title: Probing the mechanism of exocytosis at the hair cell ribbon synapse.
abstract: Hearing relies on faithful synaptic transmission at the ribbon synapse of cochlear inner hair cells (IHCs). Postsynaptic recordings from this synapse in prehearing animals had delivered strong indications for synchronized release of several vesicles. The underlying mechanism, however, remains unclear. Here, we used presynaptic membrane capacitance measurements to test whether IHCs release vesicles in a statistically independent or dependent (coordinated) manner. Exocytic changes of membrane capacitance (deltaC(m)) were repeatedly stimulated in IHCs of prehearing and hearing mice by short depolarizations to preferentially recruit the readily releasable pool of synaptic vesicles. A compound Poisson model was devised to describe hair cell exocytosis and to test the analysis. From the trial-to-trial fluctuations of the deltaC(m) we were able to estimate the apparent size of the elementary fusion event (C(app)) at the hair cell synapse to be 96-223 aF in immature and 55-149 aF in mature IHCs. We also approximated the single vesicle capacitance in IHCs by measurements of synaptic vesicle diameters in electron micrographs. The results (immature, 48 aF; mature, 45 aF) were lower than the respective C(app) estimates. This indicates that coordinated exocytosis of synaptic vesicles occurs at both immature and mature hair cell synapses. Approximately 35% of the release events in mature IHCs and approximately 50% in immature IHCs were predicted to involve coordinated fusion, when assuming a geometric distribution of elementary sizes. In summary, our presynaptic measurements indicate coordinated exocytosis but argue for a lesser degree of coordination than suggested by postsynaptic recordings.
authors.affiliation: Bernstein Center for Computational Neuroscience, Goettingen University, 37073 Goettingen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Neef
authors.forename: Darina
authors.initials: D
authors.lastname: Khimich
authors.forename: Primoz
authors.initials: P
authors.lastname: Pirih
authors.forename: Dietmar
authors.initials: D
authors.lastname: Riedel
authors.forename: Fred
authors.initials: F
authors.lastname: Wolf
authors.forename: Tobias
authors.initials: T
authors.lastname: Moser
mesh_terms: D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005089:Exocytosis / Q000502:physiology*; D006199:Hair Cells, Auditory, Inner / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D013569:Synapses / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure