Computed SGN spike conduction times with additional delay Δt per 1 µm soma diameter increase.

<p>d1 and d2 represent peripheral and central axon diameters; nmsoma denotes the number of surrounding single membrane layers in the soma region including the pre- and postsomatic segments. t1, t2, t3 and t4 denote postsynaptic delay, spike conduction time in the peripheral axon, presomatic delay and spike conduction time in the central axon, respectively. t_total  = t1+t2+t3+t4, Δt|dsoma+1 µm denotes the enlargement step of the presomatic delay when dsoma is 1 µm increased.</p

Temporal profiles of transmembrane voltages and extracellular potentials of an extracellularly stimulated feline type I cell.

<p>A small ball electrode simulates the situation of monopolar cathodic stimulation with a cochlear implant for a situation shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079256#pone-0079256-g001" target="_blank">Figure 1C</a>. (A) During application of the 100 µs stimulus pulse the voltage across the membrane is influenced in each compartment. For this electrode placement the threshold is reached in the peripheral terminal and therefore the SGN excitation is similar to natural signaling. The transmembrane voltage lines, shifted vertically according to their distance along the neural path, show AP conductance; myelinated compartment responses in dark gray, compartments with voltage sensitive ion channels in red. (B) The short spike duration is demonstrated with the redrawn transmembrane voltage of the presomatic compartment. (C) Simulated extracellular potential for the position of the center of the stimulating electrode. (D) Simulated recorded signal for natural synaptic excitation, modeled as current injection into the first compartment (E) Simulated (blue, copy of C) and experimentally recorded (black) intracochlear voltage profiles generated with a cochlear implant show similar temporal characteristics although the simulated single cell activity is compared with a compound action potential recording. The black curve is redrawn from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079256#pone.0079256-Miller1" target="_blank">[51]</a> (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079256#pone-0079256-g001" target="_blank">Figure 1</a>, intracochlear recording, cathodic pulse −11.1 dB rel. 1 mA). Simulated situations correspond to scala tympani stimulation in the basal turn. Electrode position and neural path as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079256#pone-0079256-g001" target="_blank">Figure 1C</a>; homogeneous extracellular medium with extracellular resistivity of 300 Ohm.cm and other data as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079256#pone.0079256-Rattay3" target="_blank">[7]</a>.</p

Peripheral and central process diameters of type I neurons based on 3 human specimens and 3 cat specimens.

<p>Data according to their location along the cochlea spiral.</p

Compartment models for SGNs.

<p>(A) Type I cells, rectified: Myelinated segments are shown in gray. Excitable (active) membranes with high ion channel densities (red segments) in the peripheral terminal and in the nodes of Ranvier are needed for spike amplification. In contrast to feline cells, in man the pre- and postsomatic compartments are longer, the soma is larger and not myelinated and the peripheral as well as the central axons are longer. (B) According to Ohm's law the sum of all currents to the center of a compartment is zero. The currents are defined by extracellular potential V_e, intracellular potential V_i, membrane capacitance C_m, membrane conductance G_m and intracellular resistance R. Natural excitation by synaptic current from a hair cell ribbon synapse is simulated as current injection into the first compartment (peripheral terminal). In this case extracellular potentials V_e are assumed to be zero. For nonmyelinated type II cells the same modeling approach was used with uniform ion channel densities as in the original Hodgkin-Huxley model and with constant compartment lengths in the axons. (C) The same neural pathway of a human type I cell model as used in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079256#pone.0079256-Rattay3" target="_blank">[7]</a> is placed over a cross section of a feline cochlea demonstrating a possible position of a scala tympani electrode relative to a target cell. The length relations are the same as in the rectified versions in A. Extracellular potentials are calculated for a homogeneous infinite medium which causes spherical isopotentials, indicated by dashed lines. Note that the cat soma is much closer to the electrode than the human one.</p

Visualization of SGN length measurement (A) and z-projection of a confocal image stack (B) of basal human cochlear neurons.

<p>(A) presents the volume rendered bone of an analyzed individual. The brain is illustrated in a transparent manner (blue) together with the manually segmented brainstem (white star). The starting points of the SGNs from the left and right cochleae are highlighted by the white arrows. The manually segmented Nervuli cochlearum are visualized using surface rendering (green colored). The white arrow in (B) highlights a central process connecting the cell body with the cochlear nucleus. The diameter of this neurite was measured to be 2.54 µm. Scale bar in (A) indicates 5 cm; in (B) it indicates 20 µm.</p

Summary of the detected myelinated and type II spiral ganglion cells.

