Probing the Mechanism of Exocytosis at the Hair Cell Ribbon Synapse

• DOI: 10.1523/jneurosci.1996-07.2007
• Publication Date: 2007-11-21T18:29:04Z
• Authors: Andreas Neef; Darina Khimich; Primoz Pirih; Dietmar Riedel; Fred Wolf; Tobias Moser
• Keywords: 0301 basic medicine; MEMBRANE CAPACITANCE; capacitance; ribbon; hair cell; compound Poisson process; Exocytosis; Mice; 03 medical and health sciences; FUSION; synapse; QUANTAL ANALYSIS; DENSE-CORE VESICLES; Animals; ADRENAL CHROMAFFIN CELLS; Hair Cells, Auditory, Inner; fluctuation; MULTIVESICULAR RELEASE; AFFERENT SYNAPSE; Excitatory Postsynaptic Potentials; SEQUENTIAL EXOCYTOSIS; SINGLE; COMPOUND EXOCYTOSIS; Synapses; sound encoding; exocytosis

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 (ΔCm) 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 ΔCmwe were able to estimate the apparent size of the elementary fusion event (Capp) 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 respectiveCappestimates. 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 ∼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.