiles was observed in ribbon-deficient IHCs. We conclude that ribbon-dependent synchronous release of multiple vesicles at the hair cell afferent synapse is essential for normal hearing.
              • Record: found
              • Abstract: found
              • Article: not found

              Transmitter release at the hair cell ribbon synapse.

              Neurotransmitters are released continuously at ribbon synapses in the retina and cochlea. Notably, a single ribbon synapse of inner hair cells provides the entire input to each cochlear afferent fiber. We investigated hair cell transmitter release in the postnatal rat cochlea by recording excitatory postsynaptic currents (EPSCs) from afferent boutons directly abutting the ribbon synapse. EPSCs were carried by rapidly gating AMPA receptors. EPSCs were clustered in time, indicating the possibility of coordinate release. Amplitude distributions of spontaneous EPSCs were highly skewed, peaking at 0.4 nS and ranging up to 20 times larger. Hair cell depolarization increased EPSC frequency up to 150 Hz without altering the amplitude distribution. We propose that the ribbon synapse operates by multivesicular release, possibly to achieve high-frequency transmission.

                Author and article information

                Proc Natl Acad Sci U S A
                Proc. Natl. Acad. Sci. U.S.A
                Proceedings of the National Academy of Sciences of the United States of America
                National Academy of Sciences
                11 December 2018
                21 November 2018
                21 November 2018
                : 115
                : 50
                : 12811-12816
                aSynaptic Nanophysiology Group, Max Planck Institute for Biophysical Chemistry , 37077 Göttingen, Germany;
                bInstitute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen , 37075 Göttingen, Germany;
                cAuditory Neuroscience Group, Max Planck Institute for Experimental Medicine , 37075 Göttingen, Germany
                Author notes
                1To whom correspondence should be addressed. Email: chadgrabner@ .

                Edited by A. J. Hudspeth, The Rockefeller University, New York, NY, and approved October 19, 2018 (received for review July 9, 2018)

                Author contributions: C.P.G. and T.M. designed research; C.P.G. performed research; C.P.G. contributed new reagents/analytic tools; C.P.G. analyzed data; and C.P.G. and T.M. wrote the paper.

                Copyright © 2018 the Author(s). Published by PNAS.

                This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).

                Pages: 6
                Biological Sciences


                Comment on this article