<p>Presented are the total numbers of counted myelinated type I SGN and type II SGN somata from cat and human cochleae, their percentage as well as the evaluated soma diameters. In contrast to man, the vast majority of cell bodies analyzed from cat cochleae were found to be myelinated.</p

Transmission electron microscopy images of human SGNs.

<p>(A) Cell body of a putative type I SGN completely enwrapped with myelin. Additionally, the process of the SGN shows continuous myelination (white arrow heads). The standard human SGN is shown in B. White arrows highlight an unmyelinated cell body encircled by a satellite glial cell and the myelin lacking process of a SGN. The myelination of the central process starts after about 7 µm pointed by the white arrow head. Scale bar 10 µm.</p

Main results of computed SGN conduction times.

<p>The diagram summarizes results from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079256#pone-0079256-t004" target="_blank">Table 4</a>, indicating the impact of axon diameters, soma size and myelin on the arrival time under the assumption d2 = 2*d1 (central axon has doubled diameter of the peripheral process). The spike arrival time scale at the right side shows the total signal conduction time of type I cells for different axon diameters (marked by colors) for small somas (d = 20 µm, thick vectors) and large somas (d = 25 µm, thin vectors). All these cases are simulated with 3 sheets of membranes around the soma (nmsoma = 3) with the exception of the gray vectors (nmsoma = 1) which represent the slowest cases of type I cells. The fastest signal conduction in man (1.522 ms; d1 = 2 µm, dsoma = 20 µm; purple thick vector) is toped by the shorter cat type I cell (green vector). The main part of the figure shows the four phases in SGN signal transduction as distance – time diagrams. All vectors for type I cells start with the same synaptic delay of 100 µs. The lowest vector (purple, d1 = 2 µm) is shifted vertically (according to the presomatic delay) and flattened (because velocity v2 = 2*v1) when the spike arrives at the soma (black vertical arrow). All other vectors have the same characteristic shapes with individual slopes and individual shifts at soma. Note that the vertical time shift at the soma increases when axon diameter decreases. Increase of soma diameter causes an additional delay indicated by the vertical distance between corresponding thin and thick vectors. The slow AP conductance of unmyelinated type II cells (green dashed vector) is obvious: the short presomatic delay (beyond graphical resolution) cannot compensate the 800 µs lasting synaptic delay. The process diameter enlargement at the soma position (d2 = 2*d1) is not as effective as in the myelinated cases. Angles between v2 and v1 slopes (green circle arrows) point out small velocity changes (small velocity ratio v2/v1) in unmyelinated type II neurons (upper green circle) compared to type I ganglion cells (lower green circle arrows).</p

SGN response to strong and weak synaptic stimuli.

<p>(A) Postsynaptic currents from rat experiments are characterized by amplitude, time to peak and time constant for decay. (B–E) responses of a type I SGN with parameters from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079256#pone-0079256-g008" target="_blank">Figure 8A</a> are shown for compartments # 1, 3, 5 and 25. Reduction from a typical synaptic current amplitude (B) to threshold (C) caused an essentially longer delay. Including ion current fluctuations (noisy membrane current model, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079256#pone.0079256-Rattay3" target="_blank">[7]</a>) in all compartments with active channels resulted in sharply synchronized responses for strong stimulation (D) and in late responses with large jitter (E). Compartment 25 is the fifth postsomatic node of Ranvier in the central process and represents the main part of the expected jitter at the proximal axon ending.</p

Simulated spike transduction in afferent cochlear neurons.

<p>Geometry of rectified SGNs (left, myelinated regions in gray) and transmembrane voltage profiles of the corresponding locations (right). For better comparison of phenomenological differences axon diameters and a peripheral terminal length of 10 µm are chosen to be the same in A–C. Spike initiation by a 0.5 ms pulse, 100 pA (A and B) and 500 pA for the non-myelinated case (C). Signal conduction with nearly constant velocities in the axons is indicated by the geometric construct with the broken red lines and thick blue velocity vectors. Note the attenuation of membrane voltage in the passive internodes and, most pronounced, in the presomatic region.</p