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Vestibular afferent neurons occur as two populations, regular and irregular, that provide distinct information about head motions. Differences in spike timing regularity are correlated with the different sensory responses important for vestibular processing. Relative to irregular afferents, regular afferents have more sustained firing patterns in response to depolarizing current steps, are more excitable, and have different complements of ion channels. Models of vestibular regularity and excitability emphasize the influence of increased expression of low-voltage-activated potassium currents in irregular neurons. We investigated the potential impact of different modes of voltage-gated sodium (NaV) current (transient, persistent, and resurgent) in cell bodies from vestibular ganglion neurons (VGNs), dissociated and cultured overnight. We hypothesized that regular VGNs would show the greatest impact of persistent (non-inactivating) NaVcurrents and of resurgent NaVcurrents, which flow when NaVchannels are blocked and then unblocked. Whole-cell patch clamp experiments showed that much of the NaVcurrent modes is carried by NaV1.6 channels. With simulations, we detected little substantial effect in any model VGN of persistent or resurgent modes on regularity of spike timing driven by postsynaptic current trains. For simulated irregular neurons, we also saw little effect on spike rate or firing pattern. For simulated regular VGNs, adding resurgent current changed the detailed timing of spikes during a current step, while the small persistent conductance (less than10% of transient NaVconductance density) strongly depolarized resting potential, altered spike waveform, and increased spike rate. These results suggest that persistent and resurgent NaVcurrent can have a greater effect on the regular VGNs than on irregular VGNs, where low-voltage-activated K conductances dominate.
Vestibular afferent neurons occur as two populations, regular and irregular, that provide distinct information about head motions. Differences in spike timing regularity are correlated with the different sensory responses important for vestibular processing. Relative to irregular afferents, regular afferents have more sustained firing patterns in response to depolarizing current steps, are more excitable, and have different complements of ion channels. Models of vestibular regularity and excitability emphasize the influence of increased expression of low-voltage-activated potassium currents in irregular neurons. We investigated the potential impact of different modes of voltage-gated sodium (NaV) current (transient, persistent, and resurgent) in cell bodies from vestibular ganglion neurons (VGNs), dissociated and cultured overnight. We hypothesized that regular VGNs would show the greatest impact of persistent (non-inactivating) NaVcurrents and of resurgent NaVcurrents, which flow when NaVchannels are blocked and then unblocked. Whole-cell patch clamp experiments showed that much of the NaVcurrent modes is carried by NaV1.6 channels. With simulations, we detected little substantial effect in any model VGN of persistent or resurgent modes on regularity of spike timing driven by postsynaptic current trains. For simulated irregular neurons, we also saw little effect on spike rate or firing pattern. For simulated regular VGNs, adding resurgent current changed the detailed timing of spikes during a current step, while the small persistent conductance (less than10% of transient NaVconductance density) strongly depolarized resting potential, altered spike waveform, and increased spike rate. These results suggest that persistent and resurgent NaVcurrent can have a greater effect on the regular VGNs than on irregular VGNs, where low-voltage-activated K conductances dominate.
Vestibular afferent neurons occur as two populations with differences in spike timing regularity that are independent of rate. The more excitable regular afferents have lower current thresholds and sustained spiking responses to injected currents, while irregular afferent neurons have higher thresholds and transient responses. Differences in expression of low-voltage-activated potassium (KLV) channels are emphasized in models of spiking regularity and excitability in these neurons, leaving open the potential contributions of the voltage-gated sodium (NaV) channels responsible for the spike upstroke. We investigated the impact of different NaV current modes (transient, persistent, and resurgent) with whole-cell patch clamp experiments in mouse vestibular ganglion neurons (VGNs), the cultured and dissociated cell bodies of afferents. All VGNs had transient NaV current, many had a small persistent (non-inactivating) NaV current, and a few had resurgent current, which flows after the spike when NaV channels that were blocked are unblocked. A known NaV1.6 channel blocker decreased spike rate and altered spike waveforms in both sustained and transient VGNs and affected all three modes of NaV current. A NaV channel agonist enhanced persistent current and increased spike rate and regularity. We hypothesized that persistent and resurgent currents have different effects on sustained (regular) VGNs vs. transient (irregular) VGNs. Lacking blockers specific for the different current modes, we used modeling to isolate their effects on spiking of simulated transient and sustained VGNs, driven by simulated current steps and noisy trains of simulated EPSCs. In all simulated neurons, increasing transient NaV current increased spike rate and rate-independent regularity. In simulated sustained VGNs, adding persistent current increased both rate and rate-independent regularity, while adding resurgent current had limited impact. In transient VGNs, adding persistent current had little impact, while adding resurgent current increased both rate and rate-independent irregularity by enhancing sensitivity to synaptic noise. These experiments show that the small NaV current modes may enhance the differentiation of afferent populations, with persistent currents selectively making regular afferents more regular and resurgent currents selectively making irregular afferents more irregular.
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