Dendritic Degeneration of Human Auditory Nerve Fibers and Its Impact on the Spiking Pattern Under Regular Conditions and During Cochlear Implant Stimulation.

Due to limitations of human studies, detailed computational models enable understanding the neural signaling in the degenerated auditory system and cochlear implants (CIs). Four human cochleae were used to quantify hearing levels depending on dendritic changes in diameter and myelination thickness from type I of the auditory nerve fibers (ANFs). Type I neurons transmit the auditory information as spiking pattern from the inner hair cells (IHCs) to the cochlear nucleus. The impact of dendrite diameter and degree of myelination on neural signal transmission was simulated for (1) synaptic excitation via IHCs and (2) stimulation from CI electrodes. An accurate three-dimensional human cochlear geometry, along with 30 auditory pathways, mimicked the CI environment. The excitation properties of electrical potential distribution induced by two CI were analyzed. Main findings: (1) The unimodal distribution of control dendrite diameters becomes multimodal for hearing loss cases; a group of thin dendrites with diameters between 0.3 and 1 μm with a peak at 0.5 μm appeared. (2) Postsynaptic currents from IHCs excite such thin dendrites easier and earlier than under control conditions. However, this advantage is lost as their conduction velocity decreases proportionally with the diameter and causes increased spike latency and jitter in soma and axon. Firing probability reduces through the soma passage due to the low intracellular current flow in thin dendrites during spiking. (3) Compared with dendrite diameter, variations in myelin thickness have a small impact on spiking performance. (4) Contrary to synaptic excitation, CIs cause several spike initiation sites in dendrite, soma region, and axon; moreover, fiber excitability reduces with fiber diameter. In a few cases, where weak stimuli elicit spikes of a target neuron (TN) in the axon, dendrite diameter reduction has no effect. However, in many cases, a spike in a TN is first initiated in the dendrite, and consequently, dendrite degeneration demands an increase in threshold currents. (5) Threshold currents of a TN and co-stimulation of degenerated ANFs in other frequency regions depend on the electrode position, including its distance to the outer wall, the cochlear turn, and the three-dimensional pathway of the TN.