A model of synaptic vesicle-pool depletion and replenishment can account for the interspike interval distributions and nonrenewal properties of spontaneous spike trains of auditory-nerve fibers.

In mammalian auditory systems, the spiking characteristics of each primary afferent (type I auditory-nerve fiber; ANF) are mainly determined by a single ribbon synapse in a single receptor cell (inner hair cell; IHC). ANF spike trains therefore provide a window into the operation of these synapses and cells. It was demonstrated previously (Heil et al., 2007) that the distribution of interspike intervals (ISIs) of cat ANFs during spontaneous activity can be modeled as resulting from refractoriness operating on a non-Poisson stochastic point process of excitation (transmitter release events from the IHC). Here, we investigate nonrenewal properties of these cat-ANF spontaneous spike trains, manifest as negative serial ISI correlations and reduced spike-count variability over short timescales. A previously discussed excitatory process, the constrained failure of events from a homogeneous Poisson point process, can account for these properties, but does not offer a parsimonious explanation for certain trends in the data. We then investigate a three-parameter model of vesicle-pool depletion and replenishment and find that it accounts for all experimental observations, including the ISI distributions, with only the release probability varying between spike trains. The maximum number of units (single vesicles or groups of simultaneously released vesicles) in the readily releasable pool and their replenishment time constant can be assumed to be constant (∼4 and 13.5 ms, respectively). We suggest that the organization of the IHC ribbon synapses not only enables sustained release of neurotransmitter but also imposes temporal regularity on the release process, particularly when operating at high rates.