Spontaneous Activity of Auditory-Nerve Fibers: Insights into Stochastic Processes at Ribbon Synapses

Abstract

In several sensory systems, the conversion of the representation of stimuli from graded membrane potentials into stochastic spike trains is performed by ribbon synapses. In the mammalian auditory system, the spiking characteristics of the vast majority of primary afferent auditory-nerve (AN) fibers are determined primarily by a single ribbon synapse in a single inner hair cell (IHC), and thus provide a unique window into the operation of the synapse. Here, we examine the distributions of interspike intervals (ISIs) of cat AN fibers under conditions when the IHC membrane potential can be considered constant and the processes generating AN fiber activity can be considered stationary, namely in the absence of auditory stimulation. Such spontaneous activity is commonly thought to result from an excitatory Poisson point process modified by the refractory properties of the fiber, but here we show that this cannot be the case. Rather, the ISI distributions are one to two orders of magnitude better and very accurately described as a result of a homogeneous stochastic process of excitation (transmitter release events) in which the distribution of interevent times is a mixture of an exponential and a gamma distribution with shape factor 2, both with the same scale parameter. Whereas the scale parameter varies across fibers, the proportions of exponentially and gamma distributed intervals in the mixture, and the refractory properties, can be considered constant. This suggests that all of the ribbon synapses operate in a similar manner, possibly just at different rates. Our findings also constitute an essential step toward a better understanding of the spike-train representation of time-varying stimuli initiated at this synapse, and thus of the fundamentals of temporal coding in the auditory pathway.

An Improved Model for the Rate–Level Functions of Auditory-Nerve Fibers

“…The data for this study were derived from a subset of the ANFs whose interspike interval distributions during spontaneous activity were analyzed and modeled by us previously (Heil et al, 2007). All surgical and recording procedures are described in detail by Heil et al (2007) and are therefore only briefly summarized here.…”

“…All surgical and recording procedures are described in detail by Heil et al (2007) and are therefore only briefly summarized here. All procedures were approved by the Monash University Department of Psychology Animal Ethics Committee.…”

“…The subinterval 1/[K AA ⅐ R max ⅐ (P ϩ P 0 ) ␤ ] decreases as the stimulus amplitude, P, increases, whereas the subinterval 1/R max is constant. Such a sum can be interpreted physiologically (Young and Barta, 1986;Heil et al, 2007). The constant subinterval can be conceived of as a rate-limiting mean dead time.…”

Temporal Considerations for Stimulating Spiral Ganglion Neurons with Cochlear Implants

“…In the healthy acoustically driven ear, spikes are initiated at the peripheral terminal aided by a dense population of Nav1.6 channels (Hossain et al 2005). The spike timing of the SGN inherits variability from the synaptic transmission process between an IHC that is characterized by probabilistic release of vesicles (Glowatzki and Fuchs 2002;Heil et al 2007;Safieddine et al 2012). However, the spike timing of the SGN is known to have intrinsic variability due to the inherent stochasticity of voltage-gated ion channel fluctuations (Verveen and Derksen 1968;Sigworth 1981).…”

“…As such, these neurons act as crucial contributors to the auditory system since they serve as the first layer of auditory neurons encoding afferent spiking information. Inner hair cells release synaptic vesicle packets in a probabilistic nature (Glowatzki and Fuchs 2002;Heil et al 2007;Safieddine et al 2012) which could be responsible for the high variability of SGN firing rates in acoustic stimulation. In contrast, when electrically stimulated with a cochlear implant, SGNs are directly excited by voltage-gated ion channel activity.…”