Where Is the Spike Generator of the Cochlear Nerve? Voltage-Gated Sodium Channels in the Mouse Cochlea

Abstract

The origin of the action potential in the cochlea has been a long-standing puzzle. Because voltage-dependent Na ϩ (Nav) channels are essential for action potential generation, we investigated the detailed distribution of Nav1.6 and Nav1.2 in the cochlear ganglion, cochlear nerve, and organ of Corti, including the type I and type II ganglion cells. In most type I ganglion cells, Nav1.6 was present at the first nodes flanking the myelinated bipolar cell body and at subsequent nodes of Ranvier. In the other ganglion cells, including type II, Nav1.6 clustered in the initial segments of both of the axons that flank the unmyelinated bipolar ganglion cell bodies. In the organ of Corti, Nav1.6 was localized in the short segments of the afferent axons and their sensory endings beneath each inner hair cell. Surprisingly, the outer spiral fibers and their sensory endings were well labeled beneath the outer hair cells over their entire trajectory. In contrast, Nav1.2 in the organ of Corti was localized to the unmyelinated efferent axons and their endings on the inner and outer hair cells. We present a computational model illustrating the potential role of the Nav channel distribution described here. In the deaf mutant quivering mouse, the localization of Nav1.6 was disrupted in the sensory epithelium and ganglion. Together, these results suggest that distinct Nav channels generate and regenerate action potentials at multiple sites along the cochlear ganglion cells and nerve fibers, including the afferent endings, ganglionic initial segments, and nodes of Ranvier.

Spike Encoding of Neurotransmitter Release Timing by Spiral Ganglion Neurons of the Cochlea

“…Strong immunolabeling for Na V 1.6 at the heminode adjacent to the bouton (Lacas-Gervais et al, 2004;Hossain et al, 2005;Lysakowski et al, 2011), the very rapid spike generation we observed, and the results from our two-compartment model support the view that spikes are initiated in the peripheral neurite. This unisynaptic configuration for aural spike generation, contrasting with that of most cortical neurons, is a highly specialized adaptation of structure and function that seems fundamental to the temporal code of the early auditory pathway.…”

“…Most if not all information about the acoustic scene is conveyed across these synapses, and then to the brain in spike trains of type I SGNs (comprising 90 -95% of auditory nerve fibers) (Perkins and Morest, 1975). The spike generator presumably resides near to the compact postsynaptic bouton (Hossain et al, 2005), on the short neurite, which exits the organ of Corti through the basilar membrane before the myelinated axon begins ( Fig. 1 A, B).…”

Initiation of Sodium Spikelets in Basal Dendrites of Neocortical Pyramidal Neurons

“…Locally triggered basal spikelets on the other hand, not only lack the passive boost of the somatic AP, but even worse, their generator current is sucked up by an enormous nearby current sink -the cell body. That a sudden increase in diameter at a neurite-soma junction presents a serious obstacle for propagation of sodium spikes has been shown previously in computer simulations (Goldstein & Rall, 1974;Parnas, Hochstein & Parnas, 1976;Archie & Mel, 2000;Hossain et al, 2005), and, most importantly, in experimental measurements of action potential propagation from the neuronal process into the soma (Tauc, 1962;Ramon, Joyner & Moore, 1975;Golding & Spruston, 1998;Antic et al, 2000;Golding, Staff & Spruston, 2002). Therefore, the relatively low density of sodium channels in basal dendrites, in combination with the proximity of the cell body, might be responsible for the low incidence of basal spikelets in the somatic recordings (Fig.…”

Mutation of OPA1 gene causes deafness by affecting function of auditory nerve terminals

“…Specifically, ECochG showed (1) hair cell receptor potentials to be normal consistent with normal transducer functions; (2) compound action potential of auditory nerve to be absent consistent with impaired synchronous activation of cochlear auditory nerve fibers; and (3) the appearance of low amplitude abnormally prolonged negative potential that adapts to rapid rates of stimulation consistent with neural generation. We suggest that the generators of this prolonged neural potential are the terminal unmyelinated segment of auditory nerve dendrites that are incompletely depolarized to reach threshold for generating action potentials at the first node of Ranvier, a site rich in Na channels (Hossain et al, 2005). The participation of efferent inhibitory activity of the olivocochlear bundle synapsing on auditory nerve terminals could play a role in attenuating the depolarization of auditory nerve terminal if their spontaneous activity were increased in this disorder.…”