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

Abstract

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 (ϳ4 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.

Statistical structure of neural spiking under non-Poissonian or other non-white stimulation

“…In a recent study (Peterson et al 2014), negative ISI correlations observed in auditory nerve fibres have been attributed to synaptic depression of the ribbon synapse that generates the input to a nerve fibre. In that case, the spike train was modeled as a thinned-out version of stochastic transmitter release events of the synapse.…”

Spike timing in auditory‐nerve fibers during spontaneous activity and phase locking

“…Most of the cat data were kindly provided by Philip X. Joris and are the same as those used in Figure 6 of Joris and Yin (). The remaining cat data were recorded by Peter Heil and Dexter R. F. Irvine and are used in Heil and Irvine (), Heil and Neubauer (), Heil et al (), and Peterson et al (). The gerbil data were kindly provided by Jérôme Bourien and are the same as those used in Figure 5 of Bourien et al ()…”

“…Note that, for intermediate T , shuffling leads to an increase in F ( T ). Panels D–E modified from Peterson et al ()…”

“…Changes in SR over time, even when relatively small, can give rise to long‐range temporal dependence. In particular, changes might occur when spontaneous activity is recorded from a given ANF over long periods of time (tens of seconds or minutes; for examples, see Figure 2 in Teich et al, ; Figure 4B in Peterson et al, ). Many physiological processes that directly or indirectly affect the spike rate might fluctuate over time.…”

Molecularly and structurally distinct synapses mediate reliable encoding and processing of auditory information

“…This precision is required in order to, for example, encode ITD in the microsecond range for locating a sound source . The sound pressure level is transduced into the graded receptor potentials of IHCs that then drive firing of postsynaptic SGNs at a rate reflecting the stimulus intensity (rate code) Glowatzki et al, 2008;Peterson et al, 2014). One anatomical feature of IHCs strikingly contrasts the arrangement of calyceal synapses with hundreds of active zones originating from one terminal converging onto a principal cell (Figs.…”