Abstract
In response to sound stimulation, inner hair cell triggers glutamate release onto the dendrite-like processes of primary auditory neurons and drives action potentials, which are convey to the central nervous system. Whereas knowledge of the transfer function at the ribbon synapse has considerably progress, little is known about the voltage-gated ionic channels which shape the action potential. Here, we provide a comprehensive computational model bridging the gap between the voltage-dependent currents measured in vitro on fresh isolated primary auditory neurons and spikes (extracellular action potentials) recorded in vivo from guinea pig auditory nerve fibers.Voltage-dependent currents (Na+ and K+) of SGNs somata patch-clamp recordings were fitted by a Hodgkin-Huxley model with a full trace identification algorithm. Node of Ranvier model was designed from the hypothesis that channel expressed on soma were identical, but differ in density. Simulated spikes were adjusted in order to match in vivo single-unit recordings with gradient-descent algorithm. Computation of the data allows to the identification of: i) one fast inward Na current (GNa activation: V1/2=-33 mV, τact< 0.5 ms; inactivation: V1/2=-61 mV, τinact < 2 ms); and ii) two K conductances, a high voltage-activated delayed-rectifier component (GKH, activation: V1/2=-41 mV; τact < 2.5 ms) and a low voltage-activated component (GKL, activation: V1/2=-56 mV; τact < 5 ms). Node of Ranvier model generate spikes that fit with in vivo recordings. Interestingly, the different spike durations along the tonotopic axis measured in vivo (i.e. 450 µs peak-to-peak duration versus 250 µs for 1 to 20 kHz, respectively) was explain by a gradual change in Na and K channel densities along the cochlea (GNa ~78 nS, GKL ~9 nS, GKH ~3 nS at 1 kHz versus GNa ~90 nS, GKL ~12 nS, GKH ~6 nS at 20 kHz).This study identifies the ionic conductances and densities, which shape the action potential waveform of auditory nerve fibers and suggests that the interplay of fast inward Na+ current and the two K+ enables the auditory nerve fibers to sustain high firing rates. In addition, this node of Ranvier model provides a valuable tool to design new electrical stimulation strategies for cochlear implants.